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High-dose valacyclovir HSV-2 suppression results in greater reduction in plasma HIV-1 levels compared with standard dose acyclovir among HIV-1/HSV-2 coinfected persons: a randomized, crossover trial.

ABSTRACT: Standard-dose HSV-2 suppressive therapy (acyclovir 400 mg twice daily) reduces plasma HIV-1 levels by 0.25-0.50 log(10) copies/mL. It is not known if higher doses might further suppress HIV-1 levels.We enrolled 32 HIV-1/HSV-2 dually infected Kenyan individuals who were not on antiretroviral therapy (ART) into a randomized, crossover trial of 2 dosing regimens of HSV-2 suppression: valacyclovir 1.5 g vs acyclovir 400 mg, both twice daily for 12 weeks, then a 2-week washout, and then the alternative for 12 weeks. Weekly plasma HIV-1 RNA quantity was measured (ClinicalTrials.gov number NCT01026454).Mean plasma HIV-1 levels were significantly lower on valacyclovir compared with acyclovir: 2.94 vs 3.56 log(10) copies/mL, an average difference of 0.62 log(10) copies/mL (95% confidence interval [CI]: -0.68, -0.55; P < .001), a 76% decrease. Valacyclovir resulted in a 1.23 log(10) copies/mL decrease compared with baseline HIV-1 levels without HSV-2 suppression. Adherence was similar (99.4% of dispensed study tablets taken), and high-dose valacyclovir was well tolerated.High-dose valacyclovir reduced plasma HIV-1 viral levels by 0.62 log(10) copies/mL compared with standard-dose acyclovir. The potential for higher-dose HSV-2 suppressive therapy to slow HIV-1 disease progression and reduce HIV-1 infectiousness among HIV-1/HSV-2 coinfected persons not yet eligible for ART warrants further evaluation.

SUBMITTER: Mugwanya K

PROVIDER: S-EPMC3247811 | biostudies-literature | 2011 Dec

REPOSITORIES: biostudies-literature

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High-dose valacyclovir HSV-2 suppression results in greater reduction in plasma HIV-1 levels compared with standard dose acyclovir among HIV-1/HSV-2 coinfected persons: a randomized, crossover trial.

Mugwanya Kenneth K Baeten Jared M JM Mugo Nelly R NR Irungu Elizabeth E Ngure Kenneth K Celum Connie C

The Journal of infectious diseases 20111012 12

<h4>Background</h4>Standard-dose HSV-2 suppressive therapy (acyclovir 400 mg twice daily) reduces plasma HIV-1 levels by 0.25-0.50 log(10) copies/mL. It is not known if higher doses might further suppress HIV-1 levels.<h4>Methods</h4>We enrolled 32 HIV-1/HSV-2 dually infected Kenyan individuals who were not on antiretroviral therapy (ART) into a randomized, crossover trial of 2 dosing regimens of HSV-2 suppression: valacyclovir 1.5 g vs acyclovir 400 mg, both twice daily for 12 weeks, then a 2-w ...[more]

