Small risk of sexual transmission of HIV persists through first six months of ART

A risk of HIV transmission to sexual partners persists for six months after the initiation of antiretroviral therapy, investigators from a large prospective prevention study confirm in the online edition of the Journal of Acquired Immune Deficiency Syndromes. Over 1500 serodiscordant heterosexual couples were included in the analysis. Initiation of antiretroviral therapy (ART) was accompanied by a fall in the risk of transmission, but the risk persisted during the first six months of treatment. No transmissions were observed once patients had been taking treatment for over six months.

“HIV transmission is markedly reduced once effective ART has resulted in complete virologic suppression in blood and genital secretions,” comment the authors. “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 six months of ART. They believe “the first six 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 virologically suppressive ART for over six months, but there is some evidence that a risk of transmission persists in 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 and their uninfected partners, and randomised the uninfected partner to receive either tenofovir, tenofovir plus emtricitabine (Truvada) or a placebo. Investigators from the Partners PrEP study 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 behaviour. They examined the speed of virological suppression in HIV-positive participants who did not qualify for treatment under national guidelines on 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-infected 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 three months. Cumulative probabilities of achieving blood viral suppression at three, six, nine and twelve months after treatment initiation were 65%, 85%, 89% and 91%, respectively.

HIV was detected in 12% of cervical and 21% of seminal samples collected in the first six months after initiation of treatment. Median viral load in cervical and seminal samples with detectable virus was 3.18 log10 and 2.60 log10, respectively.

There was evidence that couples were having unprotected sex during this initial six 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 six months of treatment (three infections during 168 person-years of follow-up). Incidence fell to zero after six 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 treatment. In the two 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 sero-discordant couples, we observed residual risk of HIV transmission, measured through virologic and behavioural outcomes, during the first six months of ART,” the investigators conclude. “Other prevention options such as PrEP are needed for HIV sero-discordant 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.”

References

Mujugira A et al. HIV transmission risk persists during the first 6 months of antiretroviral therapy. J Acquir Immune Defic Synr, online edition. DOI: 10.1097/QAI.000000000001019 (2016).