Background:  Limited observational studies indicate that ART is associated with decreased risk of HIV transmission, likely through reduced plasma and genital HIV levels.

Methods:  Data were from the Partners in Prevention HSV/HIV Transmission Study, a randomized clinical trial of acyclovir to reduce HIV transmission among 3408 heterosexual HIV serodiscordant couples from 7 African countries (Botswana, Kenya, Rwanda, South Africa, Tanzania, Uganda, and Zambia). We used time-dependent analysis to assess the effect of ART initiation on HIV transmission risk. By trial eligibility criteria, no HIV-infected partners met national criteria for ART initiation at enrollment. During follow-up, referral for ART was according to national guidelines and ART use by self-report was recorded quarterly. Couples were followed for up to 24 months, with HIV testing of uninfected partners every 3 months. Seroconversions were assessed for linkage within the couple by HIV sequencing.

Results:  During the study, 349 (10%) HIV-infected partners initiated ART. A higher proportion of men initiated (12%) than women (9%, P =0.01) at median CD4 counts of 192 and 204 cells/mm³, respectively (P =0.05). HIV-infected partners who initiated therapy were older (mean 35.2 vs 32.7 years, P <0.001), had higher enrollment plasma HIV levels (mean 4.4 vs 3.9 log₁₀ copies/mL, P <0.001), and lower enrollment CD4 counts (375 vs 540 cells/mm³, P<0.001). ART was initiated at CD4 counts <200 cells/mm³ in 52%, between 200 and 349 cells/mm³ in 33%, and ≥350 cells/mm³ in 15% (~1 in 3 of these were initiated on ART for prevention of mother-to-child transmission). Rates of linked HIV transmission and association with ART are shown for 103 linked infections where ART use could be assessed (see the table). For the single HIV transmission after ART initiation, the HIV-infected partner initiated ART 18 days prior to their partner’s first HIV seropositive test (HIV seronegative 90 days prior).

Conclusions:  This large prospective study demonstrates that ART use is associated with substantially lower risk for HIV transmission among heterosexual, African, HIV serodiscordant couples, where the HIV-infected partner did not meet national criteria for ART initiation at enrollment. A single transmission occurred within 1 month after ART initiation.