NATAP/IAS: Art Cuts HIV Transmission by 98% if CD4>350

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Subject: NATAP/IAS: Art Cuts HIV Transmission by 98% if CD4>350

Observational

Studies Confirm Preventive Impact of ART in HIV-Discordant Couples

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.

References

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.