Mechanism of virologic failure after substitution of a protease inhibitor by nevirapine in patients with suppressed plasma HIV-1 RNA

A prospective study was set up to evaluate the emergence of HIV-1 resistanc e after a switch from an effective protease inhibitor (PI)-containing regim en to a multitherapy regimen including nevirapine (NVP). After 6 months wit h an undetectable viral load under a Pl-containing regimen, the patients we re switched to NVP with conservation of the associated nucleoside reverse t ranscriptase inhibitors (NRTIs). Patients were followed-up at I month and t hen every 3 months after switching therapy. Nucleotide sequence analysis of the pol gene was performed at the first points of virologic failure. Thirty-four patients were included. The NRTI-naive group (22 patients) had begun antiretroviral therapy with a Pl-containing regimen, whereas 12 patie nts (experienced group) had been previously treated by nucleoside mono-and/ or dual therapy. After a median follow-up of 40 weeks, no patient of the na ive group, versus 41% of the experienced group, developed a virologic failu re after the change toward NVP (p = .003). The virologic failures were asso ciated with the appearance of NNRTI-resistant mutations. All rebound mutant s also presented NRTI-resistance mutations. These results are consistent wi th a higher risk of virologic failure after a switch to an NNRTI in patient s with prior suboptimal treatment and suggest the hypothesis that archived resistant viruses may facilitate the emergence of NNRTI resistance.