Nine Month Course of Anti-HIV Medications for People Recently Infected With HIV

NCT ID: NCT00090779

Last Updated: 2018-10-11

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE2

Total Enrollment

130 participants

Study Classification

INTERVENTIONAL

Study Start Date

2005-01-31

Study Completion Date

2011-05-31

Brief Summary

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Although some doctors favor starting anti-HIV treatment as soon as possible after patients learn they are infected, it is not known if treatment for recently infected patients results in long-term benefits or harm. The purpose of this study is to learn whether or not people should take anti-HIV drugs when they are first infected.

Detailed Description

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Combination antiretroviral therapy has resulted in significantly decreased morbidity and mortality, incidence of opportunistic infections, and hospitalizations in HIV infected people. However, because of long-term toxicities associated with long-term use of antiretrovirals and the persistence of virus in latent reservoirs, it is unclear when it is best to initiate therapy in recently infected individuals. This study compared the virologic outcomes of adults recently infected with HIV who received emtricitabine/tenofovir disoproxil fumarate (FTC/TDF), coformulated as Truvada, and lopinavir/ritonavir (LPV/RTV), coformulated as Kaletra \[immediate treatment (IT arm)\], with those who received no treatment \[deferred treatment (DT arm)\].

The original study lasted 96 weeks. Participants were randomly assigned to one of two groups (IT arm vs. DT arm). For the first 36 weeks of the study, IT arm participants received FTC/TDF once daily and LPV/RTV twice daily. Some IT arm participants received a different ART regimen as determined by the participant and study staff, if appropriate. DT arm participants received no treatment for the duration of the study. At Week 37, participants from both arms were offered treatment continuation or initiation until Week 96 if they had a high viral load, low CD4 count, or experienced HIV-related symptoms (Step 2). Study visits occurred at screening, Weeks 1, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 37, 38, 40, and every 4 weeks thereafter. Clinical assessment and blood collection occurred at all visits. Urine tests occurred at selected visits. Participants were asked to complete an adherence questionnaire at Weeks 12, 24, and 36.

Per the recommendations the DSMB review in June 2009, this protocol was terminated as originally written with the exception of those participants in the IT arm in the middle of the first 36 weeks of treatment. Those participants were to continue on treatment until the end of the 36 weeks. At that point treatment decisions were made on best practice guidelines. In addition, the study duration was extended to include a 5 year follow up of participants who did not initiate long-term antiretroviral therapy (Step 3).

The study was reviewed by an SMC on December 8, 2010. The SMC recommended the study close to long term follow-up because only very few participants enrolled in this portion of the study.

All the results except for the CD4 analysis and time to treatment initiation and deaths were based on the database frozen on July 2, 2009. The results for the CD4 analysis and time to treatment initiation and deaths were based on the database frozen on January 30, 2012.

Conditions

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HIV Infections

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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IT arm

IT (immediate treatment) arm participants received emtricitabine/tenofovir disoproxil fumarate once daily and lopinavir/ritonavir twice daily

Group Type ACTIVE_COMPARATOR

Emtricitabine/ tenofovir disoproxil fumarate

Intervention Type DRUG

once daily

Lopinavir/Ritonavir

Intervention Type DRUG

twice daily

DT arm

DT (deferred treatment) arm participants received no treatment

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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Emtricitabine/ tenofovir disoproxil fumarate

once daily

Intervention Type DRUG

Lopinavir/Ritonavir

twice daily

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Recently infected with HIV
* No prior antiretroviral therapy (ART)
* CD4 count of 350 cells/mm3 or more AND a CD4% of 14% or more within 21 days prior to study entry
* HIV viral load of 500 copies/ml or more within 21 days prior to study entry
* Required laboratory values obtained within 21 days prior to study entry
* 18 years or older
* Ability and willingness to provide written informed consent
* Willing to use acceptable forms of contraception


* subjects in DT arm who meet one of the following five criteria will be advised to enter step 2 and initiate ART:

1. CD4 cell counts below 350 cells/mm3 on 2 consecutive determinations at least 4 weeks apart at or after the step 1, week 12 study visit
2. HIV-1 RNA above 750,000 copies/mL confirmed on 2 consecutive determinations at least 1 week apart at or after the step 1, week 4 study visit
3. HIV-1 RNA above 200,000 copies/mL on 2 consecutive determinations at least 1 week apart at or after the step 1, week 12 study visit
4. Clinical progression to CDC category B or C disease
5. CD4 count below 200 cells/mm3 or CD4 percent less than 14% at any time on study
* subjects in IT arm who meet one of the following five criteria after discontinuing study medications will be advised to enter step 2 and re-initiate ART:

