Objective:
Combination antiretroviral therapy (ART) decreases the risk of sexual HIV transmission by suppressing blood and genital HIV RNA concentrations. However, HIV transmission risk may persist prior to achieving complete viral suppression.

Methods:
The Partners PrEP Study is a prospective cohort study of 4747 heterosexual HIV-serodiscordant couples in Kenya and Uganda, where couples were sexually active and planning to remain as a couple for the duration of the study. HIV-infected partners were not eligible for ART according to national guidelines at the time of enrollment. During follow-up, they received regular clinical and immunological monitoring and referrals for ART if they became eligible for treatment, initially at CD4 <200 cells/μL (Kenya) and <250 cells/μL (Uganda), which was revised to ≤350 cells/μL in both countries while the study was ongoing. ART use by HIV-infected partners and sexual behavior as reported by both members of the couple were assessed every three months. All participants received a package of HIV prevention services including individual and couple risk-reduction counseling, free condoms, and screening and treatment of sexually transmitted infections. At all study sites, HIV-uninfected women were provided with contraception counseling and free contraceptives.

Multiple markers of HIV transmission risk during the first months after ART initiation were examined: time to viral suppression in blood, persistence of HIV RNA in genital specimens, sexual risk behavior, pregnancy incidence, and HIV transmission using survival analysis and GEE logistic regression. At enrollment, every six months and at study exit, blood was collected from HIV-infected partners for HIV RNA quantification. Cervical specimens were collected at enrollment, annually and study exit. Semen collection was scheduled at the six and twelve month visits.

HIV serological testing for HIV-uninfected partners was performed monthly. Linkage between HIV seroconverters and their study partners was ascertained using HIV pol gene consensus sequencing. Follow-up time was computed beginning on the date of the study visit at which ART use was first reported (thus, after ART had started).

Results:
Of the 2184 HIV-infected persons eligible for ART in the Partners PrEP Study,1817 (83%) initiated ART (1062 women and 755 men), of which 1592 were followed for 474 person-years to assess time to first viral suppression. The cumulative probabilities of achieving blood viral suppression (<80 copies/ml) 3, 6 and 9-months after ART initiation were 65.3%, 84.8% and 89.1%, respectively. Endocervical and seminal HIV RNA were detectable in 12% and 21% of samples obtained within 6-months of ART. Among 454 swabs collected when blood HIV RNA concentrations were undetectable (<40 copies/mL), endocervical HIV RNA was detected in 8% (36 swabs from 36 women), and the median quantity was 3.14 log 10 copies/swab (IQR, 2.88-3.53). When blood HIV RNA concentrations were detectable, endocervical HIV RNA was detected in 23% (39/171) of swabs. Among 132 semen samples collected after blood HIV RNA concentrations were suppressed, 9% (12 samples from 10 men) had detectable seminal HIV RNA and the median quantity detected was 2.60 log 10 copies/mL. When blood HIV RNA concentrations were detectable, seminal HIV RNA was detected in 42% (30/72) of swabs. Pregnancy incidence was 8.8 per 100 person-years during the first 6-months of ART, and sex unprotected by condoms was reported at 10.5% of visits. Among initially uninfected partners, HIV incidence before ART was 2.08 per 100 person-years (55 infections; 2644 person-years), 1.79 for 0-6 months after ART initiation (3 infections; 168 person-years), and 0.00 (95% CI: 0,00-2,00) with >6 months of ART (0 infections; 167 person-years). All three ART-exposed HIV events were phylogenetically-linked female-to-male transmissions and occurred prior to complete viral suppression in blood and genital secretions.