Antiretroviral drug concentrations in the male and female genital tract: Implications for the sexual transmission of HIV

Department of Sexual Health and HIV Medicine, Directorate of Infection, Birmingham Heartlands Hospital, Heart of England NHS Foundation Trust, University of Birmingham, Birmingham, UK.
Current opinion in HIV and AIDS (Impact Factor: 4.68). 07/2010; 5(4):335-43. DOI: 10.1097/COH.0b013e32833a0b69
Source: PubMed


To summarize the recent literature (2008-2010) on antiretroviral (ARV) drug disposition into the male and female genital tract.
Recent studies have confirmed that penetration of antiretroviral agents into the male and female genital tracts are both drug and sex specific. Concentrations achieved vary considerably depending on the class of drug studied, the sampling techniques used and the times samples are obtained.
There appear to be several patterns of drug penetration into the male and female genital tract. In addition there appear to be different patterns of genital shedding under the influence of antiretroviral therapy. What effect these factors will have on the sexual transmission of HIV or the evolution and transmission of resistant HIV remains to be seen.

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    • "Noteworthy, one of the two factors independently associated with HIV-DNA shedding in the genital tract was a residual viremia. A low level of plasma HIV-RNA could be a marker of ongoing replication in HIV sanctuaries, particularly the genital tract where some antiretroviral drugs diffuse poorly [19], [20]. The infectiousness of HIV-DNA-containing vaginal cells is unclear. "
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    ABSTRACT: To 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. Women 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. Eighty-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. In 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.
    PLoS ONE 08/2013; 8(8):e69686. DOI:10.1371/journal.pone.0069686 · 3.23 Impact Factor
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    • "HIV-infected males may have isolated semen HIV shedding even when plasma viral load is undetectable [94, 95] and independent of semen drug levels and ARV regimen [96]. Additionally, ARV genital tract penetration varies among ARV agents [97]. "
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    ABSTRACT: Women living with HIV have fertility desires and intentions that are similar to those of uninfected women, and with advances in treatment most women can realistically plan to have and raise children to adulthood. Although HIV may have adverse effects on fertility, recent studies suggest that antiretroviral therapy may increase or restore fertility. Data indicate the increasing numbers of women living with HIV who are becoming pregnant, and that many pregnancies are unintended and contraception is underutilized, reflecting an unmet need for preconception care (PCC). In addition to the PCC appropriate for all women of reproductive age, women living with HIV require comprehensive, specialized care that addresses their unique needs. The goals of PCC for women living with HIV are to prevent unintended pregnancy, optimize maternal health prior to pregnancy, improve maternal and fetal outcomes in pregnancy, prevent perinatal HIV transmission, and prevent HIV transmission to an HIV-uninfected sexual partner when trying to conceive. This paper discusses the rationale for preconception counseling and care in the setting of HIV and reviews current literature relevant to the content and considerations in providing PCC for women living with HIV, with a primary focus on well-resourced settings.
    Infectious Diseases in Obstetrics and Gynecology 10/2012; 2012:604183. DOI:10.1155/2012/604183
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    • "Persistent HIV shedding in semen has been shown to occur for a wide range of HAART regimens, including those based on the latest molecules, irrespective of the seminal concentrations achieved by the drugs [1], [3], [4], [5], [7], [31], [34], [35]. The AZT/3TC/IDV regimen has been associated in men with persistence of HIV RNA and DNA in semen despite prolonged undetectable blood viral load [4], [36], [37], [38], [39], [40] and good seminal concentrations of all three drugs [41]. "
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    ABSTRACT: The male genital tract is suspected to constitute a viral sanctuary as persistent HIV shedding is found in the semen of a subset of HIV-infected men receiving effective antiretroviral therapy (HAART). The origin of this persistent shedding is currently unknown. Phylogenetic studies indicated that HIV in semen from untreated men arises from local sources and/or passive diffusion from the blood. We previously demonstrated in human and macaque low levels and localized infection of several semen-producing organs by HIV/SIV. Using a macaque model, this study investigates the impact of short term HAART (2-4 weeks) initiated either during the asymptomatic chronic stage or 4 h post-intravenous inoculation of SIVmac251 on the infection of male genital organs. Short term HAART during the chronic stage decreased blood viral load. No major impact of HAART was observed on SIV DNA levels in male genital organs using a sensitive nested PCR assay. Using in situ hybridization, SIV RNA+ cells were detected in all male genital tract organs from untreated and treated animals with undetectable blood viral load following HAART. Infected CD68+ myeloid cells and CD3+ T lymphocytes were detected pre- and post-HAART. In contrast, short term HAART initiated 4 h post-SIV exposure led to a drastic decrease of the male genital tissues infection, although it failed to prevent systemic infection. In both cases, HAART tended to decrease the number of CD3+ T cells in the male organs. Our results indicate that the established infection of male genital organs is not greatly impacted by short term HAART, whereas the same treatment during pre-acute phase of the infection efficiently impairs viral dissemination to the male genital tract. Further investigations are now needed to determine whether infection of male genital organs is responsible for long term persistent HIV shedding in semen despite HAART.
    PLoS ONE 05/2012; 7(5):e37348. DOI:10.1371/journal.pone.0037348 · 3.23 Impact Factor
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