Clinical trial NCT00014937: Simplified Drug Regimens for HIV Patients in ACTG 388 or Patients Who Responded to A First Potent Combination Regimen
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: HIV Infections
Keywords: 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
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
First posted: 2001-08-31
Enrollment: 240
Sex: ALL
Minimum age (years): 13
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

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.

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.

Eligibility 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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Univ of Southern California / LA County USC Med Ctr
state: California
city: Denver
country: United States
facility: Denver Dept of Health and Hosps
state: Colorado
city: Denver
country: United States
facility: Univ of Colorado Health Sciences Ctr
state: Colorado
city: Farmington
country: United States
facility: Connecticut Children's Medical Center (Pediatric)
state: Connecticut
city: Miami
country: United States
facility: Univ of Miami School of Medicine
state: Florida
city: Atlanta
country: United States
facility: Emory Univ
state: Georgia
city: Honolulu
country: United States
facility: Queens Med Ctr
state: Hawaii
city: Honolulu
country: United States
facility: Univ of Hawaii
state: Hawaii
city: Chicago
country: United States
facility: Northwestern Univ Med School
state: Illinois
city: Chicago
country: United States
facility: Rush Presbyterian - Saint Luke's Med Ctr
state: Illinois
city: Chicago
country: United States
facility: The CORE Ctr
state: Illinois
city: Indianapolis
country: United States
facility: Indiana Univ Hosp
state: Indiana
city: Indianapolis
country: United States
facility: Methodist Hosp of Indiana / Life Care Clinic
state: Indiana
city: Indianapolis
country: United States
facility: Wishard Hosp
state: Indiana
city: New Orleans
country: United States
facility: Charity Hosp / Tulane Univ Med School
state: Louisiana
city: Minneapolis
country: United States
facility: Univ of Minnesota
state: Minnesota
city: Saint Louis
country: United States
facility: Washington Univ / St Louis Connect Care
state: Missouri
city: St Louis
country: United States
facility: Washington Univ School of Medicine
state: Missouri
city: Omaha
country: United States
facility: Univ of Nebraska Med Ctr
state: Nebraska
city: Buffalo
country: United States
facility: SUNY / Erie County Med Ctr at Buffalo
state: New York
city: New York
country: United States
facility: Cornell Clinical Trials Unit - Chelsea Clinic
state: New York
city: New York
country: United States
facility: Bellevue Hosp / New York Univ Med Ctr
state: New York
city: New York
country: United States
facility: Cornell Univ Med Ctr
state: New York
city: Rochester
country: United States
facility: Univ of Rochester Medical Center
state: New York
city: Chapel Hill
country: United States
facility: Univ of North Carolina
state: North Carolina
city: Durham
country: United States
facility: Duke Univ Med Ctr
state: North Carolina
city: Cincinnati
country: United States
facility: Univ of Cincinnati
state: Ohio
city: Cleveland
country: United States
facility: Case Western Reserve Univ
state: Ohio
city: Cleveland
country: United States
facility: MetroHealth Med Ctr
state: Ohio
city: Columbus
country: United States
facility: Ohio State Univ Hosp Clinic
state: Ohio
city: Philadelphia
country: United States
facility: Univ of Pennsylvania
state: Pennsylvania
city: Seattle
country: United States
facility: Univ of Washington
state: Washington
city: Brescia
country: Italy
facility: Spedali Civili - Carosi
city: Genova
country: Italy
facility: Universita di Genova
city: Milano
country: Italy
facility: Ospedale Luigi Sacco Milazzo
city: Modena
country: Italy
facility: Universita degli Studi di Modena e Reggio Emilia
city: San Juan
country: Puerto Rico
facility: Univ of Puerto Rico
Study officials:
affiliation: University of Miami
name: Margaret Fischl, MD
role: STUDY_CHAIR
References:
citation: 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. doi: 10.1086/422518. Epub 2004 Jul 30.
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 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. doi: 10.1097/QAI.0b013e318042e204.