Systematic review of HIV transmission between heterosexual serodiscordant couples where the HIV-positive partner is fully suppressed on antiretroviral therapy

Abstract

Background: The risk of sexual HIV transmission in serodiscordant couples when the HIV-positive partner has full virologic suppression on combination antiretroviral therapy (cART) is debated. This study aims to systematically review observational studies and randomized controlled trials (RCTs), evaluating rates of sexual HIV transmission between heterosexual serodiscordant couples when the HIV-positive partner has full suppression on cART.

Methods and findings: We searched major bibliographic databases to November 2012 for relevant observational studies and RCTs without language restrictions. Conference proceedings, key journals and bibliographies were also searched. Studies reporting HIV transmission rates, cART histories and viral loads of the HIV-positive partners were included. Two reviewers extracted methodologic characteristics and outcomes. Of 20,252 citations, 3 studies met all eligibility criteria with confirmed full virologic suppression in the HIV-positive partner. We included 3 additional studies (2 cohort studies, 1 RCT) that did not confirm viral suppression in the HIV-positive partner at transmission in a secondary meta-analysis. Methodologic quality was reasonable. The rate of transmission in the 3 studies confirming virologic suppression was 0 per 100 person-years (95% CI = 0-0.05), with low heterogeneity (I(2) = 0%). When we included the 3 studies that did not confirm virologic suppression, the rate of transmission was 0.14 per 100 person-years (95%CI = 0.04-0.31) (I(2) = 0%). In a sensitivity analysis including all 6 studies, the rate of transmission was 0 per 100 person-years (95%CI = 0-0.01) after omitting all transmissions with known detectable or unconfirmed viral loads, as full suppression in these cases was unlikely. Limitations included lack of data on same-sex couples, type of sexual intercourse (vaginal vs. anal), direction of HIV transmission, exact viral load at the time of transmission, sexually transmitted infections (STI) rates, and extent of condom use.

Conclusions: Our findings suggest minimal risk of sexual HIV transmission for heterosexual serodiscordant couples when the HIV-positive partner has full viral suppression on cART with caveats regarding information on sexual intercourse type, STIs, and condom use. These findings have implications when counseling heterosexual serodiscordant couples on sexual and reproductive health. More research is needed to explore HIV transmission risk between same-sex couples.

Figure 1. Flow diagram (selection strategy) of included studies.

Figure 2. Forest plots of HIV transmission rates per 100 person-years with and without transmissions with unconfirmed viral suppression at the time of suppression.

Footnote:The first forest plot is the summary of HIV transmission rates per 100 person-years with 95% confidence interval for 6 studies with confirmed and unconfirmed viral suppression at time of transmission. The second forest plot is the sensitivity analysis of the 6 studies with confirmed and unconfirmed viral suppression at the time of transmission with forest plot of the summary of HIV transmission rates per 100 person-years with 95% confidence interval reporting on HIV transmission when HIV-positive partner on combination antiretroviral therapy had confirmed viral suppression, omitting transmissions occurring with known or unconfirmed detectable viral loads at the time of transmission (i.e. 3 studies had 4 transmissions with known or unconfirmed detectable viral loads and these transmissions were excluded, while leaving the rest of data in the analysis).