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

NCT00090779 | Terminated Phase 2 Results DMC

• 3 other identifiers: ACTG A52171U01AI068636AIEDRP AIN503
• Study Type: interventional
• Target: 130
• Locations: 2 countries
• Sites: 27

Brief Summary

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.

Conditions

HIV Infections

Keywords

Acute Infection; Treatment Naive

Outcome Measures

Primary Outcomes (3)

• Ranked Log10 HIV-1 RNA Viral Load (log10 Copies/mL) Averaged at 72 and 76 Weeks for the IT Arm and DT Arm

  The primary endpoint is (i) the average of log10 viral loads (VL) at wks 72 and 76 for participants who continued to wk 72 off ARV for the DT arm, (ii) average wk 72 and 76 VL for those who continued to wk 36 off ARV for the IT arm and (iii) an assigned VL rank for the "failures" who needed ARVs or met criteria for entry into Step 2 prior to these study visits. The assigned rank for the failures was either the last observed rank carried forward or the worst rank relative to the other possible outcomes. This approach was designed to, if anything, bias against finding a treatment effect. To illustrate, consider five participants who enter the study (A, B, C, D, and E), 4 of whom (A, B, C, D) make it to 72 wks off therapy with RNA levels that increase from A to D. Participant E enters Step 2 at wk 12, at which time his RNA is in the 50th percentile. This rank would be carried forward, so the rank order of the log10 HIV-1 RNA endpoints would be A B E C D.

  At Weeks 72 and 76

• Ranked log10 HIV-1 RNA Viral Load (log10 Copies/mL) Averaged at Weeks 72 and 76 for the IT Arm and Ranked log10 HIV-1 RNA Viral Load (log10 Copies/mL) Averaged at Weeks 36 and 40 for the DT Arm

  The primary endpoint is (i) average wk 36 and 40 VL for those who continued to wk 36 off ARV for the DT arm, (ii) average wk 72 and 76 VL for those who continued to wk 36 off ARV for the IT arm and (iii) an assigned VL rank for the "failures" who needed ARVs or met criteria for entry into Step 2 prior to these study visits. The assigned rank for the failures was either the last observed rank carried forward or the worst rank relative to the other possible outcomes. This approach was designed to, if anything, bias against finding a treatment effect. To illustrate, consider five participants who enter the study (A, B, C, D, and E), 4 of whom (A, B, C, D) make it to 72 wks off therapy with RNA levels that increase from A to D. Participant E enters Step 2 at wk 12, at which time his RNA is in the 50th percentile. This rank would be carried forward, so the rank order of the log10 HIV-1 RNA endpoints would be A B E C D.

  IT arm (weeks 72 and 76) and DT arm ( weeks 36 and 40)

• Number of Participants Experiencing Either a CDC Category B or C Diagnosis, CD4<200 Cells/mm^3 or CD4 Percent <14%.

  96 weeks since randomization

Secondary Outcomes (6)

• Change in CD4 Counts Cells/mm^3 From Week 36 for IT Arm and From Week 0 for DT Arm

  IT arm (weeks 36, 60, 72, 84 and 96) and DT arm (weeks 0, 24, 36, 48 and 60)

• Number of Participants Meeting Clinical, Virologic, or Immunologic Criteria for Treatment Initiation or Re-initiation

  96 weeks since randomization

• Number of Participants in IT Arm Off Treatment Before 36 Weeks

  At Week 36

• Time to Meeting the Clinical, Virologic, or Immunologic Criteria for Treatment Initiation or Re-initiation

  96 weeks since randomization

• Time From Study Entry in DT Arm Participants or From Week 36 in IT Arm Participants to Meeting the Clinical, Virologic, or Immunologic Criteria for Treatment Initiation or Re-initiation

  96 weeks since randomization

Study Arms (2)

