Small Risk of HIV Sexual Transmission Persists Through First 6 Months of ART

A risk of HIV transmission to sexual partners persists for 6 months after the initiation of antiretroviral therapy (ART), investigators from a large prospective prevention study confirm in the online edition of the Journal of Acquired Immune Deficiency Syndromes.

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Nearly 1600 serodiscordant heterosexual couples were included in the analysis. Initiation of ART was accompanied by a fall in the risk of transmission, but the risk persisted during the first 6 months of treatment. No transmissions were observed once patients had been taking treatment for over 6 months.

"HIV transmission is markedly reduced once effective ART has resulted in complete virologic suppression in blood and genital secretions," Andrew Mujugira and fellow investigators with the Partners PrEP Study Team commented. "However, this prospective follow up of 1592 HIV serodiscordant couples after ART initiation by the infected partner demonstrates residual risk of transmission during the first 6 months of ART." They believe "the first 6 months after ART initiation may be a period of transition and persistent risk, with declining markers of transmission but not yet minimized risk."

ART suppresses HIV replication in both blood and genital secretions. This reduces the risk of transmission to sexual partners. Large prospective studies have evaluated the impact of ART on infectiousness. No infections have been documented when a patient has been taking suppressive ART for over 6 months, but there is some evidence that a risk of transmission persists during the initial months of treatment, probably because full viral suppression has not yet been achieved in the genital tract.

The Partners PrEP study recruited HIV-positive people not yet eligible for treatment (according to older treatment guidelines) and their HIV-negative partners. Uninfected partners were randomized to receive pre-exposure prophylaxis using either tenofovir (Viread) alone, tenofovir plus emtricitabine (Truvada), or a placebo.

The investigators wanted to establish a clearer understanding of the risk of transmission during the early months of HIV therapy and its relationship with blood and genital tract viral suppression and sexual risk behavior. They examined the speed of viral suppression in HIV-positive participants who did not qualify for treatment under national guidelines upon entry to the study, but who subsequently became eligible for treatment during the study.

They therefore examined data obtained from approximately 1600 heterosexual couples in Kenya and Uganda where the HIV-positive partner started ART during the study. These patients provided paired blood and genital secretion samples that allowed the investigators to measure the decline in viral load in these compartments after ART initiation. Their uninfected partners were regularly tested for HIV and the couples provided information on their use of condoms. Data were also gathered on the incidence of pregnancy.

The ART-treated patients were followed for a total of 474 person years until first viral suppression (below 80 copies/mL) in blood. The median time until the first viral load measurement was a little over 3 months. Cumulative probabilities of achieving blood viral suppression at 3, 6, 9, and 12 months after treatment initiation were 65%, 85%, 89%, and 91%, respectively.

HIV was detected in 12% of cervical and 21% of semen samples collected during the first 6 months after initiation of treatment. Median viral load in cervical and semen samples with detectable virus was 3.18 log and 2.60 log, respectively.

There was evidence that couples were having unprotected sex during this initial 6-month period. Incidence of pregnancy was 8.8 per 100 person years and sex without condoms was reported at 10.5% of study visits.  

Starting ART reduced the risk of HIV transmission. HIV incidence among the uninfected partners was 2.08 per 100 person years in the period before their partner started HIV therapy. This fell to 1.78 per 100 person years in the first 6 months of treatment (3 infections during 168 person-years of follow-up). Incidence fell to zero after 6 months of ART (no infections during 167 person-years).

In one case, HIV transmission probably occurred just before treatment initiation, because HIV antibodies were detectable in the partner not on treatment at the time of the first viral load test 28 days after starting ART. In the 2 remaining cases transmission occurred prior to days 56 and 149 after treatment initiation. In the former case, viral load was not measured for the first time until after seroconversion was detected. In the latter case, viral load had been measured at day 86 and had been found to be detectable. Plasma viral load was measured at 872 copies/mL at this time.

"Among African HIV serodiscordant couples, we observed residual risk of HIV transmission, measured through virologic and behavioral outcomes, during the first 6 months of ART," the investigators concluded. "Other prevention options such as PrEP are needed for HIV serodiscordant couples in which the infected partner delays, declines, or is starting treatment. Ongoing studies are designed to provide further evidence of ART effectiveness for HIV prevention."

6/15/16

Reference

A Mujugira, C Celum, RW Coombs, et al. HIV Transmission Risk Persists During the First 6 Months of Antiretroviral Therapy. Journal of Acquired Immune Deficiency Syndromes. April 6, 2016 (online ahead of print).