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AIDS Res Hum Retroviruses. 2018 Feb;34(2):156-164. doi: 10.1089/AID.2017.0052. Epub 2017 Nov 27.

High Prevalence of Drug Resistance Mutations Among Patients Failing First-Line Antiretroviral Therapy and Predictors of Virological Response 24 Weeks After Switch to Second-Line Therapy in São Paulo State, Brazil.

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1 Ambulatório de referência de moléstias infecciosas, Programa de AIDS de Santo André , Santo André, Brazil .
2 Núcleo de doenças de vinculação sanguínea ou sexual, Centro de Virologia, Instituto Adolfo Lutz , São Paulo, Brazil .
3 Departamento de Clínica Médica, Faculdade de Ciências Médicas da UNICAMP , Campinas, Brazil .
4 Departamento de Clínica Médica, Hospital das Clínicas , Faculdade de Medicina, Ribeirão Preto, Brazil .
5 Instituto de Infectologia Emílio Ribas , São Paulo, Brazil .


Universal antiretroviral treatment with sustained viral suppression benefits patients and reduces HIV transmission. Effectiveness of therapy may be limited by antiretroviral drug resistance. Information on the resistance profile at treatment failure and its impact on antiretroviral drugs may subsidize subsequent treatment strategies. Partial pol sequences from 319 patients failing first-line therapy were analyzed for resistance associated mutations (RAMs) and HIV subtype. Demographic data, CD4 T cell count, viral load, and antiretroviral regimens and mutational profile at first-line failure were also investigated for associations to the response to second-line regimens. RAMs at the reverse transcriptase gene were frequent. Most sequences (88%) showed at least one mutation. A higher number of reverse transcriptase RAMs were associated to lower CD4 T cell counts and the use of tenofovir/lamivudine in first line. Among 205 with follow-up data, 76.6% were virally suppressed (below 200 copies/ml) after 24 weeks of second-line therapy. Most cases initiated second line with a regimen genotypic susceptibility score ≥2, but it did not predict viral suppression, that was independently associated with higher CD4 T cell counts and with the presence of nucleos(t)ide analog reverse transcriptase inhibitor (NRTI) RAMs. This study documented extensive resistance at first-line failure in this area in Brazil, highlights the risks of low CD4 T cell counts to second-line therapy, and supports the notion that recycled NRTIs may contribute to viral suppression even when genotypic resistance is present.


HIV; antiretroviral therapy; mutations; resistance; treatment failure

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