Poorly Controlled HIV Hastens Decline in Lung Function

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.