HIV InfectionsNCT00028366
Dual Versus Triple Protease Inhibitor Combinations, Including Ritonavir, in HIV Infected People
A study testing Fosamprenavir, Lopinavir/Ritonavir and Ritonavir in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 13 sites in United States.
Trial summary
Ritonavir (RTV) is a protease inhibitor (PI) commonly used to increase drug levels of other PIs in HIV drug treatment. The purpose of this study is to compare a combination of drugs which includes RTV and 2 protease inhibitors (PIs) with 2 combinations that include RTV and another PI. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HIV Infections
- What is being tested?
- Fosamprenavir, Lopinavir/Ritonavir and Ritonavir
- How many people
- 56 participants
- Where
- 13 sitesUnited States
- Study dates
- Start not givento Jul 2005
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- HIV infected
- Past anti-HIV therapy consisting of at least 1 PI-containing regimen or detectable viral load, and at least 1 year total anti-HIV therapy experience
- Viral load of more than 5000 copies/ml within 60 days prior to screening while on a stable anti-HIV therapy for at least 12 weeks
- Agree to use acceptable forms of contraception
Who cannot join
- More than 7 days of treatment with LPV and/or more than 7 days of treatment with APV or fosamprenavir
- HIV vaccine within 90 days of study entry
- Experimental drugs within 30 days of study entry
- Cancer chemotherapy within 30 days of study entry
- Drugs that affect the immune system within 30 days of study entry
- Certain drugs within 14 days of study entry. Patients who have used drugs that might damage the kidneys within 7 days of study entry are allowed.
Show all 11Show fewer
- Midazolam within 7 days of study entry
- Allergic or sensitive to study drugs
- Excessive drug or alcohol use
- Serious illness requiring treatment and/or hospitalization and have not completed therapy, or are not stable on therapy for at least 14 days prior to study entry
- Pregnant or breastfeeding
Trial locations and contacts
13 sites in 1 country.
13 sites in 1 country
United States13 sites
The Ponce de Leon Ctr. CRS
Atlanta, Georgia, 30308
Univ. of Cincinnati CRS
Cincinnati, Ohio, 452670405
Case CRS
Cleveland, Ohio, 44106
MetroHealth CRS
Cleveland, Ohio, 441091998
The Ohio State Univ. AIDS CRS
Columbus, Ohio, 432101228
Indiana Univ. School of Medicine, Infectious Disease Research Clinic
Indianapolis, Indiana, 462025250
Indiana Univ. School of Medicine, Wishard Memorial
Indianapolis, Indiana, 46202
Methodist Hosp. of Indiana
Indianapolis, Indiana, 46202
USC CRS
Los Angeles, California, 90033-1079
Vanderbilt Therapeutics CRS
Nashville, Tennessee, 37203
HIV Prevention & Treatment CRS
New York, New York
Ucsf Aids Crs
San Francisco, California, 94110
University of Washington AIDS CRS
Seattle, Washington, 98104
About this study
Official title: A Randomized, Comparative Study of Lopinavir/Ritonavir Versus GW433908 and Ritonavir Versus Lopinavir/Ritonavir and GW433908 (In Combination With Tenofovir Disoproxil Fumarate and One or Two Nucleoside Reverse Transcriptase Inhibitors) in HIV-1-Infected Subjects With Virologic Treatment Failure
Ritonavir (RTV) is a protease inhibitor (PI) commonly used to increase drug levels of other PIs in HIV drug treatment. The purpose of this study is to compare a combination of drugs which includes RTV and 2 protease inhibitors (PIs) with 2 combinations that include RTV and another PI. This study also will compare the effectiveness, safety, tolerability, and drug levels in the blood of these anti-HIV drug combinations.
Read the detailed description
A substantial proportion of patients on antiretroviral therapy do not achieve sustained suppression of HIV viral load. Developing strategies to improve responses to subsequent regimens is an important objective for the management of patients with HIV infection. Increasing the potency of regimens by using a pharmacoenhancer such as RTV is of interest. RTV is used widely to increase plasma concentrations of PIs, but there is little efficacy and tolerability data about different RTV-enhanced PIs. The efficacy and tolerability of a triple PI regimen will be compared to dual PI regimens; dual PI regimens will also be compared to each other.
In Step 1, patients will be selectively randomized (based on prior exposure to the study drugs) and enrolled into 1 of 3 study arms. Patients in Arm A will receive lopinavir (LPV)/RTV in combination with TDF and 1 or 2 other NRTIs; patients in Arm B will receive fosamprenavir plus RTV in combination with TDF and 1 or 2 other NRTIs; Arm C patients were to receive LPV/RTV plus fosamprenavir in combination with TDF and 1 or 2 other NRTIs. Because interim study results indicated that mean PI levels for patients in Arm C were unacceptably low, Arm C patients will now either drop LPV/RTV and add RTV or drop fosamprenavir from their regimens.
