Unexpectedly high rate of K65R mutation in patients failing first-line d4T-containing regimens in Thailand

Somnuek Sungkanuparph from Ramathibodi Hospital, Bangkok, reported genotypic resistance results in 98 patients who failed fixed-dose combination of stavudine (d4T) + lamivudine (3TC) + nevirapine (NVP) between 2003-2005.

Patients had a mean age of 35.2 (SD+/-6.3) years and 63% were male. Median duration of antiretroviral treatment was 20 (IQR,13 to 28) months. Median CD4 cell count and HIV RNA at the time of virological failure detection was 159 (IQR, 105 to 248) cells/mm3 and 4.1 (IQR, 3.7 to 4.7) log copies/mL respectively.

10/98 (10.2%) patients had tenofovir-related resistance: 6 had K65R and 4 had =3 thymidine analog mutations (TAM) inclusive of either M41L or L210W. By multivariate analysis, only log HIV viral load at failure (OR 10.48; 95%CI 1.77 to 62.13, p = 0.010) and duration of ART prior to failure (OR 1.12; 95%CI, 1.03 to 1.21, p = 0.008) predicted the occurrence of tenofovir resistance.

Resistance patterns from patients failing d4T-based FDCs has not been widely studied, but these results may caution the reliance on tenofovir to resolve patients failing treatment who are maintained on failing FDCs, especially where absence of viral load testing reduces the chance of detecting early virological failure.

Sungkanuparph S, Manosuthi W, Kiertiburanakul S et al. Tenofovir Resistance among HIV-infected Patients Failing a Fixed-dose Combination of Stavudine + Lamivudine + Nevirapine in a Resource-limited Setting. Abstract 663.
http://www.retroconference.org/2007/Abstracts/29263.htm