Safety and Antiviral Activity at 48 Weeks of Lopinavir/Ritonavir plus Nevirapine and 2 Nucleoside Reverse‐Transcriptase Inhibitors in Human Immunodeficiency Virus Type 1–Infected Protease Inhibitor–Experienced Patients

• DOI: 10.1086/339014
• Publication Date: 2002-09-30T17:28:16Z
• Authors: Constance A. Benson; Steven G. Deeks; Scott C. Brun; Roy M. Gulick; Joseph J. Eron; Harold A. Kessler; Robert L. Murphy; Charles Hicks; Martin King; David Wheeler; Judith Feinberg; Richard Stryker; Paul E. Sax; Sharon Riddler; Melanie Thompson; Kathryn Real; Ann Hsu; Dale Kempf; Anthony J. Japour; Eugene Sun
• Keywords: Adult; Male; 0301 basic medicine; Ritonavir; Anti-HIV Agents; HIV Infections; Pyrimidinones; Middle Aged; Lopinavir; CD4 Lymphocyte Count; 3. Good health; 03 medical and health sciences; Treatment Outcome; Double-Blind Method; HIV-1; Humans; RNA, Viral; Reverse Transcriptase Inhibitors; Drug Therapy, Combination; Female; Nevirapine; Prospective Studies

The safety and antiviral activity of lopinavir (Lpv), a protease inhibitor (PI) coformulated with ritonavir (Rtv) to enhance its pharmacokinetic properties, were evaluated in 70 patients with plasma human immunodeficiency virus type 1 (HIV-1) RNA levels of 1000-100,000 copies/mL on a first PI-containing regimen. Patients were randomized to substitute only the PI with Lpv/Rtv, 400/100 mg or 400/200 mg twice daily. On day 15, nevirapine (200 mg 2x/day) was added, and nucleoside reverse-transcriptase inhibitors were changed. Despite a >4-fold reduction in phenotypic susceptibility to the preentry PI in 63% of patients, mean plasma HIV-1 RNA levels declined by 1.14 log(10) copies/mL after 2 weeks of Lpv/Rtv. At week 48, 86% of subjects receiving treatment had plasma HIV-1 RNA levels of <400 copies/mL; 76% had levels <50 HIV-1 RNA copies/mL (intent-to-treat: 70% and 60%, respectively). Mean CD4 cell counts increased by 125 cells/muL. Three patients discontinued therapy for drug-related adverse events.