CROI 2012

SEATTLE – Patients with poorly controlled HIV infection have a more rapid decline of lung function over time than their uninfected counterparts, researchers reported at the Conference on Retroviruses and Opportunistic Infections.

The findings "suggest that, potentially, optimal antiretroviral therapy (ART) with HIV virological suppression may diminish the accelerated lung function decline that we are seeing," said Dr. M. Bradley Drummond, a pulmonologist at the Johns Hopkins University in Baltimore.

"Certainly, all individuals should quit smoking, but these data suggest that those with HIV should be specifically counseled about the importance of smoking cessation," he further noted in a related press briefing.

Dr. Drummond and colleagues assessed lung function over a period of 3 years in 1,064 injection drug users, about a third of whom were HIV positive.

Results showed that the rate of decline in forced expiratory volume in 1 second (FEV₁) was about 50% greater in HIV-positive individuals than in their HIV-negative counterparts overall even after taking into account potential confounders such as bacterial and Pneumocystis lung infections, pack-years of smoking, and current smoking status.

In stratified analyses, the decline was especially high – three to four times that in the HIV-negative group – for HIV-positive individuals who had poorly controlled HIV infection as indicated by high HIV viral loads or low CD4 counts.

"We conclude that markers of advanced and uncontrolled HIV disease are associated with more rapid decline in lung function. We also feel that the FEV₁ decline associated with uncontrolled HIV exceeds the effect of smoking in the general population," Dr. Drummond commented.

For the study, the investigators analyzed data from a subset of individuals enrolled in AIDS-Linked to the Intravenous Experience (ALIVE), a community-based cohort of current or former injection drug users who had semiannual clinical exams, blood tests, and spirometry measurements.

The individuals were 49 years old, on average, and predominantly male (65%), black (91%), and current or former smokers (94%). In all, 30% were HIV positive, of whom slightly more than half were on ART. The median duration of follow-up was 2.8 years.

Modeling results suggested that for typical individuals in the cohort, FEV₁ at baseline was 139 mL lower in HIV-positive individuals, compared with their HIV-negative counterparts after adjustment for potential confounders. This is statistically significant and clinically significant, Dr. Drummond commented.

In addition, over time, FEV₁ declined by 36 mL/yr in HIV-positive individuals (P = .06), or 50% faster than the 24 mL/yr decline seen in HIV-negative individuals. "That is probably not clinically significant; however, the reality about the ALIVE cohort is there is a relatively heterogeneous group of individuals with different degrees of HIV severity," he noted.

Analyses looking at the impact of viral load showed that HIV-positive individuals having a load of more than 75,000 copies/mL had a rate of FEV₁ decline of 99 mL/yr – more than four times that of HIV-negative individuals (P less than .01). But HIV-positive individuals with a lower viral load had a similar rate of decline as those who were HIV-negative.

Likewise, in analyses looking at the impact of CD4 count, the rate of FEV₁ decline steadily increased as CD4 count decreased. HIV-positive individuals having fewer than 100 CD4 cells/mm3 had a rate of 81 mL/yr – more than three times the rate among the HIV-negative group (P less than .01).

The investigators also conducted doubly stratified analyses looking at both viral load and CD4 count. "It really does look like actually the viral load effect is what’s driving most of the FEV₁ decline. So our money is on the viral load," Dr. Drummond said.

One session attendee asked whether the decline in pulmonary function was reversible when patients started ART. Dr. Drummond replied that most of the HIV-positive group did not have any changes to their therapy during observation, making it difficult to assess this. "We are doing a separate study where we are actually looking at pre- and post-ART initiation ... Hopefully, we would see some stabilization of breathing tests."

Regarding the nature of the obstructive lung disease being observed – asthma, chronic obstructive pulmonary disease, or something else – "we have done some bronchodilator reversibility testing, and it does look like it is a mix of diseases," he said.

Another attendee asked how these new data could be reconciled with those of the 1990s, when such declines in lung function were not observed in HIV-positive patients. Dr. Drummond replied that possibly clinicians weren’t looking for them much at that time or any declines observed were attributed to opportunistic lung infections.

"I think that what we are seeing is a real effect. Now whether it’s generalizable to other cohorts is going to be an important question, and our work with the Lung HIV Consortium, which is a multicenter site, will hopefully answer that question," he said. "But I think that what we are seeing is individuals who are living longer with controlled HIV, so we may be seeing much like we see accelerated cardiovascular disease [and] accelerated nephrotoxicity – that maybe the lungs are now implicated as another end organ of chronic HIV infection even when controlled."

He acknowledged that it was hard in this study to tease apart the effects of smoking and HIV on lung function, given that most of the cohort smoked. But on the flip side, "it makes it nice because it’s a homogenous population, to get rid of the effect of smoking."

Dr. Drummond disclosed that he had no relevant conflicts of interest.

SEATTLE – Patients with poorly controlled HIV infection have a more rapid decline of lung function over time than their uninfected counterparts, researchers reported at the Conference on Retroviruses and Opportunistic Infections.

The findings "suggest that, potentially, optimal antiretroviral therapy (ART) with HIV virological suppression may diminish the accelerated lung function decline that we are seeing," said Dr. M. Bradley Drummond, a pulmonologist at the Johns Hopkins University in Baltimore.

"Certainly, all individuals should quit smoking, but these data suggest that those with HIV should be specifically counseled about the importance of smoking cessation," he further noted in a related press briefing.

Dr. Drummond and colleagues assessed lung function over a period of 3 years in 1,064 injection drug users, about a third of whom were HIV positive.

Results showed that the rate of decline in forced expiratory volume in 1 second (FEV₁) was about 50% greater in HIV-positive individuals than in their HIV-negative counterparts overall even after taking into account potential confounders such as bacterial and Pneumocystis lung infections, pack-years of smoking, and current smoking status.

In stratified analyses, the decline was especially high – three to four times that in the HIV-negative group – for HIV-positive individuals who had poorly controlled HIV infection as indicated by high HIV viral loads or low CD4 counts.

"We conclude that markers of advanced and uncontrolled HIV disease are associated with more rapid decline in lung function. We also feel that the FEV₁ decline associated with uncontrolled HIV exceeds the effect of smoking in the general population," Dr. Drummond commented.

For the study, the investigators analyzed data from a subset of individuals enrolled in AIDS-Linked to the Intravenous Experience (ALIVE), a community-based cohort of current or former injection drug users who had semiannual clinical exams, blood tests, and spirometry measurements.

The individuals were 49 years old, on average, and predominantly male (65%), black (91%), and current or former smokers (94%). In all, 30% were HIV positive, of whom slightly more than half were on ART. The median duration of follow-up was 2.8 years.

Modeling results suggested that for typical individuals in the cohort, FEV₁ at baseline was 139 mL lower in HIV-positive individuals, compared with their HIV-negative counterparts after adjustment for potential confounders. This is statistically significant and clinically significant, Dr. Drummond commented.

In addition, over time, FEV₁ declined by 36 mL/yr in HIV-positive individuals (P = .06), or 50% faster than the 24 mL/yr decline seen in HIV-negative individuals. "That is probably not clinically significant; however, the reality about the ALIVE cohort is there is a relatively heterogeneous group of individuals with different degrees of HIV severity," he noted.

Analyses looking at the impact of viral load showed that HIV-positive individuals having a load of more than 75,000 copies/mL had a rate of FEV₁ decline of 99 mL/yr – more than four times that of HIV-negative individuals (P less than .01). But HIV-positive individuals with a lower viral load had a similar rate of decline as those who were HIV-negative.

Likewise, in analyses looking at the impact of CD4 count, the rate of FEV₁ decline steadily increased as CD4 count decreased. HIV-positive individuals having fewer than 100 CD4 cells/mm3 had a rate of 81 mL/yr – more than three times the rate among the HIV-negative group (P less than .01).

The investigators also conducted doubly stratified analyses looking at both viral load and CD4 count. "It really does look like actually the viral load effect is what’s driving most of the FEV₁ decline. So our money is on the viral load," Dr. Drummond said.

One session attendee asked whether the decline in pulmonary function was reversible when patients started ART. Dr. Drummond replied that most of the HIV-positive group did not have any changes to their therapy during observation, making it difficult to assess this. "We are doing a separate study where we are actually looking at pre- and post-ART initiation ... Hopefully, we would see some stabilization of breathing tests."

Regarding the nature of the obstructive lung disease being observed – asthma, chronic obstructive pulmonary disease, or something else – "we have done some bronchodilator reversibility testing, and it does look like it is a mix of diseases," he said.

Another attendee asked how these new data could be reconciled with those of the 1990s, when such declines in lung function were not observed in HIV-positive patients. Dr. Drummond replied that possibly clinicians weren’t looking for them much at that time or any declines observed were attributed to opportunistic lung infections.

"I think that what we are seeing is a real effect. Now whether it’s generalizable to other cohorts is going to be an important question, and our work with the Lung HIV Consortium, which is a multicenter site, will hopefully answer that question," he said. "But I think that what we are seeing is individuals who are living longer with controlled HIV, so we may be seeing much like we see accelerated cardiovascular disease [and] accelerated nephrotoxicity – that maybe the lungs are now implicated as another end organ of chronic HIV infection even when controlled."

He acknowledged that it was hard in this study to tease apart the effects of smoking and HIV on lung function, given that most of the cohort smoked. But on the flip side, "it makes it nice because it’s a homogenous population, to get rid of the effect of smoking."

Dr. Drummond disclosed that he had no relevant conflicts of interest.

SEATTLE – Patients with poorly controlled HIV infection have a more rapid decline of lung function over time than their uninfected counterparts, researchers reported at the Conference on Retroviruses and Opportunistic Infections.

The findings "suggest that, potentially, optimal antiretroviral therapy (ART) with HIV virological suppression may diminish the accelerated lung function decline that we are seeing," said Dr. M. Bradley Drummond, a pulmonologist at the Johns Hopkins University in Baltimore.

"Certainly, all individuals should quit smoking, but these data suggest that those with HIV should be specifically counseled about the importance of smoking cessation," he further noted in a related press briefing.

Dr. Drummond and colleagues assessed lung function over a period of 3 years in 1,064 injection drug users, about a third of whom were HIV positive.

Results showed that the rate of decline in forced expiratory volume in 1 second (FEV₁) was about 50% greater in HIV-positive individuals than in their HIV-negative counterparts overall even after taking into account potential confounders such as bacterial and Pneumocystis lung infections, pack-years of smoking, and current smoking status.

In stratified analyses, the decline was especially high – three to four times that in the HIV-negative group – for HIV-positive individuals who had poorly controlled HIV infection as indicated by high HIV viral loads or low CD4 counts.

"We conclude that markers of advanced and uncontrolled HIV disease are associated with more rapid decline in lung function. We also feel that the FEV₁ decline associated with uncontrolled HIV exceeds the effect of smoking in the general population," Dr. Drummond commented.

For the study, the investigators analyzed data from a subset of individuals enrolled in AIDS-Linked to the Intravenous Experience (ALIVE), a community-based cohort of current or former injection drug users who had semiannual clinical exams, blood tests, and spirometry measurements.

The individuals were 49 years old, on average, and predominantly male (65%), black (91%), and current or former smokers (94%). In all, 30% were HIV positive, of whom slightly more than half were on ART. The median duration of follow-up was 2.8 years.

Modeling results suggested that for typical individuals in the cohort, FEV₁ at baseline was 139 mL lower in HIV-positive individuals, compared with their HIV-negative counterparts after adjustment for potential confounders. This is statistically significant and clinically significant, Dr. Drummond commented.

In addition, over time, FEV₁ declined by 36 mL/yr in HIV-positive individuals (P = .06), or 50% faster than the 24 mL/yr decline seen in HIV-negative individuals. "That is probably not clinically significant; however, the reality about the ALIVE cohort is there is a relatively heterogeneous group of individuals with different degrees of HIV severity," he noted.

Analyses looking at the impact of viral load showed that HIV-positive individuals having a load of more than 75,000 copies/mL had a rate of FEV₁ decline of 99 mL/yr – more than four times that of HIV-negative individuals (P less than .01). But HIV-positive individuals with a lower viral load had a similar rate of decline as those who were HIV-negative.

Likewise, in analyses looking at the impact of CD4 count, the rate of FEV₁ decline steadily increased as CD4 count decreased. HIV-positive individuals having fewer than 100 CD4 cells/mm3 had a rate of 81 mL/yr – more than three times the rate among the HIV-negative group (P less than .01).

The investigators also conducted doubly stratified analyses looking at both viral load and CD4 count. "It really does look like actually the viral load effect is what’s driving most of the FEV₁ decline. So our money is on the viral load," Dr. Drummond said.

One session attendee asked whether the decline in pulmonary function was reversible when patients started ART. Dr. Drummond replied that most of the HIV-positive group did not have any changes to their therapy during observation, making it difficult to assess this. "We are doing a separate study where we are actually looking at pre- and post-ART initiation ... Hopefully, we would see some stabilization of breathing tests."

Regarding the nature of the obstructive lung disease being observed – asthma, chronic obstructive pulmonary disease, or something else – "we have done some bronchodilator reversibility testing, and it does look like it is a mix of diseases," he said.

