scholarly journals Protease Inhibitor Resistance Is Uncommon in HIV-1 Subtype C Infected Patients on Failing Second-Line Lopinavir/r-Containing Antiretroviral Therapy in South Africa

2011 ◽  
Vol 2011 ◽  
pp. 1-5 ◽  
Author(s):  
Carole L. Wallis ◽  
John W. Mellors ◽  
Willem D. F. Venter ◽  
Ian Sanne ◽  
Wendy Stevens
Keyword(s):  
South Africa ◽  
Drug Resistance ◽  
Protease Inhibitor ◽  
Virologic Failure ◽  
Second Line ◽  
Resistance Mutations ◽  
Subtype C ◽  
Resistance Patterns ◽  
Main Barrier ◽  
Hiv 1

Limited data exist on HIV-1 drug resistance patterns in South Africa following second-line protease-inhibitor containing regimen failure. This study examined drug resistance patterns emerging in 75 HIV-1 infected adults experiencing virologic failure on a second-line regimen containing 2 NRTI and lopinavir/ritonavir. Ninety six percent of patients (n=72) were infected with HIV-1 subtype C, two patients were infected with HIV-1 subtype D and one with HIV-1 subtype A1. Thirty nine percent (n=29) of patients had no resistance mutations in protease or reverse transcriptase suggesting that medication non-adherence was a major factor contributing to failure. Major lopinavir resistance mutations were infrequent (5 of 75; 7%), indicating that drug resistance is not the main barrier to future viral suppression.

Molecular Genetics and the Incidence of Transmitted Drug Resistance Among Pre-Treatment HIV-1 Infected Patients in the Eastern Cape, South Africa

2019 ◽  
Vol 17 (5) ◽  
pp. 335-342
Author(s):  
Tennison Onoriode Digban ◽  
Benson Chucks Iweriebor ◽  
Larry Chikwelu Obi ◽  
Uchechuwku Nwodo ◽  
Anthony Ifeanyi Okoh
Keyword(s):  
South Africa ◽  
Drug Resistance ◽  
Transmitted Drug Resistance ◽  
Eastern Cape ◽  
Resistance Mutations ◽  
Subtype C ◽  
Drug Resistance Mutations ◽  
Combined Antiretroviral Therapy ◽  
Pre Treatment ◽  
Hiv 1

Background: Transmitted drug resistance (TDR) remains a significant threat to Human immunodeficiency virus (HIV) infected patients that are not exposed to antiretroviral treatment. Although, combined antiretroviral therapy (cART) has reduced deaths among infected individuals, emergence of drug resistance is gradually on rise. Objective: To determine the drug resistance mutations and subtypes of HIV-1 among pre-treatment patients in the Eastern Cape of South Africa. Methods: Viral RNA was extracted from blood samples of 70 pre-treatment HIV-1 patients while partial pol gene fragment amplification was achieved with specific primers by RT-PCR followed by nested PCR and positive amplicons were sequenced utilizing ABI Prism 316 genetic sequencer. Drug resistance mutations (DRMs) analysis was performed by submitting the generated sequences to Stanford HIV drug resistance database. Results: Viral DNA was successful for 66 (94.3%) samples of which 52 edited sequences were obtained from the protease and 44 reverse transcriptase sequences were also fully edited. Four major protease inhibitor (PI) related mutations (I54V, V82A/L, L76V and L90M) were observed in seven patients while several other minor and accessory PIs were also identified. A total of 11(25.0%) patients had NRTIs related mutations while NNRTIs were observed among 14(31.8%) patients. K103N/S, V106M and M184V were the most common mutations identified among the viral sequences. Phylogenetic analysis of the partial pol gene indicated all sequences clustered with subtype C. Conclusions: This study indicates that HIV-1 subtype C still predominates and responsible for driving the epidemic in the Eastern Cape of South Africa with slow rise in the occurrence of transmitted drug resistance.

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

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Adetayo Emmanuel Obasa ◽  
Anoop T. Ambikan ◽  
Soham Gupta ◽  
Ujjwal Neogi ◽  
Graeme Brendon Jacobs
Keyword(s):  
South Africa ◽  
Drug Resistance ◽  
Reverse Transcriptase ◽  
High Throughput ◽  
High Throughput Sequencing ◽  
Second Line ◽  
Viral Quasispecies ◽  
Resistance Mutations ◽  
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 on the South African national second-line cART regimen receiving bPIs. Methods During 2017 and 2018, 67 patient samples were sequenced using high-throughput sequencing (HTS), of which 56 samples were included in the final analysis because the patient’s treatment regimen was available at the time of sampling. 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 higher PI RAMs were observed in minor viral quasispecies (25%; 14/56) compared to non-nucleoside reverse transcriptase inhibitors (9%; 5/56; p = 0.042) and integrase inhibitor RAM (4%; 2/56; p = 0.002). 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 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 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

