Background:  ART drugs significantly benefit HIV-infected persons, but they also expose them to certain toxicities. Few studies have reported the ART toxicity profiles among treated sub-Saharan Africans. We evaluated the early toxicity of ART in a home-based AIDS care (HBAC) project in rural Uganda.

Methods:  From May 2003 to December 2004, patients with symptomatic HIV disease or CD4⁺ cell count <250 cells/μL were started on ART in HBAC. HBAC consists of weekly drug delivery, field-based monitoring, and targeted clinic visits for illness or toxicity. Incident clinical toxicities were evaluated by medical officers and graded 1 to 4 (grades 3 and 4 considered severe) and cumulative Kaplan-Meier probabilities were calculated.

Results:  Starting ART, 1037 ART-naïve adults (73% women, median CD4⁺ cell count 126 cells/μL), contributed 950 patient-years (median 0.94 years/patient) of observation. The initial ART regimen was stavudine (d4T), lamivudine (3TC), and either nevirapine (NVP) for 1000 patients (96%) or efavirenz (EFV) for 37 (4%). Of the total, 417 patients (40%) developed 547 clinical toxicities:  325 patients (31%) developed neuropathy (86 [8%] severe); 59 (6%) rash (25 [2%] severe); 17 (2%) a hypersensitivity reaction; 5 (0.5%) acute hepatitis; 4 (0.4%) anemia; 3 (0.3%) acute pancreatitis; 1 (0.1%) lactic acidosis; 1 (0.1%) death; and 132 (13%) other toxicities (e.g., nausea, vomiting, asthenia, psychiatric disorder). The probability of remaining free from any toxicity at 6, 12, and 18 months was 0.76, 0.59, and 0.47, respectively; while the probability of remaining free from severe toxicities at 6, 12, and 18 months was 0.92, 0.86, and 0.84, respectively. Because of toxicity, 220 patients (21%) had 225 drug changes:  181 d4T to zidovudine (AZT), 30 NVP to EFV, 9 NVP to lopinavir (LPV), 4 AZT to tenofovir (TDF), and 1 EFV to NVP. The probability of remaining on the original regimen without change for toxicity at 6, 12, and 18 months were 0.91, 0.78, and 0.68, respectively.

Conclusions:  Clinically apparent toxicities were common, but the probability of severe clinical toxicity was moderate. Neuropathy and rash accounted for most events, and required single drug substitutions in many cases. In resource-limited settings, ART intolerance to a regimen containing d4T and NVP presents a manageable barrier to care, though more tolerable regimens would be desirable.