Cross-resistance among nonnucleoside reverse transcriptase inhibitors limits recycling efavirenz after nevirapine failure
Antinori, A.; Zaccarelli, M.; Cingolani, A.; Forbici, F.; Rizzo, M.G.; Trotta, M.P.; Di Giambenedetto, S.; Narciso, P.; Ammassari, A.; Girardi, E.; De Luca, A.; Perno, C.F.
Aids Research and Human Retroviruses 18(12): 835-838
2002
ISSN/ISBN: 0889-2229 PMID: 12201905 DOI: 10.1089/08892220260190308Document Number: 259712
Heterogeneity in genotype mutations associated with resistance of HIV to nonnucleoside reverse transcriptase inhibitors (NNRTIs) should allow identification of patients failing nevirapine (NVP) who might benefit from efavirenz (EFV)-containing salvage regimens. To establish the feasibility of recycling EFV after failure of NVP-containing regimens genotypic data on 103 NVP-failed patients were analyzed to evaluate the prevalence of EFV resistance-conferring mutations. A clinically significant resistance to EFV was found in 50 of 103 (58%) of NVP-failed subjects. Furthermore, the 3-month virological response to salvage regimens containing EFV was assessed in patients previously treated with NVP and carrying single mutations conferring resistance to this drug. A proportion of HIV RNA less than 500 copies/ml at 3 months was obtained only in 2 of 12 (17%) of EFV-treated subjects compared with 35 of 67 (52%) of those without NNRTI mutations (OR, 0.18; 95% CI, 0.03-0.79). The median HIV-1 RNA decrease after 3 months was -0.63 log(10) among patients carrying single NNRTI-associated mutations compared with -1.32 log(10) among those without any NNRTI mutations. No virological response was observed in six patients harboring a single Y181C/I mutation. On the basis of the present data, sequential use of NNRTIs should be avoided in the management of treatment failure.