scholarly journals Pretreatment and Acquired Antiretroviral Drug Resistance Among Persons Living With HIV in Four African Countries

2020 ◽  
Author(s):  
Trevor A Crowell ◽  
Brook Danboise ◽  
Ajay Parikh ◽  
Allahna Esber ◽  
Nicole Dear ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Reverse Transcriptase ◽  
Management Strategies ◽  
World Health ◽  
Resistance Mutations ◽  
Reverse Transcriptase Inhibitors ◽  
African Countries ◽  
Nucleoside Reverse Transcriptase Inhibitors ◽  
Persons Living With Hiv ◽  
Nnrti Mutation

Abstract Background Emerging HIV drug resistance (HIVDR) could jeopardize the success of standardized HIV management protocols in resource-limited settings. We characterized HIVDR among antiretroviral therapy (ART)-naive and experienced participants in the African Cohort Study (AFRICOS). Methods From January 2013 to April 2019, adults with HIV-1 RNA >1000 copies/mL underwent ART history review and HIVDR testing upon enrollment at 12 clinics in Uganda, Kenya, Tanzania, and Nigeria. We calculated resistance scores for specific drugs and tallied major mutations to non-nucleoside reverse transcriptase inhibitors (NNRTIs), nucleoside reverse transcriptase inhibitors (NRTIs), and protease inhibitors (PIs) using Stanford HIVDB 8.8 and SmartGene IDNS software. For ART-naive participants, World Health Organization surveillance drug resistance mutations (SDRMs) were noted. Results HIVDR testing was performed on 972 participants with median age 35.7 (interquartile range [IQR] 29.7–42.7) years and median CD4 295 (IQR 148–478) cells/mm3. Among 801 ART-naive participants, the prevalence of SDRMs was 11.0%, NNRTI mutations 8.2%, NRTI mutations 4.7%, and PI mutations 0.4%. Among 171 viremic ART-experienced participants, NNRTI mutation prevalence was 83.6%, NRTI 67.8%, and PI 1.8%. There were 90 ART-experienced participants with resistance to both efavirenz and lamivudine, 33 (36.7%) of whom were still prescribed these drugs. There were 10 with resistance to both tenofovir and lamivudine, 8 (80.0%) of whom were prescribed these drugs. Conclusions Participants on failing ART regimens had a high burden of HIVDR that potentially limited the efficacy of standardized first- and second-line regimens. Management strategies that emphasize adherence counseling while delaying ART switch may promote drug resistance and should be reconsidered.

scholarly journals Barcoding analysis of HIV drug resistance mutations using Oxford Nanopore MinION (ONT) sequencing

2017 ◽  
Author(s):  
Claudia Gonzalez ◽  
Jessica Gondola ◽  
Alma Y Ortiz ◽  
Juan M Castillo ◽  
Juan M Pascale ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Reverse Transcriptase ◽  
Treatment Resistance ◽  
Resistance Mutations ◽  
Reverse Transcriptase Inhibitors ◽  
Nucleoside Reverse Transcriptase Inhibitors ◽  
Hiv Drug Resistance ◽  
Drug Resistance Mutations ◽  
Oxford Nanopore ◽  
Pre Treatment

