IAS 2012

WASHINGTON  – Early use of antiretroviral therapy significantly reduced the incidence of clinical events – including tuberculosis and AIDS-defining events – among HIV positive adults in a large multinational trial.

"Overall, our interpretation was that there is a marked clinical benefit in terms of reduced clinical events by starting antiretroviral therapy early," Dr. Mina C. Hosseinipour said in a press briefing held during the meeting.

The data are the latest from the landmark HIV Prevention Trials Network study number 052 (HPTN 052), which previously had shown that use of antiretroviral therapy (ART) early – when CD4 counts were between 350 and 550 cells/mm³ – in the HIV-positive partners of a total of 1,763 serodiscordant couples reduced the rate of HIV transmission to the uninfected partner by 96%. It also showed that early ART is associated with a longer time to HIV disease progression and preservation of the immune system over 2 years in the patients themselves (N. Engl. J. Med. 2011;365:493-505).

"So, we think that combined with the preventive benefit, the clinical benefit that one can see from earlier antiretroviral therapy does support earlier antiretroviral initiation" when CD4 counts are between 350 and 550 cells per cubic millimeter, said Dr. Hosseinipour, clinical director of the University of North Carolina Project in Lilongwe, Malawi.

The new analysis, including an additional 3 months of follow-up from the earlier report, focused on clinical end points among those randomized to early vs. later (CD4 count less than 250/mm³ or the onset of AIDS) antiretroviral treatment. The data were presented at the conference by Dr. Beatriz Grinsztejn of Instituto de Pesquisa Clinica Evandro Chagas, Manguinhos, Brazil.

At baseline, the 886 participants in the immediate ART group were similar to the 875 participants in the delayed ART group with regard to gender (about 50/50); two-thirds between the ages of 26 and 40 years. Just over half (54%) were from Africa, and slightly less than a third (30%) from Asia. The rest were from South America. Baseline CD4 counts were 428 cells/mm³ for the delayed ART group and 442 cells/mm³ for the immediate group, and baseline HIV-1 RNA level was 4.4 log10 copies/mL in both groups.

During an overall median follow-up of 2.1 years, 24% (213) patients in the delayed arm initiated ART, at a median of 3.8 years to initiation. Median duration of exposure to ART was 1 year, vs. 2 years in the immediate treatment group.

The specified primary clinical events were death, World Health Organization stage 4 events, tuberculosis, severe bacterial infection, and targeted non-AIDS events, including serious cardiovascular/vascular disease, serious liver disease, end stage renal disease, non-AIDS malignancy, and diabetes mellitus.

There were no differences in primary event rates between the two groups during the first year, but by the end of the follow-up period, 9% (77) of the delayed group vs. 6% (57) of the immediate group experienced at least one primary event, for a hazard ratio of 1.37. AIDS-related events occurred in 61 of the 77 delayed-therapy group and 40 of the 57 immediate-therapy group patients. Deaths occurred in 15 and 11, respectively. Non-AIDS events occurred in 9 delayed vs.12 immediate-therapy group patients, including diabetes mellitus in 5 and 4, respectively, Dr. Grinsztejn reported.

There were no significant differences in primary event rates by region, gender, or baseline CD4 count above vs. below 450 cells/mm³, she said.

In a multivariate analysis, factors significantly associated with primary events were age 40 years and older vs. 18-24 years (HR, 2.42), having a greater pretreatment HIV-1 log10 RNA count (1.34/1 log higher), a higher hemoglobin (grade 2 or higher vs. 0/1), and hepatitis B coinfection (1.85 for yes vs. no). In addition, regardless of treatment arm, each 50 CD4 cell higher count was associated with a 10% lower risk of primary events, she reported.

Tuberculosis was significantly more frequent in the delayed treatment group, 4% (34) vs. 2% (17), as were WHO stage 4 events (2% vs. 1%), with chronic herpes simplex being the most common of those (in 8 vs. 2 patients, respectively). Serious bacterial infections were more common among the immediate treatment patients, 2% vs. 1%.

Among the secondary events, herpes zoster, oral candidiasis, and seborrheic dermatitis were the most prevalent, all being more common in the delayed-treatment group, she noted.

Combining all primary and secondary events, the incidence was 29/100 person-years for delayed treatment vs. 25/100 person-years for immediate treatment, a significant difference (P = .02). At the time of primary clinical events, the CD4 count was significantly higher in the immediate-treatment group, compared with the delayed group (502 vs. 351). There was a similar distribution with the secondary events (540 vs. 377). Approximately half of the events in the delayed arm occurred at CD4 cell counts higher than 350, Dr. Grinsztejn noted.

The HPTN 052 study is ongoing. All HIV infected subjects were offered ART and 93% of the index cases are now on it. Retention is 96% among the index cases and 85% for the discordant couples. Still undetermined are the durability of the prevention benefit and the consequences of delayed ART on clinical outcomes over a longer follow-up, she said.

In addition, giving antiretroviral therapy early to HIV-positive patients is cost effective over a 5-year and lifetime horizon, according to a subanalysis of HPTN 052.

Researchers from the Harvard Medical School, Boston, presented the cost-effectiveness analysis on behalf of the HPTN. They analyzed 5-year and lifetime survival and costs in India and South Africa.

To be deemed "very cost effective," early ART had to be less than one times the per capita gross domestic product of each country. To be "cost effective," it would need to be less than three times the gross domestic product (GDP). In South Africa, the per capita GDP was $8,100, and in India it was $1,400.

The cost of ART – whether early or delayed – was higher in South Africa than in India, largely because the costs of care were higher. Early ART for the initially infected patients cost $4,600 over the 5-year horizon in South Africa and $2,300 in India. The lifetime cost for early ART was $18,400 in South Africa, compared with $11,300 in India.

Early ART cost more than delayed ART. But survival was higher with early ART – 93%, compared with 84% for delayed ART in South Africa, for instance – and there was a marked and immediate decrease in transmission for early ART in both India and South Africa, said Dr. Kenneth A. Freedberg, director of the HIV Research Program in the division of general medicine at Massachusetts General Hospital, Boston.

The early therapy also prevented opportunistic infections in South Africa. It was deemed very cost effective in South Africa, at $700/year of life saved in the 5-year time frame, and $1,200/year of life saved over the lifetime.

In India, early ART increased survival also and reduced transmissions of the virus. It was deemed cost effective in that country, at $2,900/year of life saved over the 5-year time frame. The lifetime horizon nudged it up to very cost effective at $1,300/year of life saved.

Increased survival in both countries was a bit of a double-edged sword. Those who lived longer also tended to have more HIV transmissions, Dr. Freedberg explained. Even so, early ART appears to be a winning strategy, he said.

"The clinical data, the behavioral data, the economic data, are converging on the very clear consensus that early antiretroviral therapy is clinically effective for individuals, prevents transmission, and is very cost effective," he said in presenting the abstract.

