Comparison of Virologic, Immunologic, and Clinical Response to Five Different Initial Protease Inhibitor-Containing and Nevirapine-Containing Regimens

Abstract

Context: The effectiveness of different protease inhibitors (PIs) and non-nucleoside reverse transcriptase inhibitors outside the setting of clinical trials has not been well described. Objectives: To compare five different PI- and nevirapine (NVP)-containing regimens on virologic, immunologic, and clinical outcomes and treatment discontinuation. Design and Setting: Observational cohort study based on an HIV clinic in London. Patients: A total of 690 patients who received either saquinavir hard gel (SQV HG) (n = 183), indinavir (IDV) (n = 189), nelfinavir (NFV) (n = 109), ritonavir (RTV) (n = 42), ritonavir with saquinavir hard gel (RTV/SQV HG) (n = 45), or NVP (n = 122) as part of an initial PI- or NVP-containing treatment regimen between November 1994 and December 1998. A total of 351 (51%) patients had prior exposure to nucleoside reverse transcriptase inhibitors (NRTIs). Main Outcome Measures: The main outcome measures were virologic undetectability, subsequent virologic rebound, CD4 cell count rise, development of AIDS, and treatment discontinuation. All analyses were stratified for year of initiation of the PIor NVP-containing regimen. Results: Overall, 63% of patients attained an undetectable viral load (VL) within 6 months of starting their PI or NVP regimen. The adjusted relative hazard (95% confidence interval [CI]) for an undetectable VL relative to SQV HG was (in rank order): 2.77 (CI: 1.84-4.17) for NFV, 2.54 (CI: 1.81-3.57) for IDV, 2.43 (CI: 1.52-3.87) for RTV, 2.08 (CI: 1.28-3.37) for RTV/SQV HG, and 1.96 (CI: 1.35-2.85) for NVP. Forty-nine percent of patients experienced VL rebound within 12 months of initial attainment of undetectability, but relative to SQV HG, this did not differ significantly across the different PI and NVP regimens. The CD4 cell count response and rate of AIDS events were also similar across the different regimens. No independent predictors of VL undetectability were identified, but prior NRTI exposure was associated with VL rebound, and a lower baseline VL and CD4 cell count were associated with a reduced CD4 count response. The frequency (95% CI) of treatment discontinuation differed across the regimens; at 6 months, it was lowest for NFV (18% [CI: 13%-24%]), IDV (25% [CI: 22%-29%]), and NVP (28% [CI: 22%-34%]) and highest for RTV (41% [CI: 31%-52%]) and SQV HG (52% [CI: 48%-57%]). Conclusions: Although PI- and NVP-containing regimens were similar in their CD4 cell count response and rates of subsequent VL rebound, differences were observed in time to VL undetectability and discontinuation rates relative to SQV HG. SQV HG was consistently inferior to the other PIs and NVP. The use of NFV and IDV was associated with the highest rates of undetectability, and together with NVP, the lowest rates of discontinuation.