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July 18, 2011

Treatment as Prevention: 96% reduction in HIV transmission among HIV-serodiscordant partnerships


Treatment as Prevention: 96% reduction in HIV transmission among HIV-serodiscordant partnerships.

In Rome, a packed audience rose to applaud the lead investigators of HPTN 052, a Phase III, multi-site, randomized trial to determine the effectiveness of treatment strategies in preventing the sexual transmission of HIV in HIV-serodiscordant couples, during a session dedicated to Treatment as Prevention. Eligible couples were sero-discordant where the HIV-infected partner had a CD4 count of 350-550 cells/ mm3. HIV-infected index cases were randomized 1:1 to receiving ART plus primary care or HIV primary care without ART until the index case developed a CD4 count of 200-250 cells/ mm3, or an AIDS-defining illness. The antiretroviral regimens used were Combivir [3TC/ZDV], ATV, EFV, NVP, TDF, 3TC, ddI-EC, d4T, Kaletra/Aluvia [LPV/r], and Truvada [FTC/TDF]. The primary objective was to compare rates of HIV transmission to partners of the index cases as well as to determine the factors related to the two ART regimens (immediate vs. delayed) among index cases - including adherence to ART, virologic and immunologic efficacy, AIDS-defining illnesses, opportunistic infections and risk compensation.

Myron Cohen, the HPTN 052 Protocol Chair presented the study design and the initial results of the study.[1] Of the 10,838 individuals screened in sub-Saharan Asia, Latin America and the United States, only 1,763 couples were eligible for inclusion. HIV-infected participants were randomized to either immediate ART (N=886) or delayed ART (N=877). Twenty-eight linked transmission events occurred within 20 months of follow up, 27 in the delayed treatment arm and 1 in the immediate treatment arm (hazards ratio of immediate vs. delayed therapy, 0.037; p< 0.001). Thirty-two (82%) of the transmission events occurred in sub-Saharan Africa.

Susan Eshleman from Johns Hopkins University School of Medicine then presented the analysis of genetic linkage of HIV from the couples.[2] After conducting phylogentic as well as statistical analysis of HIV isolated from the 38 index-partner pairs, it was determined that in 29/38 cases the index case was the likely source of the partners HIV infection.

Mina Hosseinipour in a third presentation discussed the outcomes of HIV-infected index cases who had been randomized to either delayed or immediate treatment.[3] Of the 877 subjected in the delayed arm, 184 initiated treatment mostly due to decline in CD4 counts (75%). The mean time to initiation of ART in this group was 3.5 years and median CD4 225 cells/mm3. Although the magnitude of CD4 responses were similar in both arms, the absolute CD4 levels achieved were lower in the delayed arm.

Beatriz Grinsztejn (Brazil), the final panelist, presented the final results that discussed the clinical outcomes observed between the two arms.[4] 105 participants developed a primary clinical event, 40 in the immediate arm (2.4 per 100 PY) and 65 in the delayed arm (4.0 per 100PY), hazard ratio (HR) 0.59, 95% CI: (0.40, 0.88), p=0.01. The predominant outcome noted was extrapulmonary tuberculosis (3 versus 17 cases in the immediate and delayed arms respectively). A higher proportion of adverse effects related to ART were seen in the immediate vs. the delayed arm ( 24% vs. 5%). Overall immediate ART was associated with 41% reduction in HIV-related clinical events.

Dr Cohen summarized the results of the study by stating that it showed overwhelming evidence that early ART showed a 96% reduction in transmission of HIV in sero-discordant couples as well as showing improved clinical benefit to index cases who were HIV-infected This could be seen as further proof of concept for a “Test and Treat" strategy.

References:

1. Cohen M, Chen Y, McCauley M, et al. Antiretroviral treatment to prevent the sexual transmission of HIV-1: results from the HPTN 052 multinational randomized controlled trial [Oral Abstract]. Presented July 18, 2011 at the 6th IAS Conference on HIV Pathogenesis, Treatment and Prevention, Rome, Italy. Abstract MOAX0102.

2. Hughes J, Hudelson S, Redd A, et al. Analysis of genetic linkage of HIV from couples enrolled in the HIV Prevention Trials Network (HPTN) 052 trial [Oral Abstract]. Presented July 18, 2011 at the 6th IAS Conference on HIV Pathogenesis, Treatment and Prevention, Rome, Italy. Abstract MOAX0103.

3. Hosseinipour MC, Wang L, Cohen MS, et al. Immunologic and virologic disease progression and responses to ART across geographic regions: outcomes from HPTN 052 study [Abstract]. Presented July 18, 2011 at the 6th IAS Conference on HIV Pathogenesis, Treatment and Prevention, Rome, Italy. Abstract MOAX0104.

4. Grinsztejn B, Ribaudo H, Cohen MS, et al. Effects of early versus delayed initiation of antiretroviral therapy (ART) on HIV clinical outcomes: results from the HPTN 052 randomized clinical trial [Abstract]. Presented July 18, 2011 at the 6th IAS Conference on HIV Pathogenesis, Treatment and Prevention, Rome, Italy. Abstract MOAX0105.


Source: Reporting for PRN news from Rome, Italy: Anita Radix, MD