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Session 97
Poster Abstracts Impact of Virus Type/Subtype on Resistance Development Monday, 1:30 - 3:30 pm Poster Hall |
Background: The 2NN trial enrolled 1216 HIV-1+ treatment-naïve patients from 6 continents in a 48-week investigation of antiretroviral regimens containing nevirapine (NVP) and/or efavirenz (EFV) on a background of lamivudine (LMV) and stavudine (D4T). To evaluate HIV-1 genotypic characteristics, including viral subtype and resistance-associated mutations, a random sample of 174 patients was selected and a group of 102 additional patients who were considered virologic failures was identified. Since 21 of the patients in the random sample were virologic failures, the study included 123 virologic failures. The trial is completed and the results are final.
Methods: Baseline specimens from all selected patients were sequenced for reverse transcriptase (RT) and protease (PR) genes, and analyzed for subtype and predicted resistance to RT inhibitors and PR inhibitors using the VIRCO Virtual Phenotype. On-treatment specimens with viral load >1000 copies/mL from 123 virologic failures were sequenced and analyzed similarly. Comparisons included random sample versus virologic failure, and early versus late virologic failure specimens, overall and between treatment groups; p values were based on chi-squared and rank tests, as appropriate.
Results: In the random sample, 44% were subtype B, 34% subtype C and 22% other subtypes. In the virologic failures, 42% were B, 48% C, and 10% other (p = 0.011). At baseline, 1 patient from the random sample was predicted resistant to NNRTI, while 12 patients in the virologic failure group were predicted resistant to NNRTI and/or LMV. At last on-treatment observation, 70 (57%) virologic failure patients had predicted resistance to 1 or more of the drugs in their regimen. These patients had significantly higher baseline viral load and lower CD4 count than those predicted susceptible (medians 5 vs 4.6, p = 0.01; 95 vs 230, p = 0.003, respectively). With NVP twice daily there were significantly more NNRTI-associated mutations after 24 weeks than at or before 24 weeks (p = 0.003), while there was no difference with EFV (p = 0.43).
Conclusions: Virologic failure was more common in subtype C. Baseline NNRTI resistance was associated with virologic failure. Among virologic failures, predicted resistance was associated with higher baseline viral load and lower CD4 count.
Keywords: Genotype; NNRTI; Resistance
