HIV-DNA in the Genital Tract of Women on Long-Term Effective Therapy Is Associated to Residual Viremia and Previous AIDS-Defining Illnesses

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.

Immunologic, Virologic, and Pharmacologic Characterization of the Female Upper Genital Tract in HIV-Infected Women

“…41–43 Successful suppression of HIV in blood using ART does not eliminate shedding measured in the LGT. 7,44–46 HIV shedding has been assumed to be derived from the mucosal surfaces of the vagina and cervix. However, the endometrium is in direct communication with these LGT sites and it is biologically plausible for virus to pass from UGT to LGT.…”

Total HIV-1 DNA, a Marker of Viral Reservoir Dynamics with Clinical Implications

“…It can persist in the genital tract of women on long-term effective cART (HIV RNA, Ͻ50 copies/ml at Ͼ6 months) and has been linked to current residual viremia (OR, 3.4; 95% CI, 1.1 to 10.9) and to a history of AIDS-defining illness (OR, 11; 95% CI, 2 to 61) (172). The presence of HIV in genital secretions should be taken into account when estimating the residual risk of transmission.…”

Total HIV DNA: a global marker of HIV persistence

“…Quantification of HIV DNA in kidney, as well as in adipose tissue, indicates that they can be considered as anatomical reservoirs [ 48 , 49 ]. Measuring HIV DNA in genital compartments may indicate the presence of infected cells and may help to explore this risk of sexual transmission [ 50 , 51 ].…”