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
Source: PubMed


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.

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    • "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 [29]. 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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    • "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 [7], [9]. It is noteworthy that we found lower rates of viral shedding in CVS than previously reported [6]–[10], [15]–[17], [23], [26]. "
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    • "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 [96]. Additionally, ARV genital tract penetration varies among ARV agents [97]. "
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