Another attendee asked how these new data could be reconciled with those of the 1990s, when such declines in lung function were not observed in HIV-positive patients. Dr. Drummond replied that possibly clinicians weren’t looking for them much at that time or any declines observed were attributed to opportunistic lung infections.

"I think that what we are seeing is a real effect. Now whether it’s generalizable to other cohorts is going to be an important question, and our work with the Lung HIV Consortium, which is a multicenter site, will hopefully answer that question," he said. "But I think that what we are seeing is individuals who are living longer with controlled HIV, so we may be seeing much like we see accelerated cardiovascular disease [and] accelerated nephrotoxicity – that maybe the lungs are now implicated as another end organ of chronic HIV infection even when controlled."

He acknowledged that it was hard in this study to tease apart the effects of smoking and HIV on lung function, given that most of the cohort smoked. But on the flip side, "it makes it nice because it’s a homogenous population, to get rid of the effect of smoking."

Dr. Drummond disclosed that he had no relevant conflicts of interest.

SEATTLE – HIV-positive patients are increasingly initiating antiretroviral treatment early in the course of their disease, which should improve their outcomes, suggests a study conducted in San Francisco.

However, some groups are clearly not included in this favorable trend, said the study’s lead investigator, Hong-Ha M. Truong, Ph.D., an assistant professor of medicine at the University of California, San Francisco.

Overall, the findings reflect the implementation of a test-and-treat approach recently introduced in San Francisco aimed at increasing early use of antiretroviral therapy (ART) among HIV-positives and reducing CD4 cell loss in the interval between HIV diagnosis and treatment initiation, said Kholoud Porter, Ph.D., session comoderator and senior epidemiologist with the Medical Research Council (MRC) Clinical Trials Unit in London.

"Given the need for good adherence to lifelong ART, it will be crucial to monitor these individuals and document the proportion who remain on ART and maintain viral suppression," she said at the Conference on Retroviruses and Opportunistic Infections.

The disparity in early ART uptake should inform public health policy, she added.

The study involved more than 3,750 adolescents and adults from the city’s HIV/AIDS Case Registry; their infections were diagnosed between 2004 and 2010.

Dr. Truong and her colleagues showed that the proportion of patients initiating ART early, that is, at a CD4 count of greater than 350 cells/mm³, increased dramatically: Among those who had a count above this value at diagnosis and initiated ART during the study period, only about half (48%) initiated early in 2004, whereas nearly all (93%) did so in 2010, she reported.

In adjusted analyses, however, the proportion of patients initiating ART early was significantly lower among racial/ethnic minorities, young individuals, injection drug users, patients whose diagnosis was made in nonprivate facilities, and those living in impoverished areas.

"Early initiation of ART at high CD4 levels was evident in San Francisco starting as early as 2007," said Dr. Truong, noting that this trend predated changes to local treatment recommendations calling for initiation regardless of CD4 count. "However, not all groups are accessing early initiation of ART equally, and therefore [they are] not benefiting from the advantages of early treatment."

"Delays in treatment initiation explain observed disparities in survival among persons living with HIV. Disparities will persist unless treatment gaps are closed," she maintained.

There may be financial barriers to accessing antiretrovirals, she said. Insurance companies may require CD4 counts of a certain level before they will cover antiretrovirals. But more likely, individuals and their motivation to seek treatment are driving this trend, she said. San Francisco also has a countywide health care program that provides access to people who don’t have health insurance.

For the study, the investigators identified 3,778 San Francisco HIV-positive patients aged 13 years or older. Results were largely based on 1,803 having a CD4 count of greater than 350 cells/mm³ at diagnosis, and specifically the 941 who initiated ART.

National guidelines at the start of the study period in 2004 recommended that HIV-positive patients begin ART when their CD4 count dropped below 350 cells/mm³, Dr. Truong noted. (They have since been updated to recommend initiation at 500 cells/mm³ or less, with initiation at higher levels optional.)

"Recognizing the beneficial impact of early treatment on reducing morbidity and transmission, public health clinics and the Positive Health Program in San Francisco revised their guidelines in 2010," Dr. Truong explained. "The new recommendations called for initiating treatment at the time of HIV diagnosis, irrespective of CD4 counts."

The median count at diagnosis remained essentially stable during the 7-year study period, at roughly 550 cells/mm³, whereas that at ART initiation increased, from 365 to 496 cells/mm³ (P less than .001). Thus, the gap between the two values narrowed (P less than .001).

Dr. Truong and Dr. Porter reported having no relevant conflicts of interest.

SEATTLE – HIV-positive patients are increasingly initiating antiretroviral treatment early in the course of their disease, which should improve their outcomes, suggests a study conducted in San Francisco.

However, some groups are clearly not included in this favorable trend, said the study’s lead investigator, Hong-Ha M. Truong, Ph.D., an assistant professor of medicine at the University of California, San Francisco.

Overall, the findings reflect the implementation of a test-and-treat approach recently introduced in San Francisco aimed at increasing early use of antiretroviral therapy (ART) among HIV-positives and reducing CD4 cell loss in the interval between HIV diagnosis and treatment initiation, said Kholoud Porter, Ph.D., session comoderator and senior epidemiologist with the Medical Research Council (MRC) Clinical Trials Unit in London.

"Given the need for good adherence to lifelong ART, it will be crucial to monitor these individuals and document the proportion who remain on ART and maintain viral suppression," she said at the Conference on Retroviruses and Opportunistic Infections.

The disparity in early ART uptake should inform public health policy, she added.

The study involved more than 3,750 adolescents and adults from the city’s HIV/AIDS Case Registry; their infections were diagnosed between 2004 and 2010.

Dr. Truong and her colleagues showed that the proportion of patients initiating ART early, that is, at a CD4 count of greater than 350 cells/mm³, increased dramatically: Among those who had a count above this value at diagnosis and initiated ART during the study period, only about half (48%) initiated early in 2004, whereas nearly all (93%) did so in 2010, she reported.

In adjusted analyses, however, the proportion of patients initiating ART early was significantly lower among racial/ethnic minorities, young individuals, injection drug users, patients whose diagnosis was made in nonprivate facilities, and those living in impoverished areas.

"Early initiation of ART at high CD4 levels was evident in San Francisco starting as early as 2007," said Dr. Truong, noting that this trend predated changes to local treatment recommendations calling for initiation regardless of CD4 count. "However, not all groups are accessing early initiation of ART equally, and therefore [they are] not benefiting from the advantages of early treatment."

"Delays in treatment initiation explain observed disparities in survival among persons living with HIV. Disparities will persist unless treatment gaps are closed," she maintained.

There may be financial barriers to accessing antiretrovirals, she said. Insurance companies may require CD4 counts of a certain level before they will cover antiretrovirals. But more likely, individuals and their motivation to seek treatment are driving this trend, she said. San Francisco also has a countywide health care program that provides access to people who don’t have health insurance.

For the study, the investigators identified 3,778 San Francisco HIV-positive patients aged 13 years or older. Results were largely based on 1,803 having a CD4 count of greater than 350 cells/mm³ at diagnosis, and specifically the 941 who initiated ART.

National guidelines at the start of the study period in 2004 recommended that HIV-positive patients begin ART when their CD4 count dropped below 350 cells/mm³, Dr. Truong noted. (They have since been updated to recommend initiation at 500 cells/mm³ or less, with initiation at higher levels optional.)

"Recognizing the beneficial impact of early treatment on reducing morbidity and transmission, public health clinics and the Positive Health Program in San Francisco revised their guidelines in 2010," Dr. Truong explained. "The new recommendations called for initiating treatment at the time of HIV diagnosis, irrespective of CD4 counts."

The median count at diagnosis remained essentially stable during the 7-year study period, at roughly 550 cells/mm³, whereas that at ART initiation increased, from 365 to 496 cells/mm³ (P less than .001). Thus, the gap between the two values narrowed (P less than .001).

Dr. Truong and Dr. Porter reported having no relevant conflicts of interest.

SEATTLE – HIV-positive patients are increasingly initiating antiretroviral treatment early in the course of their disease, which should improve their outcomes, suggests a study conducted in San Francisco.

However, some groups are clearly not included in this favorable trend, said the study’s lead investigator, Hong-Ha M. Truong, Ph.D., an assistant professor of medicine at the University of California, San Francisco.

Overall, the findings reflect the implementation of a test-and-treat approach recently introduced in San Francisco aimed at increasing early use of antiretroviral therapy (ART) among HIV-positives and reducing CD4 cell loss in the interval between HIV diagnosis and treatment initiation, said Kholoud Porter, Ph.D., session comoderator and senior epidemiologist with the Medical Research Council (MRC) Clinical Trials Unit in London.

"Given the need for good adherence to lifelong ART, it will be crucial to monitor these individuals and document the proportion who remain on ART and maintain viral suppression," she said at the Conference on Retroviruses and Opportunistic Infections.

The disparity in early ART uptake should inform public health policy, she added.

The study involved more than 3,750 adolescents and adults from the city’s HIV/AIDS Case Registry; their infections were diagnosed between 2004 and 2010.

Dr. Truong and her colleagues showed that the proportion of patients initiating ART early, that is, at a CD4 count of greater than 350 cells/mm³, increased dramatically: Among those who had a count above this value at diagnosis and initiated ART during the study period, only about half (48%) initiated early in 2004, whereas nearly all (93%) did so in 2010, she reported.

In adjusted analyses, however, the proportion of patients initiating ART early was significantly lower among racial/ethnic minorities, young individuals, injection drug users, patients whose diagnosis was made in nonprivate facilities, and those living in impoverished areas.

"Early initiation of ART at high CD4 levels was evident in San Francisco starting as early as 2007," said Dr. Truong, noting that this trend predated changes to local treatment recommendations calling for initiation regardless of CD4 count. "However, not all groups are accessing early initiation of ART equally, and therefore [they are] not benefiting from the advantages of early treatment."

"Delays in treatment initiation explain observed disparities in survival among persons living with HIV. Disparities will persist unless treatment gaps are closed," she maintained.

There may be financial barriers to accessing antiretrovirals, she said. Insurance companies may require CD4 counts of a certain level before they will cover antiretrovirals. But more likely, individuals and their motivation to seek treatment are driving this trend, she said. San Francisco also has a countywide health care program that provides access to people who don’t have health insurance.

For the study, the investigators identified 3,778 San Francisco HIV-positive patients aged 13 years or older. Results were largely based on 1,803 having a CD4 count of greater than 350 cells/mm³ at diagnosis, and specifically the 941 who initiated ART.

National guidelines at the start of the study period in 2004 recommended that HIV-positive patients begin ART when their CD4 count dropped below 350 cells/mm³, Dr. Truong noted. (They have since been updated to recommend initiation at 500 cells/mm³ or less, with initiation at higher levels optional.)

"Recognizing the beneficial impact of early treatment on reducing morbidity and transmission, public health clinics and the Positive Health Program in San Francisco revised their guidelines in 2010," Dr. Truong explained. "The new recommendations called for initiating treatment at the time of HIV diagnosis, irrespective of CD4 counts."

The median count at diagnosis remained essentially stable during the 7-year study period, at roughly 550 cells/mm³, whereas that at ART initiation increased, from 365 to 496 cells/mm³ (P less than .001). Thus, the gap between the two values narrowed (P less than .001).

Dr. Truong and Dr. Porter reported having no relevant conflicts of interest.

SEATTLE – Almost half of patients with newly diagnosed HIV infection appeared to have impaired neuropsychological functioning, according to the findings of a prospective longitudinal study involving 70 men. Initiation of antiretroviral therapy halted this decline but did not reverse it.

Before starting antiretroviral therapy (ART), study patients, who were an average of 4 months into their infection, had declines over time in the motor neuropsychological domain and a composite measure of motor function and processing speed, Dr. Julia Peterson of the University of California, San Francisco, reported at the Conference on Retroviruses and Opportunistic Infections.

Nearly half of patients started ART during follow-up, and after doing so, these patients had stabilization – but not improvement – in both measures.

"These findings suggest that while performance in certain neuropsychological domains may improve with repeated testing, a decline in motor performance is measurable in patients with untreated HIV infection, and that this decline may be attenuated with early antiretroviral treatment," Dr. Peterson commented.

"Although it is difficult to discern the reason for the negative trajectory of the motor performance initially in primary HIV infection," an imaging study has shown "accumulating inflammation in the frontal white matter during the same period of time, so this may correspond to the motor dysfunction that we are seeing," she said. Furthermore, as suggested by other research, "there is detection of neuropathy in this same primary infection cohort, which may also lead to motor dysfunction."

When asked whether there might have been a confounding effect of patients’ psychological reaction to such a serious new diagnosis, she acknowledged that was possible, especially at the first study visit.

"I don’t know the perfect way to factor in every single thing that might be affecting the patient at that visit: It could be drug use, it could be anxiety, it could be depression, it could be another diagnosis," she said. However, neuropsychological performance at baseline did not correlate with mental health symptoms.

"Lymphocytic meningitis is common in this setting within the first few months of seroconversion," noted Dr. Rodger MacArthur of Wayne State University in Detroit, who attended the session. "So how did you adjust or correct for that, for individuals who had either symptomatic meningitis or silent meningitis?"

Only a few patients in the cohort were found to have meningitis, and they were excluded from longitudinal analyses, Dr. Peterson said.

