Background:  HIV/tuberculosis (TB) co-infection rates in KwaZulu-Natal approach 80%. Historically high mortality rates among TB/HIV co-infected patients have improved with ART, but co-treatment has raised questions related to drug interactions, immune reconstitution, and severe adverse events. Studies have reported on adverse events in sub-Saharan Africa, but few on HIV and TB co-treatment. Algorithms for optimal drug combinations have also yet to be developed.

Methods:  HIV/TB co-infected patients were enrolled in an operational research study providing standard TB medication concurrently with once-daily didanosine (ddI) + lamivudine (3TC) + efavirenz (EFV) in a rural resource-constrained setting in South Africa. Patients were followed at monthly intervals with standardized adverse event evaluation and at the time of any event occurrence, for one year after commencing TB treatment.

Results:  We followed 119 patients for a total of 164.7 patient-years of observation, mean of 17 months (range 7 days to 35 months). Mean time from start of TB medication to ART initiation was 72 days (range 18 to 245 days), with 34% patients starting ART with a mean CD4 count (cells/mm³) of <50, 52% with 51 to 200 and 13% >200. Of the total, 6 (5%) patients were lost to follow-up (after mean follow-up of 5.7 months), and 15 (12.6%) died during the study. No deaths were directly attributable to study protocol or medications (11 were suspected or confirmed multidrug-resistant-TB. There were 2 opportunistic infections (Pneumocystis carinii pneumonia [PCP], cryptococcal meningitis), and 2 other (hematemesis and acute diarrhea). Combined grade 3 grade 4 adverse events were 1.8 per 100 patient-months, 1 due to pancreatitis, and 4 to possible immune reconstitution syndrome. Lactic acidosis and other significant laboratory abnormalities were not documented. We observed 3488 grade 1 and 2 events per 100 patient-years of follow-up:  peripheral neuropathy (431), fatigue (369), bad dreams (319), mood changes (290), headache (259).

Conclusions:  Integration of HIV and TB treatment provides a safe, feasible, and effective strategy for introducing ART in rural resource-limited settings. A once a day regimen of ddI+3TC+efavirenz, specifically, was associated with excellent therapeutic benefit and low level of adverse events. This regimen warrants further investigation and recommendation as an alternate regimen for TB/HIV co-infected patients. The low serious adverse event profile provides an opportunity for primary care nursing follow-up in resource-constrained settings.