scholarly journals Development of HIV Drug Resistance in a Cohort of Adults on First-Line Antiretroviral Therapy in Tanzania during the Stavudine Era

2021 ◽  
Vol 12 (4) ◽  
pp. 847-861
Author(s):  
Raphael Z. Sangeda ◽  
Perpétua Gómes ◽  
Soo-Yon Rhee ◽  
Fausta Mosha ◽  
Ricardo J. Camacho ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Reverse Transcriptase ◽  
Nucleoside Reverse Transcriptase Inhibitor ◽  
Transcriptase Inhibitor ◽  
Resistance Mutations ◽  
First Line ◽  
Nnrti Resistance ◽  
One Year ◽  
Reverse Transcriptase Inhibitor

As more HIV patients start combination antiretroviral therapy (cART), the emergence of HIV drug resistance (HIVDR) is inevitable. This will have consequences for the transmission of HIVDR, the success of ART, and the nature and trend of the epidemic. We recruited a cohort of 223 patients starting or continuing their first-line cART in Tanzania towards the end of the stavudine era in 2010. Patients were then followed for one year. Of those with a viral load test at baseline and follow-up time, 34% had a detectable viral load at the one-year endpoint. For 41 patients, protease and reverse transcriptase genotyping were successful. Eighteen samples were from cART-naïve patients, and 23 samples were taken under therapy either at baseline for cART-experienced patients or from follow-up samples for both cART–naïve and cART–experienced patients. The isolates were subtype A, followed by C and D in 41.5%, 22%, and 12.2% of the patients, respectively. No transmitted HIVDR was detected, as scored using the surveillance drug resistance mutations (DRMs) list. However, in 3 of the 18 samples from cART-naïve patients, the clinical Rega interpretation algorithm scored 44D or 138A as non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance-associated polymorphisms. The most observed nucleoside reverse transcriptase inhibitor (NRTI) mutation was 184V. The mutation was found in 16 patients, causing resistance to lamivudine and emtricitabine. Nineteen patients had NNRTI resistance mutations, the most common of which was 103N, observed in eight patients. These high levels of resistance call for regular drug resistance surveillance in Tanzania to inform the control of the emergence and transmission of HIVDR.

scholarly journals Development of HIV drug resistance in a cohort of adults on first-line antiretroviral therapy in Tanzania during the stavudine era

2020 ◽  
Author(s):  
Raphael Z Sangeda ◽  
Perpétua Gómes ◽  
Soo-Yon Rhee ◽  
Fausta Mosha ◽  
Ricardo J. Camacho ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Reverse Transcriptase ◽  
Nucleoside Reverse Transcriptase Inhibitor ◽  
Transcriptase Inhibitor ◽  
Resistance Mutations ◽  
First Line ◽  
Nnrti Resistance ◽  
One Year ◽  
Reverse Transcriptase Inhibitor

Abstract As more HIV patients start combination antiretroviral therapy (cART), the emergence of HIV drug resistance (HIVDR) is inevitable. This will have consequences for the transmission of HIVDR, the success of ART, and the nature and trend of the epidemic. We recruited a cohort of 223 patients starting or continuing their first-line cART in Tanzania during the stavudine era in 2010. Patients were then followed up for one year. From those with a viral load test at baseline and follow-up time, 34% were failing virologically at the one-year endpoint. From 41 patients, protease and reverse transcriptase genotyping were successful. Eighteen samples were from therapy-naïve patients and 23 samples were taken under therapy either baseline for patients already under cART at study entry, or follow-up sample. The isolates were mostly subtype A, followed by C and D at 41.5%, 22% and 12.2% of the patients, respectively. No transmitted HIVDR was detected, as scored using the surveillance drug resistance mutations (DRMs) list. However, in 3 of the 18 samples from therapy-naïve patients, the clinical Rega interpretation algorithm scored 44D or 138A as non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance-associated polymorphisms. The most observed nucleoside reverse transcriptase inhibitor (NRTI) mutation was 184V. The mutation was found in 16 patients causing resistance to lamivudine and emtricitabine. Nineteen patients had NNRTI resistance mutations, the most common of which was 103N observed in 8 patients. These high levels of resistance calls for regular drug resistance surveillance in Tanzania to control the emergence and transmission of HIVDR.

scholarly journals Moderate Levels of Pretreatment HIV Drug Resistance — Zimbabwe, April–July 2015

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S424-S424
Author(s):  
Juliana Da Silva ◽  
Janet Dzangare ◽  
Elizabeth Gonese ◽  
Mutsa Mhangara ◽  
Owen Mugurungi ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Antiretroviral Therapy ◽  
Reverse Transcriptase ◽  
Nucleoside Reverse Transcriptase Inhibitor ◽  
Transcriptase Inhibitor ◽  
World Health ◽  
First Line ◽  
Cross Sectional ◽  
Hiv Drug Resistance ◽  
Reverse Transcriptase Inhibitor

