HSV-2 suppression reduces HIV and HSV shedding

12 April 2006. Related: Conference reports, HIV prevention and transmission, CROI 13 (Retrovirus) 2006.

Simon Collins, HIV i-Base

In an important proof of concept study, Nicolas Nagot and colleagues from London School of Hygiene and Tropical Medicine, investigated whether HSV suppressive treatment could impact on HIV transmission.

The study randmised 140 women who were coinfected with HIV and HSV and not eligible for ARV treatment, in a 1:1 ratio, to either 1g valacyclovir (VACV) daily for 3 months or placebo. Patients were followed for 3 months prior to randomisation and for the 3 month study duration, with HSV DNA and HIV RNA shedding measured by PCR from cervical swabbing every two weeks.

Mean CD4 count at baseline was 519 and 482 cells/mm³ in the VACV and placebo groups respectively, Overall visit attendance was reported as 93% and treatment adherence as 97%.

The reduction in HIV-1 RNA genital shedding was significantly greater in the VACV group than in the placebo group (–0.26 vs +0.09 log copies/mL, p = 0.003). HIV-1 shedding was significantly less persistent in the VACV group (14.3% vs 27.1% shed at each visit; 27.1% vs 44.3% shed at =50% of visits; 32.9% vs 14.3% shed at <50% of visits; and 25.7% vs 14.3% never shed, p = 0.007). HIV-1 plasma viral load was also reduced in the VACV group ( – 0.39 vs +0.12 log copies/mL, p <0.001), as was HSV-2 DNA shedding (–0.22 vs +0.18 log copies/mL, p <0.001). The proportion of women shedding HSV-2 at least once was 18.6% in the VACV arm and 54.3% in the placebo arm (p <0.001).

Comment

A meta analysis by Freeman et al of studies in this area concluded that a person with genital herpes is at an approximately 3-fold greater risk of aquiring HIV infection after sexual exposure. [2]

Genital ulcers provide an reduced physical barrier and a higher activation of local CD4 and dendritic cells. If the source partner is coinfected with HIV and HSV they may have higher HIV viraemia in genital fluids and therefore be more infectious.

Previous studies have highlighted the protective effect of VACV treatment on the transmission of HSV to non-nonfected partners [3], and data in this study supporting reduced risk of HIV transmission is clearly important. A similar benefit is likely using the less expensive off-patent acyclovir.

Link:
An interesting article on HSV trials to reduce HIV transmission was published in the November 2005 issue of IAVI Vax Bulletin.
http://www.iavireport.org/vax/VAXNovember2005.asp#1

References:

1. Nagot N, Ouedraogo A, Mayaud P et al. Effect of HSV-2 suppressive therapy on HIV-1 genital shedding and plasma viral load: a proof of concept randomised double-blind placebo controlled trial (ANRS 1285 Trial). 13th CROI, Denver 2006. Abstract 33LB.
2. Freeman EE, Weiss HA, Glynn JR et al. Herpes simplex virus 2 infection increases HIV acquisition in men and women: systematic review and meta-analysis of longitudinal studies. AIDS 2006;20:73-83.
3. Corey L, Wald A, Patel R et al. Once-Daily Valacyclovir to Reduce the Risk of Transmission of Genital Herpes. NEJM Volume 350:11-20 January 1, 2004.