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AIDS 2012: HPTN 052 Continues to Show Clinical Benefits of Earlier Antiretroviral Therapy

The HPTN 052 trial, best known for showing that early antiretroviral therapy (ART) can dramatically reduce the risk of HIV transmission within serodiscordant couples, also found that early treatment reduces the risk of clinical events and death, though the benefit was largely driven by extrapulmonary tuberculosis, researchers reported recently at the XIX International AIDS Conference (AIDS 2012) in Washington, DC.

"Treatment as prevention" was the big news at the 2011International AIDS Society Conference in Rome, where the primary HPTN 052 results were first presented, and it continued to be a key theme at the recent AIDS conference. But advocates have raised concern about wider use of ART by HIV positive people who are still in apparently good health, solely for the sake of their HIV negative partners.

At the Rome meeting, Beatriz Grinsztejn from Instituto de Pesquisa Clinica Evandro Chagas in Rio de Janeiro and colleagues presented additional HPTN 052 findings hailed as the first-ever evidence from a randomized clinical trial demonstrating the benefits of earlier treatment. Last month in DC, Grinsztejn presented follow-up data on clinical outcomes among study participants.

HPTN 052 enrolled 1761HIV serodiscordant couples in 9 countries in Africa, Asia, and South America. About half of the HIV positive partners were women and most were in the 26-40 year age range.

At enrollment all HIV positive participants had CD4 T-cell counts between 350 and 550 cells/mm³. The study randomly assigned them either to start combination ART immediately upon enrollment, or to wait until their CD4 count fell below 250 cells/mm³or they developed AIDS-related symptoms. The median CD4 count at ART initiation was about 440 cells/mm³in the immediate arm and 230 cells/mm³in the delayed arm.

The researchers looked primary events including death, WHO stage 4 disease, pulmonary and extrapulmonary (outside the lungs) tuberculosis (TB), severe bacterial infections, and selected serious non-AIDS events including cardiovascular disease, liver disease, end-stage kidney disease, non‐AIDS malignancies, and diabetes. They also looked at several less serious secondary events including WHO stage 2 or 3 disease, malaria, elevated liver enzymes, lipodystrophy, hypertension, thrombocytopenia (low platelets), and various non-opportunistic infections.

Results

• During a median follow-up period of 2.1 years, 213 people (24%) in the delayed arm started ART due to disease progression; the median time to ART initiation was 3.8 years.
• Looking at all AIDS and non-AIDS primary and secondary events combined, 347 people (40%) in the delayed ART arm vs 326 people (37%) in the immediate arm experienced at least 1 event, for rates of 29 vs 25 per 100 person-years, respectively.
• The overall incidence of all clinical events was significantly higher for people in the delayed treatment arm (P=0.02)
• Delayed ART was associated with significantly shorter time to first AIDS events and deaths compared with immediate ART.
• 272 individuals (31%) in the delayed arm and 220 (25%) in the immediate arm experienced at least 1 primary event, for rates of 4.5 vs 3.5 per 100 person-years, respectively.
• There was a trend towards a shorter time to AIDS and non-AIDS primary events combined in the delayed ART arm, but the difference did not reach statistical significance (P=0.07).
• People in the delayed ART arm were about twice as likely to develop TB (34 vs 17 cases, respectively) and did so sooner than those receiving immediate ART; about two-thirds of TB events were extrapulmonary.
• Non-AIDS events were uncommon and similar in the 2 treatment arms.
• 317 individuals (36%) in the delayed arm and 298 (34%) in the immediate arm experienced at least 1 secondary event, for rates of 25 vs 21 per 100 person-years.
• There was a "substantial" difference in secondary events related to immune function including herpes zoster or shingles (53 vs 17, respectively) and oral candidiasis or yeast infection (47 vs 22, respectively).
• Older age, higher HIV viral load, anemia, and hepatitis B coinfection were significant predictors of overall clinical events.

"Early ART significantly delayed the time to AIDS defining events and TB, and significantly decreased the incidence of clinical events," the researchers summarized. "We conclude that the combined treatment and prevention benefits of ART support early initiation."

A related analysis by Rochelle Walensky, Kenneth Freedberg, and colleagues found that earlier antiretroviral treatment was cost-effective, as it increased survival, prevented costly opportunistic infections, and prevented HIV transmission.

8/14/12

References

B Grinsztejn, M Hosseinipour, S Swindells, et al (HPTN 052/ACTG Study Team. Effect of early versus delayed initiation of antiretroviral therapy (ART) on clinical outcomes in the HPTN 052 randomized clinical trial. XIX International AIDS Conference (AIDS 2012). Washington, DC, July 22-27, 2012. Abstract THLBB05.

RP Walensky, EL Ross, N Kumarasamy, K Freedberg, et al. The cost-effectiveness of treatment as prevention: analysis of the HPTN 052 trial. XIX International AIDS Conference (AIDS 2012). Washington, DC, July 22-27, 2012. Abstract FRLBC01.

Other Sources

HIV Prevention Trials Network. Expanded Analysis of HPTN 052 Study Results Reveal Additional Benefits of Early HIV Treatment. Press release. July 26, 2012.

National Institutes of Health. Landmark HIV Treatment-as-Prevention Study Demonstrates Additional Health Benefits, Cost-Effectiveness. NIH News Press release. July 27, 2012.