Papular pruritic eruption (PPE) is a frequent HIV-comorbidity in tropical countries. Because of constant itching and social stigma, effective treatment is highly valued. In our HIV cohort in rural Tanzania with 12% prevalence of PPE, we have retrospectively analyzed responses to available treatments. Oral promethazine improved itching (P < 0.0058) and clinical scores (P < 0.032) significantly more than topical steroids. Disease activity did not correlate with CD4+ and CD8+ T cell counts and was independent of anti-retroviral medication. Therefore, oral antihistamines are an effective first-line treatment for PPE.