PMID: 21998479

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Project description:BackgroundMost persons who are infected with human immunodeficiency virus type 1 (HIV-1) are also infected with herpes simplex virus type 2 (HSV-2), which is frequently reactivated and is associated with increased plasma and genital levels of HIV-1. Therapy to suppress HSV-2 reduces the frequency of reactivation of HSV-2 as well as HIV-1 levels, suggesting that suppression of HSV-2 may reduce the risk of transmission of HIV-1.MethodsWe conducted a randomized, placebo-controlled trial of suppressive therapy for HSV-2 (acyclovir at a dose of 400 mg orally twice daily) in couples in which only one of the partners was seropositive for HIV-1 (CD4 count, > or = 250 cells per cubic millimeter) and that partner was also infected with HSV-2 and was not taking antiretroviral therapy at the time of enrollment. The primary end point was transmission of HIV-1 to the partner who was not initially infected with HIV-1; linkage of transmissions was assessed by means of genetic sequencing of viruses.ResultsA total of 3408 couples were enrolled at 14 sites in Africa. Of the partners who were infected with HIV-1, 68% were women, and the baseline median CD4 count was 462 cells per cubic millimeter. Of 132 HIV-1 seroconversions that occurred after randomization (an incidence of 2.7 per 100 person-years), 84 were linked within couples by viral sequencing: 41 in the acyclovir group and 43 in the placebo group (hazard ratio with acyclovir, 0.92, 95% confidence interval [CI], 0.60 to 1.41; P=0.69). Suppression with acyclovir reduced the mean plasma concentration of HIV-1 by 0.25 log(10) copies per milliliter (95% CI, 0.22 to 0.29; P<0.001) and the occurrence of HSV-2-positive genital ulcers by 73% (risk ratio, 0.27; 95% CI, 0.20 to 0.36; P<0.001). A total of 92% of the partners infected with HIV-1 and 84% of the partners not infected with HIV-1 remained in the study for 24 months. The level of adherence to the dispensed study drug was 96%. No serious adverse events related to acyclovir were observed.ConclusionsDaily acyclovir therapy did not reduce the risk of transmission of HIV-1, despite a reduction in plasma HIV-1 RNA of 0.25 log(10) copies per milliliter and a 73% reduction in the occurrence of genital ulcers due to HSV-2. (ClinicalTrials.gov number, NCT00194519.)

Project description:BackgroundHIV-HCV coinfected individuals are often more deprived than the general population. However, deprivation is difficult to measure, often relying on aggregate data which does not capture individual heterogeneity. We developed an individual-level deprivation index for HIV-HCV co-infected persons that encapsulated social, material, and lifestyle factors.MethodsWe estimated an individual-level deprivation index with data from the Canadian Coinfection Cohort, a national prospective cohort study. We used a predetermined process to select 9 out of 19 dichotomous variables at baseline visit to include in the deprivation model: income >$1500/month; education >high school; employment; identifying as gay or bisexual; Indigenous status; injection drug use in last 6 months; injection drug use ever; past incarceration, and past psychiatric hospitalization. We fitted an item response theory model with: severity parameters (how likely an item was reported), discriminatory parameters, (how well a variable distinguished index levels), and an individual parameter (the index). We considered two models: a simple one with no provincial variation and a hierarchical model by province. The Widely Applicable Information Criterion (WAIC) was used to compare the fitted models. To showcase a potential utility of the proposed index, we evaluated with logistic regression the association of the index with non-attendance to a second clinic visit (as a proxy for disengagement) and using WAIC compared it to a model containing all the individual parameters that compose the index as covariates.ResultsWe analyzed 1547 complete cases of 1842 enrolled participants. According to the WAIC the hierarchical model provided a better fit when compared to the model that does not consider the individual's province. Values of the index were similarly distributed across the provinces. Overall, past incarceration, education, and unemployment had the highest discriminatory parameters. However, in each province different components of the index were associated with being deprived reflecting local epidemiology. For example, Saskatchewan had the highest severity parameter for Indigenous status while Quebec the lowest. For the secondary analysis, 457 (30%) failed to attend a second visit. A one-unit increase in the index was associated with 17% increased odds (95% credible interval, 2% to 34%) of not attending a second visit. The model with just the index performed better than the model with all the components as covariates in terms of WAIC.ConclusionWe estimated an individual-level deprivation index in the Canadian Coinfection cohort. The index identified deprivation profiles across different provinces. This index and the methodology used may be useful in studying health and treatment outcomes that are influenced by social disparities in co-infected Canadians. The methodological approach described can be used in other studies with similar characteristics.

Dataset Information

High-dose valacyclovir HSV-2 suppression results in greater reduction in plasma HIV-1 levels compared with standard dose acyclovir among HIV-1/HSV-2 coinfected persons: a randomized, crossover trial.

Publications

High-dose valacyclovir HSV-2 suppression results in greater reduction in plasma HIV-1 levels compared with standard dose acyclovir among HIV-1/HSV-2 coinfected persons: a randomized, crossover trial.

Similar Datasets

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