Explaining the study’s rationale, she noted, "There are many reports on the persistence of mild neurological and cognitive impairment in patients with chronic HIV infection who are on suppressive treatment. Yet there is limited study on the neuropsychological testing performance early during infection."

The investigators evaluated patients repeatedly over time with 11 neuropsychological tests assessing performance in five domains. They also used two composite measures: the total Z score (reflecting all 11 tests) and the NPZ4 score (reflecting four tests of motor and processing speed). The latter is "more relevant in the clinical setting," Dr. Peterson noted.

The enrolled patients had a median age of 36 years and a median of 16 years of education, and 79% had a history of drug use. On average, they were 125 days post HIV exposure and had a CD4 count of 555 cells/mm³.

At baseline, 42% of the patients performed more than one standard deviation below the normative mean in at least two neuropsychological domains, meeting criteria for asymptomatic neurocognitive impairment or mild neurocognitive disorder.

Longitudinal analyses showed that before starting ART, the patients had declines over time in the motor domain (P = .012) and the NPZ4 composite measure (P = .027).

Forty-seven percent of the patients started ART during follow-up, a median of about 32 weeks after HIV exposure and at a median CD4 count of 433 cells/mm³.

After starting ART, these patients had stabilization in the motor domain (P = NS) and NPZ4 measure (P = NS). They also had new improvement in the executive function domain (P = .001).

"At any point when treatment is initiated, motor performance stabilizes to practically no change and no improvement, thus suggesting ... each patient will maintain any sort of accumulated impairment," commented Dr. Peterson.

Performance in the remaining domain studied, memory, did not change significantly, either before or after ART initiation.

"Treatment was not randomized," she acknowledged. Also, "there was no well-matched control group, so we had to rely on published norms, which may or may not be congruent with our own study population. It is not clear whether baseline or accrued impairment reflects premorbid factors or is actually the effect of HIV."

Dr. Peterson disclosed no relevant conflicts of interest.

SEATTLE – Almost half of patients with newly diagnosed HIV infection appeared to have impaired neuropsychological functioning, according to the findings of a prospective longitudinal study involving 70 men. Initiation of antiretroviral therapy halted this decline but did not reverse it.

Before starting antiretroviral therapy (ART), study patients, who were an average of 4 months into their infection, had declines over time in the motor neuropsychological domain and a composite measure of motor function and processing speed, Dr. Julia Peterson of the University of California, San Francisco, reported at the Conference on Retroviruses and Opportunistic Infections.

Nearly half of patients started ART during follow-up, and after doing so, these patients had stabilization – but not improvement – in both measures.

"These findings suggest that while performance in certain neuropsychological domains may improve with repeated testing, a decline in motor performance is measurable in patients with untreated HIV infection, and that this decline may be attenuated with early antiretroviral treatment," Dr. Peterson commented.

"Although it is difficult to discern the reason for the negative trajectory of the motor performance initially in primary HIV infection," an imaging study has shown "accumulating inflammation in the frontal white matter during the same period of time, so this may correspond to the motor dysfunction that we are seeing," she said. Furthermore, as suggested by other research, "there is detection of neuropathy in this same primary infection cohort, which may also lead to motor dysfunction."

When asked whether there might have been a confounding effect of patients’ psychological reaction to such a serious new diagnosis, she acknowledged that was possible, especially at the first study visit.

"I don’t know the perfect way to factor in every single thing that might be affecting the patient at that visit: It could be drug use, it could be anxiety, it could be depression, it could be another diagnosis," she said. However, neuropsychological performance at baseline did not correlate with mental health symptoms.

"Lymphocytic meningitis is common in this setting within the first few months of seroconversion," noted Dr. Rodger MacArthur of Wayne State University in Detroit, who attended the session. "So how did you adjust or correct for that, for individuals who had either symptomatic meningitis or silent meningitis?"

Only a few patients in the cohort were found to have meningitis, and they were excluded from longitudinal analyses, Dr. Peterson said.

Explaining the study’s rationale, she noted, "There are many reports on the persistence of mild neurological and cognitive impairment in patients with chronic HIV infection who are on suppressive treatment. Yet there is limited study on the neuropsychological testing performance early during infection."

The investigators evaluated patients repeatedly over time with 11 neuropsychological tests assessing performance in five domains. They also used two composite measures: the total Z score (reflecting all 11 tests) and the NPZ4 score (reflecting four tests of motor and processing speed). The latter is "more relevant in the clinical setting," Dr. Peterson noted.

The enrolled patients had a median age of 36 years and a median of 16 years of education, and 79% had a history of drug use. On average, they were 125 days post HIV exposure and had a CD4 count of 555 cells/mm³.

At baseline, 42% of the patients performed more than one standard deviation below the normative mean in at least two neuropsychological domains, meeting criteria for asymptomatic neurocognitive impairment or mild neurocognitive disorder.

Longitudinal analyses showed that before starting ART, the patients had declines over time in the motor domain (P = .012) and the NPZ4 composite measure (P = .027).

Forty-seven percent of the patients started ART during follow-up, a median of about 32 weeks after HIV exposure and at a median CD4 count of 433 cells/mm³.

After starting ART, these patients had stabilization in the motor domain (P = NS) and NPZ4 measure (P = NS). They also had new improvement in the executive function domain (P = .001).

"At any point when treatment is initiated, motor performance stabilizes to practically no change and no improvement, thus suggesting ... each patient will maintain any sort of accumulated impairment," commented Dr. Peterson.

Performance in the remaining domain studied, memory, did not change significantly, either before or after ART initiation.

"Treatment was not randomized," she acknowledged. Also, "there was no well-matched control group, so we had to rely on published norms, which may or may not be congruent with our own study population. It is not clear whether baseline or accrued impairment reflects premorbid factors or is actually the effect of HIV."

Dr. Peterson disclosed no relevant conflicts of interest.

SEATTLE – Almost half of patients with newly diagnosed HIV infection appeared to have impaired neuropsychological functioning, according to the findings of a prospective longitudinal study involving 70 men. Initiation of antiretroviral therapy halted this decline but did not reverse it.

Before starting antiretroviral therapy (ART), study patients, who were an average of 4 months into their infection, had declines over time in the motor neuropsychological domain and a composite measure of motor function and processing speed, Dr. Julia Peterson of the University of California, San Francisco, reported at the Conference on Retroviruses and Opportunistic Infections.

Nearly half of patients started ART during follow-up, and after doing so, these patients had stabilization – but not improvement – in both measures.

"These findings suggest that while performance in certain neuropsychological domains may improve with repeated testing, a decline in motor performance is measurable in patients with untreated HIV infection, and that this decline may be attenuated with early antiretroviral treatment," Dr. Peterson commented.

"Although it is difficult to discern the reason for the negative trajectory of the motor performance initially in primary HIV infection," an imaging study has shown "accumulating inflammation in the frontal white matter during the same period of time, so this may correspond to the motor dysfunction that we are seeing," she said. Furthermore, as suggested by other research, "there is detection of neuropathy in this same primary infection cohort, which may also lead to motor dysfunction."

When asked whether there might have been a confounding effect of patients’ psychological reaction to such a serious new diagnosis, she acknowledged that was possible, especially at the first study visit.

"I don’t know the perfect way to factor in every single thing that might be affecting the patient at that visit: It could be drug use, it could be anxiety, it could be depression, it could be another diagnosis," she said. However, neuropsychological performance at baseline did not correlate with mental health symptoms.

"Lymphocytic meningitis is common in this setting within the first few months of seroconversion," noted Dr. Rodger MacArthur of Wayne State University in Detroit, who attended the session. "So how did you adjust or correct for that, for individuals who had either symptomatic meningitis or silent meningitis?"

Only a few patients in the cohort were found to have meningitis, and they were excluded from longitudinal analyses, Dr. Peterson said.

Explaining the study’s rationale, she noted, "There are many reports on the persistence of mild neurological and cognitive impairment in patients with chronic HIV infection who are on suppressive treatment. Yet there is limited study on the neuropsychological testing performance early during infection."

The investigators evaluated patients repeatedly over time with 11 neuropsychological tests assessing performance in five domains. They also used two composite measures: the total Z score (reflecting all 11 tests) and the NPZ4 score (reflecting four tests of motor and processing speed). The latter is "more relevant in the clinical setting," Dr. Peterson noted.

The enrolled patients had a median age of 36 years and a median of 16 years of education, and 79% had a history of drug use. On average, they were 125 days post HIV exposure and had a CD4 count of 555 cells/mm³.

At baseline, 42% of the patients performed more than one standard deviation below the normative mean in at least two neuropsychological domains, meeting criteria for asymptomatic neurocognitive impairment or mild neurocognitive disorder.

Longitudinal analyses showed that before starting ART, the patients had declines over time in the motor domain (P = .012) and the NPZ4 composite measure (P = .027).

Forty-seven percent of the patients started ART during follow-up, a median of about 32 weeks after HIV exposure and at a median CD4 count of 433 cells/mm³.

After starting ART, these patients had stabilization in the motor domain (P = NS) and NPZ4 measure (P = NS). They also had new improvement in the executive function domain (P = .001).

"At any point when treatment is initiated, motor performance stabilizes to practically no change and no improvement, thus suggesting ... each patient will maintain any sort of accumulated impairment," commented Dr. Peterson.

Performance in the remaining domain studied, memory, did not change significantly, either before or after ART initiation.

"Treatment was not randomized," she acknowledged. Also, "there was no well-matched control group, so we had to rely on published norms, which may or may not be congruent with our own study population. It is not clear whether baseline or accrued impairment reflects premorbid factors or is actually the effect of HIV."

Dr. Peterson disclosed no relevant conflicts of interest.

SEATTLE – HIV-infected individuals have increased arterial inflammation compared with their uninfected counterparts with the same levels of traditional cardiovascular risk factors, even when the infection is so well controlled that the virus is undetectable.

This was among the key findings of an observational study of 81 individuals who underwent fluorodeoxyglucose positron emission tomography (FDG-PET). Inflammation in the thoracic aorta was assessed from the target-to-background ratio of tracer uptake.

Courtesy Dr. Tom Folks, NIAID/National Institutes of Health

Study results, reported at the Conference on Retroviruses and Opportunistic Infections, showed that inflammation in the HIV-positive individuals – none of whom had known cardiac disease and all of whom were on antiretroviral therapy (ART) – was greater than that in HIV-negative individuals having matching Framingham Risk Scores (2.23 vs. 1.89, P = .0003). Moreover, it was about equal to that in HIV-negative individuals who had known atherosclerosis (2.13).

The findings were the same when only HIV-positive patients having an undetectable viral load – the large majority of those studied – were included in analyses, reported coinvestigator Dr. Steven Grinspoon, director of the Program in Nutritional Metabolism at Massachusetts General Hospital, Boston.

"The HIV-infected patients, essentially with total virological suppression and very low Framingham Risk Scores – a group that you would ordinarily not be particularly concerned about – had very significant arterial inflammation compared to the Framingham Risk Score–matched controls," he commented. "Moreover, this group of HIV-infected patients basically had the same degree of arterial inflammation as the group of non-HIV patients with known cardiovascular disease [CVD], except that the HIV patients didn’t have known CVD."

Previous research has suggested that arterial FDG uptake like that observed is due to macrophage accumulation at the interface between the lipid core and the fibrous cap in atherosclerotic plaques (Circulation 2002;105:2708-11). And results of the new study indeed showed that arterial inflammation in the HIV-positive group was correlated with levels of soluble CD163, a marker of monocyte activation. Dr. Grinspoon speculated that the heightened arterial inflammation may thus reflect chronic immune activation.

"Increased arterial inflammation in well-controlled subjects on ART is likely to contribute to increased CVD rates in this population," he maintained. "Strategies to target this inflammation, in addition to targeting traditional risk factors, including potential strategies to reduce monocyte activation, may be useful and should be investigated."

Session attendees questioned whether there was a confounding effect of statins, which are known to be anti-inflammatory and were used by none of the HIV-positive group, a quarter of the risk-matched HIV-negative group, and two-thirds of the HIV-negative group with known atherosclerosis. But Dr. Grinspoon noted that several analyses taking statin use into account yielded the same results.

When asked if he had any hypotheses as to what is activating the monocytes and whether microbes may have a role, he replied, "We are just beginning to look at some of the other markers. The whole entire cascade of macrophage activation and [microbial translocation] needs to be looked at more carefully."

Another attendee wondered if the duration of HIV infection influenced inflammation, given that most patients studied had been infected for at least a decade. "It would be absolutely fascinating ... to look at ART-naïve patients at the height of their [viral levels]," Dr. Grinspoon replied. "I would predict that the elevation will be even higher in those and that going on to ART will slam it down, and then it festers along at a certain kind of low-grade level. Our point in this study is that festering along is a problem because there seems to be at least arterial inflammation, even when you think, ‘Oh, the patient is fine, their viral load is suppressed.’ "

The investigators enrolled in the study 27 HIV-positive patients free of known cardiac disease who were on stable ART and did not have any opportunistic infections; 27 HIV-negative individuals matched for age, sex, and Framingham Risk Score who had no known atherosclerosis; and 27 HIV-negative patients matched for sex who had known atherosclerosis.