Dr. Freedberg added that early ART should definitely be given to serodiscordant couples.

In addition, he said, "We’re moving toward the situation where the data support early antiretroviral therapy for anybody infected."

The HIV Prevention Trials Network is funded by the National Institute of Allergy and Infectious Diseases. Study drugs were donated by Abbott Laboratories, Boehringer Ingelheim Pharmaceuticals, Bristol-Myers Squibb, Gilead Sciences; GlaxoSmithKline/ViiV Healthcare, and Merck.

Dr. Grinsztejn stated that she has no additional disclosures.

Alicia Ault, a medical media reporter for IMNG, contributed to this article.

WASHINGTON  – Early use of antiretroviral therapy significantly reduced the incidence of clinical events – including tuberculosis and AIDS-defining events – among HIV positive adults in a large multinational trial.

"Overall, our interpretation was that there is a marked clinical benefit in terms of reduced clinical events by starting antiretroviral therapy early," Dr. Mina C. Hosseinipour said in a press briefing held during the meeting.

The data are the latest from the landmark HIV Prevention Trials Network study number 052 (HPTN 052), which previously had shown that use of antiretroviral therapy (ART) early – when CD4 counts were between 350 and 550 cells/mm³ – in the HIV-positive partners of a total of 1,763 serodiscordant couples reduced the rate of HIV transmission to the uninfected partner by 96%. It also showed that early ART is associated with a longer time to HIV disease progression and preservation of the immune system over 2 years in the patients themselves (N. Engl. J. Med. 2011;365:493-505).

"So, we think that combined with the preventive benefit, the clinical benefit that one can see from earlier antiretroviral therapy does support earlier antiretroviral initiation" when CD4 counts are between 350 and 550 cells per cubic millimeter, said Dr. Hosseinipour, clinical director of the University of North Carolina Project in Lilongwe, Malawi.

The new analysis, including an additional 3 months of follow-up from the earlier report, focused on clinical end points among those randomized to early vs. later (CD4 count less than 250/mm³ or the onset of AIDS) antiretroviral treatment. The data were presented at the conference by Dr. Beatriz Grinsztejn of Instituto de Pesquisa Clinica Evandro Chagas, Manguinhos, Brazil.

At baseline, the 886 participants in the immediate ART group were similar to the 875 participants in the delayed ART group with regard to gender (about 50/50); two-thirds between the ages of 26 and 40 years. Just over half (54%) were from Africa, and slightly less than a third (30%) from Asia. The rest were from South America. Baseline CD4 counts were 428 cells/mm³ for the delayed ART group and 442 cells/mm³ for the immediate group, and baseline HIV-1 RNA level was 4.4 log10 copies/mL in both groups.

During an overall median follow-up of 2.1 years, 24% (213) patients in the delayed arm initiated ART, at a median of 3.8 years to initiation. Median duration of exposure to ART was 1 year, vs. 2 years in the immediate treatment group.

The specified primary clinical events were death, World Health Organization stage 4 events, tuberculosis, severe bacterial infection, and targeted non-AIDS events, including serious cardiovascular/vascular disease, serious liver disease, end stage renal disease, non-AIDS malignancy, and diabetes mellitus.

There were no differences in primary event rates between the two groups during the first year, but by the end of the follow-up period, 9% (77) of the delayed group vs. 6% (57) of the immediate group experienced at least one primary event, for a hazard ratio of 1.37. AIDS-related events occurred in 61 of the 77 delayed-therapy group and 40 of the 57 immediate-therapy group patients. Deaths occurred in 15 and 11, respectively. Non-AIDS events occurred in 9 delayed vs.12 immediate-therapy group patients, including diabetes mellitus in 5 and 4, respectively, Dr. Grinsztejn reported.

There were no significant differences in primary event rates by region, gender, or baseline CD4 count above vs. below 450 cells/mm³, she said.

In a multivariate analysis, factors significantly associated with primary events were age 40 years and older vs. 18-24 years (HR, 2.42), having a greater pretreatment HIV-1 log10 RNA count (1.34/1 log higher), a higher hemoglobin (grade 2 or higher vs. 0/1), and hepatitis B coinfection (1.85 for yes vs. no). In addition, regardless of treatment arm, each 50 CD4 cell higher count was associated with a 10% lower risk of primary events, she reported.

Tuberculosis was significantly more frequent in the delayed treatment group, 4% (34) vs. 2% (17), as were WHO stage 4 events (2% vs. 1%), with chronic herpes simplex being the most common of those (in 8 vs. 2 patients, respectively). Serious bacterial infections were more common among the immediate treatment patients, 2% vs. 1%.

Among the secondary events, herpes zoster, oral candidiasis, and seborrheic dermatitis were the most prevalent, all being more common in the delayed-treatment group, she noted.

Combining all primary and secondary events, the incidence was 29/100 person-years for delayed treatment vs. 25/100 person-years for immediate treatment, a significant difference (P = .02). At the time of primary clinical events, the CD4 count was significantly higher in the immediate-treatment group, compared with the delayed group (502 vs. 351). There was a similar distribution with the secondary events (540 vs. 377). Approximately half of the events in the delayed arm occurred at CD4 cell counts higher than 350, Dr. Grinsztejn noted.

The HPTN 052 study is ongoing. All HIV infected subjects were offered ART and 93% of the index cases are now on it. Retention is 96% among the index cases and 85% for the discordant couples. Still undetermined are the durability of the prevention benefit and the consequences of delayed ART on clinical outcomes over a longer follow-up, she said.

In addition, giving antiretroviral therapy early to HIV-positive patients is cost effective over a 5-year and lifetime horizon, according to a subanalysis of HPTN 052.

Researchers from the Harvard Medical School, Boston, presented the cost-effectiveness analysis on behalf of the HPTN. They analyzed 5-year and lifetime survival and costs in India and South Africa.

To be deemed "very cost effective," early ART had to be less than one times the per capita gross domestic product of each country. To be "cost effective," it would need to be less than three times the gross domestic product (GDP). In South Africa, the per capita GDP was $8,100, and in India it was $1,400.

The cost of ART – whether early or delayed – was higher in South Africa than in India, largely because the costs of care were higher. Early ART for the initially infected patients cost $4,600 over the 5-year horizon in South Africa and $2,300 in India. The lifetime cost for early ART was $18,400 in South Africa, compared with $11,300 in India.

Early ART cost more than delayed ART. But survival was higher with early ART – 93%, compared with 84% for delayed ART in South Africa, for instance – and there was a marked and immediate decrease in transmission for early ART in both India and South Africa, said Dr. Kenneth A. Freedberg, director of the HIV Research Program in the division of general medicine at Massachusetts General Hospital, Boston.

The early therapy also prevented opportunistic infections in South Africa. It was deemed very cost effective in South Africa, at $700/year of life saved in the 5-year time frame, and $1,200/year of life saved over the lifetime.

