Improvement in Healing and Reduction in HIV Shedding with Episodic

Improvement in Healing and Reduction in HIV Shedding with Episodic Acyclovir Therapy as Part of Syndromic Management among Men: A Randomized, Controlled Trial.

It is uncertain whether episodic acyclovir will enhance ulcer healing if delivered at primary health care settings, because there is often a delay in treatment initiation. A double-blind, randomized, placebo-controlled trial of 5-day acyclovir (400 mg 3 times daily) was conducted among men with genital ulcers in South Africa. Participants received syndromic management; were tested for ulcer aetiology, human immunodeficiency virus (HIV), syphilis, and herpes simplex virus type 2 (HSV-2); and were seen over the course of a month to evaluate ulcer healing and HIV-1 RNA shedding. Outcomes were ulcer duration and HIV-1 RNA shedding, assessed on day 7 among HIV-1-seropositive participants with a herpetic ulcer. A total of 309 men received acyclovir, and 306 received placebo; 63% were HIV-1 positive. There were 295 HIV-1-positive participants with a herpetic ulcer. Acyclovir improved ulcer healing-61% of those receiving acyclovir healed by day 7, compared with 42% of those receiving placebo (adjusted relative risk, 1.4 [95% confidence interval, 1.1-1.8]). Acyclovir also improved healing by a median of 3 days and reduced HIV-1 ulcer shedding on day 7 (24% for acyclovir vs 37% for placebo). The authors report that addition of acyclovir to syndromic management will improve healing of genital ulcers and may potentially reduce HIV transmission in combination with other interventions.

The results of this acyclovir trial for the 63% of participants who were HIV-positive are encouraging – acyclovir healed herpes simplex-2 (HSV-2) ulcers more quickly (median of 3 days) and reduced HIV shedding from the ulcers. The latter could be due in part to the direct effect of acyclovir itself on HIV replication. WHO recommends that countries in which HSV-2 accounts for more that 30% of genital ulcer disease add antiherpetic treatment to syndromic management algorithms for genital ulcer disease. Why this is not uniformly done is unclear – the cost of treatment has been much reduced by generic acyclovir. Even though trials to date have not found that acyclovir reduces ongoing HIV transmission, it provides symptom relief and reduces herpes shedding. Given that the ulcer is often what may have brought the patient in for care, providers should take advantage of the opportunity while prescribing acyclovir to initiate discussions about HIV testing and counselling with all patients presenting with genital ulcer disease – the majority are unlikely unaware of their HIV status and are not accessing HIV prevention and treatment services.