ABSTRACTDetermination of HIV drug resistance (HIVDR) is becoming an integral baseline HIV evaluation for newly infected subjects, as the level of pre-treatment resistance is increasing worldwide. Until now, the gold standard for monitoring ART mutations is the Sanger sequencing method, however, next-generation sequencing technologies (NGS) because high-throughput capability, are gaining attention as a method for detection of HIVDR. In the present work, we evaluated the use of the Oxford Nanopore Technologies (ONT) MinION as an alternative method for detection of drug resistance mutations in pre-treatment HIV positive subjects.We evaluate 36 samples taken during November 2016 from treatment naïve subjects with age greater than 18 years old, who went to the lab for their first HIV monitoring. To evaluate the agreement between Sanger and MinION generated sequences, we aligned the sequences (∼1200bp) with muscle v. 3.8.31. Then we counted the differences and calculated the p-distance of the obtained sequences, comparing paired sequences and grouping Sanger and MinION obtained sequences. The percentage of similarity among each sequence was also evaluated.All samples were submitted to the Standford University HIV drug resistance database (HIVdb version 8.4). Then we compared the resistance predictions obtained from the sequences generated by Sanger and MinION methods.Results: The median of available pores was 1314 for the first run, 1215 for the second run, and 536 for the third run. After 3 hours with SQK-NSK007 a total of 18803 2D reads were base-called and in 16577 reads (88%) a barcode was detected.Comparing the nucleotide differences of each sample, we observed that 23 (74%) samples had identical sequence, for the other samples the percentage of identity among each analyzed sequence was greater than 95%. A good positive predictive value (100%) in the estimation of drug resistance mutations in the groups of protease inhibitors (PI), nucleoside reverse transcriptase inhibitors (NRTIs), and non-nucleoside reverse transcriptase inhibitors (NNRTIs).We present an approach for the analysis of HIV reads generated with MinION ONT, further studies are guaranteed before the application of this methodology in clinical settings to assess its suitability for HIVDR testing.

Evaluation of a novel in-house HIV-1 genotype drug resistance assay using clinical samples in China

2021 ◽  
Vol 19 ◽  
Author(s):  
Peijie Gao ◽  
Fengting Yu ◽  
Xiaozhen Yang ◽  
Dan Li ◽  
Yalun Shi ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Reverse Transcriptase ◽  
High Efficiency ◽  
Clinical Samples ◽  
Genotype Distribution ◽  
Resistance Mutations ◽  
Reverse Transcriptase Inhibitors ◽  
Nucleoside Reverse Transcriptase Inhibitors ◽  
Subtype B ◽  
Hiv 1

Background: HIV drug resistance poses a major challenge for anti-retroviral treatment (ART) and the prevention and control of HIV epidemic. Objective: The study aims to establish a novel in-house assay with high efficiency, named AP in-house method, that would be suitable for HIV-1 drug resistance detection in China. Methods: An in-house HIV-1 genotyping method was used to sequence the partial pol gene from 60 clinical plasma samples; the results of our test were compared with a commercial ViroSeq HIV-1 genotyping system. Results : Among sixty samples, 58(96.7%) were successfully amplified by AP in-house method, five of them harbored viral load below 1,000 copies/ml. The genotype distribution was 43.1% CRF07_BC (25/58), 39.7% CRF01_AE (23/58), 6.9% CRF55_01B (4/58), 5.2% subtype B (3/58) and 5.2% CRF08_BC (3/58). Compared with that of the ViroSeq system, the consistent rate of these nucleotides and amino acids obtained by AP in-house method was up to 99.5 ± 0.4% and 99.5 ± 0.4%, respectively. A total of 290 HIV-1 drug resistance mutations were identified by two methods, including 126 nucleoside reverse transcriptase inhibitors (NRTIs), 145 non-nucleoside reverse transcriptase inhibitors (NNRTIs) and 19 protease inhibitors (PIs) resistance mutations. Out of them, 94.1% (273/290) were completely concordant between the AP in-house method and the ViroSeq system. Conclusion: Overall, the evaluation of AP in-house method provided comparable results to those of the ViroSeq system on diversified HIV-1 subtypes in China.

scholarly journals Transmitted drug resistance and transmission clusters among HIV-1 treatment-naïve patients in Guangdong, China: a cross-sectional study

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Yun Lan ◽  
Linghua Li ◽  
Xiang He ◽  
Fengyu Hu ◽  
Xizi Deng ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Reverse Transcriptase ◽  
Transmitted Drug Resistance ◽  
Resistance Mutations ◽  
Reverse Transcriptase Inhibitors ◽  
Nucleoside Reverse Transcriptase Inhibitors ◽  
Cross Sectional ◽  
Genetic Transmission ◽  
Treatment Naïve ◽  
Hiv 1

