Acquired HIV drug resistance and virologic monitoring in a HIV hyper-endemic setting in KwaZulu-Natal Province, South Africa
| Autor: | Karidia Diallo, Kogieleum Naidoo, Pravi Moodley, Benjamin Chimukangara, Rochelle Nicola Adams, Richard J Lessells, Nesri Padayatchi, Linda Dlamini, Halima Dawood, Melissa B. Hagen, Lavanya Singh, Sheldon Chetty, Mary Mogashoa, Indra Grigalionyte, Nonhlanhla Yende-Zuma, Wayne A Duffus, Sibonisile Buthelezi, Tulio de Oliveira, Jennifer Giandhari |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Adult
medicine.medical_specialty Anti-HIV Agents Human immunodeficiency virus (HIV) Drug Resistance HIV Infections Drug resistance medicine.disease_cause chemistry.chemical_compound South Africa Virology Internal medicine Drug Resistance Viral medicine Humans Viraemia Pharmacology (medical) Hiv treatment KwaZulu-Natal business.industry Research Lamivudine virus diseases RC581-607 Antiretroviral therapy Cross-Sectional Studies Antiretroviral treatment chemistry Dolutegravir HIV-1 Molecular Medicine Immunologic diseases. Allergy business Kwazulu natal HIV drug resistance Acquired drug resistance medicine.drug |
| Zdroj: | AIDS Research and Therapy, Vol 18, Iss 1, Pp 1-8 (2021) AIDS Research and Therapy |
| ISSN: | 1742-6405 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
| Nepřihlášeným uživatelům se plný text nezobrazuje | K zobrazení výsledku je třeba se přihlásit. |