Nitazoxanide for persistent diarrhoea in Zambian acquired immune deficiency syndrome patients: a randomized-controlled trial

Background: Adults with acquired immune deficiency syndrome and persistent diarrhoea in Zambia have intestinal infection, predominantly protozoa. Aim: To search for treatment which can be offered with minimal investigation, we carried out a double-blind, randomized-controlled trial of nitazoxanide (a drug with a range of activity against parasites and bacteria). Methods: Patients with diarrhoea of 1 month duration or longer were randomized to receive nitazoxanide (1000 mg twice daily) or placebo for 2 weeks. End-points were clinical response, parasitological clearance and mortality. Results: Two hundred and seven adults were randomized; 42 died during the study. The primary assessment of efficacy was made after 17 days. Clinical response was observed in 56 (75%) of 75 patients receiving nitazoxanide and 45 (58%) of 77 patients receiving placebo (P = 0.03). The rate of improvement was markedly higher in patients with CD4 counts under 50 cells/mu L receiving nitazoxanide (P = 0.007). The benefit was largely restricted to the period when the drug was being administered. No difference was seen in parasitological clearance between the two groups. Mortality was 19% by 4 weeks of follow-up and did not differ with treatment allocation. Conclusions: Nitazoxanide given orally for 14 days was associated with clinical improvement in Zambian acquired immune deficiency syndrome patients with diarrhoea, especially those with very low CD4 counts.