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

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ClinicalTrials.gov Identifier: NCT00014937

Recruitment Status : Completed

First Posted : August 31, 2001

Last Update Posted : July 29, 2013

Sponsor:

Information provided by (Responsible Party):

National Institute of Allergy and Infectious Diseases (NIAID)

Study Description

Brief 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.

Condition or disease	Intervention/treatment	Phase
HIV Infections	Drug: lopinavir/ritonavir Drug: lamivudine/zidovudine Drug: efavirenz Drug: lamivudine Drug: stavudine Drug: zidovudine Drug: didanosine	Not Applicable

Detailed 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.

Study Design


Study Type :	Interventional (Clinical Trial)
Enrollment :	240 participants
Allocation:	Randomized
Intervention Model:	Factorial Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
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
Actual Primary Completion Date :	December 2004

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

U.S. FDA Resources

Arms and Interventions

Outcome Measures

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:	13 Years and older (Child, Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00014937

Show 37 Study Locations

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators


Study Chair:	Margaret Fischl, MD	University of Miami

More Information

Publications of Results:

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 efavirenz) increases limb fat but raises serum lipid levels: results of a prospective randomized trial (AIDS clinical trial group 5125s). J Acquir Immune Defic Syndr. 2007 Jun 1;45(2):193-200.

Other Publications:

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.


Responsible Party:	National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:	NCT00014937 History of Changes
Other Study ID Numbers:	A5116 AACTG 5116 Substudy AACTG A5124s Substudy AACTG A5125s ACTG A5116 10934 ( Registry Identifier: DAIDS-ES )
First Posted:	August 31, 2001 Key Record Dates
Last Update Posted:	July 29, 2013
Last Verified:	July 2013

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):


HIV-1 Didanosine Drug Therapy, Combination Zidovudine Nevirapine Stavudine HIV Protease Inhibitors Ritonavir Lamivudine	RNA, Viral Reverse Transcriptase Inhibitors Anti-HIV Agents Viral Load ABT 378 Combivir Efavirenz Treatment Experienced

Additional relevant MeSH terms:


HIV Infections Lentivirus Infections Retroviridae Infections RNA Virus Infections Virus Diseases Sexually Transmitted Diseases, Viral Sexually Transmitted Diseases Immunologic Deficiency Syndromes Immune System Diseases Ritonavir Lopinavir HIV Protease Inhibitors Lamivudine Zidovudine Stavudine	Didanosine Lamivudine, zidovudine drug combination Efavirenz Protease Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Anti-HIV Agents Anti-Retroviral Agents Antiviral Agents Anti-Infective Agents Cytochrome P-450 CYP3A Inhibitors Cytochrome P-450 Enzyme Inhibitors Reverse Transcriptase Inhibitors Nucleic Acid Synthesis Inhibitors Cytochrome P-450 CYP2C9 Inhibitors

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