School of Public Health

Rachel A. Bender Ignacio

Effect of oral and gel tenofovir on genital HSV-2 shedding in immunocompetent women

Background

Tenofovir is a potent anti-HIV agent with efficacy in studies of pre-exposure prophylaxis when taken orally or used as an intravaginal gel. Recent studies suggest that tenofovir also reduces the risk of HSV-2 acquisition. Whether oral or gel tenofovir may be useful in HSV disease management, or prevention of HSV-2 transmission, is unclear.

Methods

We randomized immunocompetent women with symptomatic HSV-2 infection 2:2:1 to oral tenofovir/placebo vaginal gel, oral placebo/tenofovir vaginal gel, or double placebo in a one-way cross-over clinical trial. Women collected twice daily genital swabs for HSV PCR and completed symptom diaries during a 4-week lead-in and 5 weeks of treatment. We compared of shedding rates and genital lesions with Poisson mixed models and shedding quantity with linear mixed models.

Results

73 women were enrolled and 64 completed the lead-in observation phase and were randomized: 24 women to oral tenofovir, 27 to tenofovir vaginal gel, and 13 to placebo. Relative to baseline, genital HSV shedding showed a trend toward a small decrease from 22.9% to 19.5%, (RR=0.86 p=0.09), in the oral tenofovir arm, but did not differ in the tenofovir vaginal gel arm (13.8% versus 12.0%; RR=0.94, p=0.54) or in the placebo arm (21.3% versus 20.4%; RR=0.90, p=0.45; Table 1). Asymptomatic shedding decreased in the oral tenofovir arm only (RR=0.74, p=0.01). There was no change in days with HSV lesions or number of shedding episodes. Shedding quantity decreased by 0.50 log10 copies in the vaginal gel arm (p=0.008), but remained consistent in the oral tenofovir (p=0.18) and placebo arms (p=0.45). The per-protocol analysis included 20 women in the oral tenofovir arm, 20 in the vaginal gel arm, and 9 in the placebo arm who completed ≥33 days of study product with ≥90% adherence. Relative to baseline, the shedding frequency was reduced in the oral tenofovir arm (RR=0.74, p=0.006), and shedding quantity was reduced in the oral (0.41 log) and gel tenofovir arms (0.6 log); otherwise the results were similar to that of the full cohort. The gel and oral tenofovir were both well tolerated, and overall adherence was high (97%) and equivalent in all arms.

Discussion

When used as directed, oral tenofovir causes small decreases in shedding and lesion rate, and quantity of virus shed. Vaginal tenofovir decreases shedding quantity minimally. In contrast to evidence that tenofovir reduces HSV acquisition by half, similar benefits in treatment of established HSV-2 infection were not seen.

URI: http://hdl.handle.net/1773/27469