Low level of the K103N HIV-1 above a threshold is associated with virological failure in treatment-naive individuals undergoing efavirenz-containing therapy
Low level of the K103N HIV-1 above a threshold is associated with virological failure in treatment-naive individuals undergoing efavirenz-containing therapy
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DOI：
10.1097/qad.0b013e3283427dcb
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发表时间：
2011-01-28
期刊：
影响因子：
3.8
通讯作者：
Svarovskaia, Evguenia S.
中科院分区：
文献类型：
--
作者：
Goodman, Derrick D.;Zhou, Yun;Svarovskaia, Evguenia S.
Background: Study GS-01-934 was a randomized open-label phase III study comparing efavirenz and tenofovir/emtricitabine to efavirenz and zidovudine/lamivudine in treatment-naive HIV-1-infected individuals. Through 144 weeks, 50 of 487 participants without baseline nonnucleoside reverse transcriptase inhibitor resistance by population sequencing (efavirenz/tenofovir/emtricitabine, n = 19; efavirenz/zidovudine/lamivudine, n = 31) experienced virologic failure (>400 copies/ml). Here, we analyzed whether the presence of low levels of K103N at baseline correlated with virologic failure.Methods: Available baseline plasma samples (n = 485) were amplified and tested for K103N using an allele-specific PCR (AS-PCR) assay with a lower detection cut-off of 0.5%.Results: Sixteen of 476 (3.4%) evaluable participants had low-level K103N at baseline by AS-PCR (0.8-15%). The abundance of the K103N subpopulation at baseline distinguished individuals with virologic failure from those who responded durably to efavirenz-containing therapy. Among six participants with at least 2000 K103N copies/ml before treatment, five experienced virologic failure, compared with only one virologic failure among 10 who had less than 2000 K103N copies/ml (P = 0.008). Multivariate logistic regression analysis showed that K103N viral load at least 2000 copies/ml increased the risk of virologic failure with an odds ratio of 47.4 (95% confidence interval 5.2-429.2, P = 0.0006).Conclusion: The presence of K103N mutant virus in plasma above 2000 copies/ml prior to therapy in treatment-naive individuals correlated with increased risk of virologic failure of these efavirenz-containing triple-drug regimens. (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins
