Initiation of antiretroviral therapy leads to a rapid decline in cervical and vaginal HIV-1 shedding

Department of Medicine, University of Washington, Seattle, Washington, USA.
AIDS (Impact Factor: 5.55). 03/2007; 21(4):501-7. DOI: 10.1097/QAD.0b013e32801424bd
Source: PubMed


Antiretroviral therapy (ART) may decrease HIV-1 infectivity in women by reducing genital HIV-1 shedding.
To evaluate the time course and magnitude of decay in cervical and vaginal HIV-1 shedding as women initiate ART.
This prospective, observational study of 20 antiretroviral-naive women initiating ART with stavudine, lamivudine, and nevirapine measured HIV-1 RNA in plasma, cervical secretions, and vaginal secretions. Qualitative polymerase chain reaction estimated HIV-1 DNA in cervical and vaginal samples. Perelson's two-phase viral decay model and non-linear random effects were used to compare RNA decay rates. Decreases in proviral DNA were evaluated using logistic regression and generalized estimating equations.
Significant decreases in the quantity of HIV-1 RNA were observed by day 2 in plasma (P < 0.001), day 2 in cervical secretions (P = 0.001), and day 4 in vaginal secretions (P < 0.001). Modeled initial and subsequent RNA decay rates in plasma, cervical secretions, and vaginal secretions were 0.6, 0.8, and 1.2 log10 virions/day, and 0.04, 0.05, and 0.06 log10 virions/day, respectively. The initial decay rate for vaginal HIV-1 RNA was more rapid than for plasma RNA (P = 0.02). Detection of HIV-1 DNA decreased significantly in vaginal secretions during the first week (P < 0.001). At day 28, 10 women had detectable HIV-1 RNA or proviral DNA in genital secretions.
Genital HIV-1 shedding decreased rapidly after ART initiation, consistent with a rapid decrease in infectivity. However, incomplete viral suppression in half of these women may indicate an ongoing risk of transmission.

2 Reads
  • Source
    • "PrEP. WHO guidelines also define the clinical contraindications of PrEP with caution (Graham et al. 2007). Another major side-effect was hepatic flare (Lim et al. 2006, van Bommel et al. 2004). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Antiretroviral drugs are being tried as candidates for the pre-exposure prophylaxis (PrEP) against HIV for a considerable period, due to their potential for immediate inhibition of viral replication. Discrepancies in the findings called for a critical review of the relevant efforts and their outcomes. A systematic literature search identified 143 eligible articles of which only 5 reported complete findings while another 11 were still on-going. Observed moderate efficacy and good safety profile seemed to identify PrEP as a promising step for minimizing the spread of HIV to relatively unaffected population and controlling the epidemic among high risk population groups. But the duration of this efficacy was found to depend heavily on the availability, adherence and other related issues like cost, political commitment, ethical consideration etc. To prevent potential cultural and behavioral modifications, proper pre-administration counseling also seemed critical for the success of PrEP as a cost-effective intervention with adequate coverage.
    Artificial Cells 07/2014; DOI:10.3109/21691401.2014.934458 · 1.02 Impact Factor
  • Source
    • "All the patients studied here were taking one of the optimized cART regimens currently used in Europe, based on systematic genotyping; in addition, self-reported adherence was excellent (data not shown) and follow-up took place in optimal conditions, contrary to previous studies in resource-poor settings [21]. Likewise, few protease inhibitor (PI)-based regimens are used in most sub-Saharan countries, while PI appear to be more effective than NNRTI in suppressing genital HIV-RNA shedding [6], [17], [22]–[24]. Finally, pretreatment HIV genotyping is not routinely used in poor countries. "
    [Show abstract] [Hide abstract]
    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
  • Source
    • "Clinical studies provide strong evidence that antiretroviral therapy (ART) leads to rapid and sustained suppression of genital HIV-1 shedding [3,4]. However, this suppression is incomplete [4,5], and persistent genital HIV-1 replication may reflect ongoing risk of transmitting the virus even in individuals on treatment [3]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Trichomonas vaginalis has been associated with increased vaginal HIV-1 RNA shedding in antiretroviral therapy (ART)-naïve women. The effect of trichomoniasis on vaginal HIV-1 shedding in ART-treated women has not been characterized. We tested the hypothesis that T. vaginalis infection would increase vaginal HIV-1 RNA shedding in women on ART, and that successful treatment would reduce vaginal HIV-1 RNA levels. We conducted a prospective cohort study including monthly follow-up of 147 women receiving ART in Mombasa, Kenya. Those with T. vaginalis infection, defined by the presence of motile trichomonads on vaginal saline wet mount, received treatment with single dose metronidazole (2 g). Test of cure was performed at the next monthly visit. Using the pre-infection visit as the reference category, we compared detection of vaginal HIV-1 RNA before versus during and after infection using generalized estimating equations. A cut-off of 100 HIV-1 RNA copies/swab was used as the lower limit for linear quantitation. Among 31 women treated for trichomoniasis, the concentration of vaginal HIV-1 RNA was above the limit for quantitation before, during, and after T. vaginalis infection in 4 (13% [95% CI 4% - 30%]), 4 (13% [95% CI 4% - 30%]), and 5 (16% [95% confidence interval {CI} 5% - 34%]) women respectively. After adjusting for potential confounding factors, we could detect no difference in the likelihood of detecting vaginal HIV-1 RNA before versus during infection (odds ratio [OR] 1.41, 95% CI 0.23 - 8.79, p = 0.7). In addition, detection of HIV-1 RNA was similar before infection versus after successful treatment (OR 0.68, 95% CI (0.13 - 3.45), p = 0.6). Detection of vaginal HIV-1 RNA during ART was uncommon at visits before, during and after T. vaginalis infection.
    BMC Infectious Diseases 11/2011; 11(1):307. DOI:10.1186/1471-2334-11-307 · 2.61 Impact Factor
Show more