Novel Four-Drug Salvage Treatment Regimens after Failure of a Human Immunodeficiency Virus Type 1 Protease Inhibitor-Containing Regimen: Antiviral Activity and Correlation of Baseline Phenotypic Drug Susceptibility with Virologic Outcome

• Published in: The Journal of infectious diseases 1999-06, Vol.179 (6), p.1375-1381
• Main Authors: Deeks, Steven G., Hellmann, Nicholas S., Grant, Robert M., Parkin, Neil T., Petropoulos, Christos J., Becker, Mark, Symonds, William, Chesney, Margaret, Volberding, Paul A.
• Format: Article
• Language: English
• Subjects: Abacavir; Adult; AIDS; AIDS/HIV; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiretrovirals; Antiviral agents; Antivirals; Biological and medical sciences; Dideoxynucleosides - therapeutic use; Drug Resistance, Microbial; Drug Therapy, Combination; Female; HIV; HIV 1; HIV Infections - blood; HIV Infections - drug therapy; HIV Protease Inhibitors - therapeutic use; HIV-1 - drug effects; HIV-1 - genetics; Human immunodeficiency virus 1; Human viral diseases; Humans; Indinavir - therapeutic use; Infectious diseases; Major Articles; Male; Medical sciences; Nelfinavir; Nelfinavir - therapeutic use; Nevirapine; Nevirapine - therapeutic use; Nucleosides; Pharmacology. Drug treatments; Phenotype; Prospective Studies; Protease inhibitors; Reverse Transcriptase Inhibitors - therapeutic use; Ritonavir - therapeutic use; RNA, Viral - blood; Salvage Therapy; Saquinavir; Saquinavir - therapeutic use; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Virology; Viruses
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1086/314775

Twenty human immunodeficiency virus—infected patients experiencing virologic failure of an indinavir- or ritonavir-containing treatment regimen were evaluated in a prospective, open-label study. Subjects received nelfinavir, saquinavir, abacavir, and either another nucleoside analog (n = 10) or nevirapine (n = 10). Patients treated with the nevirapine-containing regimen experienced significantly greater virologic suppression at week 24 than those not treated with nevirapine (P = .04). Baseline phenotypic drug susceptibility was strongly correlated with outcome in both treatment arms. Subjects with baseline virus phenotypically sensitive to 2 or 3 drugs in the salvage regimen experienced significantly greater virus load suppression than those with baseline virus sensitive to 0 or 1 drug (median week-24 change = −2.24 log and −0.35 log, respectively; P = .01). In conclusion, non-nucleoside reverse transcriptase inhibitors may represent a potent drug in salvage therapy regimens after failure of an indinavir or ritonavir regimen. Phenotypic resistance testing may provide a useful tool for selecting more effective salvage regimens.