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Low Incidence of HIV-1C Acquired Drug Resistance 10 Years after Roll-Out of Antiretroviral Therapy in Ethiopia: A Prospective Cohort Study.

Mulu A, Maier M, Liebert UG - PLoS ONE (2015)

Bottom Line: 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).Moreover, adherence reinforcement will contribute to improving overall treatment outcomes.

View Article: PubMed Central - PubMed

Affiliation: Institute of Virology, Faculty of Medicine, Leipzig University, Leipzig, Germany; Department of Microbiology, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia.

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.

No MeSH data available.


Related in: MedlinePlus

Immunological restoration among HIV-1C Ethiopian patients (N = 127 at each time point) during 30 months of ART.
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pone.0141318.g002: Immunological restoration among HIV-1C Ethiopian patients (N = 127 at each time point) during 30 months of ART.

Mentions: By the median time of 30 months on ART, 18 out of 127 patients (14.2%) were non-adherent at least once. The main reasons for non-adherence were health related problems (9/18) and drug side effects (5/18). Accordingly, treatment switching was made (3 due to clinical failure, 6 due to immunological failure and 4 due to drug associated toxicity: 3 patients stopped AZT due to anaemia, 1 stopped EFV due to neuropsychiatric disorder and 1 stopped d4T due to neuropathy and lipodystrophy) at a median time of 61 days after initiation of ART. All the patients were on appropriate ART regimen as per the National ART guideline and were clinically asymptomatic. The median CD4+ T cells count of the 127 patients at baseline was 194 (IQR, 25–229) cells/mm3 and progressively increased over time (Fig 2). The rate of CD4+ T cells count increased significantly in the first 12 months period (+183 cells/mm3) exceeding the rate of the following 24 months (+81 cells/mm3, P <0.01, 95% CI, 69–91). The rate of CD4+ T cells recovery was not different among patients who were taking NVP versus EFV based regimen (+211 vs + 217 cells/mm3; P = 0.14).


Low Incidence of HIV-1C Acquired Drug Resistance 10 Years after Roll-Out of Antiretroviral Therapy in Ethiopia: A Prospective Cohort Study.

Mulu A, Maier M, Liebert UG - PLoS ONE (2015)

Immunological restoration among HIV-1C Ethiopian patients (N = 127 at each time point) during 30 months of ART.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4626118&req=5

pone.0141318.g002: Immunological restoration among HIV-1C Ethiopian patients (N = 127 at each time point) during 30 months of ART.
Mentions: By the median time of 30 months on ART, 18 out of 127 patients (14.2%) were non-adherent at least once. The main reasons for non-adherence were health related problems (9/18) and drug side effects (5/18). Accordingly, treatment switching was made (3 due to clinical failure, 6 due to immunological failure and 4 due to drug associated toxicity: 3 patients stopped AZT due to anaemia, 1 stopped EFV due to neuropsychiatric disorder and 1 stopped d4T due to neuropathy and lipodystrophy) at a median time of 61 days after initiation of ART. All the patients were on appropriate ART regimen as per the National ART guideline and were clinically asymptomatic. The median CD4+ T cells count of the 127 patients at baseline was 194 (IQR, 25–229) cells/mm3 and progressively increased over time (Fig 2). The rate of CD4+ T cells count increased significantly in the first 12 months period (+183 cells/mm3) exceeding the rate of the following 24 months (+81 cells/mm3, P <0.01, 95% CI, 69–91). The rate of CD4+ T cells recovery was not different among patients who were taking NVP versus EFV based regimen (+211 vs + 217 cells/mm3; P = 0.14).

Bottom Line: 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).Moreover, adherence reinforcement will contribute to improving overall treatment outcomes.

View Article: PubMed Central - PubMed

Affiliation: Institute of Virology, Faculty of Medicine, Leipzig University, Leipzig, Germany; Department of Microbiology, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia.

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.

No MeSH data available.


Related in: MedlinePlus