Abstract 454 - Decreased Susceptibility, Not Hypersensitivity, to Non- Nucleoside Reverse Transcriptase Inhibitors (NNRTI) in Patients Treated with Nucleoside Analogues (NRTI).

454 Decreased Susceptibility, Not Hypersensitivity, to Non- Nucleoside Reverse Transcriptase Inhibitors (NNRTI) in Patients Treated with Nucleoside Analogues (NRTI).

S. Moreno*, J. L. Casado, A. Antela, M. J. Perez-Elias, I. Garcia-Arata, F. Dronda, and A. Moreno.
Hosp. Ramón y Cajal, Madrid, Spain.

Background:There is controversy with regard to the variations in the sensitivity to NNRTI in patients exposed to multiple NRTI.

Methods:The variations in phenotypic susceptibility to NNRTI have been evaluated in 62 NNRTI-naive patients who had been heavily pretreated with NRTI. HIV RT sequences and phenotypic analysis (recombinant virus assay, Virco) were analyzed in all patients at baseline and after 6 months of therapy with a nevirapine-containing regimen. Hypersensitivity (HS) was defined as <0.5-fold change (FC) in IC₅₀to NNRTI.

Results:Patients had received 2.63 (range 1—5) NRTIs for 34 months (range 1—102) and 2 (range 1—4) PIs for 17 months (range 1—32). Baseline HIV RNA was 4.67 logs (2.53—6.2), and CD4 count was 231 cells/mm³(7— 846). Median number of mutations in the RT gene was 10 (1—23). At baseline, only 2 (3%) patients had mutations associated with resistance to NNRTI. Phenotypic susceptibility to nevirapine was as follows: <0.5 FC in IC₅₀(hypersensitive) 2%, 0.5—1 FC 21%, 1—4 FC 47%, >4—10 FC 23%, and >10 FC 3%. Hypersensitivity was also low for the other NNRTI drugs (0% for efavirenz and 5% for delavirdine). Median time on NRTI was longer in the patients with intermediate or resistant viruses (52 months) than in the patients with sensitive (38 months) or hypersensitive (30 months) viruses. Median number of mutations in the RT gene and the frequency of specific mutation were similar in all groups of patients. Viral load decreased a median 1.55 logs in patients with hypersensitive virus, 1.3 logs in patients with susceptible or intermediately resistant virus, and 0.15 in patients with resistant virus. After 6 months of therapy with a nevirapine-containing regimen, 5% of the patients had isolates hypersensitive to nevirapine or other NNRTI.

Conclusions:Prolonged therapy with multiple NRTI may account for decreased susceptibility to NNRTI in a significant percentage of patients and is associated with a poor response to these drugs. Hypersensitivity is rarely found, and its low prevalence is similar in NNRTI-naive patients and in patients who have failed a NNRTI- containing regimen.