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.

New resistance mutations to nucleoside reverse transcriptase inhibitors at codon 184 of HIV-1 reverse transcriptase (M184L and M184T)

2018 ◽  
Vol 93 (1) ◽  
pp. 50-59 ◽  
Author(s):  
Lydia Pouga ◽  
Maria Mercedes Santoro ◽  
Charlotte Charpentier ◽  
Domenico Di Carlo ◽  
Isabella Romeo ◽  
...  
Keyword(s):  
Reverse Transcriptase ◽  
Resistance Mutations ◽  
Reverse Transcriptase Inhibitors ◽  
Nucleoside Reverse Transcriptase Inhibitors ◽  
Hiv 1

scholarly journals PREVALENCE OF DRUG RESISTANT HIV STRAINS IN HIV-INFECTED PATIENTS OF REPRODUCTIVE AGE

2016 ◽  
Vol 72 (2) ◽  
pp. 8-13
Author(s):  
N. Babii
Keyword(s):  
Reverse Transcriptase ◽  
Reproductive Age ◽  
Drug Resistant ◽  
Resistance Mutations ◽  
Reverse Transcriptase Inhibitors ◽  
Nonnucleoside Reverse Transcriptase Inhibitors ◽  
High Prevalence ◽  
High Level ◽  
Drug Resistant Strains ◽  
Level Resistance

The prevalence of drug resistant HIV strains among HIV-positive reproductive aged persons with ineffective antiretroviral therapy (ART) was assessed. The prevalence of drug resistant strains of HIV was 73.8% in the group of women and 89.29% in the group of men (totally in 80.0% of patients). In the spectrum of drug resistance mutations (DRMs) the most prevalent mutation associated with high-level resistance to nucleoside reverse transcriptase inhibitors was substitution M184V (80.36%); in addition, the high prevalence of K65R (26.79%) was indicated. The most common mutations causing a high-level resistance to nonnucleoside reverse transcriptase inhibitors were G190S/A (57.14%), Y181C (37.50%), K101E (33.93%). The DRMs to protease inhibitors were indicated with significantly less frequent (5.36%).

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 INSTIs and NNRTIs Potently Inhibit HIV-1 Polypurine Tract Mutants in a Single Round Infection Assay

Viruses ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2501
Author(s):  
Steven J. Smith ◽  
Andrea Ferris ◽  
Xuezhi Zhao ◽  
Gary Pauly ◽  
Joel P. Schneider ◽  
...  
Keyword(s):  
Reverse Transcriptase ◽  
Envelope Gene ◽  
Strand Transfer ◽  
Resistance Mutations ◽  
Reverse Transcriptase Inhibitors ◽  
Nucleoside Reverse Transcriptase Inhibitors ◽  
Integrase Gene ◽  
Polypurine Tract ◽  
Emergence Of Resistance ◽  
Hiv 1

Integrase strand transfer inhibitors (INSTIs) are a class of antiretroviral compounds that prevent the insertion of a DNA copy of the viral genome into the host genome by targeting the viral enzyme integrase (IN). Dolutegravir (DTG) is a leading INSTI that is given, usually in combination with nucleoside reverse transcriptase inhibitors (NRTIs), to treat HIV-1 infections. The emergence of resistance to DTG and other leading INSTIs is rare. However, there are recent reports suggesting that drug resistance mutations can occur at positions outside the integrase gene either in the HIV-1 polypurine tract (PPT) or in the envelope gene (env). Here, we used single round infectivity assays to measure the antiviral potencies of several FDA-approved INSTIs and non-nucleoside reverse transcriptase inhibitors (NNRTIs) against a panel of HIV-1 PPT mutants. We also tested several of our promising INSTIs and NNRTIs in these assays. No measurable loss in potency was observed for either INSTIs or NNRTIs against the HIV-1 PPT mutants. This suggests that HIV-1 PPT mutants are not able, by themselves, to confer resistance to INSTIs or NNRTIs.

