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

Boyd, Mark A.; Chetchotisakd, Ploenchan; Kumarasamy, Nagalingeswaran; Gotuzzo Herencia, José Eduardo; Cooper, David A.; van Wyk, Jean; Molina, Jean-Michel; Nwizu, Chidi; Kamarulzaman, Adeeba; SECOND-LINE Study Group; Lam, Edward P.; Moore, Cecilia L.; Teppler, Hedy; Emery, Sean

dc.contributor.author	Lam, Edward P.
dc.contributor.author	Moore, Cecilia L.
dc.contributor.author	Gotuzzo Herencia, José 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.ispartofseries	AIDS Research and Human Retroviruses
dc.rights	info:eu-repo/semantics/restrictedAccess
dc.subject	Antiretroviral Resistance	en_US
dc.subject	Antiretroviral Therapy Failure	en_US
dc.subject	HIV-1	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#3.03.08
dc.relation.issn	1931-8405