Valacyclovir Plus Zidovudine May Block Vertical Transmission of HSV-2

Brian Hoyle

March 03, 2011

March 3, 2011 (Boston, Massachusetts) — A new study has demonstrated the suppressive effects of valacyclovir on plasma HIV-1 RNA levels and the genital shedding of herpes simplex virus (HSV)-2 during pregnancy in women coinfected with HIV-1 and HSV-2 who received zidovudine prophylaxis for the prevention of mother-to-child transmission (MTCT) of HIV.

Results of the randomized double-blind placebo-controlled trial were presented here at the 18th Conference on Retroviruses and Opportunistic Infections.

"Since serum levels are a big indicator of the risk for transmitting HIV from mother to fetus during pregnancy, our results of a 38% reduction in plasma HIV-1 RNA levels following the introduction of valacyclovir therapy in women receiving zidovudine is really promising," principal investigator Alison Drake, PhD, from the University of Washington in Seattle, told Medscape Medical News.

The study was grounded in the knowledge that HSV-2 is a risk factor for MTCT of HIV-1, and that the suppression of HSV-2 decreases HIV-1 levels. However, in the context of the prevention of MTCT, these observations have never been explored clinically, said Dr. Drake.

"It's good to see that this trial was conducted and that the results are promising," Liesbeth Bollen, MD, from Family Health International, Country Office, in Jakarta, Indonesia, told Medscape Medical News.

The study enrolled pregnant women (at 32 weeks of gestation or earlier) who sought antenatal care at the Mathare North City Council Clinic or who were referred from neighboring clinics in Nairobi, Kenya, between April 2008 and June 2009.

The researchers enrolled 148 women coinfected with HIV-1 and HSV-2 who did not meet the criteria for antiretroviral therapy (WHO stage 1 or 2 HIV infection and a CD4 count above 250 cells/mm3) and who were receiving antenatal MTCT prophylaxis, consisting of oral zidovudine 300 mg every 3 h, starting at 28 weeks of gestation or later, and a single dose of nevirapine during labor (median gestational age at initiation, 29 weeks).

Subjects were randomized at 34 weeks of gestation to valacyclovir 500 mg twice a day or placebo to determine the effect of the drug on plasma HIV-1 RNA and genital HSV DNA shedding.

Blood and genital swabs were collected at 34 and 38 weeks of gestation for quantitative assays of HIV-1 RNA and HSV-2 DNA, respectively. The primary analysis was a modified intention-to-treat analysis of the change in plasma HIV-1 RNA levels. Women with no blood collection at 38 weeks or who delivered early were excluded.

The demographic and clinical characteristics of women in the 2 groups were comparable.

Blood was collected at 38 weeks of gestation from 100 of the 148 subjects. The mean plasma HIV-1 RNA viral load was 3.94 log10 copies/mL, and median CD4 count was 475 cells/mm3 at 34 weeks. Four weeks later, women in the valacyclovir group had a mean plasma HIV-1 RNA level 0.54 log10 copies/mL lower than women in the placebo group (95% confidence interval, –0.33 to –0.76; < .001).

Valacyclovir therapy was also associated with reduced genital shedding of HSV-2 (26% vs 12%) and a reduced tendency to begin to shed HSV-2 (2% vs 24%; = .002), compared with placebo.

The researchers conclude that valacyclovir suppressive therapy decreases plasma HIV-1 RNA levels and HSV-2 shedding from genital tissue in pregnant women receiving zidovudine prophylaxis for MTCT.

"These findings are significant because they show another possible way to lower plasma and genital HIV viral load, apart from HIV antiretrovirals. Although heterosexual transmission studies have not shown a reduction in transmission with valacyclovir, this might be the case for MTCT," Dr. Bollen told Medscape Medical News.

"This was a small pilot study, so more still needs to be done. But the results are pointing the way," Dr. Drake noted.

"The current study warrants future research into the prevention of MTCT. The current small cohort might shed light on this too. If, indeed, valacyclovir reduces the risk of MTCT, then it would have a public health impact on the high HSV-2 seroprevalence in Africa, with cheap generic drugs and few side effects," Dr. Bollen added.

Dr. Drake and Dr. Bollen have disclosed no relevant financial relationships.

18th Conference on Retroviruses and Opportunistic Infections (CROI): Abstract 769. Presented March 1, 2011.

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