Aetiological pattern of genital ulcer disease (GUD) in Malawi and associations between herpes simplex virus type 2 (HSV-2) and HIV-1: Time for addition of episodic treatment for genital herpes?

Background: Current syndromic management of genital ulcer disease (GUD) in Malawi covers treatment for syphilis and chancroid, but does not include treatment for genital herpes. A randomised placebo-controlled trial evaluating the impact of additional acyclovir as episodic treatment for HSV-2 on ulcer healing and HIV-1 genital shedding is underway in Lilongwe, Malawi. Methods:Patients are interviewed, examined and samples collected prior to randomisation and at follow-up visits on days 2 or 4, 7, 14 and 28. GUD aetiology is determined by real-time multiplex PCR of lesional swabs. Blood is tested for HIV-1, syphilis, and HSV-2 serologies. CD4 count and plasma HIV-1 RNA are measured among HIV-1 sero-positive patients. Results: By Nov 2005, 250 patients (204 men, 46 women) were enrolled and randomised. 60% were HIV-1 sero-positive, 74% were HSV-2 sero-positive and 4% had a positive syphilis serology. Ulcer aetiology among 177 patients showed: HSV-2 58%, H. ducreyi 19%, LGV 7%, T. pallidum 5% and no aetiology 11%. Patients who were HSV-2 sero-positive were more likely to be HIV sero-positive (69% vs. 35%, p<0.0001), as were patients with lesional HSV-2 compared to patients with other aetiologies (67% vs. 51%, p=0.03). Among HIV+ patients with CD4 count < 200, 72% of ulcers were due to HSV-2. Conclusions:HIV-1 and HSV-2 are highly prevalent infections in patients with GUD in Lilongwe and are closely associated. HSV dominates GUD aetiologies in this population, while bacterial aetiologies covered by the current management algorithm persist. There is growing evidence to revise GUD guidelines to add acyclovir episodic treatment for genital herpes in Malawi.