1. CD4 cell counts below 350 cells/mm3 on 2 consecutive determinations at least 4 weeks apart at or after the step 1, week 12 post-treatment- discontinuation study visit
2. HIV-1 RNA above 750,000 copies/mL confirmed on 2 consecutive determinations at least 1 week apart at or after the step 1, week 4 post-treatment- discontinuation study visit
3. HIV-1 RNA above 200,000 copies/mL on 2 consecutive determinations at least 1 week apart at or after the step 1, week 12 post-treatment- discontinuation study visit
4. Clinical progression to CDC category B or C disease
5. CD4 count below 200 cells/mm3 or CD4 percent less than 14% at any time on study


* Study participants who were on Step 1, IT arm and had completed or ended prematurely the 36 week course of early ART and did not on ART either because they did not meet eligibility criteria for Step 2 or because they did not start ART even after meeting the Step 2 eligibility criteria.
* Study participants on Step 1, DT arm who were not on ART either because they did not meet eligibility criteria for Step 2 or because they did not start ART even after meeting the Step 2 eligibility criteria.
* Previous A5217 participants who had either completed the study or ended prematurely their participation in the study, AND were not on ART either because they never met eligibility criteria for Step 2 or because they had not started ART even after meeting the Step 2 eligibility criteria.
* All A5217 participants who were on Step 1 and in the midst of their 36 weeks of randomized ART and who completed a portion or all of the 36 weeks of originally recommended therapy, AND chose then to interrupt their ART.

Exclusion Criteria

* HIV progression to CDC category B or C disease
* Pregnancy or breastfeeding
* History of pancreatitis or coronary artery disease
* Prior ART. Participants who took antiretrovirals for postexposure prophylaxis more than one year prior to study entry are not excluded.
* Certain medications within 21 days prior to study entry. Participants who agree to receive an alternative ART regimen approved by the investigator will not be excluded.
* Previously received an investigational anti-HIV vaccine
* Current therapy with systemic corticosteroids. Patients who are taking a short course (less than 21 days) of corticosteroids are not excluded.
* Current therapy with systemic chemotherapeutic agents; nephrotoxic systemic agents; immunomodulatory treatments, including interleukin-2; or investigational agents
* Known allergy or sensitivity to study drugs or their formulations
* Current alcohol or drug use that, in the opinion of the investigator, would interfere with the study
* Serious medical or psychiatric illness that, in the opinion of the investigator, would interfere with the study
* Hepatitis B surface antigen positive within 21 days prior to study entry
* Known resistance to one or more components of the study drug regimen

* Pregnancy or breastfeeding


* Participants who were on Step 1, IT arm of the study receiving ART.
* Participants in Step 2 or who had otherwise initiated long-term ART, regardless of whether they were on treatment.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role collaborator

Adult AIDS Clinical Trials Group

NETWORK

Sponsor Role collaborator

Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections

NETWORK

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Christine Hogan, MD

Role: STUDY_CHAIR

Division of Infectious Diseases, Columbia University College of Physicians and Surgeons

Locations

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Ucsd, Avrc Crs (701)

San Diego, California, United States

Site Status

Ucsf Aids Crs (801)

San Francisco, California, United States

Site Status

Harbor-UCLA Med. Ctr. CRS (603)

Torrance, California, United States

Site Status

University of Colorado Hospital CRS (6101)

Aurora, Colorado, United States

Site Status

University of Miami AIDS CRS (901)

Miami, Florida, United States

Site Status

The Ponce de Leon Center CRS

Atlanta, Georgia, United States

Site Status

Northwestern University CRS (2701)

Chicago, Illinois, United States

Site Status

Rush Univ. Med. Ctr. ACTG CRS (2702)

Chicago, Illinois, United States

Site Status

Indiana University Hospital (2601)

Indianapolis, Indiana, United States

Site Status

IHV Baltimore Treatment CRS (4651)

Baltimore, Maryland, United States

Site Status

Massachusetts General Hospital ACTG CRS (101)

Boston, Massachusetts, United States

Site Status

Brigham and Women's Hosp. ACTG CRS (107)

Boston, Massachusetts, United States

Site Status

Washington University CRS (2101)