On average, the members of the HIV-positive group were 52 years old, had been infected for 16 years, and had been on ART for 12 years, according to Dr. Grinspoon, who disclosed no relevant conflicts of interest related to the research. Their mean CD4 count was 592 cells/mm³, and three-fourths had undetectable HIV RNA. Their average Framingham Risk Score was 6.4.

The significantly greater inflammation in the HIV-positive group than in the risk-matched HIV-negative group was evident across a variety of subgroups, such as individuals not having any coronary calcium, nonsmokers, those not taking statins, and those having an undetectable viral load.

And in a multivariate regression analysis, HIV positivity remained significantly associated with greater arterial inflammation after potential confounders, such as coronary calcium score and statin use, were controlled for. "So [HIV positivity] seemed to be adding independently to these things," Dr. Grinspoon noted.

In the HIV-positive group, arterial inflammation did not differ with use of various classes of ART drugs patients were taking, for example, between users vs. nonusers of protease inhibitors.

In an analysis of immune and inflammatory factors in the HIV-positive group, monocyte activation, as indicated by higher soluble CD163 levels, was significantly correlated with inflammation (P = .03). In contrast, C-reactive protein, d-dimer, and measures of HIV severity were not.

Dr. Grinspoon reported having no relevant conflicts of interest.

SEATTLE – HIV-infected individuals have increased arterial inflammation compared with their uninfected counterparts with the same levels of traditional cardiovascular risk factors, even when the infection is so well controlled that the virus is undetectable.

This was among the key findings of an observational study of 81 individuals who underwent fluorodeoxyglucose positron emission tomography (FDG-PET). Inflammation in the thoracic aorta was assessed from the target-to-background ratio of tracer uptake.

Courtesy Dr. Tom Folks, NIAID/National Institutes of Health

Study results, reported at the Conference on Retroviruses and Opportunistic Infections, showed that inflammation in the HIV-positive individuals – none of whom had known cardiac disease and all of whom were on antiretroviral therapy (ART) – was greater than that in HIV-negative individuals having matching Framingham Risk Scores (2.23 vs. 1.89, P = .0003). Moreover, it was about equal to that in HIV-negative individuals who had known atherosclerosis (2.13).

The findings were the same when only HIV-positive patients having an undetectable viral load – the large majority of those studied – were included in analyses, reported coinvestigator Dr. Steven Grinspoon, director of the Program in Nutritional Metabolism at Massachusetts General Hospital, Boston.

"The HIV-infected patients, essentially with total virological suppression and very low Framingham Risk Scores – a group that you would ordinarily not be particularly concerned about – had very significant arterial inflammation compared to the Framingham Risk Score–matched controls," he commented. "Moreover, this group of HIV-infected patients basically had the same degree of arterial inflammation as the group of non-HIV patients with known cardiovascular disease [CVD], except that the HIV patients didn’t have known CVD."

Previous research has suggested that arterial FDG uptake like that observed is due to macrophage accumulation at the interface between the lipid core and the fibrous cap in atherosclerotic plaques (Circulation 2002;105:2708-11). And results of the new study indeed showed that arterial inflammation in the HIV-positive group was correlated with levels of soluble CD163, a marker of monocyte activation. Dr. Grinspoon speculated that the heightened arterial inflammation may thus reflect chronic immune activation.

"Increased arterial inflammation in well-controlled subjects on ART is likely to contribute to increased CVD rates in this population," he maintained. "Strategies to target this inflammation, in addition to targeting traditional risk factors, including potential strategies to reduce monocyte activation, may be useful and should be investigated."

Session attendees questioned whether there was a confounding effect of statins, which are known to be anti-inflammatory and were used by none of the HIV-positive group, a quarter of the risk-matched HIV-negative group, and two-thirds of the HIV-negative group with known atherosclerosis. But Dr. Grinspoon noted that several analyses taking statin use into account yielded the same results.

When asked if he had any hypotheses as to what is activating the monocytes and whether microbes may have a role, he replied, "We are just beginning to look at some of the other markers. The whole entire cascade of macrophage activation and [microbial translocation] needs to be looked at more carefully."

Another attendee wondered if the duration of HIV infection influenced inflammation, given that most patients studied had been infected for at least a decade. "It would be absolutely fascinating ... to look at ART-naïve patients at the height of their [viral levels]," Dr. Grinspoon replied. "I would predict that the elevation will be even higher in those and that going on to ART will slam it down, and then it festers along at a certain kind of low-grade level. Our point in this study is that festering along is a problem because there seems to be at least arterial inflammation, even when you think, ‘Oh, the patient is fine, their viral load is suppressed.’ "

The investigators enrolled in the study 27 HIV-positive patients free of known cardiac disease who were on stable ART and did not have any opportunistic infections; 27 HIV-negative individuals matched for age, sex, and Framingham Risk Score who had no known atherosclerosis; and 27 HIV-negative patients matched for sex who had known atherosclerosis.

On average, the members of the HIV-positive group were 52 years old, had been infected for 16 years, and had been on ART for 12 years, according to Dr. Grinspoon, who disclosed no relevant conflicts of interest related to the research. Their mean CD4 count was 592 cells/mm³, and three-fourths had undetectable HIV RNA. Their average Framingham Risk Score was 6.4.

The significantly greater inflammation in the HIV-positive group than in the risk-matched HIV-negative group was evident across a variety of subgroups, such as individuals not having any coronary calcium, nonsmokers, those not taking statins, and those having an undetectable viral load.

And in a multivariate regression analysis, HIV positivity remained significantly associated with greater arterial inflammation after potential confounders, such as coronary calcium score and statin use, were controlled for. "So [HIV positivity] seemed to be adding independently to these things," Dr. Grinspoon noted.

In the HIV-positive group, arterial inflammation did not differ with use of various classes of ART drugs patients were taking, for example, between users vs. nonusers of protease inhibitors.

In an analysis of immune and inflammatory factors in the HIV-positive group, monocyte activation, as indicated by higher soluble CD163 levels, was significantly correlated with inflammation (P = .03). In contrast, C-reactive protein, d-dimer, and measures of HIV severity were not.

Dr. Grinspoon reported having no relevant conflicts of interest.

SEATTLE – HIV-infected individuals have increased arterial inflammation compared with their uninfected counterparts with the same levels of traditional cardiovascular risk factors, even when the infection is so well controlled that the virus is undetectable.

This was among the key findings of an observational study of 81 individuals who underwent fluorodeoxyglucose positron emission tomography (FDG-PET). Inflammation in the thoracic aorta was assessed from the target-to-background ratio of tracer uptake.

Courtesy Dr. Tom Folks, NIAID/National Institutes of Health

Study results, reported at the Conference on Retroviruses and Opportunistic Infections, showed that inflammation in the HIV-positive individuals – none of whom had known cardiac disease and all of whom were on antiretroviral therapy (ART) – was greater than that in HIV-negative individuals having matching Framingham Risk Scores (2.23 vs. 1.89, P = .0003). Moreover, it was about equal to that in HIV-negative individuals who had known atherosclerosis (2.13).

The findings were the same when only HIV-positive patients having an undetectable viral load – the large majority of those studied – were included in analyses, reported coinvestigator Dr. Steven Grinspoon, director of the Program in Nutritional Metabolism at Massachusetts General Hospital, Boston.

"The HIV-infected patients, essentially with total virological suppression and very low Framingham Risk Scores – a group that you would ordinarily not be particularly concerned about – had very significant arterial inflammation compared to the Framingham Risk Score–matched controls," he commented. "Moreover, this group of HIV-infected patients basically had the same degree of arterial inflammation as the group of non-HIV patients with known cardiovascular disease [CVD], except that the HIV patients didn’t have known CVD."

Previous research has suggested that arterial FDG uptake like that observed is due to macrophage accumulation at the interface between the lipid core and the fibrous cap in atherosclerotic plaques (Circulation 2002;105:2708-11). And results of the new study indeed showed that arterial inflammation in the HIV-positive group was correlated with levels of soluble CD163, a marker of monocyte activation. Dr. Grinspoon speculated that the heightened arterial inflammation may thus reflect chronic immune activation.

"Increased arterial inflammation in well-controlled subjects on ART is likely to contribute to increased CVD rates in this population," he maintained. "Strategies to target this inflammation, in addition to targeting traditional risk factors, including potential strategies to reduce monocyte activation, may be useful and should be investigated."

Session attendees questioned whether there was a confounding effect of statins, which are known to be anti-inflammatory and were used by none of the HIV-positive group, a quarter of the risk-matched HIV-negative group, and two-thirds of the HIV-negative group with known atherosclerosis. But Dr. Grinspoon noted that several analyses taking statin use into account yielded the same results.

When asked if he had any hypotheses as to what is activating the monocytes and whether microbes may have a role, he replied, "We are just beginning to look at some of the other markers. The whole entire cascade of macrophage activation and [microbial translocation] needs to be looked at more carefully."

Another attendee wondered if the duration of HIV infection influenced inflammation, given that most patients studied had been infected for at least a decade. "It would be absolutely fascinating ... to look at ART-naïve patients at the height of their [viral levels]," Dr. Grinspoon replied. "I would predict that the elevation will be even higher in those and that going on to ART will slam it down, and then it festers along at a certain kind of low-grade level. Our point in this study is that festering along is a problem because there seems to be at least arterial inflammation, even when you think, ‘Oh, the patient is fine, their viral load is suppressed.’ "

The investigators enrolled in the study 27 HIV-positive patients free of known cardiac disease who were on stable ART and did not have any opportunistic infections; 27 HIV-negative individuals matched for age, sex, and Framingham Risk Score who had no known atherosclerosis; and 27 HIV-negative patients matched for sex who had known atherosclerosis.

On average, the members of the HIV-positive group were 52 years old, had been infected for 16 years, and had been on ART for 12 years, according to Dr. Grinspoon, who disclosed no relevant conflicts of interest related to the research. Their mean CD4 count was 592 cells/mm³, and three-fourths had undetectable HIV RNA. Their average Framingham Risk Score was 6.4.

The significantly greater inflammation in the HIV-positive group than in the risk-matched HIV-negative group was evident across a variety of subgroups, such as individuals not having any coronary calcium, nonsmokers, those not taking statins, and those having an undetectable viral load.

And in a multivariate regression analysis, HIV positivity remained significantly associated with greater arterial inflammation after potential confounders, such as coronary calcium score and statin use, were controlled for. "So [HIV positivity] seemed to be adding independently to these things," Dr. Grinspoon noted.

In the HIV-positive group, arterial inflammation did not differ with use of various classes of ART drugs patients were taking, for example, between users vs. nonusers of protease inhibitors.

In an analysis of immune and inflammatory factors in the HIV-positive group, monocyte activation, as indicated by higher soluble CD163 levels, was significantly correlated with inflammation (P = .03). In contrast, C-reactive protein, d-dimer, and measures of HIV severity were not.

Dr. Grinspoon reported having no relevant conflicts of interest.

SEATTLE – HIV-positive patients who have asymptomatic neurocognitive impairment may require especially close follow-up because of a sharply elevated risk of progression to symptomatic disease, according to an analysis from the CHARTER longitudinal cohort study.

At baseline, 35% of the 347 patients studied had neurocognitive impairments on testing but did not have any self-reported or observed declines in everyday functioning, and were thus classified as having asymptomatic neurocognitive impairment (ANI).

After a median follow-up of nearly 4 years, these patients had a 2.2- to 5.3-fold higher risk of developing symptomatic HIV-associated neurocognitive disorder relative to their counterparts who were neurocognitively normal, Dr. Igor Grant reported at the Conference on Retroviruses and Opportunistic Infections.

"The CHARTER study suggests that people with ANI do tend to progress to symptomatic status more frequently than people who don’t have any cognitive impairment," he commented. "ANI could be a harbinger for some underlying process that is worthy of monitoring."

In additional findings, certain other groups of patients defined by sociodemographic and HIV-related factors – women, substance abusers, and those with lower nadir CD4 counts, for example – also had an elevated risk of progression to the point of having symptoms.

Session attendee Dr. Lewis Haddow from the University College London wondered about the blinding of patients to their impairment on testing. "Could those with a label of ANI perhaps have overreported things on the self-report scale and subsequent follow-up?" he asked.

"They were not told their results, so those with ANI would not know it," replied Dr. Grant, who is professor and executive vice chair of the department of psychiatry at the University of California, San Diego.

Giving some study background, he noted that frank dementia in HIV-positive patients is uncommon today with effective antiretroviral therapy, but milder forms of impairment are still observed. "There has been concern among investigators as to whether particularly this entity of asymptomatic neurocognitive impairment, A, is real; and B, has clinical significance or any kind of predictive validity," he commented.

The CHARTER study was a multicenter study among HIV-positive patients receiving care in the era of highly active antiretroviral therapy. Every 6 months, a patient subset was assessed with a comprehensive battery of neurocognitive and other tests.

Symptomatic neurocognitive disorder was ascertained from self-report (requiring impairments on both the Patient Assessment of Own Functioning Inventory and Activities of Daily Living) and performance (requiring impairment on the Medication Management Test–Revised or on the Valpar System 3000 Work Samples and Computerized Assessment).

On average, the patients were about 43 years old and had been HIV positive for roughly a decade. Approximately 70% were on antiretroviral therapy; 82% were male, and 46% were white. With a median follow-up of 45 months, 32% developed symptomatic neurocognitive disorder.