HIV-1 Resistance Profile of the Novel Nucleoside Reverse Transcriptase Inhibitor β-D-2′,3′-Dideoxy-2′,3′-Didehydro-5-Fluorocytidine (Reverset™)

2003 ◽  
Vol 14 (1) ◽  
pp. 49-59 ◽  
Author(s):  
Romas Geleziunas ◽  
Karen Gallagher ◽  
Hangchun Zhang ◽  
Lee Bacheler ◽  
Sena Garber ◽  
...  
Keyword(s):  
Reverse Transcriptase ◽  
Highly Active Antiretroviral Therapy ◽  
Resistance Mutations ◽  
Reverse Transcriptase Inhibitors ◽  
Nucleoside Reverse Transcriptase Inhibitors ◽  
Resistance Profile ◽  
Wide Range ◽  
Resistant Strains ◽  
Hiv 1

Nucleoside reverse transcriptase inhibitors (NRTIs) represent the cornerstone of highly active antiretroviral therapy when combined with non-nucleoside reverse transcriptase inhibitors (NNRTIs) or HIV-1 protease inhibitors (PIs). Unlike the NNRTIs and PIs, NRTIs must be successively phosphorylated by cellular kinases to a triphosphate form, which represents the active metabolite possessing antiviral activity. Emergence of viral resistance to NRTIs has severely hampered treatment options for persons infected with HIV-1. As such, there is an urgent need to develop NRTIs capable of suppressing NRTI-resistant strains of HIV-1. We have recently reported that the cytidine analogue D-d4FC (DPC817, Reverset™) effectively inhibits clinically prevalent resistant strains of HIV-1. In this report, we have extended these findings and now describe a detailed resistance profile for this novel NRTI. By examining a panel of 50 viruses carrying RTs derived from HIV-1 clinical isolates displaying a wide range of NRTI resistance mutations, we report that the median fold increase in effective antiviral concentration for such a panel of viruses is 3.2, which is comparable to tenofovir (2.8-fold) and didanosine (2.4-fold). D-d4FC is highly effective at inhibiting subsets of lamivudine-and zidovudine-resistant variants but, like other NRTIs, seems less potent against multi-NRTI-resistant viruses, particularly those carrying the Q151M complex of mutations. Finally, in vitro selections for HIV-1 mutants capable of replicating in the presence of D-d4FC yielded a mutant carrying the RT K65R mutation. This mutation confers 5.3- to 8.7-fold resistance to D-d4FC in vitro. These findings suggest that D-d4FC may represent an alternative NRTI for the treatment of individuals infected with lamivudine- and zidovudine-resistant strains of HIV-1.

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.

HIV CRF08_BC AND X4 STRAIN ARE ASSOCIATED WITH POSING MAJOR NUCLEOSIDE AND NON-NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS RESISTANCE MUTATIONS

2015 ◽  
Vol 77 (6) ◽  
Author(s):  
Afiono Agung Prasetyo ◽  
Ratna Sariyatun
Keyword(s):  
Reverse Transcriptase ◽  
Odds Ratio ◽  
Adjusted Odds Ratio ◽  
Hiv Treatment ◽  
Genomic Sequences ◽  
Resistance Mutations ◽  
Reverse Transcriptase Inhibitors ◽  
Nucleoside Reverse Transcriptase Inhibitors ◽  
Hiv 1 ◽  
Inducing Resistance

In HIV treatment, surveillance of mutations inducing resistance to NRTIs (Nucleoside Reverse Transcriptase Inhibitors) and NNRTIs (Non-Nucleoside Reverse Transcriptase Inhibitors) is important. This study analyzed 2,071 HIV-1 genomic sequences directed to detection of major NRTIs and NNRTIs resistance mutations and viral tropism. CRF08_BC and X4 strain more likely had major NRTIs (adjusted odds ratio (aOR) 3.0, 95% CI 1.182-7.820, p=0.021 and aOR 1.7, 95% CI 1.233-2.368, p=0.001; respectively) and NNRTIs (aOR 3.3, 95% CI 1.281-8.365, p=0.013 and aOR 1.4, 95% CI 1.037-1.977, p=0.029, respectively) resistance mutations. Subtype A1 (aOR 0.2, 95% CI 0.069-0.702, p=0.011) and C (aOR 0.4, 95% CI 0.241-0.648, p<0.001) were associated with major NRTIs resistance mutations. The occurrence of major NRTIs and NNRTIs resistance mutations in HIV subtype A1, C, CRF08_BC, and X4 viruses should be a particular concern.  

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