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Valacyclovir Has No Impact on CD4s or HIV Load in Placebo Trial of HSV-2+
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53rd ICAAC, September 10-13, 2013, Denver
Mark Mascolini
Valacyclovir for 24 weeks did not affect HIV load or CD4 count when compared with placebo in antiretroviral-treated people coinfected with previously unrecognized herpes simplex virus type 2 (HSV-2) [1]. This trial at a US university medical center excluded people with a CD4 count below 250.
Although often undiagnosed, HSV-2 affects a high proportion of people with HIV. At the University of Alabama (UAB) clinic, 10% of HIV-positive people know they have HSV-2 infection; testing those who don't know yields a prevalence of 64%.The impacts of HIV on HSV-2 and vice versa are complex. UAB investigators who conducted this study noted that HSV-2 and HIV enhance transmission of each other and boost the risk of HIV or HSV-2 acquisition. HIV infection contributes to HSV-2 frequency and severity, while HSV-2 promotes HIV progression.
Randomized trials in Africa found that high-dose valacyclovir lowers HIV load in people not taking antiretroviral therapy [2,3] and that standard-dose valacyclovir tapers maternal and breast milk load in HIV-positive women receiving prophylaxis to prevent mother-to-child transmission [4]. Viral load drops in these trials were modest but statistically significant.
To determine whether standard-dose valacyclovir (1000 mg daily) affects HIV progression in people taking antiretroviral therapy, the investigators conducted this double-blind placebo-controlled trial. Study participants were attending the UAB HIV clinic and had no history of genital herpes. Everyone had a CD4 count at or above 250 and had taken antiretroviral therapy for at least 3 months.
From July 2009 through May 2011, the investigators invited 310 people to be screened for HSV-2, and 188 (61%) tested positive by HSV-2 ELISA IgG. Among 101 HSV-2-positive people who agreed to participate in the valacyclovir trial, 66 were randomized to valacyclovir and 35 to placebo. At each visit health workers delivered study medication, calculated adherence by pill count, provided genital herpes education, reviewed genital herpes outbreak history, conducted a genital exam, and collected samples for lab evaluation. Forty-five people in the valacyclovir group (68%) and 22 in the placebo group (63%) completed 24 weeks of follow-up. Adherence measured by pill count exceeded 95% in both study arms.
Among people in the valacyclovir and placebo arms who completed the trial, 44% and 59% were Caucasian and 56% and 41% were African American. About 90% of study completers were men, and age averaged 45 and 43 in the in the valacyclovir and placebo arms. Median baseline CD4 counts were 528 among valacyclovir completers and 693 among placebo completers (P = 0.098). Between 85% and 90% in each study arm had an HIV load below 500 copies.
Compared with placebo, valacyclovir did not significantly change absolute CD4 count or CD4 percent through 24 weeks. Median CD4 count rose minimally, from 528 to 536, in the valacyclovir group (P = 0.91). Nor did CD4 counts at week 8 or week 16 improve significantly from the baseline value. The proportion of people with virologic suppression remained largely unchanged through 24 weeks.
HSV-2 recurrence and asymptomatic shedding rate were low in this population. Among 1850 samples collected, HSV-2 DNA could be detected in 9 samples (0.05%) from 2 people. Neutropenia was not observed in this 24-week study, and valacyclovir had no measurable impact on liver or kidney function. Three people reported headaches.
The researchers believe their findings "do not support the use of valacyclovir in HIV-infected and HSV-2-infected people with previously unknown genital herpes for improvement in CD4 T-lymphocyte count." Session attendee Joseph Eron (University of North Carolina Chapel Hill) noted that the study excluded people with a CD4 count under 250 and suggested people with low CD4s may be a more relevant study population.
References
1. Van Wagoner N, Bachmann LH, Hook EW III. A randomized controlled trial of the effect of valacyclovir on HIV and HSV-2 outcomes in HIV-infected persons on antiretroviral therapy with previously unrecognized HSV-2. 53rd ICAAC. September 10-13, 2013. Denver. Abstract H-1531.
2. Perti T, Saracino M, Baeten JM, et al. High-dose valacyclovir decreases plasma HIV-1 RNA more than standard-dose acyclovir in persons coinfected with HIV-1 and HSV-2: a randomized crossover trial. J Acquir Immune Defic Syndr. 2013;63:201-208.
3. Mugwanya K, Baeten JM, Mugo NR, Irungu E, Ngure K, Celum C. High-dose valacyclovir HSV-2 suppression results in greater reduction in plasma HIV-1 levels compared with standard dose acyclovir among HIV-1/HSV-2 coinfected persons: a randomized, crossover trial. J Infect Dis. 2011;204:1912-1917.
4. Drake AL, Roxby AC, Ongecha-Owuor F, et al. Valacyclovir suppressive therapy reduces plasma and breast milk HIV-1 RNA levels during pregnancy and postpartum: a randomized trial. J Infect Dis. 2012;205:366-375.
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