In India, early ART increased survival also and reduced transmissions of the virus. It was deemed cost effective in that country, at $2,900/year of life saved over the 5-year time frame. The lifetime horizon nudged it up to very cost effective at $1,300/year of life saved.

Increased survival in both countries was a bit of a double-edged sword. Those who lived longer also tended to have more HIV transmissions, Dr. Freedberg explained. Even so, early ART appears to be a winning strategy, he said.

"The clinical data, the behavioral data, the economic data, are converging on the very clear consensus that early antiretroviral therapy is clinically effective for individuals, prevents transmission, and is very cost effective," he said in presenting the abstract.

Dr. Freedberg added that early ART should definitely be given to serodiscordant couples.

In addition, he said, "We’re moving toward the situation where the data support early antiretroviral therapy for anybody infected."

The HIV Prevention Trials Network is funded by the National Institute of Allergy and Infectious Diseases. Study drugs were donated by Abbott Laboratories, Boehringer Ingelheim Pharmaceuticals, Bristol-Myers Squibb, Gilead Sciences; GlaxoSmithKline/ViiV Healthcare, and Merck.

Dr. Grinsztejn stated that she has no additional disclosures.

Alicia Ault, a medical media reporter for IMNG, contributed to this article.

WASHINGTON  – Early use of antiretroviral therapy significantly reduced the incidence of clinical events – including tuberculosis and AIDS-defining events – among HIV positive adults in a large multinational trial.

"Overall, our interpretation was that there is a marked clinical benefit in terms of reduced clinical events by starting antiretroviral therapy early," Dr. Mina C. Hosseinipour said in a press briefing held during the meeting.

The data are the latest from the landmark HIV Prevention Trials Network study number 052 (HPTN 052), which previously had shown that use of antiretroviral therapy (ART) early – when CD4 counts were between 350 and 550 cells/mm³ – in the HIV-positive partners of a total of 1,763 serodiscordant couples reduced the rate of HIV transmission to the uninfected partner by 96%. It also showed that early ART is associated with a longer time to HIV disease progression and preservation of the immune system over 2 years in the patients themselves (N. Engl. J. Med. 2011;365:493-505).

"So, we think that combined with the preventive benefit, the clinical benefit that one can see from earlier antiretroviral therapy does support earlier antiretroviral initiation" when CD4 counts are between 350 and 550 cells per cubic millimeter, said Dr. Hosseinipour, clinical director of the University of North Carolina Project in Lilongwe, Malawi.

The new analysis, including an additional 3 months of follow-up from the earlier report, focused on clinical end points among those randomized to early vs. later (CD4 count less than 250/mm³ or the onset of AIDS) antiretroviral treatment. The data were presented at the conference by Dr. Beatriz Grinsztejn of Instituto de Pesquisa Clinica Evandro Chagas, Manguinhos, Brazil.

At baseline, the 886 participants in the immediate ART group were similar to the 875 participants in the delayed ART group with regard to gender (about 50/50); two-thirds between the ages of 26 and 40 years. Just over half (54%) were from Africa, and slightly less than a third (30%) from Asia. The rest were from South America. Baseline CD4 counts were 428 cells/mm³ for the delayed ART group and 442 cells/mm³ for the immediate group, and baseline HIV-1 RNA level was 4.4 log10 copies/mL in both groups.

During an overall median follow-up of 2.1 years, 24% (213) patients in the delayed arm initiated ART, at a median of 3.8 years to initiation. Median duration of exposure to ART was 1 year, vs. 2 years in the immediate treatment group.

The specified primary clinical events were death, World Health Organization stage 4 events, tuberculosis, severe bacterial infection, and targeted non-AIDS events, including serious cardiovascular/vascular disease, serious liver disease, end stage renal disease, non-AIDS malignancy, and diabetes mellitus.

There were no differences in primary event rates between the two groups during the first year, but by the end of the follow-up period, 9% (77) of the delayed group vs. 6% (57) of the immediate group experienced at least one primary event, for a hazard ratio of 1.37. AIDS-related events occurred in 61 of the 77 delayed-therapy group and 40 of the 57 immediate-therapy group patients. Deaths occurred in 15 and 11, respectively. Non-AIDS events occurred in 9 delayed vs.12 immediate-therapy group patients, including diabetes mellitus in 5 and 4, respectively, Dr. Grinsztejn reported.

There were no significant differences in primary event rates by region, gender, or baseline CD4 count above vs. below 450 cells/mm³, she said.

In a multivariate analysis, factors significantly associated with primary events were age 40 years and older vs. 18-24 years (HR, 2.42), having a greater pretreatment HIV-1 log10 RNA count (1.34/1 log higher), a higher hemoglobin (grade 2 or higher vs. 0/1), and hepatitis B coinfection (1.85 for yes vs. no). In addition, regardless of treatment arm, each 50 CD4 cell higher count was associated with a 10% lower risk of primary events, she reported.

Tuberculosis was significantly more frequent in the delayed treatment group, 4% (34) vs. 2% (17), as were WHO stage 4 events (2% vs. 1%), with chronic herpes simplex being the most common of those (in 8 vs. 2 patients, respectively). Serious bacterial infections were more common among the immediate treatment patients, 2% vs. 1%.

Among the secondary events, herpes zoster, oral candidiasis, and seborrheic dermatitis were the most prevalent, all being more common in the delayed-treatment group, she noted.

Combining all primary and secondary events, the incidence was 29/100 person-years for delayed treatment vs. 25/100 person-years for immediate treatment, a significant difference (P = .02). At the time of primary clinical events, the CD4 count was significantly higher in the immediate-treatment group, compared with the delayed group (502 vs. 351). There was a similar distribution with the secondary events (540 vs. 377). Approximately half of the events in the delayed arm occurred at CD4 cell counts higher than 350, Dr. Grinsztejn noted.

The HPTN 052 study is ongoing. All HIV infected subjects were offered ART and 93% of the index cases are now on it. Retention is 96% among the index cases and 85% for the discordant couples. Still undetermined are the durability of the prevention benefit and the consequences of delayed ART on clinical outcomes over a longer follow-up, she said.

In addition, giving antiretroviral therapy early to HIV-positive patients is cost effective over a 5-year and lifetime horizon, according to a subanalysis of HPTN 052.

Researchers from the Harvard Medical School, Boston, presented the cost-effectiveness analysis on behalf of the HPTN. They analyzed 5-year and lifetime survival and costs in India and South Africa.

To be deemed "very cost effective," early ART had to be less than one times the per capita gross domestic product of each country. To be "cost effective," it would need to be less than three times the gross domestic product (GDP). In South Africa, the per capita GDP was $8,100, and in India it was $1,400.

