Background:  A fixed-dose combination of stavudine (d4T) + lamivudine (3TC) + nevirapine (NVP) is extensively used in developing countries secondary to its affordable cost. Treatment failure from this regimen becomes more common and resistance testing is not widely accessible. Options for backbone in the second regimen are limited by nucleoside reverse transcriptase inhibitor (NRTI) cross resistance and the cost of abacavir and didanosine. Tenofovir (TDF) is expected to be available in Thailand in November 2006 with a low cost. Some mutation patterns after failing d4T+3TC+NVP may limit the use of tenofovir in the second regimen.      

Methods:  Genotypic resistance testing was conducted among HIV-infected patients who failed their initial ART regimen of a fixed-dose combination of d4T+3TC+NVP during 2003-2005. Patterns of resistance mutation contributing to tenofovir resistance were studied. Predicting factors for TDF resistance were determined from univariate and multivariate analysis.  

Results:  There were 98 patients with a mean (SD) age of  35.2 (6.3) years and 63% were male. Median (IQR) duration of ART was 20 (13 to 28) months. Median (IQR) CD4 cell count and HIV RNA at the time of virological failure detection was 159 (105 to 248) cells/mm³ and 4.1 (3.7 to 4.7) log copies/mL, respectively. Of the total, 10 (10.2%) patients had TDF resistance: 6 had K65R and 4 had ≥3 thymidine analog mutations (TAM) inclusive of either M41L or L210W. When categorized patients into 2 groups according to HIV RNA level at virological failure detection, the group with HIV RNA >4 log copies/mL at failure had a higher rate of tenofovir resistance when compared to the group with HIV RNA ≤4 log copies/mL at failure (20% vs 2.3%, p = 0.021). By multivariate analysis, only log HIV RNA 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.

Conclusions: TDF resistance is common among HIV-infected patients failing d4T+3TC+NVP regimen and having high HIV RNA at failure. Late detection of virological failure limits the use of tenofovir in the second regimen for patients failing d4T+3TC+NVP. In resource-limited settings where resistance testing is not widely accessible and options for the second regimen are limited, early detection of virological failure is crucial. Accessibility of HIV RNA assay for monitoring of treatment needs to be scaled-up along with accesibility of ART.