Clinical trial NCT00000922: A Study to Evaluate the Long-Term Effectiveness of Three Anti-HIV Drug Regimens in HIV Infected Patients Who Have Never Been Exposed to Highly Active Antiretroviral Therapy (HAART)
Official title: A Randomized, Open-Label Study of the Long-Term Effectiveness of Three Initial Highly Active Antiretroviral Therapy (HAART) Strategies in HAART-Niave, HIV-Infected Persons
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: HIV Infections
Keywords: Drug Therapy, Combination
HIV Protease Inhibitors
Reverse Transcriptase Inhibitors
Anti-HIV Agents
Treatment Naive
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
First posted: 2001-08-31
Enrollment: 1710
Sex: ALL
Minimum age (years): 13
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine whether it is better to start an anti-HIV regimen containing a protease inhibitor (PI), a non-nucleoside reverse transcriptase inhibitor (NNRTI), or a PI in combination with an NNRTI. This study will also examine which treatment regimen is best as a first treatment for HIV infection.

Detailed description: Highly active antiretroviral therapy (HAART) regimens containing PIs, NNRTIs, or nucleoside reverse transcriptase inhibitors (NRTIs) have been shown to slow disease progression. However, the long-term consequences of initial therapy with a PI, an NNRTI, or both a PI and an NNRTI are not yet known, nor is the impact on future anti-HIV treatment regimens. Patients who experience virologic failure on a particular HAART regimen typically have not been studied for subsequent response to other HAART regimens. It is possible that a regimen which is initially the most potent may not be optimal if it limits the effectiveness of subsequent anti-HIV treatment regimens.

Patients will be randomized to one of three HAART treatment arms:

* Arm 1 participants will receive one or two PIs plus two NRTIs.
* Arm 2 participants will receive one NNRTI plus two NRTIs.
* Arm 3 participants will receive one or two PIs plus an NNRTI plus one or two NRTIs.

Before randomization to a treatment arm, patients will be given the option of preselecting the drugs they will use or allowing randomization to study-specified drugs. The study-specified PIs will be indinavir (IDV), nelfinavir (NFV), or two PIs of patient and doctor choice. The study-specified NNRTIs will be nevirapine (NVP) or efavirenz (EFV). The study-specified NRTIs will be abacavir (ABC) plus lamivudine (3TC) or didanosine (ddI) plus stavudine (d4T).

The study sites will provide ABC, 3TC, ddI, or d4T to all patients who are assigned to take these medications. All other anti-HIV drugs for initial and subsequent treatment regimens are obtained by clinician prescription. At Months 1 and 4 and then every 4 months thereafter, patients will receive a medical history update, physical exam, and questionnaire. Blood samples will also be drawn to measure CD4 cell count, viral load, and genotypic antiretroviral resistance. Changes in treatment regimens may occur at any time.

Eligibility criteria: Inclusion Criteria:

* HIV infected
* Agree to practice abstinence or to use barrier methods of birth control during the study
* Are at least 13 years old or have signed informed consent from legal guardian for patients between the ages of 13 and 18

Exclusion Criteria:

* Have ever taken any anti-HIV drugs
* Are unable to complete the study for any reason
* Pregnancy
* Breastfeeding
* Any condition that, in the investigator's opinion, may interfere with the study

