Antiretroviral resistance after first-line antiretroviral therapy failure in diverse HIV-1 subtypes in the SECOND-LINE study

Lam, Edward P., Moore, Cecilia L., Gotuzzo, Eduardo, Nwizu, Chidi, Kamarulzaman, Adeeba, Chetchotisakd, Ploenchan, van Wyk, Jean, Teppler, Hedy, Kumarasamy, Nagalingeswaran, Molina, Jean-Michel, Emery, Sean, Cooper, David A. and Boyd, Mark A. (2016) Antiretroviral resistance after first-line antiretroviral therapy failure in diverse HIV-1 subtypes in the SECOND-LINE study. AIDS Research and Human Retroviruses, 32 9: 841-850. doi:10.1089/aid.2015.0331

Author Lam, Edward P.
Moore, Cecilia L.
Gotuzzo, Eduardo
Nwizu, Chidi
Kamarulzaman, Adeeba
Chetchotisakd, Ploenchan
van Wyk, Jean
Teppler, Hedy
Kumarasamy, Nagalingeswaran
Molina, Jean-Michel
Emery, Sean
Cooper, David A.
Boyd, Mark A.
Title Antiretroviral resistance after first-line antiretroviral therapy failure in diverse HIV-1 subtypes in the SECOND-LINE study
Journal name AIDS Research and Human Retroviruses   Check publisher's open access policy
ISSN 1931-8405
Publication date 2016-09-01
Year available 2016
Sub-type Article (original research)
DOI 10.1089/aid.2015.0331
Open Access Status Not yet assessed
Volume 32
Issue 9
Start page 841
End page 850
Total pages 10
Place of publication New Rochelle, NY, United States
Publisher Mary Ann Liebert
Language eng
Formatted 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/mm3 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.
Keyword Immunology
Infectious Diseases
Infectious Diseases
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
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