Abstract:
Background: Virological response to antiretroviral treatment (ART) in rural Africa is poorly described. We examined
virological efficacy and emergence of drug resistance in adults receiving first-line ART for up to 4 years in rural Tanzania.
Methods: Haydom Lutheran Hospital has provided ART to HIV-infected patients since October 2003. A combination
of stavudine or zidovudine with lamivudine and either nevirapine or efavirenz is the standard first-line regimen. Nested
in a longitudinal cohort study of patients consecutively starting ART, we carried out a cross-sectional virological efficacy
survey between November 2007 and June 2008. HIV viral load was measured in all adults who had completed at least 6
months first-line ART, and genotypic resistance was determined in patients with viral load >1000 copies/mL.
Results: Virological response was measured in 212 patients, of whom 158 (74.5%) were women, and median age was
35 years (interquartile range [IQR] 29–43). Median follow-up time was 22.3 months (IQR 14.0–29.9). Virological
suppression, defined as <400 copies/mL, was observed in 187 patients (88.2%). Overall, prevalence of ³1 clinically
significant resistance mutation was 3.9, 8.4, 16.7 and 12.5% in patients receiving ART for 1, 2, 3 and 4 years, respectively.
Among those successfully genotyped, the most frequent mutations were M184I/V (64%), conferring resistance to
lamivudine, and K103N (27%), Y181C (27%) and G190A (27%), conferring resistance to non-nucleoside reverse
transcriptase inhibitors (NNRTIs), whereas 23% had thymidine analogue mutations (TAMs), associated with crossresistance
to all nucleoside reverse transcriptase inhibitors (NRTIs). Dual-class resistance, i.e. resistance to both NRTIs
and NNRTIs, was found in 64%.
Conclusion: Virological suppression rates were good up to 4 years after initiating ART in a rural Tanzanian hospital.
However, drug resistance increased with time, and dual-class resistance was common, raising concerns about exhaustion
of future antiretroviral drug options. This study might provide a useful forecast of drug resistance and demand for
second-line antiretroviral drugs in rural Africa in the coming years.