The cost of ART – whether early or delayed – was higher in South Africa than in India, largely because the costs of care were higher. Early ART for the initially infected patients cost $4,600 over the 5-year horizon in South Africa and $2,300 in India. The lifetime cost for early ART was $18,400 in South Africa, compared with $11,300 in India.

Early ART cost more than delayed ART. But survival was higher with early ART – 93%, compared with 84% for delayed ART in South Africa, for instance – and there was a marked and immediate decrease in transmission for early ART in both India and South Africa, said Dr. Kenneth A. Freedberg, director of the HIV Research Program in the division of general medicine at Massachusetts General Hospital, Boston.

The early therapy also prevented opportunistic infections in South Africa. It was deemed very cost effective in South Africa, at $700/year of life saved in the 5-year time frame, and $1,200/year of life saved over the lifetime.

In India, early ART increased survival also and reduced transmissions of the virus. It was deemed cost effective in that country, at $2,900/year of life saved over the 5-year time frame. The lifetime horizon nudged it up to very cost effective at $1,300/year of life saved.

Increased survival in both countries was a bit of a double-edged sword. Those who lived longer also tended to have more HIV transmissions, Dr. Freedberg explained. Even so, early ART appears to be a winning strategy, he said.

"The clinical data, the behavioral data, the economic data, are converging on the very clear consensus that early antiretroviral therapy is clinically effective for individuals, prevents transmission, and is very cost effective," he said in presenting the abstract.

Dr. Freedberg added that early ART should definitely be given to serodiscordant couples.

In addition, he said, "We’re moving toward the situation where the data support early antiretroviral therapy for anybody infected."

The HIV Prevention Trials Network is funded by the National Institute of Allergy and Infectious Diseases. Study drugs were donated by Abbott Laboratories, Boehringer Ingelheim Pharmaceuticals, Bristol-Myers Squibb, Gilead Sciences; GlaxoSmithKline/ViiV Healthcare, and Merck.

Dr. Grinsztejn stated that she has no additional disclosures.

Alicia Ault, a medical media reporter for IMNG, contributed to this article.

WASHINGTON – A large international society of AIDS clinicians is endorsing the use of treatment as prevention and pre-exposure prophylaxis as a means of containing the epidemic.

With the two approaches gaining currency, primary care physicians and ob.gyns. will likely be called upon to deliver the therapies.

Alicia Ault/IMNG Medical Media

The consensus statement, issued by the International Association of Physicians in AIDS Care (IAPAC), is the end result of a gathering of experts in June.

Treatment as Prevention (TasP) gained credence after publication of the HIV Prevention Trials Network (HPTN) 052 study in the New England Journal of Medicine last August (N. Engl. J. Med. 2011;365:493-505). The trial more or less definitively proved that giving antiretroviral treatment significantly reduces the rate of sexual transmission of HIV.

Pre-Exposure Prophylaxis (PrEP) has been shown to reduce infection with the virus in heterosexuals and homosexuals who might get exposed through risky sexual activity. In July, the Food and Drug Administration approved Truvada (a drug that combines tenofovir disoproxil fumarate with emtricitabine) for use as PrEP among sexually active adults at risk for HIV infection.

Alicia Ault/IMNG Medical Media

"The group felt that the paradigm for using antiretroviral therapy as prevention had been established," said Dr. Kenneth Mayer, chairman of the IAPAC TasP/PrEP Advisory Committee, and medical research director at the Fenway Institute in Boston. "We know that this works. The issue now is implementation," he said in a press briefing at the 19th International AIDS Conference.

The consensus backs the idea of offering treatment to those who want to start. But, said Dr. Mayer, the question is, "How do we scale up training providers so they can do this in a competent way so we can manage people in an optimal way?"

Dr. Julio Montaner, also a member of the IAPAC TasP/PrEP Advisory Committee, said that studies in Africa had shown that therapy could be given by nonspecialists and even by nonphysicians. "It is abundantly clear that we have made treatment of HIV more complicated than it needs to be," said Dr. Montaner, director of the British Columbia Centre for Excellence in HIV/AIDS in Vancouver, B.C.

Now that regimens have become simpler, safer, and better tolerated, "I’m very optimistic that we are going to increasingly see treatment being supervised by people other than the specialists," he said. Dr. Montaner noted that in British Columbia, treatment is predominantly being initiated by family physicians.

Another key issue: For TasP to work, people need to know their HIV status. So the consensus backs higher levels of HIV testing.

Other challenges to implementing TasP include resource limitations; how to evaluate the quality of care; ethical issues; and how to monitor people for increases in risky behavior and suboptimal adherence, said Dr. Mayer.

Monitoring risky behavior will also be a challenge with PrEP, he said. There are also questions about the optimal dose and timing of the dose, he said, adding that much more research needs to be done on PrEP, relative to TasP.

PrEP is not a standalone therapy, he said. "It has to be part of a comprehensive prevention package," that includes behavioral interventions, said Dr. Mayer. And it is not meant to be a lifetime therapy. It should be used at a time of acute risk, he said, adding that PrEP is "a measure to get them through a period where they might otherwise become HIV infected."

The full consensus statement is available at the IAPAC website. It will also be shared with many physician groups, including the American College of Physicians, the American Academy of Family Practitioners, and the American Congress of Obstetricians and Gynecologists, said Dr. Mayer in an interview.

WASHINGTON – A large international society of AIDS clinicians is endorsing the use of treatment as prevention and pre-exposure prophylaxis as a means of containing the epidemic.

With the two approaches gaining currency, primary care physicians and ob.gyns. will likely be called upon to deliver the therapies.

Alicia Ault/IMNG Medical Media

The consensus statement, issued by the International Association of Physicians in AIDS Care (IAPAC), is the end result of a gathering of experts in June.

Treatment as Prevention (TasP) gained credence after publication of the HIV Prevention Trials Network (HPTN) 052 study in the New England Journal of Medicine last August (N. Engl. J. Med. 2011;365:493-505). The trial more or less definitively proved that giving antiretroviral treatment significantly reduces the rate of sexual transmission of HIV.

Pre-Exposure Prophylaxis (PrEP) has been shown to reduce infection with the virus in heterosexuals and homosexuals who might get exposed through risky sexual activity. In July, the Food and Drug Administration approved Truvada (a drug that combines tenofovir disoproxil fumarate with emtricitabine) for use as PrEP among sexually active adults at risk for HIV infection.

Alicia Ault/IMNG Medical Media

"The group felt that the paradigm for using antiretroviral therapy as prevention had been established," said Dr. Kenneth Mayer, chairman of the IAPAC TasP/PrEP Advisory Committee, and medical research director at the Fenway Institute in Boston. "We know that this works. The issue now is implementation," he said in a press briefing at the 19th International AIDS Conference.

The consensus backs the idea of offering treatment to those who want to start. But, said Dr. Mayer, the question is, "How do we scale up training providers so they can do this in a competent way so we can manage people in an optimal way?"