After adjustment for education, estimated verbal IQ, and comorbidity classification, patients with ANI had an increased risk of symptomatic neurocognitive disorder based on self-report only (relative risk, 2.2; P = .005) and performance only (RR, 5.3, P less than .0001).

Certain baseline sociodemographic factors including age, female gender, low levels of education, and the presence of comorbidity as well as certain HIV-related factors including low nadir CD4 count and presence of AIDS also predicted decline to symptomatic status.

The investigators have not yet looked at the predictive performance of individual measures of neurocognitive function, according to Dr. Grant, who disclosed no relevant conflicts of interest. Also, they have not assessed virologic suppression as a predictor, but being on antiretroviral therapy did not predict decline to symptomatic neurocognitive disorder.

SEATTLE – HIV-positive patients who have asymptomatic neurocognitive impairment may require especially close follow-up because of a sharply elevated risk of progression to symptomatic disease, according to an analysis from the CHARTER longitudinal cohort study.

At baseline, 35% of the 347 patients studied had neurocognitive impairments on testing but did not have any self-reported or observed declines in everyday functioning, and were thus classified as having asymptomatic neurocognitive impairment (ANI).

After a median follow-up of nearly 4 years, these patients had a 2.2- to 5.3-fold higher risk of developing symptomatic HIV-associated neurocognitive disorder relative to their counterparts who were neurocognitively normal, Dr. Igor Grant reported at the Conference on Retroviruses and Opportunistic Infections.

"The CHARTER study suggests that people with ANI do tend to progress to symptomatic status more frequently than people who don’t have any cognitive impairment," he commented. "ANI could be a harbinger for some underlying process that is worthy of monitoring."

In additional findings, certain other groups of patients defined by sociodemographic and HIV-related factors – women, substance abusers, and those with lower nadir CD4 counts, for example – also had an elevated risk of progression to the point of having symptoms.

Session attendee Dr. Lewis Haddow from the University College London wondered about the blinding of patients to their impairment on testing. "Could those with a label of ANI perhaps have overreported things on the self-report scale and subsequent follow-up?" he asked.

"They were not told their results, so those with ANI would not know it," replied Dr. Grant, who is professor and executive vice chair of the department of psychiatry at the University of California, San Diego.

Giving some study background, he noted that frank dementia in HIV-positive patients is uncommon today with effective antiretroviral therapy, but milder forms of impairment are still observed. "There has been concern among investigators as to whether particularly this entity of asymptomatic neurocognitive impairment, A, is real; and B, has clinical significance or any kind of predictive validity," he commented.

The CHARTER study was a multicenter study among HIV-positive patients receiving care in the era of highly active antiretroviral therapy. Every 6 months, a patient subset was assessed with a comprehensive battery of neurocognitive and other tests.

Symptomatic neurocognitive disorder was ascertained from self-report (requiring impairments on both the Patient Assessment of Own Functioning Inventory and Activities of Daily Living) and performance (requiring impairment on the Medication Management Test–Revised or on the Valpar System 3000 Work Samples and Computerized Assessment).

On average, the patients were about 43 years old and had been HIV positive for roughly a decade. Approximately 70% were on antiretroviral therapy; 82% were male, and 46% were white. With a median follow-up of 45 months, 32% developed symptomatic neurocognitive disorder.

After adjustment for education, estimated verbal IQ, and comorbidity classification, patients with ANI had an increased risk of symptomatic neurocognitive disorder based on self-report only (relative risk, 2.2; P = .005) and performance only (RR, 5.3, P less than .0001).

Certain baseline sociodemographic factors including age, female gender, low levels of education, and the presence of comorbidity as well as certain HIV-related factors including low nadir CD4 count and presence of AIDS also predicted decline to symptomatic status.

The investigators have not yet looked at the predictive performance of individual measures of neurocognitive function, according to Dr. Grant, who disclosed no relevant conflicts of interest. Also, they have not assessed virologic suppression as a predictor, but being on antiretroviral therapy did not predict decline to symptomatic neurocognitive disorder.

SEATTLE – HIV-positive patients who have asymptomatic neurocognitive impairment may require especially close follow-up because of a sharply elevated risk of progression to symptomatic disease, according to an analysis from the CHARTER longitudinal cohort study.

At baseline, 35% of the 347 patients studied had neurocognitive impairments on testing but did not have any self-reported or observed declines in everyday functioning, and were thus classified as having asymptomatic neurocognitive impairment (ANI).

After a median follow-up of nearly 4 years, these patients had a 2.2- to 5.3-fold higher risk of developing symptomatic HIV-associated neurocognitive disorder relative to their counterparts who were neurocognitively normal, Dr. Igor Grant reported at the Conference on Retroviruses and Opportunistic Infections.

"The CHARTER study suggests that people with ANI do tend to progress to symptomatic status more frequently than people who don’t have any cognitive impairment," he commented. "ANI could be a harbinger for some underlying process that is worthy of monitoring."

In additional findings, certain other groups of patients defined by sociodemographic and HIV-related factors – women, substance abusers, and those with lower nadir CD4 counts, for example – also had an elevated risk of progression to the point of having symptoms.

Session attendee Dr. Lewis Haddow from the University College London wondered about the blinding of patients to their impairment on testing. "Could those with a label of ANI perhaps have overreported things on the self-report scale and subsequent follow-up?" he asked.

"They were not told their results, so those with ANI would not know it," replied Dr. Grant, who is professor and executive vice chair of the department of psychiatry at the University of California, San Diego.

Giving some study background, he noted that frank dementia in HIV-positive patients is uncommon today with effective antiretroviral therapy, but milder forms of impairment are still observed. "There has been concern among investigators as to whether particularly this entity of asymptomatic neurocognitive impairment, A, is real; and B, has clinical significance or any kind of predictive validity," he commented.

The CHARTER study was a multicenter study among HIV-positive patients receiving care in the era of highly active antiretroviral therapy. Every 6 months, a patient subset was assessed with a comprehensive battery of neurocognitive and other tests.

Symptomatic neurocognitive disorder was ascertained from self-report (requiring impairments on both the Patient Assessment of Own Functioning Inventory and Activities of Daily Living) and performance (requiring impairment on the Medication Management Test–Revised or on the Valpar System 3000 Work Samples and Computerized Assessment).

On average, the patients were about 43 years old and had been HIV positive for roughly a decade. Approximately 70% were on antiretroviral therapy; 82% were male, and 46% were white. With a median follow-up of 45 months, 32% developed symptomatic neurocognitive disorder.

After adjustment for education, estimated verbal IQ, and comorbidity classification, patients with ANI had an increased risk of symptomatic neurocognitive disorder based on self-report only (relative risk, 2.2; P = .005) and performance only (RR, 5.3, P less than .0001).

Certain baseline sociodemographic factors including age, female gender, low levels of education, and the presence of comorbidity as well as certain HIV-related factors including low nadir CD4 count and presence of AIDS also predicted decline to symptomatic status.

The investigators have not yet looked at the predictive performance of individual measures of neurocognitive function, according to Dr. Grant, who disclosed no relevant conflicts of interest. Also, they have not assessed virologic suppression as a predictor, but being on antiretroviral therapy did not predict decline to symptomatic neurocognitive disorder.

SEATTLE – Switching to an antiretroviral regimen that contains tenofovir may adversely affect the skeletal health of HIV-positive patients, according to a new analysis reported at the Conference on Retroviruses and Opportunistic Infections.

The analysis came from the Bone Biomarker Substudy of the multicenter PREPARE trial, in which HIV-positive patients taking first-line zidovudine-lamivudine (AZT-3TC) who had virologic suppression were randomized to either continue on that therapy or switch to tenofovir-emtricitabine (TDF-FTC).

The 54 patients in the substudy underwent serial measurements of bone biomarkers and had dual-energy x-ray absorptiometry (DXA) scanning at baseline and 48 weeks.

Main results showed that the group that switched therapy had increases in markers of bone turnover and lost 2% of the bone mineral density (BMD) in their lumbar spine, reported lead investigator Dr. Aoife G. Cotter of University College Dublin. In contrast, those who continued on the same therapy did not have significant changes in these measures.

"The impact of these changes on future and overall risk of fracture is unknown, and prospective longitudinal studies are required to answer this question," she commented. Also, "while we show that tenofovir affects bone metabolism in vivo, whether this is a direct effect of tenofovir on bone cells versus an indirect effect of tenofovir on bone via the renal tubules remains to be answered."

Session attendee Dr. Todd Brown of Johns Hopkins University, Baltimore, noted that tenofovir has heterogeneous effects on bone across patients, and it would be nice to have a marker for early identification of patients who will lose BMD. "One way to do that potentially is with bone markers, so I was wondering if early absolute levels or early changes in bone markers predicted bone loss with tenofovir," he said.

The investigators did not assess that association, but a similar study looking at regimen simplification, called the STEAL study, did and found no correlation, according to Dr. Cotter. "However, when you look at our medians [for biomarker levels] plotted over time, the changes really weren’t maximal until at least 24 weeks, so we would need to have looked at changes up until at least 24 weeks to see if they correlated," she added.

Another attendee, Dr. Michael Yin of Columbia University Medical Center in New York, asked, "Are there plans to follow up with another DXA at a later date, because this is quite similar to the loss that you experience with initiation of ART, although in a different setting. It would be interesting to see whether or not the bone loss continues." Additionally, he wondered if the investigators were looking at other biomarkers.

"There are no plans that I know of to repeat DXA scans on these subjects or to increase the duration of follow-up," Dr. Cotter replied. "We do, however, have samples left and are currently performing vitamin D and parathyroid hormone analysis."

Adult HIV-positive patients were eligible for the PREPARE trial if they had been on a zidovudine-lamivudine–containing regimen as their first treatment for more than 2 years and had had a viral load of fewer than 50 copies of HIV RNA/mL for more than 6 months.

They had a median age of about 46 years, and the majority were male and white. They had been on zidovudine and lamivudine (brand names Retrovir and Epivir) for a median of roughly 5.5 years.

Results showed that compared with the group that continued on zidovudine-lamivudine, the group that switched to tenofovir plus emtricitabine (brand names Viread and Emtriva) had greater changes between baseline and week 48 in three biomarkers of bone turnover: type 1 collagen cross-linked C-telopeptide (P = .0005), osteocalcin (P less than .0001), and procollagen type 1 N-terminal propeptide (P less than .0001).

BMD of the lumbar spine fell by 2.04% from baseline in the group that switched (P = .01) but changed little in the group that continued on the original regimen, resulting in a significant difference between them (P = .03). Neither group had a significant change from baseline in BMD of the femoral neck.

The changes in levels of osteocalcin and procollagen type 1 N-terminal propeptide over the 48-week period were significantly inversely correlated with loss of BMD in the lumbar spine.

In a multivariate analysis adjusted for baseline biomarker level, sex, and ethnicity, the switch from zidovudine-lamivudine to tenofovir-emtricitabine was a significant independent predictor of changes in levels of all three biomarkers.

Among various study limitations, Dr. Cotter acknowledged, was "an absence of data on some classical risk factors, such as smoking and significant use of steroids." Also, "our follow-up was limited to 48 weeks; it would have been interesting to see what happened beyond that," she commented.

Dr. Cotter disclosed no relevant conflicts of interest. The PREPARE trial was supported by an unrestricted scientific grant from Gilead Sciences.

SEATTLE – Switching to an antiretroviral regimen that contains tenofovir may adversely affect the skeletal health of HIV-positive patients, according to a new analysis reported at the Conference on Retroviruses and Opportunistic Infections.

The analysis came from the Bone Biomarker Substudy of the multicenter PREPARE trial, in which HIV-positive patients taking first-line zidovudine-lamivudine (AZT-3TC) who had virologic suppression were randomized to either continue on that therapy or switch to tenofovir-emtricitabine (TDF-FTC).

The 54 patients in the substudy underwent serial measurements of bone biomarkers and had dual-energy x-ray absorptiometry (DXA) scanning at baseline and 48 weeks.

Main results showed that the group that switched therapy had increases in markers of bone turnover and lost 2% of the bone mineral density (BMD) in their lumbar spine, reported lead investigator Dr. Aoife G. Cotter of University College Dublin. In contrast, those who continued on the same therapy did not have significant changes in these measures.

"The impact of these changes on future and overall risk of fracture is unknown, and prospective longitudinal studies are required to answer this question," she commented. Also, "while we show that tenofovir affects bone metabolism in vivo, whether this is a direct effect of tenofovir on bone cells versus an indirect effect of tenofovir on bone via the renal tubules remains to be answered."

Session attendee Dr. Todd Brown of Johns Hopkins University, Baltimore, noted that tenofovir has heterogeneous effects on bone across patients, and it would be nice to have a marker for early identification of patients who will lose BMD. "One way to do that potentially is with bone markers, so I was wondering if early absolute levels or early changes in bone markers predicted bone loss with tenofovir," he said.

The investigators did not assess that association, but a similar study looking at regimen simplification, called the STEAL study, did and found no correlation, according to Dr. Cotter. "However, when you look at our medians [for biomarker levels] plotted over time, the changes really weren’t maximal until at least 24 weeks, so we would need to have looked at changes up until at least 24 weeks to see if they correlated," she added.

