A recent meta-analysis of 19 longitudinal studies suggests that HSV-2 increases HIV acquisition in men and women.1 Two abstracts at the 17th International AIDS Conference in Mexico City evaluated the role of HSV suppression on incidence of HIV-1.
Jorge Sanchez of Peru presented data from an investigation of HSV-1 sero-positive HIV-negative women and men who have sex with men in the United States, Peru and Africa.2
Participants were randomized to either acyclovir 400mg bid or placebo. Researchers measured adherence to acyclovir by monthly pill count and self-report. Both arms of the study received risk reduction counseling and treatment with episodic acyclovir for genital ulcer disease (GUD).
The endpoint was incident HIV disease. The study included 3172 participants. Researchers estimated 94% compliance with acyclovir by pill counts. Despite a 37% reduction in GUD in the acyclovir group, no difference was seen in the incidence of HIV (HR 1.16 (95% CI 0.83 - 1.62); P=0.39).
Watson-Jones et al of London presented data from a randomized double-blind placebo-controlled trial in Tanzania, which explored whether HSV-2 suppressive therapy with acyclovir 400mg bid reduced HIV incidence in HIV-negative and HSV-2-positive high risk women.3 The study included 821 women who were randomized to acyclovir or placebo. Women were censored at HIV sero-conversion, last date seen, or end of trial. HIV incidence rates per 100 person years were similar for the acyclovir and placebo arms (4.29 (3.00-6.13) and 4.24 (3.01-5.97)).
Both investigators cited reasons for the possible lack of efficacy of acyclovir in reducing HIV sero-conversion, including suboptimal adherence to treatment, lack of potency of acyclovir to fully suppress HSV-2 at the cellular level, or that GUD may have had other (non-HSV) etiologies. It is also possible that although acyclovir decreases shedding of HSV-2, residual inflammation, and HIV target cells may persist in the genital tract.
Watson-Jones et al tested for the presence of acyclovir in urine samples in a subset of participants and revealed that a significant proportion in the acyclovir group did not have acyclovir detectable, implying a level of non-adherence. Both investigators stated that use of once daily valacyclovir instead of acyclovir may have improved adherence to the HSV suppressive regimen.
References:
1. Freeman E, Weiss H, Glynn J et al. Herpes simplex virus 2 infection increases HIV acquisition in men and women: systematic review and meta-analysis of longitudinal studies. AIDS. 2006;20(1):73-83.
2. Celum C et al. Incidence of genital ulcers and HSV+ genital ulcers in trial of HSV-2 suppression to prevent. Presented at: 17th International AIDS Conference; August 3-8, 2008; Mexico City, Mexico. Abstract: THAC0302.
3. Watson-Jones, D et al. Risk factors associated with HIV incidence in HSV-2 seropositive Tanzanian women in a RCT of HSV-2 suppressive therapy. Presented at: 17th International AIDS Conference; August 3-8, 2008; Mexico City, Mexico. Abstract: THAC0304.
08/07/08
Suppressive Therapy of HSV-2 Fails to Reduce Incidence of HIV Infection
Source: Reporting from Mexico City for PRN News: Anita Radix MD, MPH and Rona Vail MD