Dr. Julio Montaner, also a member of the IAPAC TasP/PrEP Advisory Committee, said that studies in Africa had shown that therapy could be given by nonspecialists and even by nonphysicians. "It is abundantly clear that we have made treatment of HIV more complicated than it needs to be," said Dr. Montaner, director of the British Columbia Centre for Excellence in HIV/AIDS in Vancouver, B.C.

Now that regimens have become simpler, safer, and better tolerated, "I’m very optimistic that we are going to increasingly see treatment being supervised by people other than the specialists," he said. Dr. Montaner noted that in British Columbia, treatment is predominantly being initiated by family physicians.

Another key issue: For TasP to work, people need to know their HIV status. So the consensus backs higher levels of HIV testing.

Other challenges to implementing TasP include resource limitations; how to evaluate the quality of care; ethical issues; and how to monitor people for increases in risky behavior and suboptimal adherence, said Dr. Mayer.

Monitoring risky behavior will also be a challenge with PrEP, he said. There are also questions about the optimal dose and timing of the dose, he said, adding that much more research needs to be done on PrEP, relative to TasP.

PrEP is not a standalone therapy, he said. "It has to be part of a comprehensive prevention package," that includes behavioral interventions, said Dr. Mayer. And it is not meant to be a lifetime therapy. It should be used at a time of acute risk, he said, adding that PrEP is "a measure to get them through a period where they might otherwise become HIV infected."

The full consensus statement is available at the IAPAC website. It will also be shared with many physician groups, including the American College of Physicians, the American Academy of Family Practitioners, and the American Congress of Obstetricians and Gynecologists, said Dr. Mayer in an interview.

WASHINGTON – A large international society of AIDS clinicians is endorsing the use of treatment as prevention and pre-exposure prophylaxis as a means of containing the epidemic.

With the two approaches gaining currency, primary care physicians and ob.gyns. will likely be called upon to deliver the therapies.

Alicia Ault/IMNG Medical Media

The consensus statement, issued by the International Association of Physicians in AIDS Care (IAPAC), is the end result of a gathering of experts in June.

Treatment as Prevention (TasP) gained credence after publication of the HIV Prevention Trials Network (HPTN) 052 study in the New England Journal of Medicine last August (N. Engl. J. Med. 2011;365:493-505). The trial more or less definitively proved that giving antiretroviral treatment significantly reduces the rate of sexual transmission of HIV.

Pre-Exposure Prophylaxis (PrEP) has been shown to reduce infection with the virus in heterosexuals and homosexuals who might get exposed through risky sexual activity. In July, the Food and Drug Administration approved Truvada (a drug that combines tenofovir disoproxil fumarate with emtricitabine) for use as PrEP among sexually active adults at risk for HIV infection.

Alicia Ault/IMNG Medical Media

"The group felt that the paradigm for using antiretroviral therapy as prevention had been established," said Dr. Kenneth Mayer, chairman of the IAPAC TasP/PrEP Advisory Committee, and medical research director at the Fenway Institute in Boston. "We know that this works. The issue now is implementation," he said in a press briefing at the 19th International AIDS Conference.

The consensus backs the idea of offering treatment to those who want to start. But, said Dr. Mayer, the question is, "How do we scale up training providers so they can do this in a competent way so we can manage people in an optimal way?"

Dr. Julio Montaner, also a member of the IAPAC TasP/PrEP Advisory Committee, said that studies in Africa had shown that therapy could be given by nonspecialists and even by nonphysicians. "It is abundantly clear that we have made treatment of HIV more complicated than it needs to be," said Dr. Montaner, director of the British Columbia Centre for Excellence in HIV/AIDS in Vancouver, B.C.

Now that regimens have become simpler, safer, and better tolerated, "I’m very optimistic that we are going to increasingly see treatment being supervised by people other than the specialists," he said. Dr. Montaner noted that in British Columbia, treatment is predominantly being initiated by family physicians.

Another key issue: For TasP to work, people need to know their HIV status. So the consensus backs higher levels of HIV testing.

Other challenges to implementing TasP include resource limitations; how to evaluate the quality of care; ethical issues; and how to monitor people for increases in risky behavior and suboptimal adherence, said Dr. Mayer.

Monitoring risky behavior will also be a challenge with PrEP, he said. There are also questions about the optimal dose and timing of the dose, he said, adding that much more research needs to be done on PrEP, relative to TasP.

PrEP is not a standalone therapy, he said. "It has to be part of a comprehensive prevention package," that includes behavioral interventions, said Dr. Mayer. And it is not meant to be a lifetime therapy. It should be used at a time of acute risk, he said, adding that PrEP is "a measure to get them through a period where they might otherwise become HIV infected."

The full consensus statement is available at the IAPAC website. It will also be shared with many physician groups, including the American College of Physicians, the American Academy of Family Practitioners, and the American Congress of Obstetricians and Gynecologists, said Dr. Mayer in an interview.

WASHINGTON – The rate of new HIV infections among black men who have sex with men was 2.8% per year, nearly 50% higher than the rate seen in white men who have sex with men in the United States, a longitudinal cohort study conducted in six U.S. cities has found.

"Culturally tailored interventions that encourage repeated HIV/[sexually transmitted infection] testing [and] engagement with treatment/prevention, and that address social factors such as poverty, are urgently needed" for black men who have sex with men (MSM), said Beryl Koblin, Ph.D., an epidemiologist at the school of public health at Columbia University, New York.

The findings come from a study conducted within the HIV Prevention Trials Network (HPTN). The study, HPTN 061, is the largest cohort of prospectively followed black MSM in the United States. Funded by the National Institutes of Health, HPTN 061 is designed to determine the feasibility and acceptability of a multicomponent intervention for black MSM, including peer health programs. These incidence data are among the early findings from the study, Dr. Koblin said.

The study was conducted in Atlanta, Boston, Los Angeles, New York, San Francisco, and Washington between July 2009 and October 2010. Black MSM were recruited from the community or referred by sexual partners. Eligibility criteria were men who identified as men or were male at birth; were identified as black, African American, Caribbean, African, or multiethnic black; were at least 18 years old; and had had at least one episode of unprotected anal intercourse with a man in the past 6 months.

The men completed questionnaires regarding their social and sexual networks and were tested for gonorrhea, chlamydia, and syphilis. They received risk-reduction counseling and offers of services from a peer community navigator to link to clinical and social services. Those who tested positive for any infection were guided to medical care services. Participants were offered incentives to refer up to five black sexual partners for participation in the study.

A total of 1,553 black MSM enrolled, of whom 1,379 (89%) reported no prior HIV diagnosis. Of the 96% who agreed to HIV testing, 12% (165) were newly diagnosed as HIV positive, including 3 men with acute HIV infection. Among the 1,168 men who were uninfected at baseline, a little over a third were aged 30 years or younger; fewer than half had a college education or more. Fewer than a third worked full or part time, and two-thirds had an annual income of less than $20,000. About 14% had a sexually transmitted infection (STI) at the time of enrollment, Dr. Koblin said at a press briefing.

