Virological efficacy and emergence of drug resistance in adults on antiretroviral treatment in rural Tanzania

Abstract

BackgroundVirological 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.MethodsHaydom 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.ResultsVirological 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 ≥1 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 cross-resistance to all nucleoside reverse transcriptase inhibitors (NRTIs). Dual-class resistance, i.e. resistance to both NRTIs and NNRTIs, was found in 64%.ConclusionVirological 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.

Evaluation of treatment outcomes for patients on first‐line regimens in US President's Emergency Plan for AIDS Relief (PEPFAR) clinics in Uganda: predictors of virological and immunological response from RV288 analyses

“…In a systematic review of studies across sub-Saharan Africa, 78% of 13 288 patients on therapy for at least 6 months were found to be virologically suppressed [9]. Suppression rates appear to be high when patients are retained in care; for example, a study in rural Tanzania estimated that 88.2% of subjects were virologically suppressed (< 400 copies/ml after 12 months on ART) [10].…”

“…In a systematic review of studies across sub-Saharan Africa, 78% of 13 288 patients on therapy for at least 6 months were found to be virologically suppressed [9]. Suppression rates appear to be high when patients are retained in care; for example, a study in rural Tanzania estimated that 88.2% of subjects were virologically suppressed (< 400 copies/ml after 12 months on ART) [10].We observed no difference in the rates of suppression comparing the time-on-treatment strata (6-12, 13-24 and > 24 months), indicating that most patients were virologically suppressed after < 6 months on treatment. In contrast, mean CD4 cell counts were significantly higher in each successive time-on-treatment stratum, suggesting that CD4 cell reconstitution continues for a substantial period even with optimal suppression.…”

Strengthening HIV therapy and care in rural Tanzania affects rates of viral suppression

“…24,28 To our knowledge, this is the first well-powered study addressing virological effectiveness and the emergence of HIV-DRM among patients on the current WHO-recommended ART regimen in Tanzania under programmatic conditions. Our findings provide further evidence from rural African settings that higher virological suppression rates can be achieved when HIV treatment and care programmes are continuous and effectively managed.…”

“…Our findings provide further evidence from rural African settings that higher virological suppression rates can be achieved when HIV treatment and care programmes are continuous and effectively managed. 28 Furthermore, the study enabled us to estimate the prevalence of HIV-DRM in HIV-infected patients receiving ART for at least 6 months. Our findings show that approximately 80% of the individuals who experienced virological failure harboured at least one clinically relevant resistance mutation in the reverse transcriptase gene.…”

Rethinking nursing care: An ethnographic approach to nurse–patient interaction in the context of a HIV prevention programme in rural Tanzania

“…The programme entailed free treatment and care to all patients with HIV (Johannessen et al, 2009) -the standard policy of the Tanzanian government but still far from implemented in all areas. The PMTCT programme is organised through four intertwined programmes defined as a ''PMTCT Plus'' alternative (Robberstad and Evjen-Olsen, 2010).…”