Abstract
The emergence of HIV-1 drug resistance mutations has mainly been linked to the duration and composition of antiretroviral treatment (ART), as well as the level of adherence. This study reports the incidence and pattern of acquired antiretroviral drug resistance mutations and long-term outcomes of ART in a prospective cohort from Northwest Ethiopia. Two hundred and twenty HIV-1C infected treatment naïve patients were enrolled and 127 were followed-up for up to 38 months on ART. ART initiation and patients’ monitoring was based on the WHO clinical and immunological parameters. HIV viral RNA measurement and drug resistance genotyping were done at baseline (N = 160) and after a median time of 30 (IQR, 27–38) months on ART (N = 127). Viral suppression rate (HIV RNA levels ≤ 400 copies/ml) after a median time of 30 months on ART was found to be 88.2% (112/127), which is in the range for HIV drug resistance prevention suggested by WHO. Of those 15 patients with viral load >400 copies/ml, six harboured one or more drug resistant associated mutations in the reverse transcriptase (RT) region. Observed NRTIs resistance associated mutations were the lamivudine-induced mutation M184V (n = 4) and tenofovir associated mutation K65R (n = 1). The NNRTIs resistance associated mutations were K103N (n = 2), V106M, Y181S, Y188L, V90I, K101E and G190A (n = 1 each). Thymidine analogue mutations and major drug resistance mutations in the protease (PR) region were not detected. Most of the patients (13/15) with virologic failure and accumulated drug resistance mutations had not met the WHO clinical and/or immunological failure criteria and continued the failing regimen. The incidence and pattern of acquired antiretroviral drug resistance mutations is lower and less complex than previous reports from sub Saharan Africa countries. Nevertheless, the data suggest the need for virological monitoring and resistance testing for early detection of failure. Moreover, adherence reinforcement will contribute to improving overall treatment outcomes.
Highlights
The rapid scale-up of antiretroviral therapy (ART) in resource-limited countries has dramatically reduced HIV-related mortality and improved quality of life [1, 2]
HIV genotypic drug resistance testing was performed in 160 pre-ART plasma samples and on the basis of the WHO transmitted drug resistance surveillance mutations list (S1 Table), transmitted HIV drug resistance mutations were identified in 21 (13.12%) of the samples
Of 220 patients enrolled, 140 patients were on ART by median time of 30 months (IQR, 27–38) but this study has end viral load result for 127 patients
Summary
The rapid scale-up of antiretroviral therapy (ART) in resource-limited countries has dramatically reduced HIV-related mortality and improved quality of life [1, 2]. The exclusive use of clinical and immunological parameters to initiate and monitor ART in this region and the use of drugs with low genetic barrier that only require single point mutation to confer resistance, such as abacavir (ABC), lamivudine (3TC), tenofovir (TDF) and didanosine (ddI) have been associated with the emergence and accumulation of HIV-1 drug-resistant variants [7,8,9]. High level and complex profile of HIV-1 drug resistance mutations including Q151M and thymidine analogue mutations (TAMs) in individuals with first-line ART failure [8, 9, 13, 14, 15, 16] and increased prevalence of transmitted drug resistance (TDR) mutations have been reported in recent years [17, 18, 19, 20, 21], despite more promising initial observations from Africa [4, 6, 13]
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