Comparison of virologic, immunologic, and clinical response to five different initial protease inhibitor-containing and nevirapine-containing regimens

Context: The effectiveness of different protease inhibitors (PIs) and non-n ucleoside reverse transcriptase inhibitors outside the setting of clinical trials has not been well described. Objectives: To compare five different PI- and nevirapine (NVP)-containing r egimens on virologic, immunologic, and clinical outcomes and treatment disc ontinuation. Design and Setting: Observational cohort study based on an HIV clinic in Lo ndon. Patients: A total of 690 patients who received either saquinavir hard gel ( SQV HG) (n = 183), indinavir (IDV) (n = 189). nelfinavir (NFV) (n = 109), r itonavir (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 treatm ent regimen between November 1994 and December 1998. A total of 351 (51%) p atients had prior exposure to nucleoside reverse transcriptase inhibitors ( NRTIs). Main Outcome Measures: The main outcome measures were virologic undetectabi lity, subsequent virologic rebound, CD4 cell count rise, development of AID S, and treatment discontinuation. All analyses were stratified for year of initiation of the PI-or 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 [CII) for an undetectable VL relative to SQ V HG was (in rank order): 2.77 (CI: 1.84-4.17) for NFV. 2.54 (CL 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 experienc ed VL rebound within 12 months of initial attainment of undetectability, bu t relative to SQV HG. this did not differ significantly across the differen t 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 associat ed with VL rebound. and a lower baseline VL and CD4 cell count were associa ted 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 we re observed in time to VL undetectability and discontinuation rates relativ e 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 undetectabilit y. and together with NVP. the lowest rates of discontinuation.