Primary outcomes:
measure: Change in CD4 count from baseline to the average of all readings obtained at the regular follow-up visits beginning at Month 32
measure: time to disease progression, death, or CD4 count less than 200 cells/mm3 at the 4 Month visit for those patients with a baseline CD4 cell count of more than or equal to 200 cells/mm3
Secondary outcomes:
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: Community Consortium / UCSF
state: California
city: Denver
country: United States
facility: Denver CPCRA / Denver Public Hlth
state: Colorado
city: New Haven
country: United States
facility: Yale Univ School of Medicine / AIDS Program
state: Connecticut
city: Washington
country: United States
facility: Washington Reg AIDS Prog / Dept of Infect Dis
state: District of Columbia
city: Atlanta
country: United States
facility: AIDS Research Consortium of Atlanta
state: Georgia
city: Chicago
country: United States
facility: AIDS Research Alliance - Chicago
state: Illinois
city: New Orleans
country: United States
facility: Louisiana Comm AIDS Rsch Prog / Tulane Univ Med
state: Louisiana
city: Detroit
country: United States
facility: Wayne State Univ - WSU/DMC / Univ Hlth Ctr
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Hosp
state: Michigan
city: Camden
country: United States
facility: Southern New Jersey AIDS Cln Trials / Dept of Med
state: New Jersey
city: Newark
country: United States
facility: North Jersey Community Research Initiative
state: New Jersey
city: Albuquerque
country: United States
facility: Partners in Research / New Mexico
state: New Mexico
city: New York
country: United States
facility: Harlem AIDS Treatment Grp / Harlem Hosp Ctr
state: New York
city: Portland
country: United States
facility: The Research and Education Group
state: Oregon
city: Philadelphia
country: United States
facility: Philadelphia FIGHT
state: Pennsylvania
city: Houston
country: United States
facility: Univ TX Health Science Ctr
state: Texas
city: Richmond
country: United States
facility: Richmond AIDS Consortium / Div of Infect Diseases
state: Virginia
Study officials:
affiliation: University Health Center, Wayne State University
name: Rodger D. MacArthur, MD
role: STUDY_CHAIR
affiliation: University of Illinois at Chicago
name: Richard Novak, MD
role: STUDY_CHAIR
References:
citation: Moyle GJ, DeJesus E, Cahn P, Castillo SA, Zhao H, Gordon DN, Craig C, Scott TR; Ziagen Once-Daily in Antiretroviral Combination Therapy (CNA30021) Study Team. Abacavir once or twice daily combined with once-daily lamivudine and efavirenz for the treatment of antiretroviral-naive HIV-infected adults: results of the Ziagen Once Daily in Antiretroviral Combination Study. J Acquir Immune Defic Syndr. 2005 Apr 1;38(4):417-25. doi: 10.1097/01.qai.0000147521.34369.c9.
citation: Ribera E, Rodriguez-Pardo D, Rubio M, Soler A, Pedrol E, Blanco JL, Gonzalez A, Crespo M, Falco V, Ocana I, Deig E, Miro JM, Pahissa A. Efficacy and safety of once-daily combination therapy with didanosine, lamivudine and nevirapine in antiretroviral-naive HIV-infected patients. Antivir Ther. 2005;10(5):605-14.
citation: Shlay JC, Visnegarwala F, Bartsch G, Wang J, Peng G, El-Sadr WM, Gibert C, Kotler D, Grunfeld C, Raghavan S; Terry Beirn Community Programs for Clinical Research on AIDS (CPCRA). Body composition and metabolic changes in antiretroviral-naive patients randomized to didanosine and stavudine vs. abacavir and lamivudine. J Acquir Immune Defic Syndr. 2005 Feb 1;38(2):147-55. doi: 10.1097/01.qai.0000143599.64234.15.
citation: MacArthur RD, Chen L, Mayers DL, Besch CL, Novak R, van den Berg-Wolf M, Yurik T, Peng G, Schmetter B, Brizz B, Abrams D; CPCRA 058 FIRST Trial Study Team. The rationale and design of the CPCRA (Terry Beirn Community Programs for Clinical Research on AIDS) 058 FIRST (Flexible Initial Retrovirus Suppressive Therapies) trial. Control Clin Trials. 2001 Apr;22(2):176-90. doi: 10.1016/s0197-2456(01)00111-8.
citation: Tedaldi EM, Absalon J, Thomas AJ, Shlay JC, van den Berg-Wolf M. Ethnicity, race, and gender. Differences in serious adverse events among participants in an antiretroviral initiation trial: results of CPCRA 058 (FIRST Study). J Acquir Immune Defic Syndr. 2008 Apr 1;47(4):441-8. doi: 10.1097/QAI.0b013e3181609da8.
citation: van den Berg-Wolf M, Hullsiek KH, Peng G, Kozal MJ, Novak RM, Chen L, Crane LR, Macarthur RD; CPCRA 058 Study Team, the Terry Beirn Community Programs for Clinical Research on AIDS (CPCRA), and The International Network for Strategic Initiative in Global HIV Trials (INSIGHT). Virologic, immunologic, clinical, safety, and resistance outcomes from a long-term comparison of efavirenz-based versus nevirapine-based antiretroviral regimens as initial therapy in HIV-1-infected persons. HIV Clin Trials. 2008 Sep-Oct;9(5):324-36. doi: 10.1310/hct0905-324.
citation: MacArthur RD, Novak RM, Peng G, Chen L, Xiang Y, Hullsiek KH, Kozal MJ, van den Berg-Wolf M, Henely C, Schmetter B, Dehlinger M; CPCRA 058 Study Team; Terry Beirn Community Programs for Clinical Research on AIDS (CPCRA). A comparison of three highly active antiretroviral treatment strategies consisting of non-nucleoside reverse transcriptase inhibitors, protease inhibitors, or both in the presence of nucleoside reverse transcriptase inhibitors as initial therapy (CPCRA 058 FIRST Study): a long-term randomised trial. Lancet. 2006 Dec 16;368(9553):2125-35. doi: 10.1016/S0140-6736(06)69861-9.