Abstract Background Transmitted drug resistance (TDR) that affects the effectiveness of the first-line antiretroviral therapy (ART) regimen is becoming prevalent worldwide. However, its prevalence and transmission among HIV-1 treatment-naïve patients in Guangdong, China are rarely reported. We aimed to comprehensively analyze the prevalence of TDR and the transmission clusters of HIV-1 infected persons before ART in Guangdong. Methods The HIV-1 treatment-naïve patients were recruited between January 2018 and December 2018. The HIV-1 pol region was amplified by reverse transcriptional PCR and sequenced by sanger sequencing. Genotypes, surveillance drug resistance mutations (SDRMs) and TDR were analyzed. Genetic transmission clusters among patients were identified by pairwise Tamura-Nei 93 genetic distance, with a threshold of 0.015. Results A total of 2368 (97.17%) HIV-1 pol sequences were successfully amplified and sequenced from the enrolled 2437 patients. CRF07_BC (35.90%, 850/2368), CRF01_AE (35.56%, 842/2368) and CRF55_01B (10.30%, 244/2368) were the main HIV-1 genotypes circulating in Guangdong. Twenty-one SDRMs were identified among fifty-two drug-resistant sequences. The overall prevalence of TDR was 2.20% (52/2368). Among the 2368 patients who underwent sequencing, 8 (0.34%) had TDR to protease inhibitors (PIs), 22 (0.93%) to nucleoside reverse transcriptase inhibitors (NRTIs), and 23 (0.97%) to non-nucleoside reverse transcriptase inhibitors (NNRTIs). Two (0.08%) sequences showed dual-class resistance to both NRTIs and NNRTIs, and no sequences showed triple-class resistance. A total of 1066 (45.02%) sequences were segregated into 194 clusters, ranging from 2 to 414 sequences. In total, 15 (28.85%) of patients with TDR were included in 9 clusters; one cluster contained two TDR sequences with the K103N mutation was observed. Conclusions There is high HIV-1 genetic heterogeneity among patients in Guangdong. Although the overall prevalence of TDR is low, it is still necessary to remain vigilant regarding some important SDRMs.

scholarly journals Increased acquired protease inhibitor drug resistance mutations in minor HIV-1 quasispecies from infected patients suspected of failing on national second-line therapy in South Africa

2020 ◽  
Author(s):  
Adetayo Emmanuel Obasa ◽  
Anoop T Ambikan ◽  
Soham Gupta ◽  
Ujjwal Neogi ◽  
Graeme Brendon Jacobs
Keyword(s):  
South Africa ◽  
Drug Resistance ◽  
Reverse Transcriptase ◽  
Second Line ◽  
Viral Quasispecies ◽  
Resistance Mutations ◽  
Reverse Transcriptase Inhibitors ◽  
Nucleoside Reverse Transcriptase Inhibitors ◽  
Drug Resistance Mutations ◽  
Hiv 1

Abstract Background: HIV-1C has been shown to have a greater risk of virological failure and reduced susceptibility towards boosted protease inhibitors (bPIs), a component of second-line combination antiretroviral therapy (cART) in South Africa. This study entailed an evaluation of HIV-1 drug resistance-associated mutations (RAMs) among minor viral populations through high-throughput sequencing genotypic resistance testing (HTS-GRT) in patients suspected of failing on the South African national second-line cART regimen with bPIs.Methods: During 2017 and 2018, 67 patient samples were selected, of which 56 samples were successfully analyzed. All patients were receiving bPIs as part of their cART. Viral RNA was extracted, and complete pol genes were amplified and sequenced using Illumina HiSeq2500, followed by bioinformatics analysis to quantify the RAMs according to the Stanford HIV Drug Resistance Database.Results: Statistically significantly (p<0.001) higher PI RAMs were observed in minor viral quasispecies (25%; 14/56) compared to nucleoside reverse transcriptase inhibitors (11%; 6/56), non-nucleoside reverse transcriptase inhibitors (9%; 5/56) and integrase inhibitor RAM (4%; 2/56). The majority of the drug resistance mutations in the minor viral quasispecies were observed in the V82A mutation (n=13) in protease and K65R (n=5), K103N (n=7) and M184V (n=5) in reverse transcriptase.Conclusions: HTS-GRT improved the identification of PI and reverse transcriptase inhibitor (RTI) RAMs in second-line cART patients from South Africa compared to the conventional GRT with ≥20% used in Sanger-based sequencing. Several RTI RAMs, such as K65R, M184V or K103N and PI RAM V82A, were identified in <20% of the population. Deep sequencing could be of greater value in detecting acquired resistance mutations early.

