Virologic suppression in response to antiretroviral therapy despite extensive resistance within HIV-1 reverse transcriptase after the first virologic failure

Abstract

BackgroundIncomplete virologic suppression results in mutations associated with resistance and is a major obstacle to disease control. We analyzed the genotypic profiles of HIV-1 patients at the time of the first virologic failure and the response to a salvage regimen after 48 weeks.MethodsThis work was a cross-sectional, retrospective, analytical study based on data collected from medical records and genotyping tests between 2006 and 2016. The sample consisted of data on individuals living with HIV (PLWH) from three major reference centers.ResultsA total of 184 patients were included in the data analysis. Viral subtype B was the most common (81.3%) as well as M184 V/I (85.3%) and K103 codon mutations (65.8%). Forty-eight weeks after switching to a salvage regimen, 67.3% of patients achieved an undetectable viral load.DiscussionThe number of mutations associated with nucleos(t)ide reverse transcriptase inhibitors (NRTI(t)s) did not affect virologic suppression (9.3% for zero NRTI(t)-associated mutations vs 48.6% for 1–2 NRTI(t)-associated mutations vs 42.1% for ≥3 NRTI(t)-associated mutations, p = 0.179). An ARV time (the beginning of the first ARV regimen up to genotyping) of > 36 months was a protective factor for detectable viral load (PR = 0.60, 95% CI = 0.39–0.92, p = 0.020) and a risk factor for developing ≥3 NRTI(t)-associated mutations (PR = 2.43, 95% CI 1.38–4.28, p = 0.002).ConclusionsWe found that extensive resistance to NRTI(t)s at the time of the first virologic failure did not impact virologic suppression at 48 weeks after switching to a second-line therapy based on NRTI(t)s plus protease inhibitors.

Prevalence of acquired drug resistance mutations in antiretroviral- experiencing subjects from 2012 to 2017 in Hunan Province of central South China

“…Although M184V/I causes high-level in vitro resistance to 3TC, M184V/I is not a contraindication to continued treatment with 3TC because it increases susceptibility to AZT, and in addition, it is associated with clinically significant reductions in HIV-1 replication [14,24,25]. Similar to our study finding, a high prevalence of M184 V/I mutation has been reported in Asia, Sub-Saharan Africa and Latin America, but a lower prevalence in western Europe [26][27][28][29][30][31]. This difference can be explained by the more frequent use of 3TC in low-and middle-income countries than in West European countries.…”

Clinical significance and management of low‐level HIV viremia in the era of integrase strand transfer inhibitors

“…ART aims to achieve virologic suppression (VS) in people living with HIV (PLWH). Adequate VS could prevent the development of resistance mutations, reduce HIV transmission and improve clinical outcomes [2].…”

Simplificação terapêutica com lamivudina e dolutegravir em pacientes vivendo com HIV no Ceará (Estudo LAMDO)

“…Os regimes baseados em DTG são recomendados como a melhor opção para iniciar ou como alternativa a TARV devido a sua potência e barreira genética que proporcionam rápida supressão viral, baixo potencial para interações medicamentosas, baixo risco de desenvolvimento de resistência medicamentosa, melhor tolerabilidade, menor número de comprimidos e disponibilidade como formulações em dose fixa (Cento et al, 2020). Dos indivíduos sob tratamento com ARV, estima-se que 20% trocarão as medicações devido à falha virológica (Oliveira et al, 2018). Reações adversas, falha terapêutica, interações com outros medicamentos, simplificação do tratamento, redução do custo, gravidez, ocorrência de coinfecções são exemplos de outros motivos que levam às modificações da TARV (Cesar et al, 2010;Kumarasamy et al, 2011).…”