Abstract Background The World Health Organization (WHO) HIV Drug Resistance (HIVDR) report 2012 demonstrated that the levels of HIVDR to first-line antiretroviral therapy (ART) are increasing. This finding threatens to reverse a decade of gains in HIV/AIDS epidemic control. The WHO Global Action Plan for HIVDR emphasizes strengthening surveillance of drug resistance through the implementation of national cross-sectional surveys. We conducted such survey to determine the prevalence of HIVDR among ART-naive patients in Zimbabwe and to describe the profile of the surveillance drug resistance mutations (SDRM) encountered in the country. Methods A prospective, nationally representative, cross-sectional survey was conducted in 35 clinical sites selected using two stage probability proportional to size sampling. Patients were enrolled during April–July 2015. Specimens were sent for genotyping to CDC Atlanta. SDRM were interpreted using Stanford HIV Drug Resistance Database classification. Results A total of 361 subjects were surveyed. Most participants were female (60.3%) and the median age was 35.8 years. Thirty-four out of 361subjects presented with ≥1 SDRM (9.4%, 95% confidence interval: 6.8–12.8%) prior to initiation antiretroviral therapy (ART). Non-nucleoside reverse transcriptase inhibitor (NNRTI) mutations were the most commonly detected mutation (n = 30). Only two patients presented with a nucleoside reverse transcriptase inhibitor mutation and one patient presented with a protease inhibitor mutation. In two patients, ≥3 SDRMs were detected, which may suggest they were not truly ART-naïve. Conclusion This study provides national estimates of HIVDR in a high burden country with broad access to ART and provides valuable inisight on the state of HIVDR in such setting. Zimbabwe has reached moderate levels of HIVDR in ART-naive patients, as specified by the WHO classification. These levels may impact the ability to achieve viral suppression in a significant number of patients initiating standard ART regimens in Zimbabwe, where NNRTI-based regimens are used as the first line. The use of drugs with high resistance barrier, such as dolutegravir, may improve the care of patients in the developing world, where individualized pretreatment genotype is not feasible. Disclosures All authors: No reported disclosures.

Diversity of HIV-1 subtypes and transmitted drug-resistance mutations among minority HIV-1 variants in a Turkish cohort

2021 ◽  
Vol 19 ◽  
Author(s):  
Rabia Can Sarinoglu ◽  
Uluhan Sili ◽  
Ufuk Hasdemir ◽  
Burak Aksu ◽  
Guner Soyletir ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Reverse Transcriptase ◽  
Transcriptase Inhibitor ◽  
Transmitted Drug Resistance ◽  
Resistance Mutations ◽  
Drug Resistance Mutations ◽  
Subtype B ◽  
Treatment Naïve ◽  
Reverse Transcriptase Inhibitor ◽  
Hiv 1

Background: The World Health Organization (WHO) recommends the surveillance of transmitted drug resistance mutations (TDRMs) to ensure the effectiveness and sustainability of HIV treatment programs. Objective: Our aim was to determine the TDRMs and evaluate the distribution of HIV-1 subtypes using and compared next-generation sequencing (NGS) and Sanger-based sequencing (SBS) in a cohort of 44 antiretroviral treatment-naïve patients. Methods: All samples that were referred to the microbiology laboratory for HIV drug resistance analysis between December 2016 and February 2018 were included in the study. After exclusions, 44 treatment-naive adult patients with a viral load of >1000 copies/mL were analyzed. DNA sequencing for reverse transcriptase and protease regions was performed using both DeepChek ABL single round kit and Sanger-based ViroSeq HIV-1 Genotyping System. The mutations and HIV-1 subtypes were analyzed using the Stanford HIVdb version 8.6.1 Genotypic Resistance software, and TDRMs were assessed using the WHO surveillance drug-resistance mutation database. HIV-1 subtypes were confirmed by constructing a maximum-likelihood phylogenetic tree using Los Alamos IQ-Tree software. Results: NGS identified nucleos(t)ide reverse transcriptase inhibitor (NRTI)-TDRMs in 9.1% of the patients, non-nucleos(t)ide reverse transcriptase inhibitor (NNRTI)-TDRMs in 6.8% of the patients, and protease inhibitor (PI)-TDRMs in 18.2% of the patients at a detection threshold of ≥1%. Using SBS, 2.3% and 6.8% of the patients were found to have NRTI- and NNRTI-TDRMs, respectively, but no major PI mutations were detected. M41L, L74I, K65R, M184V, and M184I related to NRTI, K103N to NNRTI, and N83D, M46I, I84V, V82A, L24I, L90M, I54V to the PI sites were identified using NGS. Most mutations were found in low-abundance (frequency range: 1.0% - 4.7%) HIV-1 variants, except M41L and K103N. The subtypes of the isolates were found as follows; 61.4% subtype B, 18.2% subtype B/CRF02_AG recombinant, 13.6% subtype A, 4.5% CRF43_02G, and 2.3% CRF02_AG. All TDRMs, except K65R, were detected in HIV-1 subtype B isolates.. Conclusion: The high diversity of protease site TDRMs in the minority HIV-1 variants and prevalence of CRFs were remarkable in this study. All minority HIV-1 variants were missed by conventional sequencing. TDRM prevalence among minority variants appears to be decreasing over time at our center.

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