Rachel A Bender Ignacio1, Tara Perti2, Amalia S Magaret3, Sharanya Rajagopal4, Claire E Stevens5, Meei-Li Huang6, Stacy Selke7, Christine Johnston1, Jeanne Marrazzo2, Anna Wald8. 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 oraltenofovir 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.
RCT Entities:
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.
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