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Antiretroviral Resistance After First-Line Antiretroviral Therapy Failure in Diverse HIV-1 Subtypes in the SECOND-LINE Study

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dc.contributor.author Lam, Edward P.
dc.contributor.author Moore, Cecilia L.
dc.contributor.author Gotuzzo, Eduardo
dc.contributor.author Nwizu, Chidi
dc.contributor.author Kamarulzaman, Adeeba
dc.contributor.author Chetchotisakd, Ploenchan
dc.contributor.author van Wyk, Jean
dc.contributor.author Teppler, Hedy
dc.contributor.author Kumarasamy, Nagalingeswaran
dc.contributor.author Molina, Jean-Michel
dc.contributor.author Emery, Sean
dc.contributor.author Cooper, David A.
dc.contributor.author Boyd, Mark A.
dc.contributor.author SECOND-LINE Study Group
dc.date.accessioned 2019-02-22T14:54:32Z
dc.date.available 2019-02-22T14:54:32Z
dc.date.issued 2016
dc.identifier.uri https://hdl.handle.net/20.500.12866/5671
dc.description.abstract We investigate mutations and correlates according to HIV-1 subtype after virological failure (VF) of standard first-line antiretroviral therapy (ART) (non-nucleoside/nucleotide reverse transcriptase inhibitor [NNRTI] +2 nucleoside/nucleotide reverse transcriptase inhibitor [N(t)RTI]). SECOND-LINE study participants were assessed at baseline for HIV-1 subtype, demographics, HIV-1 history, ART exposure, viral load (VL), CD4(+) count, and genotypic ART resistance. We used backward stepwise multivariate regression (MVR) to assess associations between baseline variables and presence of 3 N(t)RTI mutations, 1 NNRTI mutation, 3 thymidine analog-N(t)RTI [ta-N(t)RTI] mutations (TAMs), the K65/K70 mutation, and predicted etravirine (ETV)/rilpivirine (RPV) activity. The inclusion p-value for MVR was p<.2. The exclusion p-value from stepwise elimination was p>.05. Of 541 participants, 491 (91%) had successfully characterized baseline viral isolates. Subtype distribution: B (n=123, 25%), C (n=202, 41%), CRF01_AE (n=109, 22%), G (n=25, 5%), and CRF02_AG (n=27, 5%). Baseline CD4(+) 200-394 cells/mm(3) were associated with <3 N(t)RTI mutations (OR=0.47; 95% CI 0.29-0.77; p=.003), absence of the K65/K70 mutation (OR=0.43; 95% CI 0.26-0.73; p=.002), and higher ETV sensitivity (OR=0.52; 95% CI 0.35-0.78; p=.002). Recent tenofovir (TDF) use was associated with K65/K70 mutations (OR=8.91; 95% CI 5.00-15.85; p<.001). Subtype CRF01_AE was associated with 3 N(t)RTI mutations (OR=2.34; 95% CI 1.31-4.17; p=.004) and higher RPV resistance (OR=2.13; 95% CI 1.30-3.49; p=.003), and subtype C was associated with <3 TAMs (OR=0.45; 95% CI 0.21-0.99; p=.015). Subtypes CRF01_AE (OR=2.46; 95% CI 1.26-4.78; p=.008) and G (OR=4.77; 95% CI 1.44-15.76; p=.01) were associated with K65/K70 mutations. Higher VL at confirmed first-line VF was associated with 3 N(t)RTI mutations (OR=1.39; 95% CI 1.07-1.78; p=.013) and 3 TAMs (OR=1.62; 95% CI 1.15-2.29; p=.006). The associations of first-line resistance mutations across the HIV-1 subtypes in this study are consistent with knowledge derived from subtype B, with some exceptions. Patterns of resistance after failure of a first-line ta-N(t)RTI regimen support using TDF in N(t)RTI-containing second-line regimens, or using N(t)RTI-sparing regimens. en_US
dc.language.iso eng
dc.publisher Mary Ann Liebert
dc.relation.ispartof urn:issn:1931-8405
dc.rights info:eu-repo/semantics/restrictedAccess
dc.rights.uri https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
dc.subject UNAVAILABLE en_US
dc.title Antiretroviral Resistance After First-Line Antiretroviral Therapy Failure in Diverse HIV-1 Subtypes in the SECOND-LINE Study en_US
dc.type info:eu-repo/semantics/article
dc.identifier.doi https://doi.org/10.1089/aid.2015.0331
dc.subject.ocde https://purl.org/pe-repo/ocde/ford#3.02.00 es_PE
dc.subject.ocde https://purl.org/pe-repo/ocde/ford#3.03.08


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