Objective:To evaluate the safety, tolerability, and anti-HIV activity of ritonavirnelfinavir (RTV-NFV).
Design:Single-site, open-label, nonrandomized, multiple-dose trial of RTV combined with two doses of NFV in protease inhibitor (PI)-naive, HIV-infected patients.
Methods:Mean baseline HIV RNA was 39,500 copies/ml; mean baseline CD4 count was 323 cells/mm3. All patients received RTV at a dosage of 400 mg twice daily. Cohorts I (N = 10) and II (N = 10) received NFV at a dosage of 500 mg and 750 mg twice daily, respectively, for the initial 12 weeks of the study before allowing intensification with reverse transcriptase inhibitors.
Results:The commonest effects of RTV-NFV therapy were study drug-related moderate-to-severe diarrhea (9 patients in cohorts I and II) and drug-related moderateto-severe nausea (4 patients in cohorts I and II). HIV RNA was suppressed in a biphasic manner. At 48 weeks in cohort I, mean HIV RNA reduction was 2.82 log10 copies/ml (standard error [SE] = .61; p = .001; N = 4); mean CD4 cell count increase was 236 cells/mm3 (SE = 67.1; p = .006; N = 4). In cohort II, mean HIV RNA reduction at Week 48 was 2.21 log10 copies/ml (SE = .430; p = .001; N = 8); mean CD4 cell count increase was 120 cells/mm3 (SE = 47.5; p = .03; n = 8). In cohort I patients, 2 of 4 completing Week 48 had HIV RNA <20 copies/ml; and 3 of 4 had HIV RNA <400 copies/ml. In cohort II, 2 of 8 patients completing Week 48 had HIV RNA <20 copies/ml and 4 of 8 had HIV RNA <400 copies/ml. In addition, 3 patients in cohort I withdrew because of virologic failure not thought to be related to poor compliance. Moreover, 15 patients elected to add new reverse-transcriptase inhibitors (RTIs) after week 12.
Conclusions:RTV-NFV with concomitant reverse transcriptase inhibitors is a potential dual-PI option for Pi-naive patients.
Address correspondence and reprint requests to Charles Raines, Johns Hopkins University School of Medicine, 1830 East Monument Street, Room 453, Baltimore, MD 21205, U.S.A.; e-mail: CRaines410@aol.com
This paper was presented in part at the Fifth Conference on Retroviruses and Opportunistic Infections, Chicago, Illinois, U.S.A., 1998, and the XII International Conference on AIDS, Geneva, Switzerland, 1998, and in its entirety at the Sixth Conference on Retroviruses and Opportunistic Infections, Chicago, Illinois, U.S.A. February 1999.
C. Flexner and J. E. Gallant were paid consultants for Abbott Laboratories during the conduct of this study and are disclosing this information in accordance with guidelines of the Committee on Conflict of Interest of the Johns Hopkins University School of Medicine.
Manuscript received March 13, 2000; accepted July 13, 2000.
© 2000 Lippincott Williams & Wilkins, Inc.