scholarly journals Prevalence of transmitted drug resistance among HIV-1 treatment-naive patients in Beijing

2018 ◽  
Vol 146 (3) ◽  
pp. 339-344 ◽  
Author(s):  
Y.X. Song ◽  
R.L. Xin ◽  
Z.C. Li ◽  
H.W. Yu ◽  
W.H. Lun ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Reverse Transcriptase ◽  
Transmitted Drug Resistance ◽  
Resistance Mutations ◽  
Reverse Transcriptase Inhibitors ◽  
Nucleoside Reverse Transcriptase Inhibitors ◽  
Frequent Mutations ◽  
Treatment Naïve ◽  
Sex With Men ◽  
Hiv 1

AbstractTo optimise patients’ outcomes and gain insight into transmitted drug resistance (TDR) among human immunodeficiency virus (HIV)-1 treatment-naive patients in Beijing, the prevalence of TDR was assessed. Demographic and clinical data of 1241 treatment-naive patients diagnosed between April 2014 and February 2015 were collected. TDR was defined using the Stanford University HIV drug resistance mutations database. The risk factors were evaluated by multi-logistic regression analysis. Among 932 successfully amplified cases, most were male (96.78%) and infected through men having sex with men (91.74%). Genotype were CRF01_AE (56.44%), B (20.60%), CRF07_BC (19.96%), C (1.61%) and other genotypes (1.39%). The overall prevalence of TDR was 6.12%. Most frequent mutations occurred in non-nucleoside reverse transcriptase inhibitors (NNRTIs) (3.11%), followed by protease inhibitors (PIs) (2.25%) and nucleoside reverse transcriptase inhibitors (NRTIs) (1.32%). Furthermore, HIV-1 genotype was associated with high risk of resistance, in which genotype C and other genotype may have higher risk for resistance. The prevalence among treatment-naive patients in Beijing was low. Resistance to NNRTIs was higher than with PIs or NRTIs. Continuous monitoring of regional levels of HIV-1 TDRs would contribute to improve treatment outcomes and prevent failures.

scholarly journals Higher Frequency of HIV-1 Drug Resistance and Increased Nucleoside Reverse Transcriptase Inhibitor Mutations among the HIV-1 Positive Antiretroviral Therapy–Naïve patients Coinfected With Mycobacterium tuberculosis Compared With Only HIV Infection in India

2018 ◽  
Vol 11 ◽  
pp. 117863371878887
Author(s):  
Sanjeev Sinha ◽  
Kartik Gupta ◽  
Nawaid Hussain Khan ◽  
Dibyakanti Mandal ◽  
Mikashmi Kohli ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Mycobacterium Tuberculosis ◽  
Antiretroviral Therapy ◽  
Reverse Transcriptase ◽  
Resistance Mutations ◽  
Reverse Transcriptase Inhibitors ◽  
Nucleoside Reverse Transcriptase Inhibitors ◽  
Drug Resistance Mutations ◽  
Group 2 ◽  
Hiv 1

