HIV-1 Resistance to Antiretroviral Drugs

2019 ◽  
pp. 245-256
Author(s):  
Tamara Bininashvili ◽  
Quentin Doperalski ◽  
Naiel Nassar
Keyword(s):  
Drug Resistance ◽  
Significant Role ◽  
Antiretroviral Drugs ◽  
Cross Resistance ◽  
Previous Exposure ◽  
Resistance Mutations ◽  
Hiv Drug Resistance ◽  
Drug Resistance Mutations ◽  
Resistance Patterns ◽  
Hiv 1

Discuss the different HIV drug resistance mutations and cross-resistance patterns in each class of HIV medication. In recent years, newer HIV medications have been introduced, and several studies have identified resistance mutations associated with the newer medications. • Previous exposure to antiretroviral (ARV) medications has a significant role in the development of drug resistance, especially in patients who are noncompliant with medications....

scholarly journals Rapid Detection of Common HIV-1 Drug Resistance Mutations by Use of High-Resolution Melting Analysis and Unlabeled Probes

2016 ◽  
Vol 55 (1) ◽  
pp. 122-133 ◽  
Author(s):  
David Sacks ◽  
Johanna Ledwaba ◽  
Lynn Morris ◽  
Gillian M. Hunt
Keyword(s):  
Drug Resistance ◽  
High Resolution ◽  
High Resolution Melting ◽  
Antiretroviral Drugs ◽  
High Resolution Melting Analysis ◽  
Resistance Mutations ◽  
Drug Resistance Mutations ◽  
Melting Analysis ◽  
Analytical Sensitivities ◽  
Hiv 1

ABSTRACTHIV rapidly accumulates resistance mutations following exposure to subtherapeutic concentrations of antiretroviral drugs that reduces treatment efficacy. High-resolution melting analysis (HRMA) has been used to successfully identify single nucleotide polymorphisms (SNPs) and to genotype viral and bacterial species. Here, we tested the ability of HRMA incorporating short unlabeled probes to accurately assign drug susceptibilities at the 103, 181, and 184 codons of the HIV-1 reverse transcriptase gene. The analytical sensitivities of the HRMA assays were 5% of mixed species for K103N and Y181C and 20% for M184V. When applied to 153 HIV-1 patient specimens previously genotyped by Sanger population sequencing, HRMA correctly assigned drug sensitivity or resistance profiles to 80% of the samples at codon 103 (K103K/N) (Cohen's kappa coefficient [κ] > 0.6;P< 0.05), 90% at 181 (Y181Y/C) (κ > 0.74,P< 0.05), and 80% at 184 (M184M/V) (κ > 0.62;P< 0.05). The frequency of incorrect genotypes was very low (≤1 to 2%) for each assay, which in most cases was due to the higher sensitivity of the HRMA assay. Specimens for which drug resistance profiles could not be assigned (9 to 20%) often had polymorphisms in probe binding regions. Thus, HRMA is a rapid, inexpensive, and sensitive method for the determination of drug sensitivities caused by major HIV-1 drug resistance mutations and, after further development to minimize the melting effects of nontargeted polymorphisms, may be suitable for surveillance purposes.

PREVALENCE AND STRUCTURE OF HIV-1 DRUG RESISTANCE AMONG TREATMENT NAÏVE PATIENTS SINCE THE INTRODUCTION OF ANTIRETROVIRAL THERAPY IN THE RUSSIAN FEDERATION

2019 ◽  
Vol 11 (2) ◽  
pp. 75-83 ◽  
Author(s):  
A. A. Kirichenko ◽  
D. E. Kireev ◽  
A. E. Lopatukhin ◽  
A. V. Murzakova ◽  
I. A. Lapovok ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Reverse Transcriptase ◽  
Russian Federation ◽  
Antiretroviral Drugs ◽  
Transmitted Drug Resistance ◽  
Resistance Mutations ◽  
Drug Resistance Mutations ◽  
Treatment Naïve ◽  
The Russian Federation ◽  
Hiv 1

Aim: to analyze the prevalence, structure of drug resistance and drug resistance mutations in the protease and reverse transcriptase genes of HIV-1 among treatment naïve patients.Materials and methods. We analyzed protease and reverse transcriptase sequences from 1560 treatment naïve HIV-infected patients from all Federal Districts of the Russian Federation with the first positive immune blot during 1998–2017. Sequences were analyzed for the presence of drug resistance mutations and predicted drug resistance to antiretroviral drugs using two algorithms — Stanford HIVDR Database (HIVdb) and the 2009 SDRM list (CPR).Results. The prevalence of drug resistance mutations was 11,1%. More often the prevalence of drug resistance was found for non-nucleoside reverse transcriptase inhibitor drugs (rilpivirine, nevirapine, efavirenz). The prevalence of transmitted drug resistance associated with mutations from the SDRM list was 5,3%, which is classified by the WHO as a moderate level. However, it should be noted that since the large-scale use of antiretroviral drugs in the Russian Federation, there has been a trend towards a gradual increase in the level of the transmitted drug resistance, and in 2016 it has already reached 6,1%.Conclusion. The results demonstrate the need for regular surveillance of the prevalence of HIV drug resistance to antiretroviral drugs among treatment naïve patients in the Russian Federation.