Another attendee, Dr. Michael Yin of Columbia University Medical Center in New York, asked, "Are there plans to follow up with another DXA at a later date, because this is quite similar to the loss that you experience with initiation of ART, although in a different setting. It would be interesting to see whether or not the bone loss continues." Additionally, he wondered if the investigators were looking at other biomarkers.

"There are no plans that I know of to repeat DXA scans on these subjects or to increase the duration of follow-up," Dr. Cotter replied. "We do, however, have samples left and are currently performing vitamin D and parathyroid hormone analysis."

Adult HIV-positive patients were eligible for the PREPARE trial if they had been on a zidovudine-lamivudine–containing regimen as their first treatment for more than 2 years and had had a viral load of fewer than 50 copies of HIV RNA/mL for more than 6 months.

They had a median age of about 46 years, and the majority were male and white. They had been on zidovudine and lamivudine (brand names Retrovir and Epivir) for a median of roughly 5.5 years.

Results showed that compared with the group that continued on zidovudine-lamivudine, the group that switched to tenofovir plus emtricitabine (brand names Viread and Emtriva) had greater changes between baseline and week 48 in three biomarkers of bone turnover: type 1 collagen cross-linked C-telopeptide (P = .0005), osteocalcin (P less than .0001), and procollagen type 1 N-terminal propeptide (P less than .0001).

BMD of the lumbar spine fell by 2.04% from baseline in the group that switched (P = .01) but changed little in the group that continued on the original regimen, resulting in a significant difference between them (P = .03). Neither group had a significant change from baseline in BMD of the femoral neck.

The changes in levels of osteocalcin and procollagen type 1 N-terminal propeptide over the 48-week period were significantly inversely correlated with loss of BMD in the lumbar spine.

In a multivariate analysis adjusted for baseline biomarker level, sex, and ethnicity, the switch from zidovudine-lamivudine to tenofovir-emtricitabine was a significant independent predictor of changes in levels of all three biomarkers.

Among various study limitations, Dr. Cotter acknowledged, was "an absence of data on some classical risk factors, such as smoking and significant use of steroids." Also, "our follow-up was limited to 48 weeks; it would have been interesting to see what happened beyond that," she commented.

Dr. Cotter disclosed no relevant conflicts of interest. The PREPARE trial was supported by an unrestricted scientific grant from Gilead Sciences.

SEATTLE – Switching to an antiretroviral regimen that contains tenofovir may adversely affect the skeletal health of HIV-positive patients, according to a new analysis reported at the Conference on Retroviruses and Opportunistic Infections.

The analysis came from the Bone Biomarker Substudy of the multicenter PREPARE trial, in which HIV-positive patients taking first-line zidovudine-lamivudine (AZT-3TC) who had virologic suppression were randomized to either continue on that therapy or switch to tenofovir-emtricitabine (TDF-FTC).

The 54 patients in the substudy underwent serial measurements of bone biomarkers and had dual-energy x-ray absorptiometry (DXA) scanning at baseline and 48 weeks.

Main results showed that the group that switched therapy had increases in markers of bone turnover and lost 2% of the bone mineral density (BMD) in their lumbar spine, reported lead investigator Dr. Aoife G. Cotter of University College Dublin. In contrast, those who continued on the same therapy did not have significant changes in these measures.

"The impact of these changes on future and overall risk of fracture is unknown, and prospective longitudinal studies are required to answer this question," she commented. Also, "while we show that tenofovir affects bone metabolism in vivo, whether this is a direct effect of tenofovir on bone cells versus an indirect effect of tenofovir on bone via the renal tubules remains to be answered."

Session attendee Dr. Todd Brown of Johns Hopkins University, Baltimore, noted that tenofovir has heterogeneous effects on bone across patients, and it would be nice to have a marker for early identification of patients who will lose BMD. "One way to do that potentially is with bone markers, so I was wondering if early absolute levels or early changes in bone markers predicted bone loss with tenofovir," he said.

The investigators did not assess that association, but a similar study looking at regimen simplification, called the STEAL study, did and found no correlation, according to Dr. Cotter. "However, when you look at our medians [for biomarker levels] plotted over time, the changes really weren’t maximal until at least 24 weeks, so we would need to have looked at changes up until at least 24 weeks to see if they correlated," she added.

Another attendee, Dr. Michael Yin of Columbia University Medical Center in New York, asked, "Are there plans to follow up with another DXA at a later date, because this is quite similar to the loss that you experience with initiation of ART, although in a different setting. It would be interesting to see whether or not the bone loss continues." Additionally, he wondered if the investigators were looking at other biomarkers.

"There are no plans that I know of to repeat DXA scans on these subjects or to increase the duration of follow-up," Dr. Cotter replied. "We do, however, have samples left and are currently performing vitamin D and parathyroid hormone analysis."

Adult HIV-positive patients were eligible for the PREPARE trial if they had been on a zidovudine-lamivudine–containing regimen as their first treatment for more than 2 years and had had a viral load of fewer than 50 copies of HIV RNA/mL for more than 6 months.

They had a median age of about 46 years, and the majority were male and white. They had been on zidovudine and lamivudine (brand names Retrovir and Epivir) for a median of roughly 5.5 years.

Results showed that compared with the group that continued on zidovudine-lamivudine, the group that switched to tenofovir plus emtricitabine (brand names Viread and Emtriva) had greater changes between baseline and week 48 in three biomarkers of bone turnover: type 1 collagen cross-linked C-telopeptide (P = .0005), osteocalcin (P less than .0001), and procollagen type 1 N-terminal propeptide (P less than .0001).

BMD of the lumbar spine fell by 2.04% from baseline in the group that switched (P = .01) but changed little in the group that continued on the original regimen, resulting in a significant difference between them (P = .03). Neither group had a significant change from baseline in BMD of the femoral neck.

The changes in levels of osteocalcin and procollagen type 1 N-terminal propeptide over the 48-week period were significantly inversely correlated with loss of BMD in the lumbar spine.

In a multivariate analysis adjusted for baseline biomarker level, sex, and ethnicity, the switch from zidovudine-lamivudine to tenofovir-emtricitabine was a significant independent predictor of changes in levels of all three biomarkers.

Among various study limitations, Dr. Cotter acknowledged, was "an absence of data on some classical risk factors, such as smoking and significant use of steroids." Also, "our follow-up was limited to 48 weeks; it would have been interesting to see what happened beyond that," she commented.

Dr. Cotter disclosed no relevant conflicts of interest. The PREPARE trial was supported by an unrestricted scientific grant from Gilead Sciences.

SEATTLE – Elevated blood pressure may warrant more aggressive management in HIV-positive individuals, suggest results from a cohort study reported at the Conference on Retroviruses and Opportunistic Infections.

In addition, the findings suggest that "we also need to address prehypertension, because we saw an increased risk of AMI [acute myocardial infarction] among prehypertensive people," said Kaku Armah, a doctoral student with the University of Pittsburgh’s Graduate School of Public Health.

"Prehypertension is treated with lifestyle modifications in uninfected people, and we think that should also be used in HIV-infected people," he advised.

He and his colleagues studied 82,490 veterans included in the Veterans Aging Cohort Study–Virtual Cohort, identified HIV-positive patients, and then matched each for age, sex, race/ethnicity, and clinical site to two HIV-negative patients. Blood pressures from the three most recent outpatient visits were averaged to obtain a baseline blood pressure.

All the veterans were free of cardiovascular disease at baseline. During a median 4.6-year follow-up, 443 of them had a fatal or nonfatal acute myocardial infarction (AMI).

Initial analyses showed that within each systolic and diastolic blood pressure bracket, the rate of AMI was consistently higher for the HIV-positive patients than for the HIV-negative patients, although there was some overlap of 95% confidence intervals, Mr. Armah reported.

A first multivariate analysis (adjusted for lipids, smoking, body mass index, comorbidities, and other potential confounders) considered systolic blood pressure, using HIV-negative patients having a value of less than 120 mm Hg and not taking any blood pressure medication as the reference group.

Compared with that group, HIV-positive patients had a significantly elevated risk of AMI if they had a systolic blood pressure of 120-139 mm Hg (prehypertension) and were not taking any medication (hazard ratio, 1.7); had a systolic blood pressure of less than 140 mm Hg and were taking medication (HR, 2.2); or had a systolic blood pressure of 140 mm Hg or greater regardless of medication use (HR, 2.4).

Among HIV-negative patients, the corresponding elevations of AMI risk in these categories were smaller; moreover, the elevated risk was significant only in the group having a systolic blood pressure of 140 mm Hg or greater regardless of medication use (HR, 1.6).

In light of these findings, recommendations for the general population to reduce blood pressure below 140/90 mm Hg may not be sufficient for HIV-positive patients, said Dr. Christopher Nguyen, an internist with the Tom Waddell Health Center in San Francisco. Perhaps HIV-positive patients need to be aiming for targets similar to those used for renal or diabetic patients whose target blood pressure is below 130/80 mm Hg.

The findings were much the same in a second multivariate analysis that instead evaluated AMI risk according to diastolic blood pressure categories.

Mr. Armah said that since the findings are observational, there is not enough evidence yet to recommend such a change in practice.

Session comoderator Caroline Sabin, Ph.D., of University College London inquired about the potential role of antiretroviral therapy, because it has been associated with hypertension and elevated MI rates.

Mr. Armah noted that because the study models included both HIV-positive and HIV-negative patients, it was not possible to adjust for antiretroviral therapy, "but we may do a subset analysis looking at just the HIV-infected people."

In addition, analyses have not yet been done to look at the role of inflammatory markers or the severity of HIV infection in the observed associations.

Mr. Armah reported having no relevant conflicts of interest.

SEATTLE – Elevated blood pressure may warrant more aggressive management in HIV-positive individuals, suggest results from a cohort study reported at the Conference on Retroviruses and Opportunistic Infections.

In addition, the findings suggest that "we also need to address prehypertension, because we saw an increased risk of AMI [acute myocardial infarction] among prehypertensive people," said Kaku Armah, a doctoral student with the University of Pittsburgh’s Graduate School of Public Health.

"Prehypertension is treated with lifestyle modifications in uninfected people, and we think that should also be used in HIV-infected people," he advised.

He and his colleagues studied 82,490 veterans included in the Veterans Aging Cohort Study–Virtual Cohort, identified HIV-positive patients, and then matched each for age, sex, race/ethnicity, and clinical site to two HIV-negative patients. Blood pressures from the three most recent outpatient visits were averaged to obtain a baseline blood pressure.

All the veterans were free of cardiovascular disease at baseline. During a median 4.6-year follow-up, 443 of them had a fatal or nonfatal acute myocardial infarction (AMI).

Initial analyses showed that within each systolic and diastolic blood pressure bracket, the rate of AMI was consistently higher for the HIV-positive patients than for the HIV-negative patients, although there was some overlap of 95% confidence intervals, Mr. Armah reported.

A first multivariate analysis (adjusted for lipids, smoking, body mass index, comorbidities, and other potential confounders) considered systolic blood pressure, using HIV-negative patients having a value of less than 120 mm Hg and not taking any blood pressure medication as the reference group.

Compared with that group, HIV-positive patients had a significantly elevated risk of AMI if they had a systolic blood pressure of 120-139 mm Hg (prehypertension) and were not taking any medication (hazard ratio, 1.7); had a systolic blood pressure of less than 140 mm Hg and were taking medication (HR, 2.2); or had a systolic blood pressure of 140 mm Hg or greater regardless of medication use (HR, 2.4).

Among HIV-negative patients, the corresponding elevations of AMI risk in these categories were smaller; moreover, the elevated risk was significant only in the group having a systolic blood pressure of 140 mm Hg or greater regardless of medication use (HR, 1.6).

In light of these findings, recommendations for the general population to reduce blood pressure below 140/90 mm Hg may not be sufficient for HIV-positive patients, said Dr. Christopher Nguyen, an internist with the Tom Waddell Health Center in San Francisco. Perhaps HIV-positive patients need to be aiming for targets similar to those used for renal or diabetic patients whose target blood pressure is below 130/80 mm Hg.

The findings were much the same in a second multivariate analysis that instead evaluated AMI risk according to diastolic blood pressure categories.

Mr. Armah said that since the findings are observational, there is not enough evidence yet to recommend such a change in practice.

Session comoderator Caroline Sabin, Ph.D., of University College London inquired about the potential role of antiretroviral therapy, because it has been associated with hypertension and elevated MI rates.

Mr. Armah noted that because the study models included both HIV-positive and HIV-negative patients, it was not possible to adjust for antiretroviral therapy, "but we may do a subset analysis looking at just the HIV-infected people."

In addition, analyses have not yet been done to look at the role of inflammatory markers or the severity of HIV infection in the observed associations.

Mr. Armah reported having no relevant conflicts of interest.

SEATTLE – Elevated blood pressure may warrant more aggressive management in HIV-positive individuals, suggest results from a cohort study reported at the Conference on Retroviruses and Opportunistic Infections.

In addition, the findings suggest that "we also need to address prehypertension, because we saw an increased risk of AMI [acute myocardial infarction] among prehypertensive people," said Kaku Armah, a doctoral student with the University of Pittsburgh’s Graduate School of Public Health.

