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Clinical and virologic response to episodic acyclovir for genital ulcers among HIV-1 seronegative, herpes simplex virus type 2 seropositive African women: a randomized, placebo-controlled trial.

ABSTRACT: In a randomized trial among African women with recurrent genital herpes, episodic acyclovir therapy resulted in modestly greater likelihood of lesion healing (hazard ratio [HR] = 1.48, P = 0.098; mean, 5.1 vs. 6.0 days) and cessation of herpes simplex virus shedding (HR = 1.88, P = 0.008; mean, 3.0 vs. 5.0 days) compared with placebo, similar to results of studies in high-income countries (ClinicalTrials.gov registration NCT00808405).

SUBMITTER: Baeten JM

PROVIDER: S-EPMC3244838 | biostudies-literature | 2012 Jan

REPOSITORIES: biostudies-literature

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Clinical and virologic response to episodic acyclovir for genital ulcers among HIV-1 seronegative, herpes simplex virus type 2 seropositive African women: a randomized, placebo-controlled trial.

Baeten Jared M JM Reid Stewart E SE Delany-Moretlwe Sinead S Hughes James P JP Wang Richard S RS Wilcox Ellen E Limbada Mohammed M Akpomiemie Godspower G Corey Lawrence L Wald Anna A Celum Connie C

Sexually transmitted diseases 20120101 1

In a randomized trial among African women with recurrent genital herpes, episodic acyclovir therapy resulted in modestly greater likelihood of lesion healing (hazard ratio [HR] = 1.48, P = 0.098; mean, 5.1 vs. 6.0 days) and cessation of herpes simplex virus shedding (HR = 1.88, P = 0.008; mean, 3.0 vs. 5.0 days) compared with placebo, similar to results of studies in high-income countries (ClinicalTrials.gov registration NCT00808405). ...[more]

PMID: 22183840

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Project description:Genital herpes simplex virus (HSV) reactivation is thought to be anatomically and temporally localized, coincident with limited ganglionic infection. Short, subclinical shedding episodes are the most common form of HSV-2 reactivation, with host clearance mechanisms leading to rapid containment. The anatomic distribution of shedding episodes has not been characterized. To precisely define patterns of anatomic reactivation, we divided the genital tract into a 22-region grid and obtained daily swabs for 20 days from each region in 28 immunocompetent, HSV-2-seropositive persons. HSV was detected via PCR, and sites of asymptomatic HSV shedding were subjected to a biopsy procedure within 24 h. CD4(+) and CD8(+) T cells were quantified by immunofluorescence, and HSV-specific CD4(+) T cells were identified by intracellular cytokine cytometry. HSV was detected in 868 (7%) of 11,603 genital swabs at a median of 12 sites per person (range, 0 to 22). Bilateral HSV detection occurred on 83 (67%) days with shedding, and the median quantity of virus detected/day was associated with the number of sites positive (P < 0.001). In biopsy specimens of asymptomatic shedding sites, we found increased numbers of CD8(+) T cells compared to control tissue (27 versus 13 cells/mm(2), P = 0.03) and identified HSV-specific CD4(+) T cells. HSV reactivations emanate from widely separated anatomic regions of the genital tract and are associated with a localized cellular infiltrate that was demonstrated to be HSV specific in 3 cases. These data provide evidence that asymptomatic HSV-2 shedding contributes to chronic inflammation throughout the genital tract.This detailed report of the anatomic patterns of genital HSV-2 shedding demonstrates that HSV-2 reactivation can be detected at multiple bilateral sites in the genital tract, suggesting that HSV establishes latency throughout the sacral ganglia. In addition, genital biopsy specimens from sites of asymptomatic HSV shedding have increased numbers of CD8(+) T cells compared to control tissue, and HSV-specific CD4(+) T cells are found at sites of asymptomatic shedding. These findings suggest that widespread asymptomatic genital HSV-2 shedding is associated with a targeted host immune response and contributes to chronic inflammation throughout the genital tract.

Dataset Information

Clinical and virologic response to episodic acyclovir for genital ulcers among HIV-1 seronegative, herpes simplex virus type 2 seropositive African women: a randomized, placebo-controlled trial.

Publications

Clinical and virologic response to episodic acyclovir for genital ulcers among HIV-1 seronegative, herpes simplex virus type 2 seropositive African women: a randomized, placebo-controlled trial.

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