scholarly journals Patterns of acquired HIV-1 drug resistance mutations and predictors of virological failure in Moshi, northern Tanzania

2020 ◽  
Author(s):  
Shabani Ramadhani Mziray ◽  
Happiness H Kumburu ◽  
Hellen B Assey ◽  
Tolbert B Sonda ◽  
Michael J Mahande ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Reverse Transcriptase ◽  
Virological Failure ◽  
Health Concern ◽  
Resistance Mutations ◽  
Hiv Drug Resistance ◽  
Drug Resistance Mutations ◽  
Northern Tanzania ◽  
Hiv Drugs ◽  
Hiv 1

AbstractDrug resistance is a public health concern. Profiles of HIV drug resistance mutations (HIVDRM) and virological failure (VF) are not extensively studied in Tanzania. This study aimed to determine HIVDRM and predictors of VF in HIV-infected individuals failing first-line HIV drugs in Moshi, northern Tanzania. A case-control study was conducted at KCMC, Mawenzi, Pasua and Majengo health facilities with HIV-care and treatment clinics in Moshi from October, 2017 to August, 2018. Cases and controls were HIV-infected individuals with VF and viral suppression (VS) respectively. HIV-1 reverse transcriptase and protease genes were amplified and sequenced. Stanford University’s HIV drug resistance database and REGA HIV-1 Subtyping tool 3.0 determined HIVDRM and HIV-1 subtypes respectively. Odds ratios with 95% confidence intervals investigated predictors of VF. P-value <5% was considered statistically significant. A total of 124 participants were recruited, of whom 63 (50.8%) had VF and 61 (49.2%) had VS. Majority (66.1%) were females. Median [IQR] age and duration on ART were 45 [35-52] years and 72 [48-104] months respectively. Twenty five out of 26 selected HIV-1 RNA samples from cases were successively sequenced. Twenty four samples (96%) had at least one major mutation conferring resistance to HIV drugs, with non-nucleoside reverse transcriptase inhibitor (NNRTI) associated mutations as the majority (92%). Frequent NNRTI resistance mutations were K103N (n=11), V106M (n=5) and G190A (n=5). Prevalent nucleoside reverse transcriptase inhibitors mutations were M184V (n=17), K70R (n=7) and D67N (n=6). Dual-class resistance was observed in 16 (64%) samples. Thirteen samples (52%) had at least one thymidine analogue-associated resistance mutation (TAM). Three samples (12%) had T69D mutation with at least 1 TAM. Age was independently associated with VF [aOR 0.94 (0.90-0.97) p<0.001]. In conclusion, HIV drug resistance is common among people failing antiretroviral therapy and resistance testing will help to guide switching of HIV drugs.

An HIV-1 integrase genotype assay for the detection of drug resistance mutations

Sexual Health ◽  
2009 ◽  
Vol 6 (4) ◽  
pp. 305 ◽  
Author(s):  
Anna C. Hearps ◽  
Vicki Greengrass ◽  
Jennifer Hoy ◽  
Suzanne M. Crowe
Keyword(s):  
Drug Resistance ◽  
Antiretroviral Drugs ◽  
Plasma Samples ◽  
Integrase Inhibitors ◽  
Resistance Mutations ◽  
Assay Sensitivity ◽  
Integrase Gene ◽  
Drug Resistance Mutations ◽  
Hiv 1

Background: The integrase inhibitors (e.g. Raltegravir) are a new class of antiretroviral drugs that have recently become available for the treatment of patients with multi-drug resistant HIV-1 within Australia. The emergence of mutations that confer resistance to the integrase inhibitors has been observed in vivo; however, no commercial genotyping assay is currently available to screen for resistance to these drugs. Methods: The HIV-1 integrase gene was amplified from plasma-derived HIV-1 viral RNA via reverse transcription-polymerase chain reaction and genotype determined via population DNA sequencing. Drug resistance mutations and polymorphisms were detected using the Stanford University online HIV database. Assay sensitivity and reproducibility were determined using clinical and laboratory-derived samples. Results: Our in-house assay was capable of genotyping the integrase gene from all samples tested (n = 30) of HIV-1 subtypes B, C, D, F, CFR01_AE and CRF02_AG and can amplify the integrase region from plasma samples containing as few as 50 HIV RNA copies/mL. The assay is highly reproducible (average nucleotide concordance = 99.6%, n = 4) and is capable of detecting resistance-associated mutations. Conclusions:This assay is suitable for routine drug resistance screening of plasma samples from HIV-infected patients receiving integrase inhibitor antiretroviral drugs and also serves as a useful research tool.