"Prehypertension is treated with lifestyle modifications in uninfected people, and we think that should also be used in HIV-infected people," he advised.

He and his colleagues studied 82,490 veterans included in the Veterans Aging Cohort Study–Virtual Cohort, identified HIV-positive patients, and then matched each for age, sex, race/ethnicity, and clinical site to two HIV-negative patients. Blood pressures from the three most recent outpatient visits were averaged to obtain a baseline blood pressure.

All the veterans were free of cardiovascular disease at baseline. During a median 4.6-year follow-up, 443 of them had a fatal or nonfatal acute myocardial infarction (AMI).

Initial analyses showed that within each systolic and diastolic blood pressure bracket, the rate of AMI was consistently higher for the HIV-positive patients than for the HIV-negative patients, although there was some overlap of 95% confidence intervals, Mr. Armah reported.

A first multivariate analysis (adjusted for lipids, smoking, body mass index, comorbidities, and other potential confounders) considered systolic blood pressure, using HIV-negative patients having a value of less than 120 mm Hg and not taking any blood pressure medication as the reference group.

Compared with that group, HIV-positive patients had a significantly elevated risk of AMI if they had a systolic blood pressure of 120-139 mm Hg (prehypertension) and were not taking any medication (hazard ratio, 1.7); had a systolic blood pressure of less than 140 mm Hg and were taking medication (HR, 2.2); or had a systolic blood pressure of 140 mm Hg or greater regardless of medication use (HR, 2.4).

Among HIV-negative patients, the corresponding elevations of AMI risk in these categories were smaller; moreover, the elevated risk was significant only in the group having a systolic blood pressure of 140 mm Hg or greater regardless of medication use (HR, 1.6).

In light of these findings, recommendations for the general population to reduce blood pressure below 140/90 mm Hg may not be sufficient for HIV-positive patients, said Dr. Christopher Nguyen, an internist with the Tom Waddell Health Center in San Francisco. Perhaps HIV-positive patients need to be aiming for targets similar to those used for renal or diabetic patients whose target blood pressure is below 130/80 mm Hg.

The findings were much the same in a second multivariate analysis that instead evaluated AMI risk according to diastolic blood pressure categories.

Mr. Armah said that since the findings are observational, there is not enough evidence yet to recommend such a change in practice.

Session comoderator Caroline Sabin, Ph.D., of University College London inquired about the potential role of antiretroviral therapy, because it has been associated with hypertension and elevated MI rates.

Mr. Armah noted that because the study models included both HIV-positive and HIV-negative patients, it was not possible to adjust for antiretroviral therapy, "but we may do a subset analysis looking at just the HIV-infected people."

In addition, analyses have not yet been done to look at the role of inflammatory markers or the severity of HIV infection in the observed associations.

Mr. Armah reported having no relevant conflicts of interest.

SEATTLE – Treatment with the antidiabetic drug metformin halted the progression of coronary artery calcification in HIV-positive patients who had metabolic syndrome in a randomized clinical trial.

Lifestyle modification had a smaller, nonsignificant benefit, slowing down the progression of coronary artery calcification (CAC), according to the results of the 1-year trial, which enrolled 50 adult patients, Kathleen Fitch reported at the Conference on Retroviruses and Opportunistic Infections.

After 1 year of treatment, CAC scores had increased by 43 points with placebo, by 19 points with lifestyle modification alone, and by 1 point with metformin alone, and had decreased by 4 points with the combination of metformin and lifestyle modification (P = .03 for trend across groups).

Both interventions were well tolerated, and each had some additional benefits, said Ms. Fitch of the Program in Nutritional Metabolism at Massachusetts General Hospital, Boston. For example, metformin reduced insulin resistance, and lifestyle modification improved high-density lipoprotein cholesterol levels, fat content of muscle, C-reactive protein levels, and measures of physical fitness.

"Modification of risk factors for CVD [cardiovascular disease] is important in the management of HIV infection, including strategies for insulin resistance. Metformin may be a useful drug to modify CVD risk," she commented. "A larger study may be required to show lifestyle modification’s effect on CAC."

The study not only showed that metformin had a preventive effect on CAC progression, but also provided a window on the natural history of CAC progression over 1 year in these HIV-infected patients with metabolic syndrome, she said. In fact, the rate of progression seen in the placebo group was about twice the rate that has been reported for the general population.

To put the findings into clinical context, the investigators calculated adjusted Framingham risk scores for a hypothetical patient representative of their study population. At baseline, he had a 10-year risk of CVD events (12%) putting him at intermediate risk, but after a year with no intervention and the expected increase in CAC score, his risk more than doubled (25%), now putting him at high risk. "Importantly, this change would be preventable by metformin since we observed no progression of CAC among those taking metformin," Ms. Fitch said.

Dr. Jens Lundgren of the University of Copenhagen noted that the study may have been limited by the fact that only about half of patients had detectable CAC at baseline, reducing the population that could benefit. "So if you screened for CAC at baseline, would that optimize your power?" he asked.

"Initially, we weren’t sure if every patient would have detectable CAC. We also would hope that metformin would prevent development of CAC in these subjects," Ms. Fitch replied; however, it is possible that subsequent studies might include only patients having detectable CAC.

Dr. James Stein of the University of Wisconsin, Madison, said it was a "great study," but he questioned the possible impact of an imbalance in patients having detectable CAC at baseline, noting that "the single biggest predictor of CAC progression is the presence of CAC to begin with." He recommended repeating the analysis, taking that factor into account. "In the context of many other things that have been looked at for calcium progression, it’s a surprise to see such a change in such a small study," he added.

HIV-positive patients were eligible for the trial if they were 18-65 years old, had been on a stable treatment regimen for more than 6 months, and met criteria for metabolic syndrome but did not have diabetes. "Very few established treatment options exist for this population," Ms. Fitch said.

They were randomized nearly equally to four groups treated on a double-blind basis: placebo with and without lifestyle modification, and metformin with and without lifestyle modification.

Lifestyle modification consisted of 60 minutes three times weekly of cardiovascular and strength training, plus weekly nutrition counseling. Metformin (Glucophage and others) was given at a dose of 500 mg twice daily for 3 months, and then 850 mg twice daily thereafter. CAC was assessed with computed tomography.

The patients’ average age was about 47 years, and 76% were men. The majority were already taking antihypertensive and lipid-lowering medications. Overall, 44% had detectable CAC at baseline.

The four groups had similar rates of treatment discontinuation and similarly high rates of treatment compliance, Ms. Fitch reported. Both interventions were well tolerated: There were six cases of gastrointestinal adverse effects with metformin and two cases of muscle strain with the lifestyle modification.

"Further studies are clearly needed to understand the mechanisms of metformin to prevent CAC progression," she concluded. "And larger, longer-term studies using metformin in HIV-infected patients with metabolic syndrome and insulin resistance will be useful to determine whether this strategy will prevent CVD events."

Ms. Fitch disclosed that she had no relevant conflicts of interest.

SEATTLE – Treatment with the antidiabetic drug metformin halted the progression of coronary artery calcification in HIV-positive patients who had metabolic syndrome in a randomized clinical trial.

Lifestyle modification had a smaller, nonsignificant benefit, slowing down the progression of coronary artery calcification (CAC), according to the results of the 1-year trial, which enrolled 50 adult patients, Kathleen Fitch reported at the Conference on Retroviruses and Opportunistic Infections.

After 1 year of treatment, CAC scores had increased by 43 points with placebo, by 19 points with lifestyle modification alone, and by 1 point with metformin alone, and had decreased by 4 points with the combination of metformin and lifestyle modification (P = .03 for trend across groups).

Both interventions were well tolerated, and each had some additional benefits, said Ms. Fitch of the Program in Nutritional Metabolism at Massachusetts General Hospital, Boston. For example, metformin reduced insulin resistance, and lifestyle modification improved high-density lipoprotein cholesterol levels, fat content of muscle, C-reactive protein levels, and measures of physical fitness.

"Modification of risk factors for CVD [cardiovascular disease] is important in the management of HIV infection, including strategies for insulin resistance. Metformin may be a useful drug to modify CVD risk," she commented. "A larger study may be required to show lifestyle modification’s effect on CAC."

The study not only showed that metformin had a preventive effect on CAC progression, but also provided a window on the natural history of CAC progression over 1 year in these HIV-infected patients with metabolic syndrome, she said. In fact, the rate of progression seen in the placebo group was about twice the rate that has been reported for the general population.

To put the findings into clinical context, the investigators calculated adjusted Framingham risk scores for a hypothetical patient representative of their study population. At baseline, he had a 10-year risk of CVD events (12%) putting him at intermediate risk, but after a year with no intervention and the expected increase in CAC score, his risk more than doubled (25%), now putting him at high risk. "Importantly, this change would be preventable by metformin since we observed no progression of CAC among those taking metformin," Ms. Fitch said.

Dr. Jens Lundgren of the University of Copenhagen noted that the study may have been limited by the fact that only about half of patients had detectable CAC at baseline, reducing the population that could benefit. "So if you screened for CAC at baseline, would that optimize your power?" he asked.

"Initially, we weren’t sure if every patient would have detectable CAC. We also would hope that metformin would prevent development of CAC in these subjects," Ms. Fitch replied; however, it is possible that subsequent studies might include only patients having detectable CAC.

Dr. James Stein of the University of Wisconsin, Madison, said it was a "great study," but he questioned the possible impact of an imbalance in patients having detectable CAC at baseline, noting that "the single biggest predictor of CAC progression is the presence of CAC to begin with." He recommended repeating the analysis, taking that factor into account. "In the context of many other things that have been looked at for calcium progression, it’s a surprise to see such a change in such a small study," he added.

HIV-positive patients were eligible for the trial if they were 18-65 years old, had been on a stable treatment regimen for more than 6 months, and met criteria for metabolic syndrome but did not have diabetes. "Very few established treatment options exist for this population," Ms. Fitch said.

They were randomized nearly equally to four groups treated on a double-blind basis: placebo with and without lifestyle modification, and metformin with and without lifestyle modification.

Lifestyle modification consisted of 60 minutes three times weekly of cardiovascular and strength training, plus weekly nutrition counseling. Metformin (Glucophage and others) was given at a dose of 500 mg twice daily for 3 months, and then 850 mg twice daily thereafter. CAC was assessed with computed tomography.

The patients’ average age was about 47 years, and 76% were men. The majority were already taking antihypertensive and lipid-lowering medications. Overall, 44% had detectable CAC at baseline.

The four groups had similar rates of treatment discontinuation and similarly high rates of treatment compliance, Ms. Fitch reported. Both interventions were well tolerated: There were six cases of gastrointestinal adverse effects with metformin and two cases of muscle strain with the lifestyle modification.

"Further studies are clearly needed to understand the mechanisms of metformin to prevent CAC progression," she concluded. "And larger, longer-term studies using metformin in HIV-infected patients with metabolic syndrome and insulin resistance will be useful to determine whether this strategy will prevent CVD events."

Ms. Fitch disclosed that she had no relevant conflicts of interest.

SEATTLE – Treatment with the antidiabetic drug metformin halted the progression of coronary artery calcification in HIV-positive patients who had metabolic syndrome in a randomized clinical trial.

Lifestyle modification had a smaller, nonsignificant benefit, slowing down the progression of coronary artery calcification (CAC), according to the results of the 1-year trial, which enrolled 50 adult patients, Kathleen Fitch reported at the Conference on Retroviruses and Opportunistic Infections.

After 1 year of treatment, CAC scores had increased by 43 points with placebo, by 19 points with lifestyle modification alone, and by 1 point with metformin alone, and had decreased by 4 points with the combination of metformin and lifestyle modification (P = .03 for trend across groups).

Both interventions were well tolerated, and each had some additional benefits, said Ms. Fitch of the Program in Nutritional Metabolism at Massachusetts General Hospital, Boston. For example, metformin reduced insulin resistance, and lifestyle modification improved high-density lipoprotein cholesterol levels, fat content of muscle, C-reactive protein levels, and measures of physical fitness.

"Modification of risk factors for CVD [cardiovascular disease] is important in the management of HIV infection, including strategies for insulin resistance. Metformin may be a useful drug to modify CVD risk," she commented. "A larger study may be required to show lifestyle modification’s effect on CAC."

The study not only showed that metformin had a preventive effect on CAC progression, but also provided a window on the natural history of CAC progression over 1 year in these HIV-infected patients with metabolic syndrome, she said. In fact, the rate of progression seen in the placebo group was about twice the rate that has been reported for the general population.

To put the findings into clinical context, the investigators calculated adjusted Framingham risk scores for a hypothetical patient representative of their study population. At baseline, he had a 10-year risk of CVD events (12%) putting him at intermediate risk, but after a year with no intervention and the expected increase in CAC score, his risk more than doubled (25%), now putting him at high risk. "Importantly, this change would be preventable by metformin since we observed no progression of CAC among those taking metformin," Ms. Fitch said.

Dr. Jens Lundgren of the University of Copenhagen noted that the study may have been limited by the fact that only about half of patients had detectable CAC at baseline, reducing the population that could benefit. "So if you screened for CAC at baseline, would that optimize your power?" he asked.

"Initially, we weren’t sure if every patient would have detectable CAC. We also would hope that metformin would prevent development of CAC in these subjects," Ms. Fitch replied; however, it is possible that subsequent studies might include only patients having detectable CAC.

