Abstract
ObjectivesTo assess the impact of long-term combined antiretroviral therapy (cART) on HIV-RNA and HIV-DNA levels in cervicovaginal secretions of HIV-1-infected women with sustained undetectable plasma RNA viral load (PVL); to explore factors predictive of residual viral shedding; and to evaluate the risk of heterosexual transmission.MethodsWomen with undetectable PVL (<50 copies/mL) for >6 months were included in this cross-sectional study. HIV-RNA and HIV-DNA were measured in blood and cervicovaginal lavage fluid (CVL). Women were systematically tested for genital infections. The risk of transmission to male partners during unprotected intercourse was estimated.ResultsEighty-one women composed the study population: all had HIV-RNA <40 copies/mL in CVL. HIV-DNA was detectable in CVL of 29/78 patients (37%). There was a weak positive correlation between HIV-DNA levels in PBMCs and CVL (r = 0.20; p = 0.08). In multivariate analysis, two factors were associated with HIV-DNA detection in CVL: previous AIDS-defining illnesses (OR = 11; 95%CI = 2–61) and current residual viremia (20<PVL<50 cp/mL) (OR = 3.4; 95%CI = 1.1–10.9). Neither the classes of cART regimen nor the presence of genital bacterial or fungal colonization were associated with HIV-DNA detection in CVL. Twenty-eight percent of the women had unprotected intercourse with their regular HIV-seronegative male partner, for between 8 and 158 months. None of their male partners became infected, after a total of 14 000 exposures.ConclusionIn our experience, HIV-RNA was undetectable in the genital tract of women with sustained control of PVL on cART. HIV-DNA shedding persisted in about one third of cases, with no substantial evidence of residual infectiousness.
Highlights
It is important to determine the conditions in which unprotected sexual intercourse carries a negligible risk of HIV transmission, both for prevention and for establishing guidelines
In cervicovaginal secretions (CVS), cell-free HIV-RNA viral load is the best predictor of the risk of sexual transmission, and cell-associated HIV-DNA is a marker of potential infectiousness [10,11]
We found that HIV-RNA was undetectable in the genital tract of women who had sustained plasma viral load below 50 copies/mL on combined antiretroviral therapy (cART), regardless of the drugs used, and that none of their male partners became infected during the study period
Summary
It is important to determine the conditions in which unprotected sexual intercourse carries a negligible risk of HIV transmission, both for prevention and for establishing guidelines. Several studies have shown that plasma HIV-RNA suppression by combined antiretroviral therapy (cART) is associated with a huge reduction in the risk of sexual HIV transmission in serodifferent couples [1,2,3]. In cervicovaginal secretions (CVS), cell-free HIV-RNA viral load is the best predictor of the risk of sexual transmission, and cell-associated HIV-DNA is a marker of potential infectiousness [10,11]. The slightest distribution of some antiretroviral drugs in the genital tract, which might contribute to maintain productive infected cells, can lead to a viral compartmentalization. The residual risk of HIV transmission to male partners of women on long-term effective cART has not been studied in terms of both HIV-RNA and HIV-DNA levels in the genital tract
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