scholarly journals Independent Evolution of Human Immunodeficiency Virus (HIV) Drug Resistance Mutations in Diverse Areas of the Brain in HIV-Infected Patients, with and without Dementia, on Antiretroviral Treatment

2004 ◽  
Vol 78 (18) ◽  
pp. 10133-10148 ◽  
Author(s):  
Theresa K. Smit ◽  
Bruce J. Brew ◽  
Wallace Tourtellotte ◽  
Susan Morgello ◽  
Benjamin B. Gelman ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Drug Resistance ◽  
Antiretroviral Therapy ◽  
Resistance Mutation ◽  
Antiretroviral Drugs ◽  
Resistance Mutations ◽  
Drug Resistance Mutations ◽  
Independent Evolution ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT AIDS dementia complex (ADC) in human immunodeficiency virus (HIV)-infected patients continues to be a problem in the era of highly active antiretroviral therapy (HAART). A better understanding of the drug resistance mutation patterns that emerge in the central nervous system (CNS) during HAART is of paramount importance as these differences in drug resistance mutations may explain underlying reasons for poor penetration of antiretroviral drugs into the CNS and suboptimal concentrations of the drugs that may reside in the brains of HIV-infected individuals during therapy. Thus, we provide a detailed analysis of HIV type 1 (HIV-1) protease and reverse transcriptase (RT) genes derived from different regions of the brains of 20 HIV-1-infected patients (5 without ADC, 2 with probable ADC, and 13 with various stages of ADC) on antiretroviral therapy. We show the compartmentalization and independent evolution of both primary and secondary drug resistance mutations to both RT and protease inhibitors in diverse regions of the CNS of HIV-infected patients, with and without dementia, on antiretroviral therapy. Our results suggest that the independent evolution of drug resistance mutations in diverse areas of the CNS may emerge as a consequence of incomplete suppression of HIV, probably related to suboptimal drug levels in the CNS and drug selection pressure. The emergence of resistant virus in the CNS may have considerable influence on the outcome of neurologic disease and also the reseeding of HIV in the systemic circulation upon failure of therapy.

scholarly journals High Detection Rate of HIV Drug Resistance Mutations among Patients Who Fail Combined Antiretroviral Therapy in Manaus, Brazil

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Yury Oliveira Chaves ◽  
Flávio Ribeiro Pereira ◽  
Rebeca de Souza Pinheiro ◽  
Diego Rafael Lima Batista ◽  
Antônio Alcirley da Silva Balieiro ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Antiretroviral Therapy ◽  
Reverse Transcriptase ◽  
Protease Inhibitors ◽  
People Living With Hiv ◽  
Resistance Mutations ◽  
Hiv Drug Resistance ◽  
Drug Resistance Mutations ◽  
Combined Antiretroviral Therapy ◽  
Hiv 1

Virologic failure may occur because of poor treatment adherence and/or viral drug resistance mutations (DRM). In Brazil, the northern region exhibits the worst epidemiological scenarios for the human immunodeficiency virus (HIV). Thus, this study is aimed at investigating the genetic diversity of HIV-1 and DRM in Manaus. The cross-sectional study included people living with HIV on combined antiretroviral therapy and who had experienced virological failure during 2018-2019. Sequencing of the protease/reverse transcriptase (PR/RT) and C2V3 of the viral envelope gp120 (Env) regions was analyzed to determine subtypes/variants of HIV-1, DRMs, and tropism. Ninety-two individuals were analyzed in the study. Approximately 72% of them were male and 74% self-declared as heterosexual. Phylogenetic inference (PR/RT-Env) showed that most sequences were B subtype, followed by BF1 or B C mosaic genomes and few F1 and C sequences. Among the variants of subtype B at PR/RT, 84.3% were pandemic ( B PAN ), and 15.7% were Caribbean ( B CAR ). The DRMs most frequent were M184I/V (82.9%) for nucleoside reverse transcriptase inhibitors (NRTI), K103N/S (63.4%) for nonnucleoside reverse transcriptase inhibitor (NNRTI), and V82A/L/M (7.3%) for protease inhibitors (PI). DRM analysis depicted high levels of resistance for lamivudine and efavirenz in over 82.9% of individuals; although, low (7.7%) cross-resistance to etravirine was observed. A low level of resistance to protease inhibitors was found and included patients that take atazanavir/ritonavir (16.6%) and lopinavir (11.1%), which confirms that these antiretrovirals can be used—for most individuals. The thymidine analog mutations-2 (TAM-2) resistance pathway was higher in B CAR than in B PAN . Similar results from other Brazilian studies regarding HIV drug resistance were observed; however, we underscore a need for additional studies regarding subtype B CAR variants. Molecular epidemiology studies are an important tool for monitoring the prevalence of HIV drug resistance and can influence the public health policies.

