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Abstract
BackgroundThe emergence, accumulation and spread of HIV-1 drug resistance strains in Africa could compromise the effectiveness of HIV treatment programs. This study was aimed at determining the incidence of virological failure and acquired drug resistance mutations overtime and identifying the most common mutational pathways of resistance in a well characterized HIV-1C infected Ethiopian cohort.MethodsA total of 320 patients (220 ART naïve and 100 on first lines ART) were included and followed. ART initiation and patients’ monitoring was based on the WHO clinical and immunological parameters. HIV viral load measurement and genotypic drug resistance testing were done at baseline (T0-2008) and after on average at a median time of 30 months on ART at three time points (T1-2011, T2-2013, T3-2015).FindingsThe incidence of virological failure has increased overtime from 11 at T1 to 17 at T2 and then to 30% at T3. At all time point’s almost all of the patients with virological failure and accumulated drug resistance mutations had not met the WHO clinical and immunologic failure criteria and continued the failing regimen. A steep increase in the incidence and accumulation of major acquired NRTI and NNRTI drug resistance mutations have been observed (from 40% at T1 to 64% at T2 and then to 66% at T3). The most frequent NRTIs drug resistance associated mutations are mainly the lamivudine-induced mutation M184V which was detected in 4 patients at T1 and showed a 2 fold increase in the following time points (T2: n = 8) and at (T3: n = 12) and the thymidine analogue mutations (such as D67N, K70R and K219E) which were not-detected at baseline T0 and T1 but were increased progressively to 10 at T2 and to 17 at T3. The most frequent NNRTIs associated mutations were K103N, V106M and Y188C.ConclusionsAn upward trend in the incidence of virological failure and accumulation of NRTI and NNRTI associated acquired antiretroviral drug resistance mutations are observed. The data suggest the need for virological monitoring, resistance testing for early detection of failure and access for TDF and PI containing drugs. Population-level and patient targeted interventions to prevent the spread of mutant variants is warranted.
Highlights
In Africa, over the past decade a remarkable increase in access to combination antiretroviral therapy has been continued and has substantially contributed to the dramatic reduction in morbidity and mortality
The data suggest the need for virological monitoring, resistance testing for early detection of failure and access for TDF and protease inhibitors (PIs) containing drugs
Few available studies on long term virological outcomes showed that virological failure remains undetected and patients continue to be on failing regimen until either clinical or immunological failure occurs [8] which leads to high rates of treatment failure with virological failure rates of greater than 20% after 24 months of ART and development of resistance with the potential of reducing the efficacy of available first-line regimens [8, 9] in up to 90% of patients and being considered as a major threat for ongoing and future treatment options[8,9,10,11,12]
Summary
In Africa, over the past decade a remarkable increase in access to combination antiretroviral therapy (cART) has been continued and has substantially contributed to the dramatic reduction in morbidity and mortality It has improved quality of life and life expectancy and altered perceptions on HIV/AIDS from an epidemic to a manageable chronic illness [1, 2]. These achievements are based on the WHO public health approach of using clinical and immunological parameters as the standard for ART initiation and monitoring, despite its limitations compared with the reference virological parameters based approach [3, 4]. This study was aimed at determining the incidence of virological failure and acquired drug resistance mutations overtime and identifying the most common mutational pathways of resistance in a well characterized HIV-1C infected Ethiopian cohort
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