Changing to Nonprotease Inhibitor Treatment to Improve Side Effects

HIV Infections Clinical Trial

Official title:

Phase II, Randomized, Open-Label Study of Switching to Protease Inhibitor-Sparing Regimens for Improvement of Metabolic Abnormalities

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00021463
• Other study ID #: ACTG A5103
• Secondary ID: AACTG A5103
• Status: Completed
• Phase: Phase 2
• First received: July 14, 2001
• Last updated: February 24, 2011

Study information

• Verified date: January 2003
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to learn whether changing from a type of anti-HIV drug called a protease inhibitor (PI) to another type of anti-HIV drug will help to lower the amount of fats or sugars in the blood.

PIs have been effective at keeping HIV viral load (amount of HIV in the blood) down. However, some people who take PIs have higher than normal levels of fats and/or sugars in the blood. Doctors believe that switching to anti-HIV drugs that do not contain PIs will improve the abnormal side effects. This study will test 3 different combinations of non-PI drugs to see which may improve side effects while keeping viral loads low.

Description:

Protease inhibitor (PI)-containing antiretroviral regimens are potent suppressors of HIV replication. Increasingly, metabolic abnormalities such as hypercholesterolemia and triglyceridemia are associated with PI use, reasons cited for switching to PI-sparing regimens. Yet optimal switch regimens that take into account both improvements in side effects and continued virologic suppression have not been defined. This study will compare the effect on chemical metabolic abnormalities of switching to an all nucleoside regimen versus dual nucleoside plus nonnucleoside reverse transcriptase inhibitor (NNRTI) therapy. Determining the effects of each regimen on chemical metabolic abnormalities and maintenance of virologic suppression will define which of the switch strategies being studied improves metabolic abnormalities without compromising viral suppression.

Patients are stratified on the basis of fasting non-HDL cholesterol and triglyceride levels and on ritonavir- or nonritonavir-containing pre-entry PI regimens. Patients are assigned randomly to add to their pre-entry regimen 1 of the following 3 treatments: Arm A - ABC; Arm B - NVP; or Arm C - EFV.

Patients discontinue pre-entry PIs after Day 14. Patients are followed to determine the effect of the maintenance regimens on fasting non-high-density lipoprotein (HDL), cholesterol, and triglycerides at Week 24. Fasting total cholesterol, HDL cholesterol, direct low-density lipoprotein, and triglycerides are measured at Weeks 12, 24, and 48. Fasting glucose, insulin, C-peptide, apolipoproteins A-1 and B, lipoprotein a, and homocysteine are measured at Weeks 24 and 48. Anthropometrics, body mass index, and body image are measured at Weeks 12, 24, and 48. HIV viral load is measured at Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, and 48. If HIV RNA stays below 200 copies/ml, therapy continues unchanged. If confirmed HIV RNA of 200 copies/ml or higher is found, an HIV genotype is obtained providing the viral load is sufficient to yield results, the best medical therapy is instituted (not supplied by the study), and off treatment/on study follow-up is continued. If patients are intolerant to a study drug, an alternate study drug (ABC, EFV, or NVP supplied by the study) is permitted and switched treatment/on study follow-up continued, or the best medical therapy is instituted (not supplied by the study), and off treatment/on study follow-up is continued. Patients are followed until the last patient enrolled has completed 48 weeks on study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 342
• Est. primary completion date: February 2002
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 13 Years and older

Eligibility

Inclusion Criteria

Patients may be eligible for this study if they:

• Are HIV infected.

• Are on their first combination of stable anti-HIV drugs (have not changed drugs for at least 6 months, except for reasons other than failing treatment or short interruptions of less than 7 days).

• Have 2 measurements of viral load (amount of HIV in the blood) during the 6 months before entering the study that are below 400 copies/ml by RT-PCR test or below 500 copies/ml by branched DNA test, measured at least 8 weeks apart.

• Have a viral load below 50 copies/ml within 30 days prior to entry.

• Have a CD4 cell count of 200 copies/ml or higher within 60 days of study entry.

• Are receiving medications and/or medications at certain doses that might interfere with the study.

• Are at least 13 years old and have signed consent of parent or guardian if under 18 years of age.

• Have a negative pregnancy test within 14 days of study entry, if a woman able to have children.

• Agree to use a barrier method of birth control, men and women, while receiving study drugs and for 3 months afterwards.

Exclusion Criteria

Patients will not be eligible for this study if they:

• Are receiving high doses of testosterone. Low doses are allowed if received for 60 or more days before entering the study with no plans to change the dose during the first 24 weeks of the study.

• Have had treatment with any nonnucleoside reverse transcriptase inhibitor (NNRTI).

• Have had treatment with ABC.

• Are allergic to study drugs or any ingredient in them.

• Are pregnant or breast-feeding.

• Have used any HIV vaccine or drugs affecting the immune system within 30 days prior to entering the study.

• Have had systemic treatment for cancer within 30 days of entering the study.

• Have had systemic treatment with certain other drugs that may interfere with the study within 14 days of entering the study.

• Have a serious illness that required systemic treatment or a hospital stay unless treatment was completed at least 14 days prior to entering the study, or are on stable treatment, in the doctor's opinion, for at least 14 days prior to entering the study.

• Abuse drugs or alcohol.

• Have or suspect they have acute hepatitis within 30 days of entering the study.

Study Design

Primary Purpose: Treatment

Related Conditions & MeSH terms

• HIV Infections
• Lipodystrophy

Intervention

Drug:
• Abacavir sulfate, Lamivudine and Zidovudine

• Abacavir sulfate

• Efavirenz

• Nevirapine

Locations

Country	Name	City	State
United States	Emory Univ	Atlanta	Georgia
United States	Univ of Alabama at Birmingham	Birmingham	Alabama
United States	Boston Med Ctr	Boston	Massachusetts
United States	Brigham and Women's Hosp	Boston	Massachusetts
United States	Northwestern Univ Med School	Chicago	Illinois
United States	The CORE Ctr	Chicago	Illinois
United States	Bellevue Hosp / New York Univ Med Ctr	New York	New York
United States	Beth Israel Med Ctr	New York	New York
United States	Univ of Pennsylvania	Philadelphia	Pennsylvania
United States	Univ of Pittsburgh	Pittsburgh	Pennsylvania
United States	Georgetown Univ Med Ctr	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)

Country where clinical trial is conducted

United States, 

External Links

•   Click here for more information about Abacavir sulfate
•   Click here for more information about Abacavir sulfate, Lamivudine and Zidovudine
•   Click here for more information about Efavirenz
•   Click here for more information about Nevirapine