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.


METHODS
Observational cohort of HIV-positive individuals.


METHODS
Viral load, CD4+ and CD8+ T lymphocyte counts were assessed at intervals of 1-3 months in subjects commencing therapy between July 1996 and November 1996. Adverse events were evaluated as well as risk factors for therapeutic failures.


RESULTS
A group of 56 male patients were included and followed for 48 weeks. Of these, 66% had already taken a protease inhibitor. Viral load dropped by a median 1.98 log10 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-responders (HIV RNA reduction < 0.5 log10 copies/ml) and 23% were incomplete responders (nadir of HIV RNA > 400 copies/ml). After 48 weeks, viral load remained undetectable in 49%. Median CD4+ T lymphocyte count increased 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 selected for drug-resistant viral mutants, only the protease inhibitor experience was identified as a risk factor for therapeutic failure. Adverse events occurred in 73% of patients and led to a change of therapy in 9%.


CONCLUSIONS
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 after 48 weeks and frequent adverse events complicated therapy.
Centre for Immunology, St Vincent's Hospital, Sydney, NSW, Australia.
G R
GR
Kaufmann
C
C
Duncombe
P
P
Cunningham
A
A
Beveridge
A
A
Carr
D
D
Sayer
M
M
French
D A
DA
Cooper
D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D016516:CD4-CD8 Ratio; D015331:Cohort Studies; D004359:Drug Therapy, Combination; D015658:HIV Infections / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D015497:HIV-1; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D019370:Observation; D012307:Risk Factors; D019438:Ritonavir / Q000627:therapeutic use*; D019258:Saquinavir / Q000627:therapeutic use*; D017211:Treatment Failure; D019562:Viral Load; D015215:Zidovudine / Q000627:therapeutic use
D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D019259:Lamivudine; D015215:Zidovudine; D019258:Saquinavir; D019438:Ritonavir