Simplified Drug Regimens for HIV Patients in ACTG 388 or Patients Who Responded to A First Potent Combination Regimen

HIV Infections Clinical Trial

Official title:

A Randomized, Controlled Trial of Two Potent, Simplified Regimens Utilizing A Protease Inhibitor-Sparing Regimen Versus A Nucleoside-Sparing Regimen for HIV-Infected Subjects Who Participated in ACTG 388 or Who Responded to A First Potent Combination Regimen and Have 200 or Less HIV-1 RNA Copies/ml

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00014937
• Other study ID #: A5116
• Secondary ID: AACTG 5116Substu
• Status: Completed
• Phase: N/A
• First received: April 14, 2001
• Last updated: July 26, 2013

Study information

• Verified date: July 2013
• 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

ACTG 388 was a clinical trial that compared three- and four-drug anti-HIV drug regimens and demonstrated the effectiveness of a three-drug regimen. This study will compare the ability of two different three-drug anti-HIV drug regimens to reduce levels of HIV in the blood. The study will also evaluate whether patients discontinue the regimens because of drug side effects.

Description:

ACTG 388 was designed to evaluate two four-drug regimens compared with a three-drug regimen in patients who were relatively treatment naive. Based on the increased complexity and toxicity of four-drug regimens and the resultant negative impact on response as compared with three-drug regimens, studies evaluating simplified potent regimens appear warranted. This study will evaluate simpilified drug regimens designed to enhance virologic activity without necessarily increasing the number of antiretroviral drugs. The study regimens will be assessed for both virologic control and tolerability. The study population will include patients previously enrolled in ACTG 388 and patients with prior advanced HIV disease who received and responded to potent antiretroviral therapy without evidence of virologic relapse.

Patients will be stratified according to ACTG 388 treatment or non-ACTG 388 study participation. Patients will then be randomized to receive either a protease inhibitor (PI)-sparing regimen of 2 nucleoside reverse transcriptase inhibitors (NRTIs) with efavirenz (EFV) (Arm I) or an NRTI-sparing regimen of EFV with lopinavir/ritonavir (LPV/r) (Arm II). Arm I options are enteric-coated didanosine (ddI-EC) plus lamivudine (3TC), ddI-EC plus zidovudine (ZDV), ZDV plus 3TC (or Combivir), stavudine (d4T) plus 3TC, or ddI-EC plus d4T (with exceptions as noted in the protocol). Only LPV/r, EFV, d4T, and ddI are provided by the study; other medications are obtained by nonstudy prescription.

All patients are evaluated for safety and for virologic and immunologic responses at Weeks 4 and 8, then every 8 weeks until the study ends. In addition, all patients have assessments for fat redistribution, fasting lipid profiles, fasting insulin levels, venous lactate levels, and treatment adherence. Patients will be followed for 1.5 to 3 years. Interim safety analyses will be conducted in June 2002 and June 2003. Patients in this study may also enroll in A5125s, a fat distribution and bone mineral density substudy.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 240
• Est. primary completion date: December 2004
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 13 Years and older

Eligibility

Inclusion Criteria for ACTG 388 Participants

• HIV-1 RNA level <= 200 copies/ml within 70 days of study entry

• Stable anti-HIV drug plan without harmful drug side effects or serious illness at the time of study entry

Inclusion Criteria for Non-ACTG 388 Participants

• Potent anti-HIV drug regimen as a first HIV treatment for at least 18 months

• HIV-1 RNA level >= 80,000 copies/ml or CD4+ count <= 200 cells/mm3 prior to starting anti-HIV drug regimen

• HIV-1 RNA level <= 400 copies/ml (or less than 500 copies/ml by bDNA) within 32 weeks of initial therapy

• HIV-1 RNA level <= 200 copies/ml within 60 days of study entry

Inclusion Criteria for Both ACTG 388 and Non-ACTG 388 Participants

• Acceptable methods of contraception

• Consent of parent or legal guardian if under 18 years of age

Exclusion Criteria for ACTG 388 Participants

• Viral resistance to study drugs as determined by resistance studies during ACTG 388

Exclusion Criteria for ACTG 388 and Non-ACTG 388 Participants

• Pregnancy or breastfeeding

• Certain heart medicines (flecainide or propafenone); antihistamines (astemizole and terfenadine); rifampin; ergot derivatives (dihydroergotamine, ergonovine, ergotamine, or methylergonovine); intestinal agents (cisapride); herbal products (St. John's wort); lovastatin or simvastatin; neuroleptics (pimozide); and sedatives/hypnotics (midazolam or triazolam)

