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J Infect Dis. 2015 Dec 15;212(12):1949-56. doi: 10.1093/infdis/jiv317. Epub 2015 Jun 4.

Oral and Vaginal Tenofovir for Genital Herpes Simplex Virus Type 2 Shedding in Immunocompetent Women: A Double-Blind, Randomized, Cross-over Trial.

Author information

1
Division of Allergy and Infectious Diseases, Department of Medicine Department of Medicine Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
2
Division of Allergy and Infectious Diseases, Department of Medicine Department of Medicine.
3
Department of Laboratory Medicine Department of Biostatistics Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
4
Department of Epidemiology, University of Washington Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
5
Department of Medicine.
6
Department of Laboratory Medicine Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
7
Department of Laboratory Medicine.
8
Division of Allergy and Infectious Diseases, Department of Medicine Department of Medicine Department of Laboratory Medicine Department of Epidemiology, University of Washington Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.

Abstract

BACKGROUND:

Tenofovir is a potent anti-human immunodeficiency virus (HIV) agent that decreased risk of herpes simplex virus type 2 (HSV-2) acquisition in HIV pre-exposure prophylaxis trials. Whether tenofovir has utility in established HSV-2 disease is unclear.

METHODS:

We randomized immunocompetent women with symptomatic HSV-2 infection to oral tenofovir disoproxil fumarate (TDF)/placebo vaginal gel, oral placebo/tenofovir (TFV) vaginal gel, or double placebo (ratio 2:2:1) in a one-way cross-over trial. Women collected genital swabs twice daily for HSV PCR during 4-week lead-in and 5-week treatment phases. The primary intent-to-treat end point was within-person comparison of genital HSV shedding and lesion rates.

RESULTS:

64 women completed the lead-in phase and were randomized. Neither TDF nor TFV gel decreased overall shedding or lesion rate in the primary analysis; TFV gel decreased quantity of HSV DNA by -0.50 (-0.86-0.13) log10 copies/mL. In the per-protocol analysis, TDF reduced shedding (relative risk [RR] = 0.74, P = .006) and lesion rates (RR = 0.75, P = .032); quantity of virus shed decreased by 0.41 log10 copies/mL.

CONCLUSIONS:

Oral TDF modestly decreased HSV shedding and lesion rate, and quantity of virus shed when used consistently. Vaginal TFV gel decreased quantity of virus shed by 60%. In contrast to effects on HSV-2 acquisition, tenofovir is unlikely to provide clinically meaningful reductions in the frequency of HSV shedding or genital lesions.

CLINICAL TRIALS REGISTRATION:

NCT01448616.

KEYWORDS:

HIV acquisition; HSV-2 transmission; genital herpes; herpes simplex virus-2 (HSV-2); tenofovir; vaginal microbicide

PMID:
26044291
PMCID:
PMC4655855
DOI:
10.1093/infdis/jiv317
[Indexed for MEDLINE]
Free PMC Article

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