Early virological failure and HIV drug resistance in Ugandan adults co-infected with tuberculosis

Abstract

PurposeThis cross-sectional study took place in the integrated tuberculosis (TB) clinic of a large outpatient clinic for HIV-infected patients in Kampala, Uganda. The purpose of this study was to describe the proportion of TB/HIV co-infected adults with virological failure, type and frequency of HIV drug resistance-associated mutations, and the proportion of patients with suboptimal efavirenz levels.MethodsHIV-1 plasma viral loads, CD4 cell count measurements, and efavirenz serum concentrations were done in TB/HIV co-infected adults. Genotypic resistance testing was performed in case of confirmed virological failure.ResultsAfter a median time on ART of 6 months, virological failure was found in 22/152 patients (14.5%). Of 147 participants with available efavirenz serum concentration, 26 (17.6%) had at least one value below the reference range, including 20/21 (95.2%) patients with confirmed virological failure. Genotypic resistance testing was available for 16/22 (72.7%) patients, of which 15 (93.8%) had at least one major mutation, most commonly M184V (81.2%) and K103NS (68.8%).ConclusionWe found a high proportion of TB/HIV co-infected patients with virological failure, the majority of which had developed relevant resistance-mutations after a median time on anti-retroviral treatment (ART) of 6 months. Virological monitoring should be prioritized in TB/HIV co-infected patients in resource-limited settings.

Comparison of HIV drug resistance profiles across HIV-1 subtypes A and D for patients receiving a tenofovir-based and zidovudine-based first line regimens in Uganda

“…Furthermore, Lamivudine has a low genetic barrier. TAMs and K65R had a prevalence of 35.7% and 23.1% respectively, similar to a study done in Uganda [48] where K65R mutation had a prevalence of 25%. K65R is highly selected for in TDF containing regimens [51].…”

“…It is also possible that most of these patients do not keep their appointments for scheduled viral load and drug resistance monitoring such that by the time they report back to the clinic, they have been on a failing regimen for quite some time. For NNRTI class, K103N mutation (53.8%) was indicated as the most prevalent mutation followed by G190A/S/E/G (30.2%) similar to a study done in sub-Saharan Africa [48] that indicated K103N (38.7%) and G190A/S/E/G (21.8%) as the most prevalent. This was anticipated given the fact that Efavirenz is highly used as the preferred NNRTI in this region and mutations K103N, G190A are among the most common single mutations that confer high-level resistance to all the firstgeneration NNRTIs [49].…”

“…Recent reports from studies done in Uganda show prevalence at 95.2% [48] and sub-Saharan countries at 98% [26]. The study further noted that within the NRTI class, M184V/I mutations had the highest prevalence of 65.9% similar to a study done in Uganda [48] where M184V was noted with the highest prevalence of 81.2%. The high prevalence of M184V might be attributed to the continued usage of lamivudine as a backbone in all regimens in Uganda and all over sub-Saharan since the presence of this mutation reduces the viral replicative fitness and increases susceptibility to TDF and AZT [49,50].…”

“…Similar studies in sub-Saharan countries had a prevalence of DRMs at 70% [46] and in South Africa, the prevalence of DRMs was at 86% [47]. Recent reports from studies done in Uganda show prevalence at 95.2% [48] and sub-Saharan countries at 98% [26]. The study further noted that within the NRTI class, M184V/I mutations had the highest prevalence of 65.9% similar to a study done in Uganda [48] where M184V was noted with the highest prevalence of 81.2%.…”

Model of care and risk factors for poor outcomes in patients on multi-drug resistant tuberculosis treatment at two facilities in eSwatini (formerly Swaziland), 2011–2013

“…These patients established on ART and developing TB are HIV failure per definition[ 27 ] and may have benefited from early switch to second line ART[ 28 ]. This underscores the importance and need of strengthening HIV programs and HIV management with early switch of those patients who present with ART failure and severely sick due to MDR-TB[ 29 ].…”