• Allergy study drugs

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Factorial Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• HIV Infections

Intervention

Drug:
• lopinavir/ritonavir

• lamivudine/zidovudine

• efavirenz

• lamivudine

• stavudine

• zidovudine

• didanosine

Locations

Country	Name	City	State
Italy	Spedali Civili - Carosi	Brescia
Italy	Universita di Genova	Genova
Italy	Ospedale Luigi Sacco Milazzo	Milano
Italy	Universita degli Studi di Modena e Reggio Emilia	Modena
Puerto Rico	Univ of Puerto Rico	San Juan
United States	Emory Univ	Atlanta	Georgia
United States	SUNY / Erie County Med Ctr at Buffalo	Buffalo	New York
United States	Univ of North Carolina	Chapel Hill	North Carolina
United States	Northwestern Univ Med School	Chicago	Illinois
United States	Rush Presbyterian - Saint Luke's Med Ctr	Chicago	Illinois
United States	The CORE Ctr	Chicago	Illinois
United States	Univ of Cincinnati	Cincinnati	Ohio
United States	Case Western Reserve Univ	Cleveland	Ohio
United States	MetroHealth Med Ctr	Cleveland	Ohio
United States	Ohio State Univ Hosp Clinic	Columbus	Ohio
United States	Denver Dept of Health and Hosps	Denver	Colorado
United States	Univ of Colorado Health Sciences Ctr	Denver	Colorado
United States	Duke Univ Med Ctr	Durham	North Carolina
United States	Connecticut Children's Medical Center (Pediatric)	Farmington	Connecticut
United States	Queens Med Ctr	Honolulu	Hawaii
United States	Univ of Hawaii	Honolulu	Hawaii
United States	Indiana Univ Hosp	Indianapolis	Indiana
United States	Methodist Hosp of Indiana / Life Care Clinic	Indianapolis	Indiana
United States	Wishard Hosp	Indianapolis	Indiana
United States	Univ of Southern California / LA County USC Med Ctr	Los Angeles	California
United States	Univ of Miami School of Medicine	Miami	Florida
United States	Univ of Minnesota	Minneapolis	Minnesota
United States	Charity Hosp / Tulane Univ Med School	New Orleans	Louisiana
United States	Bellevue Hosp / New York Univ Med Ctr	New York	New York
United States	Cornell Clinical Trials Unit - Chelsea Clinic	New York	New York
United States	Cornell Univ Med Ctr	New York	New York
United States	Univ of Nebraska Med Ctr	Omaha	Nebraska
United States	Univ of Pennsylvania	Philadelphia	Pennsylvania
United States	Univ of Rochester Medical Center	Rochester	New York
United States	Washington Univ / St Louis Connect Care	Saint Louis	Missouri
United States	Univ of Washington	Seattle	Washington
United States	Washington Univ School of Medicine	St Louis	Missouri

Sponsors (1)

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

Countries where clinical trial is conducted

United States,  Italy,  Puerto Rico, 

References & Publications (2)

Demeter LM, Ribaudo HJ, Erice A, Eshleman SH, Hammer SM, Hellmann NS, Fischl MA; AIDS Clinical Trials Group Protocol 388. HIV-1 drug resistance in subjects with advanced HIV-1 infection in whom antiretroviral combination therapy is failing: a substudy of AIDS Clinical Trials Group Protocol 388. Clin Infect Dis. 2004 Aug 15;39(4):552-8. Epub 2004 Jul 30. — View Citation

Tebas P, Zhang J, Yarasheski K, Evans S, Fischl MA, Shevitz A, Feinberg J, Collier AC, Shikuma C, Brizz B, Sattler F; AIDS Clinical Trials Group (ACTG). Switching to a protease inhibitor-containing, nucleoside-sparing regimen (lopinavir/ritonavir plus efa — View Citation

External Links

•   Click here for more information about didanosine.
•   Click here for more information about efavirenz.
•   Click here for more information about lamivudine.
•   Click here for more information about lamivudine/zidovudine.
•   Click here for more information about lopinavir/ritonavir.
•   Click here for more information about stavudine.
•   Click here for more information about zidovudine.
•   Haga clic aquí para ver información sobre este ensayo clínico en español.