Herpes drugs and viral load: valaciclovir works better than aciclovir

The anti-herpes drug valaciclovir (Valtrex, valacyclovir in the US) produced a 17-fold (1.23 log) reduction in HIV viral load in Kenyan patients not taking treatment, the sixth International AIDS Society conference (IAS 2011) in Rome heard last Wednesday.

Last Monday, the IAS conference in Rome heard that treating HIV patients in Uganda with the herpes drug aciclovir (acyclovir in the US) suppressed HIV viral load by about 0.5 log (a threefold drop) and made them 27% less likely to experience a fall in the CD4 cells to below 200 cells/mm³ (see Daily aciclovir slows HIV disease progression and reduces viral load). It also meant people with baseline viral loads over 50,000 copies/ml were 38% less likely to start treatment during the two years of the study, and people with lower viral loads 10% less likely.

Two trials in neighbouring Kenya has found that valaciclovir produced considerably greater falls in viral load than aciclovir. One found that valaciclovir slowed HIV disease progression in pregnant and breastfeeding women.

“Given the constraints on ART programmes, the potential for high dose HSV-2 suppression to delay ART initiation warrants further evaluation.” Kenneth Mugwanya

In the other study, 32 patients dually infected with HIV and the genital herpes virus HSV-2, and not on treatment for either, were randomised to receive either valaciclovir 1.5g or aciclovir 400 mg, both twice daily, for twelve weeks. After a two-week ‘washout’ period where they took no drug, they then took whichever of the two drugs they had not previously taken for another twelve weeks. This ‘crossover’ trial design is one way to minimise population effects that may bias results, though the study was open-label (patients knew which drug they were taking).

Seventeen (53%) of the patients were women, their median age was 37, their median CD4 count at baseline (before the start of the study) was 441 cells/mm³ and their mean blood viral load for HIV at baseline was 12,500 copies/ml (4.1 log).

At follow-up (three weeks after the last drug dose was given) the average viral load in patients who had been taking valaciclovir was 871 copies/ml (2.94 log) and in patients who had taken aciclovir was 3630 copies/ml (3.56 log) – four times lower. The average viral load drop from baseline in patients taking valaciclovir was 1.23 log copies/ml – a 17-fold drop. Aciclovir produced a quarter of this viral load drop – a 3.5-fold (0.56 log) drop.

This study, unlike the aciclovir one presented on Monday, did not measure CD4 count or time taken to HIV therapy.

Presenter Kenneth Mugwanya of the University of Washington, Seattle said that “Given the constraints on ART programmes, the potential for high dose HSV-2 suppression to delay ART initiation warrants further evaluation.”

While valaciclovir became available widely in generic form in 2009, it is still about ten times as expensive as aciclovir, and indeed more expensive than anti-HIV drugs, but further studies may provide an incentive for agencies to negotiate lower prices.

Mugwanya KK et al. 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. Sixth IAS conference, Rome. Abstract WEPDB0106, 2011.

View the abstract on the conference website.