Antiretroviral Drug Concentrations and HIV RNA in the Genital Tract of HIV-Infected Women Receiving Long-Term Highly Active Antiretroviral Therapy

Department of Pathology and Laboratory Medicine, Emory University, Atlanta, Georgia, United States
Clinical Infectious Diseases (Impact Factor: 8.89). 04/2008; 46(5):719-25. DOI: 10.1086/527387
Source: PubMed


Our objective was to determine antiretroviral drug concentrations and human immunodeficiency virus (HIV) RNA rebound in cervicovaginal fluid (CVF) in relation to blood plasma (BP) in women receiving suppressive highly active antiretroviral therapy (HAART).
Thirty-four HIV-infected women who had plasma HIV RNA levels < or =80 copies/mL for at least 6 months were enrolled. Sixty-eight paired CVF and BP drug concentrations and HIV RNA levels were determined before and 3-4 h after drug administration. For each woman and antiretroviral drug, the CVF:BP drug concentration ratios before and after drug administration were calculated. The nonparametric Wilcoxon rank sum test was used to determine if these ratios were different from 1.0.
Lamivudine (administered to 20 patients) and tenofovir (administered to 16) had significantly higher concentrations in CVF than in BP before drug administration, with mean CVF:BP concentration ratios of 3.19 (95% confidence interval, 1.2-8.5) and 5.2 (95% confidence interval, 1.2-22.6), respectively. Efavirenz (administered to 13 patients) and lopinavir (administered to 6) had significantly lower concentrations in CVF, with mean CVF:BP concentration ratios of 0.01 (95% confidence interval, 0.00-0.03) and 0.03 (0.01-0.11), respectively. During the study visit (median time after enrollment, 6 months), BP and CVF detectable HIV RNA levels were observed 7 patients (20.6%) and 1 patient (2.9%), respectively.
Despite lower CVF concentrations of key HAART components, such as efavirenz and lopinavir, virologic rebound was rare. The high concentrations of tenofovir and lamivudine in CVF may have implications for the prevention of sexual transmission during HAART and for pre-exposure or postexposure prophylaxis.

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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.
    Full-text · Article · Aug 2013 · PLoS ONE
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    • "Most PIs alone are only moderately absorbed in the gastrointestinal tract and their diffusion though anatomical barrier is usually moderate, in part due to high plasma protein binding (90-99%), which make PIs concentration lower in sanctuary sites such as the genital tract [10,11] and the CNS [12] in comparison with plasma. Compared with other PIs, fosamprenavir, lopinavir and darunavir possess better diffusion to sanctuary sites [13,14]. "
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    ABSTRACT: The impact of highly active antiretroviral therapy (HAART) in the natural history of AIDS disease has been allowed to prolong the survival of people with HIV infection, particularly whose with increased HIV viral load. Additionally, the antiretroviral therapy could exert a certain degree of protection against parasitic diseases. A number of studies have been evidenced a decrease in the incidence of opportunistic parasitic infections in the era of HAART. Although these changes have been attributed to the restoration of cell-mediated immunity, induced by either non-nucleoside reverse transcriptase inhibitors or HIV protease inhibitors, in combination with at least two nucleoside reverse transcriptase inhibitors included in HAART, there are evidence that the control of these parasitic infections in HIV-positive persons under HAART, is also induced by the inhibition of the proteases of the parasites. This review focuses on the principal available data related with therapeutic HIV-protease inhibitors and their in vitro and in vivo effects on the opportunistic protozoan parasites.
    Full-text · Article · Mar 2011 · The Open Medicinal Chemistry Journal
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    ABSTRACT: Heterosexual spread of HIV remains the major risk factor for transmission worldwide. Genital secretions from the infected partner contain both cell-free and cell-associated virus. Although the exact mechanism of heterosexual transmission is unknown, genital virus plays an important role. Decreasing the genital shedding of HIV is an important step in slowing the spread of the disease. Recent studies have shown that antiretroviral penetration into the genital tract varies by class and that antiretroviral therapy significantly decreases HIV levels. Compartmentalization between the blood and genital tract is based on viral load levels, resistant variants, viral diversity, and coreceptor usage. HSV-2, lack of lactobacilli, and plasma cell endometritis increased HIV genital shedding. HSV-2 suppressive therapy significantly reduces plasma and genital tract viral load. Data are conflicting on the effect of hormonal contraception on HIV genital shedding. Further studies are needed to translate these findings into decreased spread on a population level.
    No preview · Article · Dec 2008 · Current Infectious Disease Reports
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