Genital tract HIV-1 RNA shedding among women with below detectable plasma viral load
Division of Infectious Diseases, Department of Medicine, Miriam Hospital/Alpert Medical School, Brown University, Providence, Rhode Island 02906, USA. AIDS (London, England)
(Impact Factor: 5.55).
10/2010; 24(16):2489-97. DOI: 10.1097/QAD.0b013e32833e5043
Few studies have assessed longitudinal genital tract HIV-1 shedding. We determined patterns of genital tract HIV-1 RNA shedding over time among women with suppressed plasma viral load (PVL) on antiretroviral treatment.
Paired plasma and genital tract HIV-1 RNA were measured every 4 weeks. Participants were classified as persistent, intermittent, or nonshedders. Longitudinal analysis examined rates of genital tract shedding and the association with PVL, CD4 cell count, and genital tract infections. Markov transition models were used to describe the dynamics of HIV-1 RNA in plasma and genital tract using visit-to-visit transitions from and to detectable and undetectable PVL or genital tract HIV-1 RNA.
Fifty-nine women contributed 582 study visits of whom 95 and 98% had below-detectable PVL and genital tract viral load, respectively, at baseline. Thirty-two of 59 women (54%) had detectable HIV-1 RNA at least once in the genital tract. Twenty-two of 59 (37%) women had detectable genital tract HIV-1 RNA during a study visit when PVL was undetectable; 6.8% of the women were persistent shedders, 31% were intermittent shedders, and 45.8% were nonshedders. Sampling three subcompartments increased detection of HIV-1 genital tract viral load compared to sampling a single subcompartment. Overall, genital tract HIV-1 RNA shedding in any subcompartment occurred at about 13% of visits. Shedding in at least one of the three subcompartments occurred at 9% of visits when PVL was undetectable (95% confidence interval 6-14%).
Women with below-detectable PVL may have less risk of HIV sexual transmission on a population level, but may continue to be infectious on an individual level.
Available from: Sarah Fidler
- "HIV viral load is the key determinant of viral transmission, as demonstrated clearly in observational studies of sexual transmission among HIV-discordant couples; in those studies, no transmission was seen when the index case had a plasma viral load below 1,000 copies HIV ribonucleic acid (RNA)/mL [25,26]. By reducing plasma viral load to undetectable levels (<50 copies HIV RNA/mL), it is assumed that ART will also suppress viral burden in the genital tract to levels at which transmission is unlikely to occur [27,28], although genital shedding of HIV can sometimes occur even when plasma viraemia is suppressed . While vertical HIV transmission occurs via a different route, proof of concept is provided by trials of PMTCT, which have demonstrated that HIV transmission from mother to child before, during, or after delivery is largely prevented by ART [10-12]. "
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ABSTRACT: Effective interventions to reduce HIV incidence in sub-Saharan Africa are urgently needed. Mathematical modelling and the HIV Prevention Trials Network (HPTN) 052 trial results suggest that universal HIV testing combined with immediate antiretroviral treatment (ART) should substantially reduce incidence and may eliminate HIV as a public health problem. We describe the rationale and design of a trial to evaluate this hypothesis.
A rigorously-designed trial of universal testing and treatment (UTT) interventions is needed because: i) it is unknown whether these interventions can be delivered to scale with adequate uptake; ii) there are many uncertainties in the models such that the population-level impact of these interventions is unknown; and ii) there are potential adverse effects including sexual risk disinhibition, HIV-related stigma, over-burdening of health systems, poor adherence, toxicity, and drug resistance.In the HPTN 071 (PopART) trial, 21 communities in Zambia and South Africa (total population 1.2 m) will be randomly allocated to three arms. Arm A will receive the full PopART combination HIV prevention package including annual home-based HIV testing, promotion of medical male circumcision for HIV-negative men, and offer of immediate ART for those testing HIV-positive; Arm B will receive the full package except that ART initiation will follow current national guidelines; Arm C will receive standard of care. A Population Cohort of 2,500 adults will be randomly selected in each community and followed for 3 years to measure the primary outcome of HIV incidence. Based on model projections, the trial will be well-powered to detect predicted effects on HIV incidence and secondary outcomes.
Trial results, combined with modelling and cost data, will provide short-term and long-term estimates of cost-effectiveness of UTT interventions. Importantly, the three-arm design will enable assessment of how much could be achieved by optimal delivery of current policies and the costs and benefits of extending this to UTT.Trial registration: ClinicalTrials.gov NCT01900977.
Available from: Thierry Prazuck
- "One important limitation of this study is its cross-sectional nature. The results obtained here do not rule out the possibility that HIV-RNA is occasionally shed in the genital tract of HIV-infected women with undetectable PVL, as reported elsewhere , . It is noteworthy that we found lower rates of viral shedding in CVS than previously reported –, –, , . "
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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.
Available from: Mary Jo Hoyt
- "Although effective ARV therapy decreases virus in genital secretions, discordance between plasma and genital viral loads has been reported. 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 . Additionally, ARV genital tract penetration varies among ARV agents . "
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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.
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