2021 ◽  
Author(s):  
Adetayo Emmanuel Obasa ◽  
Anoop T Ambikan ◽  
Soham Gupta ◽  
Ujjwal Neogi ◽  
Graeme Brendon Jacobs
Keyword(s):  
South Africa ◽  
Drug Resistance ◽  
Reverse Transcriptase ◽  
High Throughput ◽  
High Throughput Sequencing ◽  
Second Line ◽  
Viral Quasispecies ◽  
Resistance Mutations ◽  
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 on the South African national second-line cART regimen receiving bPIs.Methods: During 2017 and 2018, 67 patient samples were sequenced using high throughput sequencing (HTS), of which 56 samples were included in the analysis because the patient’s treatment regimen were available at the time of sampling. 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 higher PI RAMs were observed in minor viral quasispecies (25%; 14/56) compared to non-nucleoside reverse transcriptase inhibitors (9%; 5/56; p=0.042) and integrase inhibitor RAM (4%; 2/56; p=0.002). 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 HIV-1 Subtype C Drug Resistance Mutations in Heavily Treated Patients Failing Integrase Strand Transfer Inhibitor-Based Regimens in Botswana

Viruses ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 594
Author(s):  
Kaelo K. Seatla ◽  
Dorcas Maruapula ◽  
Wonderful T. Choga ◽  
Tshenolo Ntsipe ◽  
Nametso Mathiba ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Virologic Failure ◽  
Resistance Testing ◽  
Strand Transfer ◽  
Resistance Mutations ◽  
Subtype C ◽  
Genotypic Resistance Testing ◽  
Transfer Inhibitor ◽  
Integrase Strand Transfer Inhibitor ◽  
Hiv 1

There are limited real-world mutational and virological outcomes data of treatment-experienced persons diagnosed with HIV-1 subtype C (HIV-1 C) who are failing Integrase Strand Transfer Inhibitor-based regimens. Requisition forms sent for HIV-1 genotypic resistance testing (GRT) between May 2015 and September 2019 were reviewed and participants experiencing virologic failure while on dolutegravir (DTG) or raltegravir (RAL) cART at sampling recruited. Sanger sequencing of the HIV-1 Pol gene was performed from residual plasma samples and drug resistance mutational (DRM) analysis performed using the Stanford University HIV drug resistance database. 40 HIV-1C integrase sequences were generated from 34 individuals, 24 of whom were on DTG cART, three on RAL cART and seven on an unknown (DTG or RAL)-anchored cART at time of GRT. 11/34 (32%) individuals had DRMs to DTG and other integrase inhibitors. 7/11 (64%) patients had exposure to a RAL-based cART at the time of sampling. Out of the 11 individuals with DRMs, one (9%) had 2-class, 6 (55%) had 3-class, and 4 (36%) had 4-class multidrug-resistant HIV-1C. 7/11 individuals (64%) are currently virologically suppressed. Of the four individuals not virologically suppressed, three had extensive DRMs involving 4-classes of ARV drugs and one individual has demised. Resistance to DTG occurs more often in patients exposed to RAL cART. Individuals with 4-class DRMs plus integrase T97 and E157Q mutations appear to have worse outcomes. There is a need for frequent VL monitoring and GRT amongst treatment-experienced HIV-1C diagnosed individuals.

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.

scholarly journals MiDRMpol: A High-Throughput Multiplexed Amplicon Sequencing Workflow to Quantify HIV-1 Drug Resistance Mutations against Protease, Reverse Transcriptase, and Integrase Inhibitors

Viruses ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 806
Author(s):  
Shambhu G. Aralaguppe ◽  
Anoop T. Ambikan ◽  
Manickam Ashokkumar ◽  
Milner M. Kumar ◽  
Luke Elizabeth Hanna ◽  
...  
Keyword(s):  
Drug Resistance ◽  
High Throughput ◽  
Large Scale ◽  
High Throughput Sequencing ◽  
Polymorphism Analysis ◽  
Resistance Mutations ◽  
Subtype C ◽  
Bioinformatics Pipeline ◽  
Drug Resistance Mutations ◽  
Hiv 1

The detection of drug resistance mutations (DRMs) in minor viral populations is of potential clinical importance. However, sophisticated computational infrastructure and competence for analysis of high-throughput sequencing (HTS) data lack at most diagnostic laboratories. Thus, we have proposed a new pipeline, MiDRMpol, to quantify DRM from the HIV-1 pol region. The gag-vpu region of 87 plasma samples from HIV-infected individuals from three cohorts was amplified and sequenced by Illumina HiSeq2500. The sequence reads were adapter-trimmed, followed by analysis using in-house scripts. Samples from Swedish and Ethiopian cohorts were also sequenced by Sanger sequencing. The pipeline was validated against the online tool PASeq (Polymorphism Analysis by Sequencing). Based on an error rate of <1%, a value of >1% was set as reliable to consider a minor variant. Both pipelines detected the mutations in the dominant viral populations, while discrepancies were observed in minor viral populations. In five HIV-1 subtype C samples, minor mutations were detected at the <5% level by MiDRMpol but not by PASeq. MiDRMpol is a computationally as well as labor efficient bioinformatics pipeline for the detection of DRM from HTS data. It identifies minor viral populations (<20%) of DRMs. Our method can be incorporated into large-scale surveillance of HIV-1 DRM.

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