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  XIX International AIDS Conference
July 22-27, 2012
Washington, DC
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Observational Studies Confirm Preventive Impact of ART in HIV-Discordant Couples: transmission rate cut by 98% when CD4>350
  XIX International AIDS Conference, July 22-27, 2012, Washington, DC

Mark Mascolini

Analysis of 7 studies that weighed the impact of antiretroviral therapy (ART) in blocking HIV transmission from an infected partner to an HIV-negative partner confirmed the key result of HPTN 052: If the positive partner takes antiretrovirals, risk of HIV transmission to the negative partner drops substantially [1].

The international HPTN 052 trial randomized the HIV-positive partners in 1763 HIV-discordant couples to begin combination ART immediately (at a CD4 count between 350 and 550) or to wait for the count to fall below 250 or for HIV-related symptoms to develop [2]. Of 28 HIV transmissions verified genetically, only 1 occurred in the early-treatment group to yield a 96% lower transmission rate in that group (hazard ratio 0.04, 95% confidence interval [CI] 0.01 to 0.27, P < 0.001).

To determine whether combined observational studies of ART in discordant couples reflect this HPTN 052 result, a team of researchers scoured electronic databases and conference reports to identify cohort studies and case-control studies that addressed this issue. They identified 1814 references, assessed 24 studies in detail, and ultimately analyzed 7 studies.

Of the 436 HIV transmissions in these 7 studies, 71 (16%) occurred in couples with an antiretroviral-treated positive partner and 365 (84%) occurred in couples with an untreated positive partner.

Statistical analysis indicated that ART cut the HIV transmission rate 66% (rate ratio [RR] 0.34, 95% CI 0.13 to 0.92). Although impressive, this protective rate was much lower than in HPTN 052. Heterogeneity among studies was substantial. When the researchers excluded two studies with inadequate person-time data, they estimated that ART trimmed the transmission rate 84% (RR 0.16, 95% CI 0.07 to 0.35), and there was no heterogeneity between these studies.

Finally, the investigators limited the analysis to couples in which the positive partner had a CD4 count at or above 350, as among early-treated partners in HPTN 052. In this analysis ART sliced the transmission rate 98% (RR 0.02, 95% CI 0.00 to 2.87), similar to the 96% protective effect in HPTN 052. In the subgroup of couples whose positive partner had a CD4 count at or above 350, all 61 HIV transmissions occurred in couples with untreated positive partners.

The researchers concluded that observational studies support the main finding of HPTN 052, although the estimated overall effectiveness of ART in preventing HIV transmission is 8-fold lower in the combined observational studies than in HPTN 052.


1. Anglemyer A, Rutherford G, Baggaley R, Egger M, Siegfried N. Antiretroviral therapy for prevention of HIV transmission in HIV-discordant couples: a systematic review of the observational literature. XIX International AIDS Conference. July 22-27, 2012. Washington, DC. Abstract MOPDC0105.

2. Cohen MS, Chen YQ, McCauley M, et al. Prevention of HIV-1 infection with early antiretroviral therapy. N Engl J Med. 2011;365:493-505. http://www.nejm.org/doi/full/10.1056/NEJMoa1105243.