After 1 year of follow-up, among the 1,009 who had at least one follow-up test at 6 months or 1 year, the overall incidence of new HIV infection was 2.8%. Men aged 18-30 years and younger had a significantly higher HIV incidence than did those who were older (5.9% vs. 1.0%).

Among men aged 30 and younger, the incidence of new HIV infections among black MSM was three times the rate seen in white MSM of the same age, Dr. Koblin said.

Men who reported having unprotected anal intercourse had an annual HIV incidence rate of 5%, and the annual incidence rate among those with an STI at baseline was 6%. For those who reported having male partners only, the annual incidence rate was 4%. For men identifying as exclusively gay/homosexual, the incidence was 5%, compared with just 1.5% for those who identified as bisexual.

Compared with the 1,168 HIV-negative men, the 174 who reported a prior HIV diagnosis and the 165 who were newly diagnosed were more likely to be unemployed (82% for both HIV-positive groups vs. 65% for those who were HIV negative), to have household incomes less than $50,000 per year (94% vs. 87%), to have a homosexual or gay identity (69% of those previously diagnosed and 58% of the newly diagnosed vs. 47% of those who were HIV negative), and to have had unprotected receptive anal intercourse (55%, 57%, and 43%, respectively.

The HIV-negative men were more likely to have had a female partner in the past 6 months (49% vs. 25% of those previously diagnosed and 35% of the newly diagnosed). Other STIs were twice as common among both HIV-positive groups (25% and 27%, respectively), compared with 13% among the HIV-negative subjects.

"These data are important in terms of identifying [at risk] subpopulations," she said, adding that particular focus should be paid to young men, those reporting receptive anal sex at baseline, those reporting exclusively male partners and who are gay identified, and those who had an STI diagnosed at baseline.

Dr. Koblin stated that she had no financial disclosures.

WASHINGTON – The rate of new HIV infections among black men who have sex with men was 2.8% per year, nearly 50% higher than the rate seen in white men who have sex with men in the United States, a longitudinal cohort study conducted in six U.S. cities has found.

"Culturally tailored interventions that encourage repeated HIV/[sexually transmitted infection] testing [and] engagement with treatment/prevention, and that address social factors such as poverty, are urgently needed" for black men who have sex with men (MSM), said Beryl Koblin, Ph.D., an epidemiologist at the school of public health at Columbia University, New York.

The findings come from a study conducted within the HIV Prevention Trials Network (HPTN). The study, HPTN 061, is the largest cohort of prospectively followed black MSM in the United States. Funded by the National Institutes of Health, HPTN 061 is designed to determine the feasibility and acceptability of a multicomponent intervention for black MSM, including peer health programs. These incidence data are among the early findings from the study, Dr. Koblin said.

The study was conducted in Atlanta, Boston, Los Angeles, New York, San Francisco, and Washington between July 2009 and October 2010. Black MSM were recruited from the community or referred by sexual partners. Eligibility criteria were men who identified as men or were male at birth; were identified as black, African American, Caribbean, African, or multiethnic black; were at least 18 years old; and had had at least one episode of unprotected anal intercourse with a man in the past 6 months.

The men completed questionnaires regarding their social and sexual networks and were tested for gonorrhea, chlamydia, and syphilis. They received risk-reduction counseling and offers of services from a peer community navigator to link to clinical and social services. Those who tested positive for any infection were guided to medical care services. Participants were offered incentives to refer up to five black sexual partners for participation in the study.

A total of 1,553 black MSM enrolled, of whom 1,379 (89%) reported no prior HIV diagnosis. Of the 96% who agreed to HIV testing, 12% (165) were newly diagnosed as HIV positive, including 3 men with acute HIV infection. Among the 1,168 men who were uninfected at baseline, a little over a third were aged 30 years or younger; fewer than half had a college education or more. Fewer than a third worked full or part time, and two-thirds had an annual income of less than $20,000. About 14% had a sexually transmitted infection (STI) at the time of enrollment, Dr. Koblin said at a press briefing.

After 1 year of follow-up, among the 1,009 who had at least one follow-up test at 6 months or 1 year, the overall incidence of new HIV infection was 2.8%. Men aged 18-30 years and younger had a significantly higher HIV incidence than did those who were older (5.9% vs. 1.0%).

Among men aged 30 and younger, the incidence of new HIV infections among black MSM was three times the rate seen in white MSM of the same age, Dr. Koblin said.

Men who reported having unprotected anal intercourse had an annual HIV incidence rate of 5%, and the annual incidence rate among those with an STI at baseline was 6%. For those who reported having male partners only, the annual incidence rate was 4%. For men identifying as exclusively gay/homosexual, the incidence was 5%, compared with just 1.5% for those who identified as bisexual.

Compared with the 1,168 HIV-negative men, the 174 who reported a prior HIV diagnosis and the 165 who were newly diagnosed were more likely to be unemployed (82% for both HIV-positive groups vs. 65% for those who were HIV negative), to have household incomes less than $50,000 per year (94% vs. 87%), to have a homosexual or gay identity (69% of those previously diagnosed and 58% of the newly diagnosed vs. 47% of those who were HIV negative), and to have had unprotected receptive anal intercourse (55%, 57%, and 43%, respectively.

The HIV-negative men were more likely to have had a female partner in the past 6 months (49% vs. 25% of those previously diagnosed and 35% of the newly diagnosed). Other STIs were twice as common among both HIV-positive groups (25% and 27%, respectively), compared with 13% among the HIV-negative subjects.

"These data are important in terms of identifying [at risk] subpopulations," she said, adding that particular focus should be paid to young men, those reporting receptive anal sex at baseline, those reporting exclusively male partners and who are gay identified, and those who had an STI diagnosed at baseline.

Dr. Koblin stated that she had no financial disclosures.

WASHINGTON – The rate of new HIV infections among black men who have sex with men was 2.8% per year, nearly 50% higher than the rate seen in white men who have sex with men in the United States, a longitudinal cohort study conducted in six U.S. cities has found.

"Culturally tailored interventions that encourage repeated HIV/[sexually transmitted infection] testing [and] engagement with treatment/prevention, and that address social factors such as poverty, are urgently needed" for black men who have sex with men (MSM), said Beryl Koblin, Ph.D., an epidemiologist at the school of public health at Columbia University, New York.

The findings come from a study conducted within the HIV Prevention Trials Network (HPTN). The study, HPTN 061, is the largest cohort of prospectively followed black MSM in the United States. Funded by the National Institutes of Health, HPTN 061 is designed to determine the feasibility and acceptability of a multicomponent intervention for black MSM, including peer health programs. These incidence data are among the early findings from the study, Dr. Koblin said.