The study will last 24 to 48 weeks. Medications and clinical assessment and blood collection will be performed at 2 weeks prior to entry, entry, and Weeks 2, 4, 8, 12, 16, 24, 32, 40, and 48. Blood samples to test for amprenavir (APV) and LPV pharmacokinetics will be collected at Weeks 12, 24, 48, and at confirmed virologic failure visits. In substudy A5147S, intensive 12-hour pharmacokinetic sampling for APV, LPV, and RTV will be conducted. The first 20-25 patients enrolled in each arm will be enrolled in the substudy 14-28 days after starting study treatment.
- Conditions
- HIV Infections
- Being tested
- Fosamprenavir, Lopinavir/Ritonavir, Ritonavir, Tenofovir disoproxil fumarate
- Keywords
- HIV-1, Drug Therapy, Combination, HIV Protease Inhibitors, Ritonavir, RNA, Viral, Reverse Transcriptase Inhibitors, Viral Load, ABT 378, tenofovir disoproxil, VX-175, Treatment Experienced
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FosamprenavirDrug
Lopinavir/RitonavirDrug
RitonavirDrug
Tenofovir disoproxil fumarateDrug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Dec 2001 (estimated)
- Study completionJul 2005
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for HIV InfectionsStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 56 participants
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Ann C. Collier, MD, Study chair, University of Washington
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00028366
- Sponsor's protocol ID
- A5143
- Other IDs
- 10681, ACTG A5143, AACTG A5143, Substudy AACTG A5147S, Substudy ACTG A5147S
- Status last verified
- Oct 2021
- First submitted
- 27 Dec 2001
- Last updated
- 1 Nov 2021
- Results posted
- No
Publications
Cooper CL, van Heeswijk RP, Gallicano K, Cameron DW. A review of low-dose ritonavir in protease inhibitor combination therapy. Clin Infect Dis. 2003 Jun 15;36(12):1585-92. doi: 10.1086/375233. Epub 2003 Jun 5.
PubMed 12802760Cvetkovic RS, Goa KL. Lopinavir/ritonavir: a review of its use in the management of HIV infection. Drugs. 2003;63(8):769-802. doi: 10.2165/00003495-200363080-00004.
PubMed 12662125Moyle GJ, Back D. Principles and practice of HIV-protease inhibitor pharmacoenhancement. HIV Med. 2001 Apr;2(2):105-13. doi: 10.1046/j.1468-1293.2001.00063.x.
PubMed 11737387Nadler J. New anti-HIV protease inhibitors provide more treatment options. AIDS Patient Care STDS. 2003 Nov;17(11):551-64. doi: 10.1089/108729103322555944.
PubMed 14746663van Heeswijk RP, Veldkamp A, Mulder JW, Meenhorst PL, Lange JM, Beijnen JH, Hoetelmans RM. Combination of protease inhibitors for the treatment of HIV-1-infected patients: a review of pharmacokinetics and clinical experience. Antivir Ther. 2001 Dec;6(4):201-29.
PubMed 11878403Kashuba AD, Tierney C, Downey GF, Acosta EP, Vergis EN, Klingman K, Mellors JW, Eshleman SH, Scott TR, Collier AC. Combining fosamprenavir with lopinavir/ritonavir substantially reduces amprenavir and lopinavir exposure: ACTG protocol A5143 results. AIDS. 2005 Jan 28;19(2):145-52. doi: 10.1097/00002030-200501280-00006.
PubMed 15668539
Study at a glance
From the registry record, last updated by the sponsor on 1 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Comparative Study of Lopinavir/Ritonavir Versus GW433908 and Ritonavir Versus Lopinavir/Ritonavir and GW433908 (In Combination With Tenofovir Disoproxil Fumarate and One or Two Nucleoside Reverse Transcriptase Inhibitors) in HIV-1-Infected Subjects With Virologic Treatment Failure
- ClinicalTrials.gov ID
- NCT00028366
- Acronym / sponsor ID
- A5143
- Conditions
- HIV Infections
- Keywords
- HIV-1, Drug Therapy, Combination, HIV Protease Inhibitors, Ritonavir, RNA, Viral, Reverse Transcriptase Inhibitors, Viral Load, ABT 378
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 56 participants
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study completion
- Jul 2005 (actual)
- First posted
- 28 Dec 2001 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Ritonavir (RTV) is a protease inhibitor (PI) commonly used to increase drug levels of other PIs in HIV drug treatment. The purpose of this study is to compare a combination of drugs which includes RTV and 2 protease inhibitors (PIs) with 2 combinations that include RTV and another PI. This study also will compare the effectiveness, safety, tolerability, and drug levels in the blood of these anti-HIV drug combinations.
