TREATMENT RESPONSE AND DURABILITY OF A DOUBLE PROTEASE INHIBITOR THERAPY WITH SAQUINAVIR AND RITONAVIR IN AN OBSERVATIONAL COHORT OF HIV-1-INFECTED INDIVIDUALS

Objective: To evaluate treatment response, durability and tolerance of a four-drug regimen including saquinavir and ritonavir in combination with either zidovudine/lamivudine or stavudine/lamivudine. Design: Ob servational cohort of HIV-positive individuals. Methods: Viral load, C D4+ and CD8+ T lymphocyte counts were assessed at intervals of 1-3 mon ths in subjects commencing therapy between July 1996 and November 1996 . Adverse events were evaluated as well as risk factors for therapeuti c failures. Results: A group of 56 male patients were included and fol lowed for 48 weeks. Of these, 66% had already taken a protease inhibit or. Viral load dropped by a median 1.98 log(10) HIV RNA copies/ml from baseline (interquartile range: 1.49-2.46) and became undetectable (< 400 copies/ml) in 68% of patients. Response varied: 9% were non-respon ders (HIV RNA reduction < 0.5 log(10) copies/ml) and 23% were incomple te responders (nadir of HIV RNA > 400 copies/ml). After 48 weeks, vira l load remained undetectable in 49%. Median CD4+ T lymphocyte count in creased from 191 x 10(6) to 418 x 10(6) cells/l (range, 241-537 x 10(6 ) cells/l). Although protease inhibitor and nucleoside pretreatment se lected for drug-resistant viral mutants, only the protease inhibitor e xperience was identified as a risk factor for therapeutic failure. Adv erse events occurred in 73% of patients and led to a change of therapy in 9%. Conclusion: Despite advanced HIV disease and pretreatment with multiple antiretroviral drugs, a strong initial treatment response to this drug regimen was observed. However, virological failure occurred in 51% of patients ater 48 weeks and frequent adverse events complica ted therapy. (C) 1998 Lippincott Williams & Wilkins.