Open Access Highly Accessed Research article

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

Asgeir Johannessen12*, Ezra Naman2, Sokoine L Kivuyo3, Mabula J Kasubi4, Mona Holberg-Petersen5, Mecky I Matee6, Svein G Gundersen78 and Johan N Bruun19

Author Affiliations

1 Ulleval Department of Infectious Diseases, Oslo University Hospital, Oslo, Norway

2 HIV Care and Treatment Centre, Haydom Lutheran Hospital, Mbulu, Tanzania

3 National Institute for Medical Research, Haydom Research Station, Mbulu, Tanzania

4 Department of Microbiology and Immunology, Muhimbili National Hospital, Dar es Salaam, Tanzania

5 Ulleval Department of Microbiology, Oslo University Hospital, Oslo, Norway

6 Department of Microbiology and Immunology, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania

7 Research Unit, Sorlandet Hospital HF, Kristiansand, Norway

8 Centre for Development Studies, University of Agder, Kristiansand, Norway

9 Department of Infectious Diseases, University Hospital of North Norway, Tromso, Norway

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BMC Infectious Diseases 2009, 9:108  doi:10.1186/1471-2334-9-108

Published: 7 July 2009

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 ≥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%.

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.