Detailed description
A substantial proportion of patients on antiretroviral therapy do not achieve sustained suppression of HIV viral load. Developing strategies to improve responses to subsequent regimens is an important objective for the management of patients with HIV infection. Increasing the potency of regimens by using a pharmacoenhancer such as RTV is of interest. RTV is used widely to increase plasma concentrations of PIs, but there is little efficacy and tolerability data about different RTV-enhanced PIs. The efficacy and tolerability of a triple PI regimen will be compared to dual PI regimens; dual PI regimens will also be compared to each other.
In Step 1, patients will be selectively randomized (based on prior exposure to the study drugs) and enrolled into 1 of 3 study arms. Patients in Arm A will receive lopinavir (LPV)/RTV in combination with TDF and 1 or 2 other NRTIs; patients in Arm B will receive fosamprenavir plus RTV in combination with TDF and 1 or 2 other NRTIs; Arm C patients were to receive LPV/RTV plus fosamprenavir in combination with TDF and 1 or 2 other NRTIs. Because interim study results indicated that mean PI levels for patients in Arm C were unacceptably low, Arm C patients will now either drop LPV/RTV and add RTV or drop fosamprenavir from their regimens.
The study will last 24 to 48 weeks. Medications and clinical assessment and blood collection will be performed at 2 weeks prior to entry, entry, and Weeks 2, 4, 8, 12, 16, 24, 32, 40, and 48. Blood samples to test for amprenavir (APV) and LPV pharmacokinetics will be collected at Weeks 12, 24, 48, and at confirmed virologic failure visits. In substudy A5147S, intensive 12-hour pharmacokinetic sampling for APV, LPV, and RTV will be conducted. The first 20-25 patients enrolled in each arm will be enrolled in the substudy 14-28 days after starting study treatment.
Study design
- Primary purpose
- Treatment
- Intervention model
- Parallel groups
- Masking
- None (open label)
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- HIV infected
- Past anti-HIV therapy consisting of at least 1 PI-containing regimen or detectable viral load, and at least 1 year total anti-HIV therapy experience
- Viral load of more than 5000 copies/ml within 60 days prior to screening while on a stable anti-HIV therapy for at least 12 weeks
- Agree to use acceptable forms of contraception
Key exclusion criteria (11 listed)
- More than 7 days of treatment with LPV and/or more than 7 days of treatment with APV or fosamprenavir
- HIV vaccine within 90 days of study entry
- Experimental drugs within 30 days of study entry
- Cancer chemotherapy within 30 days of study entry
- Drugs that affect the immune system within 30 days of study entry
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Fosamprenavir | Drug | – |
| Lopinavir/Ritonavir | Drug | – |
| Ritonavir | Drug | – |
| Tenofovir disoproxil fumarate | Drug | – |
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Nov 2021.
- Background: PubMed 12802760Cooper CL, van Heeswijk RP, Gallicano K, Cameron DW. A review of low-dose ritonavir in protease inhibitor combination therapy. Clin Infect Dis. 2003 Jun 15;36(12):1585-92. doi: 10.1086/375233. Epub 2003 Jun 5.
- Background: PubMed 12662125Cvetkovic RS, Goa KL. Lopinavir/ritonavir: a review of its use in the management of HIV infection. Drugs. 2003;63(8):769-802. doi: 10.2165/00003495-200363080-00004.
- Background: PubMed 11737387Moyle GJ, Back D. Principles and practice of HIV-protease inhibitor pharmacoenhancement. HIV Med. 2001 Apr;2(2):105-13. doi: 10.1046/j.1468-1293.2001.00063.x.
- Background: PubMed 14746663Nadler J. New anti-HIV protease inhibitors provide more treatment options. AIDS Patient Care STDS. 2003 Nov;17(11):551-64. doi: 10.1089/108729103322555944.
- Background: PubMed 11878403van Heeswijk RP, Veldkamp A, Mulder JW, Meenhorst PL, Lange JM, Beijnen JH, Hoetelmans RM. Combination of protease inhibitors for the treatment of HIV-1-infected patients: a review of pharmacokinetics and clinical experience. Antivir Ther. 2001 Dec;6(4):201-29.
- Results publication: PubMed 15668539Kashuba AD, Tierney C, Downey GF, Acosta EP, Vergis EN, Klingman K, Mellors JW, Eshleman SH, Scott TR, Collier AC. Combining fosamprenavir with lopinavir/ritonavir substantially reduces amprenavir and lopinavir exposure: ACTG protocol A5143 results. AIDS. 2005 Jan 28;19(2):145-52. doi: 10.1097/00002030-200501280-00006.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ann C. Collier, MD study chair
University of Washington
13 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Fosamprenavir, Lopinavir/Ritonavir and Ritonavir in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 13 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00028366, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Nov 2021.