Valaciclovir prophylaxis prevents herpes simplex attacks in HIV patients even with advanced disease

Twice daily valaciclovir can safely and effectively prevent the recurrence of genital and facial herpes simplex virus (HSV) in HIV-positive individuals, according to a multicentre, randomised, placebo controlled study, reported in the October 1^st edition of the Journal of Infectious Diseases, which is available on-line.

Valaciclovir has greater bioavailability than aciclovir, the standard HSV treatment, and requires fewer daily doses. Studies have shown that it is effective at preventing the recurrence of genital herpes attacks in HIV-negative individuals and comparable to aciclovir at preventing repeat attacks of herpes in patients with HIV with a CD4 cell count above 100 cells/mm³.

The current study evaluated the safety and efficacy of 500mg of valaciclovir twice daily as a prophylaxis for genital herpes in HIV-positive patients who had experienced four attacks of the painful ulcerative condition in the past year. Patients were randomised on a two-to-one basis to receive valaciclovir or a placebo. The primary end-point of the study was the proportion of patients who did not experience a recurrence of HSV at six months.

At baseline HIV and HSV histories were obtained and tests performed to establish HSV serology, HIV viral load and CD4 cell count. Study participants were asked to keep a diary card recording daily adherence to study medication, use of any other prescription drugs, including HAART, side-effects, and recurrent attacks of HSV. In the event of an attack, patients were asked to return to their study centre where the HSV lesion was swabbed and the patient offered five days of open label valaciclovir therapy to suppress the attack (dosed at 1000mg twice daily), before re-entering the study with open-label valaciclovir.

A total of 293 patients were recruited to the study at HIV treatment centres in the US, UK and Canada. Nearly half (49%) had received long-term suppressive HSV therapy before entry onto the study. Median HIV viral load was comparable between the two arms of the study at 398 copies/mL. In addition, 43% of patients in both arms had an HIV viral load above 400 copies/mL. A quarter of patients enrolled had a CD4 cell count below 200 cells/mm³ and median CD4 cell count was 313 cells/mm³ in the placebo arm and 336 cells/mm³ in the valaciclovir arm. A third of patients had been diagnosed with an AIDS-defining condition and were evenly distributed across the two arms of the study. At baseline, 94% of patients in the valaciclovir arm were taking HAART, as were 93% of patients in the placebo arm.

The proportion of patients who did not have a recurrence of genital herpes was significantly higher in the valaciclovir arm (65%) than the placebo arm (26%, relative risk 2.5, 95% CI, 1.8 - 3.5). In addition, investigators established that the time to first recurrence of herpes was significantly shorter in the placebo arm (mean 59 days) than the valaciclovir arm (median above 180 days HR 5.0, 95% CI, 3.30 - 7.70).

None of the covariates examined (gender, age, CD4 cell count, HIV viral load, stage of HIV disease) were found to be predictive of a recurrence of HSV. Median HIV viral load and CD4 cell count remained unchanged for both arms of the study throughout the six months of the trial.

A total of three patients discontinued because of adverse events, and 58% of the placebo arm and 75% of the valaciclovir arm reported side-effects, including headache, vomiting, diarrhoea and flu-like symptoms. Rash was reported more frequently in the valaciclovir -treated patients (eight instances) than amongst patients treated with a placebo (one instance). However, there was no evidence that the rash was valaciclovir -related in any of the instances, and treatment was only withdrawn form one patient.

Three severe adverse events were attributed by the investigators to valaciclovir and all occurred in the same individual who had a history of abnormal liver function.

Amongst the 48 patients who had a recurrence of HSV, three (6%) were found to have resistance to aciclovir, all of whom had had an AIDS-defining illness and a history of suppressive anti-HSV medication ranging from one to four years. In all cases, patients responded to a five day course of 1000mg valaciclovir twice-daily.

The investigators conclude, “ours is the first multicentre, placebo-controlled study to demonstrate the efficacy of suppressive antiherpes therapy in a heterogeneneous population of individuals with HIV infection” including individuals with very advanced HIV disease. They add “we have established an important treatment option for the management of genital herpes...a convenient, twice-daily regimen of valaciclovir suppressive therapy was well tolerated in HIV-infected individuals and effectively reduced the risk of genital and oral HSV recurrences.”

Further information on this website

Herpes simplex - overview

Herpes - factsheet

Valaciclovir - overview