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Objectives: Limited availability of viral load (VL) monitoring in HIV treatment programmes in sub-Saharan Africa can delay switching to second-line ART, leading to the accumulation of drug resistance mutations (DRMs). The objective of this study was to evaluate the accumulation of resistance to reverse transcriptase inhibitors after continued virological failure on first-line ART, among adults and children in sub-Saharan Africa.
Methods: HIV-1-positive adults and children on an NNRTI-based first-line ART were included. Retrospective VL and, if VL ≥1000 copies/mL, pol genotypic testing was performed. Among participants with continued virological failure (≥2 VL ≥1000 copies/mL), drug resistance was evaluated.
Results: At first virological failure, DRM(s) were detected in 87% of participants: K103N (38.7%), G190A (21.8%), Y181C (20.2%), V106M (8.4%), K101E (8.4%), any E138 (7.6%) and V108I (7.6%) associated with NNRTIs, and M184V (69.7%), any thymidine analogue mutation (9.2%), K65R (5.9%) and K70R (5.0%) associated with NRTIs. New DRMs accumulated with an average rate of 1.45 (SD 2.07) DRM per year; 0.62 (SD 1.11) NNRTI DRMs and 0.84 (SD 1.38) NRTI DRMs per year, respectively. The predicted susceptibility declined significantly after continued virological failure for all reverse transcriptase inhibitors (all P < 0.001). Acquired drug resistance patterns were similar in adults and children.
Conclusions: Patterns of drug resistance after virological failure on first-line ART are similar in adults and children in sub-Saharan Africa. Improved VL monitoring to prevent accumulation of mutations, and new drug classes to construct fully active regimens, are required.
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http://dx.doi.org/10.1093/jac/dkw218 | DOI Listing |
Mol Biol Rep
December 2024
Department of Internal Medicine II, Hamamatsu University School of Medicine, 1-20-1 Handayama, Chuo-ku, Hamamatsu, Shizuoka, 431-3192, Japan.
Background: Neprilysin (NEP) is a metalloprotease that has become a therapeutic target for the treatment of heart failure and hypertension. However, the significance of NEP in chronic liver diseases has rarely been investigated. In this study, we investigated the serum NEP levels in patients with chronic liver disease and their relationship with clinical parameters.
View Article and Find Full Text PDFAntiviral Res
December 2024
Department of Molecular and Medical Virology, Ruhr University Bochum, Bochum, Germany; German Centre for Infection Research (DZIF), External Partner Site, Bochum, Germany. Electronic address:
Infection with one or several of the five known hepatitis viruses is a leading cause of liver disease and poses a high risk of developing hepatocellular carcinoma upon chronic infection. Chronicity is primarily caused by hepatitis B virus (HBV) and hepatitis C virus (HCV) and poses a significant health burden worldwide. Co-infection of chronic HBV infected patients with hepatitis D virus (HDV) is less common but is marked as the most severe form of chronic viral hepatitis.
View Article and Find Full Text PDFAIDS Res Ther
December 2024
Mbeya College of Health and Allied Sciences, University of Dar es Salaam, Mbeya, Tanzania.
Background: The World Health Organization recommends dolutegravir-based antiretroviral therapy (ART) as the preferred first-line regimen for HIV treatment. This retrospective cohort study evaluated the long-term virologic outcomes and safety of transitioning from an efavirenz-based regimen (tenofovir, lamivudine, efavirenz [TLE]) to a dolutegravir-based regimen (tenofovir, lamivudine, dolutegravir [TLD]) among adult HIV participants in Mbeya, Tanzania.
Methods: Medical records of 250 adult HIV participants who transitioned from TLE to TLD at Mbeya Zonal Referral Hospital were reviewed from August 2022 to December 2022.
J Int Assoc Provid AIDS Care
December 2024
Chantal BIYA International Reference Centre for Research on HIV/AIDS Prevention and Management, Yaoundé, Cameroon.
Introduction: In low-and-middle-income-countries (LMIC), viral suppression is defined as plasma viral load (PVL) below 1000 copies/mL (low-level viremia [LLV]) and threshold for HIV drug resistance (HIVDR) testing. However, there is evidence that drug resistance mutations (DRMs) may emerge at LLV, thus compromising antiretroviral treatment (ART) response We evaluated sequencing success rates (SSR) at LLV, described HIVDR profiles and adequacy with potential efficacy of tenofovir-lamivudine-dolutegravir (TLD).
Methods: A cross-sectional study was conducted among individuals with LLV at the Chantal BIYA International Reference Centre, Yaoundé, Cameroon from January 2020 through August 2021.
AIDS Res Ther
December 2024
Veterans Affairs (VA) Connecticut Healthcare System Cooperative Studies Program Clinical Epidemiology Research Center (CSP-CERC), 950 Campbell Avenue, West Haven, CT, 06516-2770, USA.
Background: Real-world data on treatment patterns and clinical outcomes for newer drugs, including integrase strand transfer inhibitors, among older people with human immunodeficiency virus (PWH) are limited.
Methods: This cohort study included PWH enrolled in the Veterans Aging Cohort Study (VACS) who were prescribed a standard 3-drug antiretroviral therapy (ART) regimen containing dolutegravir (DTG), bictegravir (BIC), cobicistat boosted elvitegravir (EVG), raltegravir (RAL), or darunavir/ritonavir (DRV) plus 2 nucleoside reverse transcriptase inhibitors between January 1, 2014, and March 31, 2020, and who were ≥50 years at regimen initiation. The association between regimen and virologic effectiveness or discontinuation was assessed using logistic regression models with inverse probability of treatment weights.
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