Antiretroviral resistance following immunological monitoring in a resource-limited setting of western India: A cross-sectional study.

Autor: Karade SK; HIV Drug Resistance Laboratory, National AIDS Research Institute (ICMR), Pune, India.; Department of Microbiology, Armed Forces Medical College, Pune, India., Kulkarni SS; Department of Virology, National AIDS Research Institute (ICMR), Pune, India., Ghate MV; Department of Clinical Sciences, National AIDS Research Institute (ICMR), Pune, India., Patil AA; HIV Drug Resistance Laboratory, National AIDS Research Institute (ICMR), Pune, India., Londhe R; Department of Virology, National AIDS Research Institute (ICMR), Pune, India., Salvi SP; Department of Medicine, BJ Medical College and Sasoon General Hospital, Pune, India., Kadam DB; Department of Medicine, BJ Medical College and Sasoon General Hospital, Pune, India., Joshi RK; Department of Epidemiology and Biostatistics, National AIDS Research Institute (ICMR), Pune, India.; Department of Community Medicine, Armed Forces Medical college, Pune, India., Rewari BB; Department of AIDS Control, National AIDS Control Organization, New Delhi, India., Gangakhedkar RR; Department of Clinical Sciences, National AIDS Research Institute (ICMR), Pune, India.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2017 Aug 01; Vol. 12 (8), pp. e0181889. Date of Electronic Publication: 2017 Aug 01 (Print Publication: 2017).
DOI: 10.1371/journal.pone.0181889
Abstrakt: Background: The free antiretroviral therapy (ART) program in India still relies on the clinico-immunological monitoring for diagnosis of treatment failure. As the nucleoside reverse transcriptase inhibitor (NRTI) backbone is shared in first- and second-line regimens, accumulation of drug resistant mutations (DRMs) can compromise the efficacy of NRTI. This study was undertaken to describe the pattern of HIV DRMs following immunological monitoring and investigate its impact on the cycling of NRTI between first- and second-line ART.
Methods and Findings: This cross-sectional study was performed at a state-sponsored ART clinic of Pune city in western India between January and June 2016. Consecutive adults receiving first-line ART with immunological failure (IF) were recruited for plasma viral load (PVL) estimation. Randomly selected 80 participants with PVL >1000 copies/mL underwent HIV drug resistance genotyping. Of these, 75 plasma sample were successfully genotyped. The median CD4 count and duration of ART at the time of failure were 98 (IQR: 61.60-153.50) cells/μL and 4.62 (IQR: 3.17-6.15) years, respectively. The prevalence of NRTI, non-NRTI, and major protease inhibitor resistance mutations were 89.30%, 96%, and 1.33%, respectively. Following first-line failure, sequences from 56.67% of individuals indicated low- to high-level resistance to all available NRTI. The proportion of sequences with ≥2 thymidine analogue mutations (TAMs) and ≥3 TAMs were 62.12% and 39.39%, respectively. An average of 1.98 TAMs per sequence were observed following IF as compared to 0.37 TAMs per sequence following targeted PVL monitoring at 12 months of ART from a prior study; this difference was significant (p<0.001).
Conclusion: The option of cycling of NRTI analogues between first- and second-line regimens would no longer be effective if individuals are followed-up by immunological monitoring due to accumulation of mutations. Introduction of routine PVL monitoring is a priority for the long-term sustainability of free ART program in India.
Databáze: MEDLINE
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