scholarly journals HIV Drug Resistance Mutations Detection by Next-Generation Sequencing during Antiretroviral Therapy Interruption in China

Pathogens ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 264
Author(s):  
Miaomiao Li ◽  
Shujia Liang ◽  
Chao Zhou ◽  
Min Chen ◽  
Shu Liang ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Next Generation Sequencing ◽  
Antiretroviral Therapy ◽  
Detection Threshold ◽  
Next Generation ◽  
Resistance Mutations ◽  
Hiv Drug Resistance ◽  
Drug Resistance Mutations ◽  
Therapy Interruption ◽  
Generation Sequencing

Patients with antiretroviral therapy interruption have a high risk of virological failure when re-initiating antiretroviral therapy (ART), especially those with HIV drug resistance. Next-generation sequencing may provide close scrutiny on their minority drug resistance variant. A cross-sectional study was conducted in patients with ART interruption in five regions in China in 2016. Through Sanger and next-generation sequencing in parallel, HIV drug resistance was genotyped on their plasma samples. Rates of HIV drug resistance were compared by the McNemar tests. In total, 174 patients were included in this study, with a median 12 (interquartile range (IQR), 6–24) months of ART interruption. Most (86.2%) of them had received efavirenz (EFV)/nevirapine (NVP)-based first-line therapy for a median 16 (IQR, 7–26) months before ART interruption. Sixty-one (35.1%) patients had CRF07_BC HIV-1 strains, 58 (33.3%) CRF08_BC and 35 (20.1%) CRF01_AE. Thirty-four (19.5%) of the 174 patients were detected to harbor HIV drug-resistant variants on Sanger sequencing. Thirty-six (20.7%), 37 (21.3%), 42 (24.1%), 79 (45.4%) and 139 (79.9) patients were identified to have HIV drug resistance by next-generation sequencing at 20% (v.s. Sanger, p = 0.317), 10% (v.s. Sanger, p = 0.180), 5% (v.s. Sanger, p = 0.011), 2% (v.s. Sanger, p < 0.001) and 1% (v.s. Sanger, p < 0.001) of detection thresholds, respectively. K65R was the most common minority mutation, of 95.1% (58/61) and 93.1% (54/58) in CRF07_BC and CRF08_BC, respectively, when compared with 5.7% (2/35) in CRF01_AE (p < 0.001). In 49 patients that followed-up a median 10 months later, HIV drug resistance mutations at >20% frequency such as K103N, M184VI and P225H still existed, but with decreased frequencies. The prevalence of HIV drug resistance in ART interruption was higher than 15% in the survey. Next-generation sequencing was able to detect more minority drug resistance variants than Sanger. There was a sharp increase in minority drug resistance variants when the detection threshold was below 5%.

scholarly journals Nationwide Study of Drug Resistance Mutations in HIV-1 Infected Individuals under Antiretroviral Therapy in Brazil

2021 ◽  
Vol 22 (10) ◽  
pp. 5304
Author(s):  
Ana Santos-Pereira ◽  
Vera Triunfante ◽  
Pedro M. M. Araújo ◽  
Joana Martins ◽  
Helena Soares ◽  
...  
Keyword(s):  
Drug Resistance ◽  
People Living With Hiv ◽  
Resistance Mutations ◽  
Subtype C ◽  
Viral Loads ◽  
Drug Resistance Mutations ◽  
Subtype B ◽  
Low Prevalence ◽  
Living With Hiv ◽  
Hiv 1

The success of antiretroviral treatment (ART) is threatened by the emergence of drug resistance mutations (DRM). Since Brazil presents the largest number of people living with HIV (PLWH) in South America we aimed at understanding the dynamics of DRM in this country. We analyzed a total of 20,226 HIV-1 sequences collected from PLWH undergoing ART between 2008–2017. Results show a mild decline of DRM over the years but an increase of the K65R reverse transcriptase mutation from 2.23% to 12.11%. This increase gradually occurred following alterations in the ART regimens replacing zidovudine (AZT) with tenofovir (TDF). PLWH harboring the K65R had significantly higher viral loads than those without this mutation (p < 0.001). Among the two most prevalent HIV-1 subtypes (B and C) there was a significant (p < 0.001) association of K65R with subtype C (11.26%) when compared with subtype B (9.27%). Nonetheless, evidence for K65R transmission in Brazil was found both for C and B subtypes. Additionally, artificial neural network-based immunoinformatic predictions suggest that K65R could enhance viral recognition by HLA-B27 that has relatively low prevalence in the Brazilian population. Overall, the results suggest that tenofovir-based regimens need to be carefully monitored particularly in settings with subtype C and specific HLA profiles.

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