+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Randomised, multicentre phase III study of saquinavir plus zidovudine plus zalcitabine in previously untreated or minimally pretreated HIV-infected patients

Randomised, multicentre phase III study of saquinavir plus zidovudine plus zalcitabine in previously untreated or minimally pretreated HIV-infected patients

Clinical Drug Investigation 20(5): 295-307

Background: PISCES (SV14604) was the largest study of antiretroviral therapy to assess clinical end-points. The study data provides a repository of important information, much of which remains relevant today. This paper reviews the results of the PISCES study, placing the findings in context with today's treatment practices. Objective: To determine the antiretroviral efficacy of saquinavir hard gelatin capsule (SQV; Invirase(R)) plus two nucleoside analogues (zidovudine (ZDV) and zalcitabine (ddC)) using clinical end-points. Design: Prospective, randomised, double-blind international study. Patients: HIV-1-infected individuals (CD4 50 to 350 cells/mul) who were antiretroviral-naive or minimally pretreated with zidovudine (ZDV; ltoreq16 weeks) were randomised. Interventions: Patients received: (i) SQV + ZDV + ddC, (ii) SQV + ZDV, (iii) ZDV + ddC, or (iv) ZDV for gtoreq80 weeks or until the common closure date, at daily oral dosages of SQV 1800mg, ddC 2.25mg and ZDV 600mg. After 14 months, ZDV monotherapy patients were reallocated to receive additional SQV + ddC in a double-blinded manner. Main Outcome Measure: Time to clinical end-point of first AIDS-defining event (ADE) or death. Results: A total of 3591 patients were randomised, and 3485 received therapy. Median duration of study therapy was 58.4 to 63.3 weeks and mean duration of follow-up was 73.9 to 75.6 weeks. The time to first ADE or death was significantly reduced with triple therapy relative to ZDV + ddC (p = 0.0001, log rank test). The proportion of patients progressing to the primary clinical end-point was 8.0% for the triple therapy group compared with 15.1% for ZDV + ddC. Initiating triple therapy reduced the risk of progression by 50% relative to ZDV + ddC (risk ratio 0.502; (95% CI 0.379-0.663) p = 0.0001). Patients with prior ZDV therapy for <8 weeks achieved the greatest clinical benefit. HIV-1 RNA was reduced more by triple therapy than by either dual therapy (p = 0.0001), and this reduction explained 64% of the treatment effect. In an exploratory analysis, the primary end-point was reached by 8.0% of patients receiving immediate triple therapy, compared with 17.8% receiving initial ZDV monotherapy followed by triple therapy (p = 0.0001). Conclusions: This study was the first to show the benefit of triple therapy over dual therapy using clinical outcome measures; treatment with SQV + ZDV + ddC producing a statistically significant prolongation of time to first ADE or death in antiretroviral-naive/minimally pretreated patients, compared with combined nucleoside analogues only. The study also confirms the outcome benefit (time to first ADE or death) of immediate triple therapy over delayed triple therapy and the prognostic value of monitoring HIV-1 RNA (but not CD4 count). The potential of patient/clinician perception of therapy to influence study outcome was also demonstrated.

Please choose payment method:

(PDF emailed within 0-6 h: $19.90)

Accession: 011243097

Download citation: RISBibTeXText

DOI: 10.2165/00044011-200020050-00001

Related references

Quality of life outcomes of combination zalcitabine-zidovudine, saquinavir-zidovudine, and saquinavir-zalcitabine-zidovudine therapy for HIV-infected adults with CD4 cell counts between 50 and 350 per cubic millimeter. PISCES (SV14604) Study Group. Aids 13(7): 851-858, 1999

Saquinavir + zalcitabine vs saquinavir or zalcitabine monotherapy in HIV-infected patients discontinuing or intolerant to zidovudine Results of a randomized, double blind trial. AIDS (London) 10(Suppl. 2): S17, 1996

Resistance mutations to zidovudine and saquinavir in patients receiving zidovudine plus saquinavir or zidovudine and zalcitabine plus saquinavir in AIDS clinical trials group 229. Journal of Infectious Diseases 179(1): 249-253, 1999

Resistance Mutations to Zidovudine and Saquinavir in Patients Receiving Zidovudine Plus Saquinavir or Zidovudine and Zalcitabine Plus Saquinavir in Aids Clinical Trials Group 229. The Journal of Infectious Diseases 179(1): 249-253, 1999

A randomized controlled trial of a protease inhibitor (saquinavir) in combination with zidovudine in previously untreated patients with advanced HIV infection. Antiviral Therapy 1(3): 129-140, 1996

CHOP versus GEM-P in previously untreated patients with peripheral T-cell lymphoma (CHEMO-T): a phase 2, multicentre, randomised, open-label trial. Lancet. Haematology 5(5): E190-E200, 2018

Delta: A randomised double-blind controlled trial comparing combinations of zidovudine plus didanosine or zalcitabine with zidovudine alone in HIV-infected individuals. Lancet (North American Edition) 348(9023): 283-291, 1996

A multicentre study to determine the efficacy and tolerability of a combination of nelfinavir (VIRACEPT), zalcitabine (HIVID) and zidovudine in the treatment of HIV infected Nigerian patients. West African Journal of Medicine 21(2): 83-86, 2002

Atezolizumab plus bevacizumab versus sunitinib in patients with previously untreated metastatic renal cell carcinoma (IMmotion151): a multicentre, open-label, phase 3, randomised controlled trial. Lancet 393(10189): 2404-2415, 2019

Chlorambucil plus ofatumumab versus chlorambucil alone in previously untreated patients with chronic lymphocytic leukaemia (COMPLEMENT 1): a randomised, multicentre, open-label phase 3 trial. Lancet 385(9980): 1873-1883, 2015

Delta: a randomised double-blind controlled trial comparing combinations of zidovudine plus didanosine or zalcitabine with zidovudine alone in HIV-infected individuals. Delta Coordinating Committee. Lancet 348(9023): 283-291, 1996

Oral cladribine for B-cell chronic lymphocytic leukaemia: Report of a phase II trial with a 3-d, 3-weekly schedule in untreated and pretreated patients, and a long-term follow-up of 126 previously untreated patients. British Journal of Haematology 116(3): 538-548, 2002

The rabbit study: ritonavir and saquinavir in combination in saquinavir-experienced and previously untreated patients. Aids Research and Human Retroviruses 15(13): 1181-1189, 1999

Quality of life outcomes of saquinavir, zalcitabine and combination saquinavir plus zalcitabine therapy for adults with advanced HIV infection with CD4 counts between 50 and 300 cells/mm3. Antiviral Therapy 4(1): 35-44, 1999

Extended treatment with saquinavir , zidovudine , and zalcitabine vs SAQ and ZDV vs ddC and ZDV. Abstracts of the Interscience Conference on Antimicrobial Agents & Chemotherapy 35: 236, 1995