ABSTRACT:
It is not known whether the failure of nevirapine in combination with protease inhibitors (PIs) is associated with the emergence of resistance to non-nucleoside reverse transcriptase (RT) inhibitors (NNRTIs). We studied the rate of resistance after 6 months among 88 patients who received nevirapine in a rescue regimen in combination with nelfinavir, nelfinavir plus saquinavir or ritonavir plus saquinavir. Phenotypic susceptibility was determined by recombinant virus assay (Antivirogram, Virco). Patients had received a mean of 1.8 PIs over 510 days (49-725). Mean CD4 cell count was 215 cells/mm3 and HIV load was 4.5 log10copies/ml. At entry, nearly half of patients showed viruses >10-fold resistant to PIs, but only 8% were resistant to nevirapine. At month 6, a HIV load <200 copies/ml was observed in 39% of patients. Treatment failure in 39 patients was followd with resistance to nevirapine (>82.2-fold), and only 8% remained susceptible. Baseline resistance to PIs was the only factor associated with the emergence of nevirapine resistance. At this time, 73% of the viral isolates were resistant to delavirdine and 70% to efavirenz. There was a correlation between the increased IC50 to nevirapine and that observed for efavirenz (r=0.56, P<0.01). In those viral isolates resistant to nevirapine, a 69-fold increase was seen in the efavirenz IC50 and 81% showed resistance to this drug. Treatment failure due to PI resistance is followed by the emergence of nevirapine resistance in most of the patients. The results showed a correlation in the increase of the IC50 between the different NNRTIs, but nearly one third of nevirapine-resistant clinical isolates remained susceptible to efavirenz.