IT arm

ACTIVE COMPARATOR

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

Drug: Emtricitabine/ tenofovir disoproxil fumarate; Drug: Lopinavir/Ritonavir

DT arm

NO INTERVENTION

DT (deferred treatment) arm participants received no treatment

Interventions

Emtricitabine/ tenofovir disoproxil fumarate DRUG

once daily

IT arm

Lopinavir/Ritonavir DRUG

twice daily

IT arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• years or older
• Ability and willingness to provide written informed consent
• Willing to use acceptable forms of contraception

You may not qualify if:

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

Sponsors & Collaborators

• Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator
• Adult AIDS Clinical Trials Group: collaborator

Study Sites (27)

Ucsd, Avrc Crs (701)

San Diego, California, 92103, United States

Location

Ucsf Aids Crs (801)

San Francisco, California, 94110, United States

Location

Harbor-UCLA Med. Ctr. CRS (603)

Torrance, California, 90502, United States

Location

University of Colorado Hospital CRS (6101)

Aurora, Colorado, 80045, United States

Location

University of Miami AIDS CRS (901)

Miami, Florida, 33139, United States

Location

The Ponce de Leon Center CRS

Atlanta, Georgia, 30308, United States

Location

Northwestern University CRS (2701)

Chicago, Illinois, 60611, United States

Location

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

Chicago, Illinois, 60612, United States

Location

Indiana University Hospital (2601)

Indianapolis, Indiana, 46202-5250, United States

Location

IHV Baltimore Treatment CRS (4651)

Baltimore, Maryland, 21201, United States

Location

Massachusetts General Hospital ACTG CRS (101)

Boston, Massachusetts, 02114, United States

Location

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

Boston, Massachusetts, 02115, United States

Location

Washington University CRS (2101)

St Louis, Missouri, 63110, United States

Location

Beth Israel Medical Center

New York, New York, 10003, United States

Location

HIV Prevention & Treatment CRS (30329)

New York, New York, 10032, United States

Location

AIDS Care CRS (1108)

Rochester, New York, 14642, United States

Location

University of Rochester ACTG CRS (1101)

Rochester, New York, 14642, United States

Location

Unc Aids Crs (3201)

Chapel Hill, North Carolina, 27516, United States

Location

Moses H. Cone Memorial Hospital CRS (3203)

Greensboro, North Carolina, 27401, United States

Location

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

Greensboro, North Carolina, 27401, United States

Location

The Ohio State Univ. AIDS CRS (2301)

Columbus, Ohio, 43210, United States

Location

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

Philadelphia, Pennsylvania, 19104, United States

Location

The Miriam Hosp. ACTG CRS (2951)

Providence, Rhode Island, 02906, United States

Location

University of Washington AIDS CRS (1401)

Seattle, Washington, 98104, United States

Location

UW Primary Infection Clinic CRS (1404)

Seattle, Washington, 98104, United States

Location

San Miguel CRS

San Miguel, Lima region, Peru

Location

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

Lima, 18 PE, Peru

Location

Related Publications (6)

• 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.

  PMID: 12370504 BACKGROUND

• 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.

  PMID: 15156484 BACKGROUND

• 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.

  PMID: 12167680 BACKGROUND

• 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.

  PMID: 15057296 BACKGROUND

• 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.

  PMID: 16962381 RESULT

• 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.

  PMID: 22180621 RESULT

Related Links

• Click here for more information about the AIEDRP CORE01 study

MeSH Terms

Conditions

HIV Infections

Interventions

Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Lopinavir

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Tenofovir; Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Emtricitabine; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Drug Combinations; Pharmaceutical Preparations; Pyrimidinones

Results Point of Contact

• Title: ACTG ClinicalTrials.gov Coordinator
• Organization: ACTG Network Coordinating Center, Social and Scientific Systems, Inc.

ACTGCT.Gov@s-3.com

(301) 628-3313

Study Officials

• Christine Hogan, MD

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

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 3, 2004
• First Posted: September 6, 2004
• Study Start: January 1, 2005
• Primary Completion: July 1, 2009
• Study Completion: May 1, 2011
• Last Updated: October 11, 2018
• Results First Posted: December 18, 2012

Record last verified: 2018-09

Locations

US (25); PE (2)