The study was conducted in Atlanta, Boston, Los Angeles, New York, San Francisco, and Washington between July 2009 and October 2010. Black MSM were recruited from the community or referred by sexual partners. Eligibility criteria were men who identified as men or were male at birth; were identified as black, African American, Caribbean, African, or multiethnic black; were at least 18 years old; and had had at least one episode of unprotected anal intercourse with a man in the past 6 months.

The men completed questionnaires regarding their social and sexual networks and were tested for gonorrhea, chlamydia, and syphilis. They received risk-reduction counseling and offers of services from a peer community navigator to link to clinical and social services. Those who tested positive for any infection were guided to medical care services. Participants were offered incentives to refer up to five black sexual partners for participation in the study.

A total of 1,553 black MSM enrolled, of whom 1,379 (89%) reported no prior HIV diagnosis. Of the 96% who agreed to HIV testing, 12% (165) were newly diagnosed as HIV positive, including 3 men with acute HIV infection. Among the 1,168 men who were uninfected at baseline, a little over a third were aged 30 years or younger; fewer than half had a college education or more. Fewer than a third worked full or part time, and two-thirds had an annual income of less than $20,000. About 14% had a sexually transmitted infection (STI) at the time of enrollment, Dr. Koblin said at a press briefing.

After 1 year of follow-up, among the 1,009 who had at least one follow-up test at 6 months or 1 year, the overall incidence of new HIV infection was 2.8%. Men aged 18-30 years and younger had a significantly higher HIV incidence than did those who were older (5.9% vs. 1.0%).

Among men aged 30 and younger, the incidence of new HIV infections among black MSM was three times the rate seen in white MSM of the same age, Dr. Koblin said.

Men who reported having unprotected anal intercourse had an annual HIV incidence rate of 5%, and the annual incidence rate among those with an STI at baseline was 6%. For those who reported having male partners only, the annual incidence rate was 4%. For men identifying as exclusively gay/homosexual, the incidence was 5%, compared with just 1.5% for those who identified as bisexual.

Compared with the 1,168 HIV-negative men, the 174 who reported a prior HIV diagnosis and the 165 who were newly diagnosed were more likely to be unemployed (82% for both HIV-positive groups vs. 65% for those who were HIV negative), to have household incomes less than $50,000 per year (94% vs. 87%), to have a homosexual or gay identity (69% of those previously diagnosed and 58% of the newly diagnosed vs. 47% of those who were HIV negative), and to have had unprotected receptive anal intercourse (55%, 57%, and 43%, respectively.

The HIV-negative men were more likely to have had a female partner in the past 6 months (49% vs. 25% of those previously diagnosed and 35% of the newly diagnosed). Other STIs were twice as common among both HIV-positive groups (25% and 27%, respectively), compared with 13% among the HIV-negative subjects.

"These data are important in terms of identifying [at risk] subpopulations," she said, adding that particular focus should be paid to young men, those reporting receptive anal sex at baseline, those reporting exclusively male partners and who are gay identified, and those who had an STI diagnosed at baseline.

Dr. Koblin stated that she had no financial disclosures.

HIV-infected adults should start antiretroviral therapy as soon as possible, regardless of CD4 count, according to a recommendation from the International Antiviral Society–USA presented at the AIDS 2012 meeting in Washington.

The recommendation represents a major change from the last set of guidelines, issued in 2010. Those earlier guidelines recommended starting antiretrovirals when CD4 counts fell beneath 500 cells/mL, and "considering" treatment in patients with higher counts.

In writing the new guidelines, which also appear in the July 25 issue of JAMA (2012;308:387-402), Dr. Melanie A. Thompson and a panel convened by the International Antiviral Society–USA (IAS-USA) conducted a literature review of all new published data and data presented at scientific conferences between July 2010 and May 2012.

All recommendations were applicable only to HIV-infected adults in resource-rich settings, and dealt with antiretroviral therapies that were either already approved or in late-stage development.

The field of HIV prophylaxis has also seen significant progress since the 2010 update, and the new guidelines reflect those advances.

"Recently, antiretroviral therapy used as oral pre-exposure prophylaxis (PrEP) has been shown to be effective in three large trials using daily tenofovir/emtricitabine or tenofovir in gay and bisexual men and transgender women (iPrEx), heterosexual HIV-serodiscordant couples (Partners PrEP), and heterosexual men and women (TDF2)," wrote Dr. Thompson of the AIDS Research Consortium of Atlanta.

Indeed, following the iPrEx results, the Centers for Disease Control and Prevention issued interim guidance (MMWR 2011;60:65-8) for HIV-negative homosexual men who elect to take tenofovir/emtricitabine for prophylaxis.

And July 16, the Food and Drug Administration approved the use of an oral once-daily combination antiviral medication, Truvada (tenofovir and emtricitabine), for prevention in uninfected people at high risk for acquiring HIV.

While efficacy in PrEP has been positively correlated with medication adherence (as measured by serum drug levels), "pharmacokinetic and pharmacodynamic variability and the presence of vaginal or rectal inflammation also may affect outcome."

As in the 2010 recommendations (JAMA 2010;304:321-33), the initial choice of prophylactic therapy "continues to be based on a combination of two nucleos(t)ide reverse transcriptase inhibitors and a potent third agent," the authors noted, with the once-daily fixed-dose combination of tenofovir plus emtricitabine remaining the first choice.

Although tenofovir is well tolerated, its use has been linked with kidney injury, "which appears to increase in incidence with long-term administration and concurrent [protease inhibitor, ritonavir-boosted] use," the authors cautioned.

Tenofovir is also associated with decreased bone mineral density of the spine and hip. Thus, given the increased risk of fragility fractures in postmenopausal women, ‘it may be prudent to consider avoiding tenofovir as part of initial therapy in this group," the authors wrote.

Another choice, the once-daily abacavir/lamivudine fixed-dose combination, is now a recommended initial therapy. In 2010, it was considered only a possible alternative.

"Screening for [the HLA-B*5701 gene] markedly reduces the risk of potentially life-threatening hypersensitivity reaction to abacavir," the guideline authors wrote.

In addition, some studies have found abacavir to be associated with a higher risk of acute myocardial infarction.

Dr. Thompson and her colleagues disclosed multiple financial and professional relationships with several pharmaceutical companies, including the makers of antiretroviral therapies. They stated that members of the panel who developed the recommendations did not participate in industry promotional activities such as speakers bureaus or lectures during their membership, and that members with previous conflicts recused themselves from evaluating evidence when a conflict was present.

The development of the recommendations was sponsored by the IAS-USA, according to the authors.

HIV-infected adults should start antiretroviral therapy as soon as possible, regardless of CD4 count, according to a recommendation from the International Antiviral Society–USA presented at the AIDS 2012 meeting in Washington.