Dr. James Stein of the University of Wisconsin, Madison, said it was a "great study," but he questioned the possible impact of an imbalance in patients having detectable CAC at baseline, noting that "the single biggest predictor of CAC progression is the presence of CAC to begin with." He recommended repeating the analysis, taking that factor into account. "In the context of many other things that have been looked at for calcium progression, it’s a surprise to see such a change in such a small study," he added.

HIV-positive patients were eligible for the trial if they were 18-65 years old, had been on a stable treatment regimen for more than 6 months, and met criteria for metabolic syndrome but did not have diabetes. "Very few established treatment options exist for this population," Ms. Fitch said.

They were randomized nearly equally to four groups treated on a double-blind basis: placebo with and without lifestyle modification, and metformin with and without lifestyle modification.

Lifestyle modification consisted of 60 minutes three times weekly of cardiovascular and strength training, plus weekly nutrition counseling. Metformin (Glucophage and others) was given at a dose of 500 mg twice daily for 3 months, and then 850 mg twice daily thereafter. CAC was assessed with computed tomography.

The patients’ average age was about 47 years, and 76% were men. The majority were already taking antihypertensive and lipid-lowering medications. Overall, 44% had detectable CAC at baseline.

The four groups had similar rates of treatment discontinuation and similarly high rates of treatment compliance, Ms. Fitch reported. Both interventions were well tolerated: There were six cases of gastrointestinal adverse effects with metformin and two cases of muscle strain with the lifestyle modification.

"Further studies are clearly needed to understand the mechanisms of metformin to prevent CAC progression," she concluded. "And larger, longer-term studies using metformin in HIV-infected patients with metabolic syndrome and insulin resistance will be useful to determine whether this strategy will prevent CVD events."

Ms. Fitch disclosed that she had no relevant conflicts of interest.

SEATTLE – Greater efforts are needed to get people with HIV infection into medical care, a necessary prerequisite to therapy and viral suppression, suggests a cross-sectional survey of 4,217 HIV-positive adults conducted by the Centers for Disease Control and Prevention.

Survey results, reported at the Conference on Retroviruses and Opportunistic Infections, also showed that only an estimated 36% of adults living with HIV in 2009 had at least one medical care visit between January and April of that year.

© Dr. A. Harrison; Dr. P. Feorino / CDC

But within this group, measures of therapy were good: 89% had received at least one prescription for antiretroviral therapy (ART) in the past year, and 72% had achieved a suppressed HIV viral load, defined as having 200 copies/mL or less of the virus at the most recent measurement in the past year.

"Increasing the size of the in-care population is critical to increase the overall proportion of HIV-infected persons who are on ART and suppressed," said Dr. Jacek Skarbinski, an investigator in the Division of HIV/AIDS Prevention at the CDC. "We find that most HIV-infected adults in care are already on ART."

Analyses have suggested that expanding guidelines regarding when to initiate ART – from the current recommendation (presence of AIDS or a nadir CD4 cell count of 500 cells/mL or lower) to a new one covering all HIV-infected people (regardless of CD4 cell count) – would have only a small impact. Such expansion would increase the percentage of people in care who are on ART by just 3%.

In additional study findings, certain groups of people in care – young adults, blacks, and those living in poverty, among others – were significantly less likely to be prescribed ART, to achieve viral suppression, or both. Thus, "we need to address disparities in HIV care and treatment, especially by age, race, and income," Dr. Skarbinski maintained.

"The study is interesting as it highlights what can be achieved through use of basic epidemiological tools to provide estimates of the numbers receiving treatment across the country as a whole and within subgroups," Kholoud Porter, Ph.D., session comoderator and senior epidemiologist with the MRC Clinical Trials Unit in London, said in an interview. "This is important information for health care planning."

"The continuum of engagement in HIV care includes HIV diagnosis, linkage to and retention in care, prescription of ART, and viral suppression," Dr. Skarbinski said.

To obtain national estimates of these outcomes, he and colleagues analyzed data from the Medical Monitoring Project, a supplemental surveillance system that captures information on nationally representative samples of HIV-infected people in care.

In 2009, it collected data from 17 states and territories, 461 facilities within those states and territories, and 4,217 HIV-infected patients receiving care in those facilities. Patients were interviewed and their medical records were abstracted to ascertain prescription of ART and achievement of viral suppression.

The patients represented an estimated 421,186 adults in care at the population level, or just 36% of all 1.2 million people living with HIV nationally on the basis of a recent estimate (MMWR Morb. Mortal. Wkly. Rep. 2011;60:689-93). The value was higher, but still only 41%, when analyses were annualized to reflect receipt of care during the whole year and not just the first 4 months.

Patients in care were predominantly 40 years of age or older (75%), male (71%), non-Hispanic black (41%) or white (34%), and men who had sex with men (47%). The majority had more than a high school education (51%) but also lived below the poverty line (54%) and had public health insurance (62%). Half were at least 10 years out from diagnosis, and two-thirds had AIDS.

Multivariate analyses showed that individuals in care were significantly less likely to be prescribed ART if they were aged 18-29, non-Hispanic black, female, in the first 4 years after diagnosis, and did not have AIDS (regardless of nadir CD4 cell count).

Similarly, individuals in care were significantly less likely to be prescribed antiretroviral therapy if they were aged 18-49, non-Hispanic black or of "other" race/ethnicity, were living at or below the poverty level, and did not have AIDS and had a nadir CD4 cell count of greater than 500.

The study data suggested that nationally, 45,133 HIV-infected adults in care were not prescribed ART, of whom 74% were eligible under current treatment guidelines.

Dr. Skarbinski disclosed that he had no relevant conflicts of interest.

SEATTLE – Greater efforts are needed to get people with HIV infection into medical care, a necessary prerequisite to therapy and viral suppression, suggests a cross-sectional survey of 4,217 HIV-positive adults conducted by the Centers for Disease Control and Prevention.

Survey results, reported at the Conference on Retroviruses and Opportunistic Infections, also showed that only an estimated 36% of adults living with HIV in 2009 had at least one medical care visit between January and April of that year.

© Dr. A. Harrison; Dr. P. Feorino / CDC

But within this group, measures of therapy were good: 89% had received at least one prescription for antiretroviral therapy (ART) in the past year, and 72% had achieved a suppressed HIV viral load, defined as having 200 copies/mL or less of the virus at the most recent measurement in the past year.

"Increasing the size of the in-care population is critical to increase the overall proportion of HIV-infected persons who are on ART and suppressed," said Dr. Jacek Skarbinski, an investigator in the Division of HIV/AIDS Prevention at the CDC. "We find that most HIV-infected adults in care are already on ART."

Analyses have suggested that expanding guidelines regarding when to initiate ART – from the current recommendation (presence of AIDS or a nadir CD4 cell count of 500 cells/mL or lower) to a new one covering all HIV-infected people (regardless of CD4 cell count) – would have only a small impact. Such expansion would increase the percentage of people in care who are on ART by just 3%.

In additional study findings, certain groups of people in care – young adults, blacks, and those living in poverty, among others – were significantly less likely to be prescribed ART, to achieve viral suppression, or both. Thus, "we need to address disparities in HIV care and treatment, especially by age, race, and income," Dr. Skarbinski maintained.

"The study is interesting as it highlights what can be achieved through use of basic epidemiological tools to provide estimates of the numbers receiving treatment across the country as a whole and within subgroups," Kholoud Porter, Ph.D., session comoderator and senior epidemiologist with the MRC Clinical Trials Unit in London, said in an interview. "This is important information for health care planning."

"The continuum of engagement in HIV care includes HIV diagnosis, linkage to and retention in care, prescription of ART, and viral suppression," Dr. Skarbinski said.

To obtain national estimates of these outcomes, he and colleagues analyzed data from the Medical Monitoring Project, a supplemental surveillance system that captures information on nationally representative samples of HIV-infected people in care.

In 2009, it collected data from 17 states and territories, 461 facilities within those states and territories, and 4,217 HIV-infected patients receiving care in those facilities. Patients were interviewed and their medical records were abstracted to ascertain prescription of ART and achievement of viral suppression.

The patients represented an estimated 421,186 adults in care at the population level, or just 36% of all 1.2 million people living with HIV nationally on the basis of a recent estimate (MMWR Morb. Mortal. Wkly. Rep. 2011;60:689-93). The value was higher, but still only 41%, when analyses were annualized to reflect receipt of care during the whole year and not just the first 4 months.

Patients in care were predominantly 40 years of age or older (75%), male (71%), non-Hispanic black (41%) or white (34%), and men who had sex with men (47%). The majority had more than a high school education (51%) but also lived below the poverty line (54%) and had public health insurance (62%). Half were at least 10 years out from diagnosis, and two-thirds had AIDS.

Multivariate analyses showed that individuals in care were significantly less likely to be prescribed ART if they were aged 18-29, non-Hispanic black, female, in the first 4 years after diagnosis, and did not have AIDS (regardless of nadir CD4 cell count).

Similarly, individuals in care were significantly less likely to be prescribed antiretroviral therapy if they were aged 18-49, non-Hispanic black or of "other" race/ethnicity, were living at or below the poverty level, and did not have AIDS and had a nadir CD4 cell count of greater than 500.

The study data suggested that nationally, 45,133 HIV-infected adults in care were not prescribed ART, of whom 74% were eligible under current treatment guidelines.

Dr. Skarbinski disclosed that he had no relevant conflicts of interest.

SEATTLE – Greater efforts are needed to get people with HIV infection into medical care, a necessary prerequisite to therapy and viral suppression, suggests a cross-sectional survey of 4,217 HIV-positive adults conducted by the Centers for Disease Control and Prevention.

Survey results, reported at the Conference on Retroviruses and Opportunistic Infections, also showed that only an estimated 36% of adults living with HIV in 2009 had at least one medical care visit between January and April of that year.

© Dr. A. Harrison; Dr. P. Feorino / CDC

But within this group, measures of therapy were good: 89% had received at least one prescription for antiretroviral therapy (ART) in the past year, and 72% had achieved a suppressed HIV viral load, defined as having 200 copies/mL or less of the virus at the most recent measurement in the past year.

"Increasing the size of the in-care population is critical to increase the overall proportion of HIV-infected persons who are on ART and suppressed," said Dr. Jacek Skarbinski, an investigator in the Division of HIV/AIDS Prevention at the CDC. "We find that most HIV-infected adults in care are already on ART."

Analyses have suggested that expanding guidelines regarding when to initiate ART – from the current recommendation (presence of AIDS or a nadir CD4 cell count of 500 cells/mL or lower) to a new one covering all HIV-infected people (regardless of CD4 cell count) – would have only a small impact. Such expansion would increase the percentage of people in care who are on ART by just 3%.

In additional study findings, certain groups of people in care – young adults, blacks, and those living in poverty, among others – were significantly less likely to be prescribed ART, to achieve viral suppression, or both. Thus, "we need to address disparities in HIV care and treatment, especially by age, race, and income," Dr. Skarbinski maintained.

"The study is interesting as it highlights what can be achieved through use of basic epidemiological tools to provide estimates of the numbers receiving treatment across the country as a whole and within subgroups," Kholoud Porter, Ph.D., session comoderator and senior epidemiologist with the MRC Clinical Trials Unit in London, said in an interview. "This is important information for health care planning."

"The continuum of engagement in HIV care includes HIV diagnosis, linkage to and retention in care, prescription of ART, and viral suppression," Dr. Skarbinski said.

To obtain national estimates of these outcomes, he and colleagues analyzed data from the Medical Monitoring Project, a supplemental surveillance system that captures information on nationally representative samples of HIV-infected people in care.

In 2009, it collected data from 17 states and territories, 461 facilities within those states and territories, and 4,217 HIV-infected patients receiving care in those facilities. Patients were interviewed and their medical records were abstracted to ascertain prescription of ART and achievement of viral suppression.

The patients represented an estimated 421,186 adults in care at the population level, or just 36% of all 1.2 million people living with HIV nationally on the basis of a recent estimate (MMWR Morb. Mortal. Wkly. Rep. 2011;60:689-93). The value was higher, but still only 41%, when analyses were annualized to reflect receipt of care during the whole year and not just the first 4 months.

Patients in care were predominantly 40 years of age or older (75%), male (71%), non-Hispanic black (41%) or white (34%), and men who had sex with men (47%). The majority had more than a high school education (51%) but also lived below the poverty line (54%) and had public health insurance (62%). Half were at least 10 years out from diagnosis, and two-thirds had AIDS.

Multivariate analyses showed that individuals in care were significantly less likely to be prescribed ART if they were aged 18-29, non-Hispanic black, female, in the first 4 years after diagnosis, and did not have AIDS (regardless of nadir CD4 cell count).

Similarly, individuals in care were significantly less likely to be prescribed antiretroviral therapy if they were aged 18-49, non-Hispanic black or of "other" race/ethnicity, were living at or below the poverty level, and did not have AIDS and had a nadir CD4 cell count of greater than 500.

The study data suggested that nationally, 45,133 HIV-infected adults in care were not prescribed ART, of whom 74% were eligible under current treatment guidelines.

Dr. Skarbinski disclosed that he had no relevant conflicts of interest.