The Pharmacokinetics of Double Boosted Protease Inhibitors in Antiretroviral-naive HIV-1 Infected Patients

Pharmacokinetics of and Rate of HIV-1 RNA Decline in ARV-naive HIV-1 Infected Patients Treated With Low- or Standard-dose Saquinavir HGC (Invirase®) and Lopinavir/Ritonavir (Kaletra®

Treatment with only protease inhibitors might benefit HIV patients. Laboratory data have shown that the combination of saquinavir with lopinavir and ritonavir may a good regimen. This study will explore this idea.

Study Overview

• Status: Completed
• Conditions: HIV Infections
• Intervention / Treatment: Drug: Saquinavir, lopinavir, ritonavir

Detailed Description

Treatment with only protease inhibitors might benefit HIV patients, who experience problems with the other antiretrovirals drugs classes. Another reason to only use protease inhibitors is that the remaining classes are spared. This leaves the option to use these classes in the future, for instance in cases of drug resistance. Laboratory data have shown that the combination of saquinavir with lopinavir and ritonavir may a good regimen. This study will explore this idea.

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 2

Contacts and Locations

Study Locations

• Thailand
  • Bangkok, Thailand, 10330
    • The HIV Netherlands Australia Thailand Research Collaboration

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. written informed consent
2. ARV-naïve
3. HIV-1 infected Thai male or female > 18 years old
4. Documented positive test for HIV-1 infection

Exclusion Criteria:

1. Inability to understand the nature and extent of the study and the procedures required.
2. Pregnancy or lactating
3. Active opportunistic infection
4. ALT/ AST more than 2x upper limit
5. creatinine more than 1.5 time the upper limit
6. Smoke cigarettes more than 10 cigarettes a day.
7. Drink alcohol more than 2 units a day
8. Relevant history or current condition, illness that might interfere with drug absorption, distribution, metabolism or excretion.
9. Use of concomitant medication that may interfere with the pharmacokinetics of lopinavir/ritonavir or saquinavir

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; different dose per arm	Drug: Saquinavir, lopinavir, ritonavir; arm 1 = LPV/RTV 400/100 mg BID + SQV 1000 mg BID arm 2 = LPV/RTV 400/100 mg BID + SQV 600 mg BID arm 3 = LPV/RTV 266/66 mg BID + SQV 1000 mg BID arm 4 = LPV/RTV 266/66 mg BID + SQV 600 mg BID
Experimental: 2; different dose per arm	Drug: Saquinavir, lopinavir, ritonavir; arm 1 = LPV/RTV 400/100 mg BID + SQV 1000 mg BID arm 2 = LPV/RTV 400/100 mg BID + SQV 600 mg BID arm 3 = LPV/RTV 266/66 mg BID + SQV 1000 mg BID arm 4 = LPV/RTV 266/66 mg BID + SQV 600 mg BID
Experimental: 3; different dose per arm	Drug: Saquinavir, lopinavir, ritonavir; arm 1 = LPV/RTV 400/100 mg BID + SQV 1000 mg BID arm 2 = LPV/RTV 400/100 mg BID + SQV 600 mg BID arm 3 = LPV/RTV 266/66 mg BID + SQV 1000 mg BID arm 4 = LPV/RTV 266/66 mg BID + SQV 600 mg BID
Experimental: 4; different dose per arm	Drug: Saquinavir, lopinavir, ritonavir; arm 1 = LPV/RTV 400/100 mg BID + SQV 1000 mg BID arm 2 = LPV/RTV 400/100 mg BID + SQV 600 mg BID arm 3 = LPV/RTV 266/66 mg BID + SQV 1000 mg BID arm 4 = LPV/RTV 266/66 mg BID + SQV 600 mg BID

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
study the pharmacokinetics of low dose and standard dose lopinavir/ritonavir and saquinavir HGC in ARV naive HIV-1 infected Thai patients	1 year

Secondary Outcome Measures

Outcome Measure	Time Frame
To describe short-term tolerability, toxicity and efficacy of combinations of low-dose and standard dose lopinavir/ritonavir and saquinavirHGC given to the patients in this trial	1 year

Collaborators and Investigators

• Sponsor: The HIV Netherlands Australia Thailand Research Collaboration
• Collaborators: Roche Pharma AG; Kirby Institute; International Antiviral Therapy Evaluation Center
• Investigators: Principal Investigator: Kiat Ruxrunghtam, MD, PhD, The HIV Netherlands Australia Thailand Research Collaboration; Study Chair: Joep Lange, MD, PhD, International Antiviral Therapy Evaluation Center (IATEC), Center for Poverty-related Communicable Diseases, Department of Internal Medicine, Academic Medical Center (AMC), University of Amsterdam (UVA); Study Chair: Praphan Phanuphak, MD, PhD, The HIV Netherlands Australia Thailand Research Collaboration; Study Chair: David Cooper, MD, PhD, National Center in HIV Epidemiology and Clinical Research

Publications and helpful links

General Publications

• van der Lugt J, Autar RS, Ubolyam S, Garcia EF, Sankote J, Avihingsanon A, Chuenyam T, Cooper DA, Lange J, Phanuphak P, Wit F, Ruxrungtham K, Burger D; HIV-NAT 019 Study Team. Pharmacokinetics and short-term efficacy of a double-boosted protease inhibitor regimen in treatment-naive HIV-1-infected adults. J Antimicrob Chemother. 2008 May;61(5):1145-53. doi: 10.1093/jac/dkn050. Epub 2008 Feb 18. Erratum In: J Antimicrob Chemother. 2008 Oct;62(4):852. Avihingson, Anchalee [corrected to Avihingsanon, Anchalee].
• Maughan RT, Feeney ER, Capel E, Capeau J, Domingo P, Giralt M, Lange JM, Phanuphak P, Cooper DA, Reiss P, Mallon PW; HIVNAT-019 Study Group. Improved adipose tissue function with initiation of protease inhibitor-only ART. J Antimicrob Chemother. 2016 Nov;71(11):3212-3221. doi: 10.1093/jac/dkw301. Epub 2016 Aug 11.

Study record dates

Study Major Dates

• Study Start: March 1, 2004
• Primary Completion (Actual): December 1, 2006
• Study Completion (Actual): December 1, 2006

Study Registration Dates

• First Submitted: November 9, 2006
• First Submitted That Met QC Criteria: November 16, 2006
• First Posted (Estimate): November 17, 2006

Study Record Updates

• Last Update Posted (Estimate): April 5, 2012
• Last Update Submitted That Met QC Criteria: April 3, 2012
• Last Verified: April 1, 2012

More Information

Terms related to this study

• Keywords: pharmacokinetics; Treatment Naive; protease inhibitor; HIV-1 infection; double boosted protease inhibitors; PIs
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Protease Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Ritonavir; Lopinavir; Saquinavir
• Other Study ID Numbers: HIV-NAT 019