867 
Etravirine-resistance Mutations in Patients with Virologic Failure on Nevirapine or Efavirenz-based HAART
Babafemi Taiwo*1, B Chaplin2, J Stanton1, S Meloni2, S Akanmu3, W Gashau4, J Idoko5, I Adewole6, R Murphy1, and P Kanki2
1Feinberg Sch of Med, Northwestern Univ, Chicago, IL, US; 2Harvard Sch of Publ Hlth, Boston, MA, US; 3Lagos Univ Teaching Hosp, Nigeria; 4Univ of Maiduguri Teaching Hosp Nigeria; 5Jos Univ Teaching Hosp, Nigeria; and 6Univ Coll Hosp, Ibadan, Nigeria
Background: Etravirine (TMC125) is a potent diarylpyrimidine
NNRTI with a high genetic barrier to resistance, and clinical activity against
nevirapine and efavirenz-resistant HIV-1 strains. The DUET studies showed that
significant resistance to TMC125 is predicted by the presence of ≥3 of 13
TMC125-resistance mutations (V90I, A98G, L100I, K101E, K101P, V106I, V179D,
V179F, Y181C, Y181I, Y181V, G190A, and G190S). Since September 2005, genotypic
testing has been performed on patients in virologic failure as part of the APIN
Plus/Harvard PEPFAR program in Nigeria. This analysis was performed to determine
the prevalence of TMC125-resistance mutations in efavirenz or nevirapine
virologic failures; and to determine the potential effect of current drug-resistance
mutations on the efficacy of TMC125.
Methods: We analyzed subtypes and genotypes from
Nigerian patients in virologic failure whose isolates had been sequenced
earlier for clinical management. Virologic failure was defined as plasma HIV
RNA >1000 copies/ml despite ≥6 months of ART. Predicted TMC125
resistance was defined as presence of ≥3 of the 13 TMC125-resistance
mutations. The duration of prior NNRTI-based HAART was extracted from the
clinical databases.
Results: Data from 214 patients were analyzed. All
had HIV-1 infection with subtype distribution: CRF02: 43%, G: 43%, A: 5%,
CRF06: 4%, recombinant: 3%, other: 2%. TMC125-resistance mutations were absent
in 32%; 1 mutation was present in 35%; 2 mutations in 23%; and ≥3
mutations in 10%. Detection of TMC125-mutation(s) correlated with duration of
prior NNRTI-based therapy with a mean duration (months) of 18.9 for 0 mutations
vs 25.4 for ≥1 mutation(s), p = 0.0001. There was a trend toward
longer duration with ≥3 mutations (27.8) vs 0 to 2 mutations (22.8), p
= 0.0651.
Conclusions: TMC125 is likely to be effective in 90%
of the patients in this cohort. Early discontinuation of a failing first-line
NNRTI may prevent the accumulation of TMC125-mutations. The prevalence of A98G
(18%) in our cohort is higher than reported from settings with different HIV-1
subtype distributions. Further studies are needed to fully characterize TMC125-resistance
mutations, and determine if subtype-specific factors contribute to the high
prevalence of A98G in our population.
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