St Louis, Missouri, United States

Site Status

Beth Israel Medical Center

New York, New York, United States

Site Status

HIV Prevention & Treatment CRS (30329)

New York, New York, United States

Site Status

AIDS Care CRS (1108)

Rochester, New York, United States

Site Status

University of Rochester ACTG CRS (1101)

Rochester, New York, United States

Site Status

Unc Aids Crs (3201)

Chapel Hill, North Carolina, United States

Site Status

Moses H. Cone Memorial Hospital CRS (3203)

Greensboro, North Carolina, United States

Site Status

Regional Center for Infectious Disease, Wendover Medical Center CRS (3203)

Greensboro, North Carolina, United States

Site Status

The Ohio State Univ. AIDS CRS (2301)

Columbus, Ohio, United States

Site Status

Hosp. of the Univ. of Pennsylvania CRS (6201)

Philadelphia, Pennsylvania, United States

Site Status

The Miriam Hosp. ACTG CRS (2951)

Providence, Rhode Island, United States

Site Status

University of Washington AIDS CRS (1401)

Seattle, Washington, United States

Site Status

UW Primary Infection Clinic CRS (1404)

Seattle, Washington, United States

Site Status

San Miguel CRS

San Miguel, Lima region, Peru

Site Status

Asociacion Civil Impacta Salud y Educacion - Miraf CRS (11301)

Lima, , Peru

Site Status

Countries

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United States Peru

References

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Fidler S, Oxenius A, Brady M, Clarke J, Cropley I, Babiker A, Zhang HT, Price D, Phillips R, Weber J. Virological and immunological effects of short-course antiretroviral therapy in primary HIV infection. AIDS. 2002 Oct 18;16(15):2049-54. doi: 10.1097/00002030-200210180-00010.

Reference Type BACKGROUND
PMID: 12370504 (View on PubMed)

Kassutto S, Rosenberg ES. Primary HIV type 1 infection. Clin Infect Dis. 2004 May 15;38(10):1447-53. doi: 10.1086/420745. Epub 2004 Apr 30.

Reference Type BACKGROUND
PMID: 15156484 (View on PubMed)

Little SJ, Holte S, Routy JP, Daar ES, Markowitz M, Collier AC, Koup RA, Mellors JW, Connick E, Conway B, Kilby M, Wang L, Whitcomb JM, Hellmann NS, Richman DD. Antiretroviral-drug resistance among patients recently infected with HIV. N Engl J Med. 2002 Aug 8;347(6):385-94. doi: 10.1056/NEJMoa013552.

Reference Type BACKGROUND
PMID: 12167680 (View on PubMed)

Pilcher CD, Eron JJ Jr, Galvin S, Gay C, Cohen MS. Acute HIV revisited: new opportunities for treatment and prevention. J Clin Invest. 2004 Apr;113(7):937-45. doi: 10.1172/JCI21540.

Reference Type BACKGROUND
PMID: 15057296 (View on PubMed)

Messer K, Vaida F, Hogan C. Robust analysis of biomarker data with informative missingness using a two-stage hypothesis test in an HIV treatment interruption trial: AIEDRP AIN503/ACTG A5217. Contemp Clin Trials. 2006 Dec;27(6):506-17. doi: 10.1016/j.cct.2006.07.003. Epub 2006 Jul 25.

Reference Type RESULT
PMID: 16962381 (View on PubMed)

Hogan CM, Degruttola V, Sun X, Fiscus SA, Del Rio C, Hare CB, Markowitz M, Connick E, Macatangay B, Tashima KT, Kallungal B, Camp R, Morton T, Daar ES, Little S; A5217 Study Team. The setpoint study (ACTG A5217): effect of immediate versus deferred antiretroviral therapy on virologic set point in recently HIV-1-infected individuals. J Infect Dis. 2012 Jan 1;205(1):87-96. doi: 10.1093/infdis/jir699. Epub 2011 Dec 15.

Reference Type RESULT
PMID: 22180621 (View on PubMed)

Related Links

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http://clinicaltrials.gov/ct/show/NCT00086372

Click here for more information about the AIEDRP CORE01 study

Other Identifiers

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1U01AI068636

Identifier Type: NIH

Identifier Source: secondary_id

View Link

AIEDRP AIN503

Identifier Type: -

Identifier Source: secondary_id

ACTG A5217

Identifier Type: -

Identifier Source: secondary_id

ACTG A5217

Identifier Type: -

Identifier Source: org_study_id

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