Background: Emergence of human immunodeficiency virus (HIV) drug resistance mutations prior to highly active antiretroviral therapy is a serious problem in clinical management of HIV/AIDS. Risk factors for appearance of drug resistance mutations are not known. We hypothesize that Mycobacterium tuberculosis infection may contribute to rapid emergence of such mutations in antiretroviral therapy–naïve patients. Methods: A total of 115 patients were recruited in this study of which 75 were HIV+TB+ coinfected (group 1) and 40 were HIV+TB− (group 2). Blood samples from all the patients were collected and CD4+ cell counts; HIV-1 plasma viral load and sequencing of protease and two-third region of reverse transcriptase of HIV-1 was performed and analyzed for drug resistance pattern. Results: For patients with HIV+TB+, 10.6% (8/75) had mutations to non-nucleoside reverse transcriptase inhibitors (NNRTIs), 4% (3/75) to nucleoside reverse transcriptase inhibitors, and only 2.6% (2/75) patients had mutations to protease inhibitors. Interestingly, for group 2 (HIV+TB−), there were only NNRTI mutations found among these patients, and only 3 patients (7.5%) had these drug-resistant mutations. Clade typing and phylogenetic tree analysis showed HIV-1 subtype C predominance in these patients. Conclusions: Our study showed that higher percentage of HIV drug resistance mutations was found among HIV+TB+ individuals compared with tuberculosis-uninfected patients. Tuberculosis coinfection may be a risk factor for emergence of high frequency of drug resistance mutations. Studies with a larger sample size will help to confirm these findings from the Indian population.

scholarly journals Prevalence and Transmission Dynamics of HIV-1 Transmitted Drug Resistance in a Southeastern Cohort

2018 ◽  
Vol 5 (8) ◽  
Author(s):  
Sara N Levintow ◽  
Nwora Lance Okeke ◽  
Stephane Hué ◽  
Laura Mkumba ◽  
Arti Virkud ◽  
...  
Keyword(s):  
North Carolina ◽  
Drug Resistance ◽  
Reverse Transcriptase ◽  
Transmission Dynamics ◽  
Resistance Testing ◽  
Transmitted Drug Resistance ◽  
Resistance Mutations ◽  
Reverse Transcriptase Inhibitors ◽  
Nucleoside Reverse Transcriptase Inhibitors ◽  
Transmission Networks

Abstract Background Transmitted drug resistance (TDR) compromises clinical management and outcomes. Transmitted drug resistance surveillance and identification of growing transmission clusters are needed in the Southeast, the epicenter of the US HIV epidemic. Our study investigated prevalence and transmission dynamics in North Carolina. Methods We analyzed surveillance drug resistance mutations (SDRMs) using partial pol sequences from patients presenting to 2 large HIV outpatient clinics from 1997 to 2014. Transmitted drug resistance prevalence was defined as ≥1 SDRMs among antiretroviral therapy (ART)–naïve patients. Binomial regression was used to characterize prevalence by calendar year, drug class, and demographic and clinical factors. We assessed the transmission networks of patients with TDR with maximum likelihood trees and Bayesian methods including background pol sequences (n = 15 246). Results Among 1658 patients with pretherapy resistance testing, ≥1 SDRMs was identified in 199 patients, with an aggregate TDR prevalence of 12% (95% confidence interval, 10% to 14%) increasing over time (P = .02). Resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs; 8%) was common, followed by nucleoside reverse transcriptase inhibitors (4%) and protease inhibitors (2%). Factors associated with TDR were being a man reporting sex with men, white race, young age, higher CD4 cell count, and being a member of a transmission cluster. Transmitted drug resistance was identified in 106 clusters ranging from 2 to 26 members. Cluster resistance was primarily NNRTI and dominated by ART-naïve patients or those with unknown ART initiation. Conclusions Moderate TDR prevalence persists in North Carolina, predominantly driven by NNRTI resistance. Most TDR cases were identified in transmission clusters, signifying multiple local transmission networks and TDR circulation among ART-naïve persons. Transmitted drug resistance surveillance can detect transmission networks and identify patients for enhanced services to promote early treatment.

scholarly journals Prevalence of Transmitted HIV-1 Drug Resistance Among Treatment-naive Individuals in China, 2000-2016

