Research at recent conference highlights issues of co-infection

HSV-2 infection is an important dynamic in HIV transmission and progression: according to the Centers for Disease Control and Prevention, genital ulcers from HSV allow easier entry of fluids that carry HIV, and the inflammation caused by outbreaks attracts an abundance of the cells that HIV targets. Also, HIV transmission is more likely to occur from those also infected with HSV-2.

This symbiotic relationship has led to a surfeit of studies on the interaction between HSV-2 and HIV, including the impact treating one virus may have on the other. A wealth of new research was presented at the July 2011 International AIDS Society (IAS) Conference on HIV Pathogenesis, Treatment, and Prevention in Rome, a sampling of which is summarized below. You can search and download abstracts and presentations from the conference online.

• Data from Uganda offer more evidence that HSV-2 daily suppressive therapy with acyclovir also slows HIV disease progression. Researchers from the U.S. and Africa randomized 440 subjects infected with both HSV-2/HIV-1, and not receiving treatment for HIV, to receive either suppressive therapy with acyclovir or placebo. At 24 months of follow-up HIV disease progression among those in the treatment group was reduced by 27%, with the most dramatic effect among participants who entered the study with high HIV viral loads.
• To assess and compare the impact of acyclovir and another HSV antiviral, valacyclovir, medications in reducing plasma levels of HIV, researchers conducting trials in Kenya enrolled 32 HIV-1/HSV-2 infected subjects who were given either the standard suppressive dose of acyclovir (400 mg twice daily) or 1.5 g of valacyclovir twice daily. Valacyclovir is a prodrug that converts to acyclovir after absorption into the system, and the dose recommended in the 2010 STD Treatment Guidelines for suppressive therapy calls for up to 1g daily. Subjects were randomized to receive either regimen for 12 weeks, with two weeks of no treatment followed by 12 weeks of the alternative regimen. HIV plasma levels were assessed weekly using PCR serology. The valacyclovir regimen led to a 76% decrease in mean HIV-1 plasma levels (by 0.62 log10 copies/mL). Also, HIV was undetectable in 13.5 % of weeks during the valacyclovir arm (fewer than 40 copies/mL), compared with only 3.2% with acyclovir. The authors say these results point to the need for more research to examine the potential of high-dose HSV-2 suppressive therapy in slowing HIV disease progression.
• Suppressive therapy with valacyclovir was also effective in reducing breast milk and plasma levels of HIV in postpartum women co-infected with HSV-2/HIV-1. Compared to those in a placebo group, the risk of detecting HIV in breast milk of women who received twice-daily doses of valacyclovir was 30% lower at six weeks after giving birth, and 46% lower at 14 weeks. At six months, plasma levels of HIV were also lower among those in the treatment group. While there was no difference in this study in mother to child transmission rates (the women were all on HIV antiretroviral therapy) the authors say that given HIV levels in plasma and breast milk are ”…important predictors of postnatal mother-to-child HIV-1 transmission…” valacyclovir “…could be a useful adjunct with short-course antiretrovirals in resource-limited settings” a point that hits home given that valacyclovir is relatively inexpensive drug.

References
The Role of STD Detection and Treatment in HIV Prevention – CDC Fact Sheet.  

Mugwanya K, Baet ugo N, Irungu E, Ngure K, Celum C. High-dose valacyclovir suppressive therapy results in greater reduction in plasma HIV-1 levels compared to standard dose acyclovir suppression among HIV-1/HSV-2 co-infected persons: a randomized, open-label, crossover trial. Poster presented at: 6th IAS Conference on HIV Pathogenesis, Treatment, and Prevention; July 17-20, 2011; Rome, Italy. Poster WEPDB0106.

Drake A, Roxby A, Ongecha-Owuor F, Kiarie J, Wald A, John-Stewart G, et al. Valacyclovir suppression reduces breast milk and plasma HIV-1 RNA postpartum: results of a randomized clinical trial. Oral presentation at: 6th IAS Conference on HIV Pathogenesis, Treatment, and Prevention; July 17-20, 2011; Rome, Italy. Abstract MOAC0201.

Reynolds S, Makumbi F, Kiwanuka N, Newell K, Ssebbowa P, Ssempijja V, et al. Impact of HSV-2 suppressive therapy with daily acyclovir on HIV-1 disease progression: a randomized placebo-controlled trial in Rakai, Uganda. Oral presentation at: 6th IAS Conference on HIV Pathogenesis, Treatment, and Prevention; July 17-20, 2011; Rome, Italy. Abstract TUAB0104.