The recommendation represents a major change from the last set of guidelines, issued in 2010. Those earlier guidelines recommended starting antiretrovirals when CD4 counts fell beneath 500 cells/mL, and "considering" treatment in patients with higher counts.

In writing the new guidelines, which also appear in the July 25 issue of JAMA (2012;308:387-402), Dr. Melanie A. Thompson and a panel convened by the International Antiviral Society–USA (IAS-USA) conducted a literature review of all new published data and data presented at scientific conferences between July 2010 and May 2012.

All recommendations were applicable only to HIV-infected adults in resource-rich settings, and dealt with antiretroviral therapies that were either already approved or in late-stage development.

The field of HIV prophylaxis has also seen significant progress since the 2010 update, and the new guidelines reflect those advances.

"Recently, antiretroviral therapy used as oral pre-exposure prophylaxis (PrEP) has been shown to be effective in three large trials using daily tenofovir/emtricitabine or tenofovir in gay and bisexual men and transgender women (iPrEx), heterosexual HIV-serodiscordant couples (Partners PrEP), and heterosexual men and women (TDF2)," wrote Dr. Thompson of the AIDS Research Consortium of Atlanta.

Indeed, following the iPrEx results, the Centers for Disease Control and Prevention issued interim guidance (MMWR 2011;60:65-8) for HIV-negative homosexual men who elect to take tenofovir/emtricitabine for prophylaxis.

And July 16, the Food and Drug Administration approved the use of an oral once-daily combination antiviral medication, Truvada (tenofovir and emtricitabine), for prevention in uninfected people at high risk for acquiring HIV.

While efficacy in PrEP has been positively correlated with medication adherence (as measured by serum drug levels), "pharmacokinetic and pharmacodynamic variability and the presence of vaginal or rectal inflammation also may affect outcome."

As in the 2010 recommendations (JAMA 2010;304:321-33), the initial choice of prophylactic therapy "continues to be based on a combination of two nucleos(t)ide reverse transcriptase inhibitors and a potent third agent," the authors noted, with the once-daily fixed-dose combination of tenofovir plus emtricitabine remaining the first choice.

Although tenofovir is well tolerated, its use has been linked with kidney injury, "which appears to increase in incidence with long-term administration and concurrent [protease inhibitor, ritonavir-boosted] use," the authors cautioned.

Tenofovir is also associated with decreased bone mineral density of the spine and hip. Thus, given the increased risk of fragility fractures in postmenopausal women, ‘it may be prudent to consider avoiding tenofovir as part of initial therapy in this group," the authors wrote.

Another choice, the once-daily abacavir/lamivudine fixed-dose combination, is now a recommended initial therapy. In 2010, it was considered only a possible alternative.

"Screening for [the HLA-B*5701 gene] markedly reduces the risk of potentially life-threatening hypersensitivity reaction to abacavir," the guideline authors wrote.

In addition, some studies have found abacavir to be associated with a higher risk of acute myocardial infarction.

Dr. Thompson and her colleagues disclosed multiple financial and professional relationships with several pharmaceutical companies, including the makers of antiretroviral therapies. They stated that members of the panel who developed the recommendations did not participate in industry promotional activities such as speakers bureaus or lectures during their membership, and that members with previous conflicts recused themselves from evaluating evidence when a conflict was present.

The development of the recommendations was sponsored by the IAS-USA, according to the authors.

HIV-infected adults should start antiretroviral therapy as soon as possible, regardless of CD4 count, according to a recommendation from the International Antiviral Society–USA presented at the AIDS 2012 meeting in Washington.

The recommendation represents a major change from the last set of guidelines, issued in 2010. Those earlier guidelines recommended starting antiretrovirals when CD4 counts fell beneath 500 cells/mL, and "considering" treatment in patients with higher counts.

In writing the new guidelines, which also appear in the July 25 issue of JAMA (2012;308:387-402), Dr. Melanie A. Thompson and a panel convened by the International Antiviral Society–USA (IAS-USA) conducted a literature review of all new published data and data presented at scientific conferences between July 2010 and May 2012.

All recommendations were applicable only to HIV-infected adults in resource-rich settings, and dealt with antiretroviral therapies that were either already approved or in late-stage development.

The field of HIV prophylaxis has also seen significant progress since the 2010 update, and the new guidelines reflect those advances.

"Recently, antiretroviral therapy used as oral pre-exposure prophylaxis (PrEP) has been shown to be effective in three large trials using daily tenofovir/emtricitabine or tenofovir in gay and bisexual men and transgender women (iPrEx), heterosexual HIV-serodiscordant couples (Partners PrEP), and heterosexual men and women (TDF2)," wrote Dr. Thompson of the AIDS Research Consortium of Atlanta.

Indeed, following the iPrEx results, the Centers for Disease Control and Prevention issued interim guidance (MMWR 2011;60:65-8) for HIV-negative homosexual men who elect to take tenofovir/emtricitabine for prophylaxis.

And July 16, the Food and Drug Administration approved the use of an oral once-daily combination antiviral medication, Truvada (tenofovir and emtricitabine), for prevention in uninfected people at high risk for acquiring HIV.

While efficacy in PrEP has been positively correlated with medication adherence (as measured by serum drug levels), "pharmacokinetic and pharmacodynamic variability and the presence of vaginal or rectal inflammation also may affect outcome."

As in the 2010 recommendations (JAMA 2010;304:321-33), the initial choice of prophylactic therapy "continues to be based on a combination of two nucleos(t)ide reverse transcriptase inhibitors and a potent third agent," the authors noted, with the once-daily fixed-dose combination of tenofovir plus emtricitabine remaining the first choice.

Although tenofovir is well tolerated, its use has been linked with kidney injury, "which appears to increase in incidence with long-term administration and concurrent [protease inhibitor, ritonavir-boosted] use," the authors cautioned.

Tenofovir is also associated with decreased bone mineral density of the spine and hip. Thus, given the increased risk of fragility fractures in postmenopausal women, ‘it may be prudent to consider avoiding tenofovir as part of initial therapy in this group," the authors wrote.

Another choice, the once-daily abacavir/lamivudine fixed-dose combination, is now a recommended initial therapy. In 2010, it was considered only a possible alternative.

"Screening for [the HLA-B*5701 gene] markedly reduces the risk of potentially life-threatening hypersensitivity reaction to abacavir," the guideline authors wrote.

In addition, some studies have found abacavir to be associated with a higher risk of acute myocardial infarction.

Dr. Thompson and her colleagues disclosed multiple financial and professional relationships with several pharmaceutical companies, including the makers of antiretroviral therapies. They stated that members of the panel who developed the recommendations did not participate in industry promotional activities such as speakers bureaus or lectures during their membership, and that members with previous conflicts recused themselves from evaluating evidence when a conflict was present.

The development of the recommendations was sponsored by the IAS-USA, according to the authors.