2021 ◽  
Author(s):  
Huangbo Yuan ◽  
Zhenqiu Liu ◽  
Xuefu Wu ◽  
Mingshan Wu ◽  
Qiwen Fang ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Reverse Transcriptase ◽  
Genetic Relationships ◽  
Transmitted Drug Resistance ◽  
Resistance Mutations ◽  
Reverse Transcriptase Inhibitors ◽  
Nucleoside Reverse Transcriptase Inhibitors ◽  
Relative Transmission ◽  
Treatment Naïve ◽  
Hiv 1

Abstract HIV with transmitted drug-resistance (TDR) limits the therapeutic options available for treatment-naive HIV patients. This study aimed to further our understanding of the prevalence and transmission characteristics of HIV with TDR for the application of first-line antiretroviral regimens. A total of 6578 HIV-1 protease/reverse-transcriptase sequences from treatment-naive individuals in China between 2000 and 2016, were obtained from the Los Alamos HIV Sequence Database and were analyzed for TDR. Transmission networks were constructed to determine genetic relationships. The spreading routes of large TDR clusters were identified using a Bayesian phylogeographic framework. TDR mutations were detected in 274 (4.51%) individuals, with 1.40% harboring TDR to nucleoside reverse transcriptase inhibitors, 1.52% to non-nucleoside reverse transcriptase inhibitors, and 1.87% to protease inhibitors. The most frequent mutation was M46L (58, 0.89%), followed by K103N (36, 0.55%), M46I (36, 0.55%), and M184V (26, 0.40%). The prevalence of total TDR initially decreased between 2000 and 2010 (OR = 0.83, 95% CI 0.73–0.95), and then increased thereafter (OR = 1.50, 95% CI 1.13–1.97). The proportion of sequences in a cluster (clustering rate) among HIV with TDR sequences was lower than that of sequences without TDR (40.5% vs. 48.8%, P = 0.023) and increased from 27.3% in 2005–2006 to 63.6% in 2015–2016 (P < 0.001). While most TDR mutations were associated with reduced relative transmission fitness, mutation M46I was associated with higher relative transmission fitness than the wild-type strain. This study identified a low-level prevalence of TDR HIV in China during the last two decades. However, the increasing TDR HIV rate sicn 2010, the persistent circulation of drug resistance mutations, and the expansion of self-sustaining drug resistance reservoirs may compromise the efficacy of antiretroviral therapy programs.

scholarly journals HIV Drug Resistance Mutations in Patients with HIV and HIV-TB Coinfection After Failure of First-Line Therapy: A Prevalence Study in a Resource-Limited Setting

2019 ◽  
Vol 18 ◽  
pp. 232595821984906
Author(s):  
Nawaid Hussain Khan ◽  
Mikashmi Kohli ◽  
Kartik Gupta ◽  
Bimal Kumar Das ◽  
Ravindra Mohan Pandey ◽  
...  
Keyword(s):  
Reverse Transcriptase ◽  
Drug Resistant ◽  
Resistance Mutations ◽  
Reverse Transcriptase Inhibitors ◽  
Nucleoside Reverse Transcriptase Inhibitors ◽  
First Line Therapy ◽  
Resource Limited ◽  
High Prevalence ◽  
Hiv 1 ◽  
Limited Setting

Introduction: The present study aimed to report the prevalent HIV-1 drug-resistant mutations in patients with HIV-1 alone and tuberculosis (TB) coinfection alone to improve our understanding of the mutation patterns and aid treatment decisions. Methods: Patients with HIV-1 and HIV-TB on treatment for more than 1 year with suspected failure were recruited. Sequencing of protease and two-thirds of the region of reverse transcriptase gene was done for drug-resistant mutations. Results: In the HIV-TB group (n = 25), 88%, 92%, and 12% had mutations to nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), and protease inhibitors (PIs), respectively. In the HIV-alone group (n = 25), 84%, 100%, and 4% had mutations to NRTIs, NNRTIs, and PIs, respectively. M184V, M41L, D67N, G190A, A98G, and K103N were the most common mutations seen. Conclusion: There is a high prevalence of drug-resistant mutations in HIV and HIV-TB coinfected patients.

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