Initiation of antiretroviral therapy leads to a rapid decline in cervical and vaginal HIV-1 shedding.
ABSTRACT 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.
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ABSTRACT: Consistent and correct condom use and suppressive antiretroviral therapy for the infected partner are two of the primary strategies recommended for prevention of heterosexual HIV transmission in serodiscordant couples today. The applied effectiveness of treatment as a prevention strategy in China is still under investigation, and much less is known about its effects in the presence of other prevention strategies such as consistent condom use.PLoS ONE 11/2014; 9(11):e111175. · 3.53 Impact Factor
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ABSTRACT: Detectable HIV-1 in body compartments can lead to transmission and antiretroviral resistance. Although sex differences in viral shedding have been demonstrated, mechanisms and magnitude are unclear. We compared RNA levels in blood, genital-secretions and saliva; and drug resistance in plasma and genital-secretions of men and women starting/changing antiretroviral therapy (ART) in the AIDS Clinical Trials Group (ACTG) 5077 study. Blood, saliva and genital-secretions (compartment fluids) were collected from HIV-infected adults (≥13 years) at 14 United-States sites, who were initiating or changing ART with plasma viral load (VL) ≥2,000 copies/mL. VL testing was performed on all compartment fluids and HIV resistance genotyping on plasma and genital-secretions. Spearman rank correlations were used to evaluate concordance and Fisher's and McNemar's exact tests to compare VL between sexes and among compartments. Samples were available for 143 subjects; 36% treated (23 men, 29 women) and 64% 'untreated' (40 men, 51 women). RNA detection was significantly more frequent in plasma (100%) than genital-secretions (57%) and saliva (64%) (P<0.001). A higher proportion of men had genital shedding versus women (78% versus 41%), and RNA detection was more frequent in saliva versus genital-secretions in women when adjusted for censoring at the limit of assay detection. Inter-compartment fluid VL concordance was low in both sexes. In 22 (13 men, 9 women) paired plasma-genital-secretion genotypes from treated subjects, most had detectable resistance in both plasma (77%) and genital-secretions (68%). Resistance discordance was observed between compartments in 14% of subjects. HIV shedding and drug resistance detection prior to initiation/change of ART in ACTG 5077 subjects differed among tissues and between sexes, making the gold standard blood-plasma compartment assessment not fully representative of HIV at other tissue sites. Mechanisms of potential sex-dependent tissue compartmentalization should be further characterized to aid in optimizing treatment and prevention of HIV transmission. ClinicalTrials.gov NCT00007488.PLoS ONE 04/2014; 9(4):e93537. · 3.53 Impact Factor
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ABSTRACT: Although stigmatization has long been recognized as a major obstacle to HIV prevention. The lack of a valid and reliable measurement tool for stigmatization is a major gap in the research. This study aimed to: 1) develop a scale of stigmatizing attitudes towards people living with HIV (SAT-PLWHA-S) and 2) demonstrate its reliability and validity. French and English-speaking experts (n = 21) from different professional communities (academics, practitioners) assessed the clarity and relevance of the proposed items. The psychometric properties of the SAT-PLWHA-S were assessed with a random digit dial population based telephone survey (n = 1,500) of respondents in Quebec, Canada. Analyses included exploratory and confirmatory factor analyses, correlations, multiple linear regressions, t-tests, hypothesis testing of factorial structure invariance, and Cronbach's alpha. Confirmatory factor analysis (CFA) supported a 27-item structure with seven factors: 1) concerns about occasional encounters; 2) avoidance of personal contact; 3) responsibility and blame, 4) liberalism, 5) non-discrimination, 6) confidentiality of seropositive status, and 7) criminalization of HIV transmission. Cronbach's alphas indicate satisfactory internal consistency. An assessment of concurrent validity using Pearson's correlation and multiple linear regression shows that homophobia and HIV transmission knowledge are significant determinants of stigmatizing attitudes toward PLHIV. Discriminant validity (t-test) results suggest that the SAT-PLWHA-S can differentiate attitudes between different groups and indicates invariant factor structure across language. The results of this study suggest that the SAT-PLWHA-S is a reliable and valid tool for measuring stigmatizing attitudes toward PLHIV and that it can contribute to a deeper understanding of HIV stigma.BMC Public Health 12/2014; 14(1):1246. · 2.32 Impact Factor