Safety, tolerability, and antiretroviral effects of ritonavir-nelfinavir combination therapy administered for 48 weeks.

OBJECTIVE: To evaluate the safety, tolerability, and anti-HIV activity of ritonavir-nelfinavir (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 moderate-to-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.

Efficacy of salvage therapy containing ritonavir and saquinavir after failure of single protease inhibitor-containing regimens.

OBJECTIVE: To assess the efficacy of salvage therapy containing ritonavir and saquinavir after failure of indinavir- or nelfinavir-containing regimens, and to determine correlates of success or failure. DESIGN: Retrospective chart review. SETTING. The Moore Clinic - the HIV clinic of Johns Hopkins Hospital. PATIENTS: Forty-one HIV-infected patients were identified through physician contacts, referrals from other providers, and review of a comprehensive clinical database. MAIN OUTCOME MEASURES: To determine response to salvage therapy, HIV-1 viral RNA (absolute and log10-transformed) was measured using the Roche Amplicor quantitative HIV-1 RNA assay after initiation of the salvage regimen. Potential correlates of response included: viral RNA at the time of switch; viral RNA at the time of switch as a percentage of baseline viral RNA; magnitude of decline in viral RNA; and the interval between virologic failure of single protease inhibitor therapy and switch to the salvage regimen. RESULTS: Thirteen (56.5%) of 23 patients failing indinavir responded to salvage therapy (HIV RNA < 400 copies/ml) with persistence throughout the follow-up period (median of 37 weeks; range 18-67 weeks). Mean absolute viral RNA at the time of switch was 20 238 copies/ml (median, 9281) compared with 42 953 copies/ml (median, 24 650) for the 10 non-responders. Mean log10 viral RNA at switch was 3.804 for responders versus 4.405 for non-responders (P = 0.040). Among four responders who had failed nelfinavir, mean viral RNA was 9634 copies/ml and mean log10 viral RNA was 3.749 at the time of switch. Two non-responders had a mean viral RNA of 21 551 and a mean log10 viral RNA of 4.037 at switch. CONCLUSIONS: In contrast with previous reports, salvage regimens containing ritonavir and/or saquinavir can be effective and durable following the failure of combination regimens containing either indinavir or nelfinavir. Salvage therapy may be more likely to succeed when it is initiated early in failure at low viral loads.