Thomas Macharia, Anthony Amoroso, Martine Etienne-Mesubi and Anthony Edozien
Background: Toxicities that led to antiretroviral substitution in a multi-country treatment program were described. Methods: First line regimens included stavudine, lamivudine and nevirapine or efavirenz. Alternative therapy included zidovudine, tenofovir, efavirenz and lopinavir/ritonavir. Clinicians were trained to diagnose common antiretroviral side effects. Facilities had access to safety laboratory assays. Toxicity was detected clinically, and confirmed or monitored using specific laboratory assays where indicated. Results: Between 2004 and 2006, among 6,520 patients in Uganda, Kenya and Zambia, initiating antiretroviral therapy, toxicity-related substitutions were observed for stavudine 24.6%, zidovudine 13%, nevirapine 6.6%, efavirenz 3.4%, lopinavir/ritonavir 2% and tenofovir 0.7%. Mean time to switch ranged from 25 days for Lopinavir/ ritonavir, to 141 days for stavudine. Most common toxicities included neuropathy (stavudine), anemia (zidovudine), rash and liver toxicity (nevirapine). Conclusions: Toxicity rates in the study were comparable to reports in Food and Drug Administration (FDA) label package inserts and other smaller published reports in Africa and Asia. These toxicity rates could be used to inform drug forecasting for resource-limited settings. Comparably high tolerability of tenofovir and efavirenz may support their preferential use.