scholarly journals Acquired HIV drug resistance and virologic monitoring in a HIV hyper-endemic setting in KwaZulu-Natal Province, South Africa

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Benjamin Chimukangara ◽  
Richard J. Lessells ◽  
Lavanya Singh ◽  
Indra Grigalionyte ◽  
Nonhlanhla Yende-Zuma ◽  
...  
Keyword(s):  
South Africa ◽  
Drug Resistance ◽  
Sequence Data ◽  
Hiv Treatment ◽  
Close Monitoring ◽  
Second Line ◽  
First Line ◽  
Treatment Regimens ◽  
Kwazulu Natal ◽  
Hiv 1

Abstract Background Introduction of tenofovir (TDF) plus lamivudine (3TC) and dolutegravir (DTG) in first- and second-line HIV treatment regimens in South Africa warrants characterization of acquired HIV-1 drug resistance (ADR) mutations that could impact DTG-based antiretroviral therapy (ART). In this study, we sought to determine prevalence of ADR mutations and their potential impact on susceptibility to drugs used in combination with DTG among HIV-positive adults (≥ 18 years) accessing routine care at a selected ART facility in KwaZulu-Natal, South Africa. Methods We enrolled adult participants in a cross-sectional study between May and September 2019. Eligible participants had a most recent documented viral load (VL) ≥ 1000 copies/mL after at least 6 months on ART. We genotyped HIV-1 reverse transcriptase and protease genes by Sanger sequencing and assessed ADR. We characterized the effect of ADR mutations on the predicted susceptibility to drugs used in combination with DTG. Results From 143 participants enrolled, we obtained sequence data for 115 (80%), and 92.2% (95% CI 85.7–96.4) had ADR. The proportion with ADR was similar for participants on first-line ART (65/70, 92.9%, 95% CI 84.1–97.6) and those on second-line ART (40/44, 90.9%, 95% CI 78.3–97.5), and was present for the single participant on third-line ART. Approximately 89% (62/70) of those on first-line ART had dual class NRTI and NNRTI resistance and only six (13.6%) of those on second-line ART had major PI mutations. Most participants (82%) with first-line viraemia maintained susceptibility to Zidovudine (AZT), and the majority of them had lost susceptibility to TDF (71%) and 3TC (84%). Approximately two in every five TDF-treated individuals had thymidine analogue mutations (TAMs). Conclusions Susceptibility to AZT among most participants with first-line viraemia suggests that a new second-line regimen of AZT + 3TC + DTG could be effective. However, atypical occurrence of TAMs in TDF-treated individuals suggests a less effective AZT + 3TC + DTG regimen in a subpopulation of patients. As most patients with first-line viraemia had at least low-level resistance to TDF and 3TC, identifying viraemia before switch to TDF + 3TC + DTG is important to avoid DTG functional monotherapy. These findings highlight a need for close monitoring of outcomes on new standardized treatment regimens.

scholarly journals High-Levels of Acquired Drug Resistance in Adult Patients Failing First-Line Antiretroviral Therapy in a Rural HIV Treatment Programme in KwaZulu-Natal, South Africa

PLoS ONE ◽  
2013 ◽  
Vol 8 (8) ◽  
pp. e72152 ◽  
Author(s):  
Justen Manasa ◽  
Richard J. Lessells ◽  
Andrew Skingsley ◽  
Kevindra K. Naidu ◽  
Marie-Louise Newell ◽  
...  
Keyword(s):  
South Africa ◽  
Drug Resistance ◽  
Antiretroviral Therapy ◽  
Hiv Treatment ◽  
Adult Patients ◽  
Treatment Programme ◽  
First Line ◽  
Acquired Drug Resistance ◽  
Kwazulu Natal

scholarly journals Rates of virological suppression and drug resistance in adult HIV-1-positive patients attending primary healthcare facilities in KwaZulu-Natal, South Africa

2017 ◽  
Vol 72 (11) ◽  
pp. 3141-3148 ◽  
Author(s):  
Gillian M Hunt ◽  
E. Kainne Dokubo ◽  
Simbarashe Takuva ◽  
Tulio de Oliveira ◽  
Johanna Ledwaba ◽  
...  
Keyword(s):  
South Africa ◽  
Drug Resistance ◽  
Primary Healthcare ◽  
Virological Suppression ◽  
Healthcare Facilities ◽  
Kwazulu Natal ◽  
Hiv 1

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.

