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  • Title: Prevalence and risk factors for developing K65R mutations among HIV-1 infected patients who fail an initial regimen of fixed-dose combination of stavudine, lamivudine, and nevirapine.
    Author: Sungkanuparph S, Manosuthi W, Kiertiburanakul S, Saekang N, Pairoj W, Chantratita W.
    Journal: J Clin Virol; 2008 Apr; 41(4):310-3. PubMed ID: 18316243.
    Abstract:
    BACKGROUND: A fixed-dose combination of stavudine, lamivudine, and nevirapine (d4T/3TC/NVP) is extensively used as initial antiretroviral regimen in developing countries. K65R mutations that occur after failing this regimen prevent the use of tenofovir, didanosine, and abcavir in the second-line regimen. OBJECTIVES: To determine the prevalence and risk factors of K65R mutations after failing d4T/3TC/NVP. STUDY DESIGN: Genotypic resistance testing was conducted among HIV-1 infected patients who experienced virological failure with an initial regimen of d4T/3TC/NVP. RESULTS: There were 122 patients who received antiretroviral therapy (ART) for a median (IQR) duration of 19 (13-27) months. Median (IQR) CD4 cell count and plasma HIV-1 RNA at virological failure was 174 (109-264) cells/mm(3) and 4.0 (3.7-4.6)log copies/mL, respectively. The prevalence of K65R mutations was 7%. Patients with K65R mutations had higher plasma HIV-1 RNA at virological failure compared to patients without K65R mutations (4.9log copies/mL vs. 4.0log copies/mL, p=0.001). By logistic regression analysis only plasma HIV-1 RNA at failure correlated with the occurrence of K65R mutations [OR 4.2 (95% CI, 1.5-11.2) per 0.5log copies/mL increment of HIV-1 RNA]. CONCLUSIONS: Seven percent of patients had K65R mutations after failing an initial d4T/3TC/NVP regimen. Tenofovir, didanosine, and abcavir cannot be used in second-line regimen for these patients. HIV-1 RNA at the time that virological failure was detected correlated with the occurrence of K65R mutations.
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