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 resistance after a switch from an effective protease inhibitor (PI)-containing regimen to a multitherapy regimen including nevirapine (NVP). After 6 months with an undetectable viral load under a PI-containing regimen, the patients were switched to NVP with conservation of the associated nucleoside reverse transcriptase inhibitors (NRTIs). Patients were followed-up at 1 month and then 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 PI-containing regimen, whereas 12 patients (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 naive group, versus 41% of the experienced group, developed a virologic failure after the change toward NVP ( p =.003). The virologic failures were associated with the appearance of NNRTI-resistant mutations. All rebound mutants also presented NRTI-resistance mutations. These results are consistent with a higher risk of virologic failure after a switch to an NNRTI in patients with prior suboptimal treatment and suggest the hypothesis that archived resistant viruses may facilitate the emergence of NNRTI resistance.
Masquelier
B
B
Laboratoire de Virologie, Centre Hospitalier Universitaire de Bordeaux, France. bernard.masquelier@chu-bordeaux.fr
Neau
D
D
Chêne
G
G
Larbère
J
J
Birac
V
V
Ragnaud
J M
JM
Fleury
H J
HJ
D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D010450:Endopeptidases / Q000235:genetics; D015751:Genes, pol; D005838:Genotype; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000821:virology; D054303:HIV Reverse Transcriptase / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D009154:Mutation; D019829:Nevirapine / Q000627:therapeutic use*; D011446:Prospective Studies; D011480:Protease Inhibitors / Q000627:therapeutic use*; D012367:RNA, Viral / Q000097:blood*; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D013997:Time Factors; D019562:Viral Load
D019380:Anti-HIV Agents; D011480:Protease Inhibitors; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D019829:Nevirapine; D054303:HIV Reverse Transcriptase; D010450:Endopeptidases