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 Increasing HIV-1 Drug Resistance Between 2010 and 2012 in Adults Participating in Population-Based HIV Surveillance in Rural KwaZulu-Natal, South Africa

2016 ◽  
Vol 32 (8) ◽  
pp. 763-769 ◽  
Author(s):  
Justen Manasa ◽  
Siva Danaviah ◽  
Richard Lessells ◽  
Muna Elshareef ◽  
Frank Tanser ◽  
...  
Keyword(s):  
South Africa ◽  
Drug Resistance ◽  
Population Based ◽  
Hiv Surveillance ◽  
Kwazulu Natal ◽  
Hiv 1

scholarly journals Rates of virological suppression and drug resistance in adult HIV-1-positive patients attending primary healthcare facilities in KwaZulu-Natal, South Africa

2017 ◽  
Vol 72 (11) ◽  
pp. 3222-3222
Author(s):  
Gillian M Hunt ◽  
E Kainne Dokubo ◽  
Simbarashe Takuva ◽  
Tulio de Oliveira ◽  
Johanna Ledwaba ◽  
...  
Keyword(s):  
South Africa ◽  
Drug Resistance ◽  
Primary Healthcare ◽  
Virological Suppression ◽  
Healthcare Facilities ◽  
Kwazulu Natal ◽  
Hiv 1

scholarly journals Drug Resistance After Failure of WHO Recommended First-Line Antiretroviral Regimen for Adult HIV-1 Infection in South Africa: A Modeling Analysis

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S424-S424
Author(s):  
Yajun Ding ◽  
Robert Glaubius ◽  
Ume Abbas
Keyword(s):  
South Africa ◽  
Drug Resistance ◽  
Fast Track ◽  
Acquired Resistance ◽  
Initial Population ◽  
Second Line ◽  
Total Resistance ◽  
First Line ◽  
Relative Contribution ◽  
Hiv Epidemic

Abstract Background Antiretroviral therapy (ART) is critical for ending the HIV epidemic. Tenofovir-containing ART is the first-line regimen in many countries including South Africa, with limited access to second-line ART. High levels of drug resistance have been reported among patients after virologic failure on tenofovir-containing first-line regimens (TenoRes Study, Lancet Infect Dis 2016). We assessed drug resistance at the population level using mathematical modeling. Methods We developed a stochastic individual-based model of the heterosexual HIV epidemic in KwaZulu-Natal South Africa, and compared drug resistance from scenarios of tenofovir-containing ART scale-up, either CD4-based (threshold &lt; 500 cells/mL) or Fast-track (80% coverage by 2020). The model represents details of HIV transmission and disease progression, demography, sexual behavior, condom use, circumcision, treatment interventions and drug resistance dynamics including key mutations (M184V, K65R and non-nucleoside reverse transcriptase inhibitor (NNRTI)). Using an initial population of 2.5 million, we performed 100 simulations from 1978 to 2030. We examined the prevalence of (majority) transmitted and acquired resistance by 2030. Results The total resistance (proportion of HIV-infected persons with drug resistance) reached 34% from CD4-based ART by 2030, with 30% relative contribution from transmitted resistance and 70% from acquired resistance. In contrast, Fast-track ART reduced the total resistance to 22%; though, there was an increased relative contribution from transmitted resistance (~ 50%). In both scenarios, NNRTI mutations were the most prevalent, followed by M184V and K65R mutations. About 48% of persons with acquired drug- resistance harbored dual drug mutations, 44.7% had triple mutations and 7.3% just single mutations, from CD4-based ART. The respective estimates from Fast-track ART were similar; 49% for dual, 44.1% for triple and 6.9% for single mutations. In both scenarios, NNRTI mutations comprised about 80% of prevalent transmitted resistance. Conclusion Current WHO-recommended first-line ART could lead to substantial drug resistance. Effective surveillance for resistance transmission and access to second-line regimens would be crucial. Disclosures All authors: No reported disclosures.

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