Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/123920
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Type: | Journal article |
Title: | Antiretroviral resistance after first-line antiretroviral therapy failure in diverse HIV-1 subtypes in the SECOND-LINE study |
Author: | Lam, E.P. Moore, C.L. Gotuzzo, E. Nwizu, C. Kamarulzaman, A. Chetchotisakd, P. Van Wyk, J. Teppler, H. Kumarasamy, N. Molina, J.M. Emery, S. Cooper, D.A. Boyd, M.A. |
Citation: | AIDS Research and Human Retroviruses, 2016; 32(9):841-850 |
Publisher: | Mary Ann Liebert |
Issue Date: | 2016 |
ISSN: | 0889-2229 1931-8405 |
Statement of Responsibility: | Edward P. Lam, Cecilia L. Moore, Eduardo Gotuzzo, Chidi Nwizu, Adeeba Kamarulzaman, Ploenchan Chetchotisakd, Jean van Wyk, Hedy Teppler, Nagalingeswaran Kumarasamy, Jean-Michel Molina, Sean Emery, David A. Cooper, and Mark A. Boyd, for the SECOND-LINE study group |
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. |
Keywords: | HIV-1 |
Rights: | © Mary Ann Liebert, Inc. |
DOI: | 10.1089/aid.2015.0331 |
Published version: | http://dx.doi.org/10.1089/aid.2015.0331 |
Appears in Collections: | Aurora harvest 3 Ecology, Evolution and Landscape Science publications |
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hdl_123920.pdf | Accepted version | 367.73 kB | Adobe PDF | View/Open |
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