Virological outcome and patterns of HIV-1 drug resistance in patients with 36 months' antiretroviral therapy experience in Cameroon

Introduction: The current expansion of antiretroviral treatment (ART) in the developing world without routine virological monitoring still raises concerns on the outcome of the strategy in terms of virological success and drug resistance burden. We assessed the virological outcome and drug resistance mutations in patients with 36 months' ART experience, and monitored according to the WHO public health approach in Cameroon. Methods: We consecutively recruited between 2008 and 2009 patients attending a national reference clinic in Yaounde - Cameroon, for their routine medical visits at month 36 +/- 2. Observance data and treatment histories were extracted from medical records. Blood samples were collected for viral load (VL) testing and genotyping of drug resistance when HIV-1 RNA >= 1000 copies/ml. Results: Overall, 376 HIV-1 infected adults were recruited during the study period. All, but four who received PMTCT, were ART-naive at treatment initiation, and 371/376 (98.7%) started on a first-line regimen that included 3TC + d4T/AZT + NVP/EFV. Sixty-six (17.6%) patients experienced virological failure (VL >= 1000 copies/ml) and 53 carried a resistant virus, thus representing 81.5% (53/65) of the patients who failed. Forty-two out of 53 were resistant to nucleoside and non-nucleoside reverse-transcriptase inhibitors (NRTIs + NNRTIs), one to protease inhibitors (PI) and NNRTIs, two to NRTIs only and eight to NNRTIs only. Among patients with NRTI resistance, 18/44 (40.9%) carried Thymidine Analog Mutations (TAMs), and 13/44 (29.5%) accumulated at least three NRTI resistance mutations. Observed NNRTI resistance mutations affected drugs of the regimen, essentially nevirapine and efavirenz, but several patients (10/51, 19.6%) accumulated mutations that may have compromised etravirine use. Conclusions: We observed a moderate level of virological failure after 36 months of treatment, but a high proportion of patients who failed developed drug resistance. Although we found that for the majority of patients, second-line regimens recommended in Cameroon would be still effective, accumulated resistance mutations are of concern and may compromise future treatment strategies, stressing the need for virological monitoring in resource-limited settings.