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

11 september 2018 bijgewerkt door: AIDS Clinical Trials Group

The SETPOINT Study - A Randomized Study of the Effect of Immediate Treatment With Potent Antiretroviral Therapy Versus Observation With Treatment as Indicated in Newly Infected HIV-1 Infected Subjects: Does Early Therapy After the Virologic Setpoint?

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.

Studie Overzicht

Toestand

Beëindigd

Conditie

Interventie / Behandeling

Gedetailleerde beschrijving

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.

Studietype

Ingrijpend

Inschrijving (Werkelijk)

130

Fase

  • Fase 2

Contacten en locaties

In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.

Studie Locaties

  • Peru
      • Lima, Peru, 18 PE
        • Asociacion Civil Impacta Salud y Educacion - Miraf CRS (11301)
    • Lima
      • San Miguel, Lima, Peru
        • San Miguel CRS
  • Verenigde Staten
    • California
      • San Diego, California, Verenigde Staten, 92103
        • Ucsd, Avrc Crs (701)
      • San Francisco, California, Verenigde Staten, 94110
        • Ucsf Aids Crs (801)
      • Torrance, California, Verenigde Staten, 90502
        • Harbor-UCLA Med. Ctr. CRS (603)
    • Colorado
      • Aurora, Colorado, Verenigde Staten, 80045
        • University of Colorado Hospital CRS (6101)
    • Florida
      • Miami, Florida, Verenigde Staten, 33139
        • University of Miami AIDS CRS (901)
    • Georgia
      • Atlanta, Georgia, Verenigde Staten, 30308
        • The Ponce de Leon Center CRS
    • Illinois
      • Chicago, Illinois, Verenigde Staten, 60611
        • Northwestern University CRS (2701)
      • Chicago, Illinois, Verenigde Staten, 60612
        • Rush Univ. Med. Ctr. ACTG CRS (2702)
    • Indiana
      • Indianapolis, Indiana, Verenigde Staten, 46202-5250
        • Indiana University Hospital (2601)
    • Maryland
      • Baltimore, Maryland, Verenigde Staten, 21201
        • IHV Baltimore Treatment CRS (4651)
    • Massachusetts
      • Boston, Massachusetts, Verenigde Staten, 02114
        • Massachusetts General Hospital ACTG CRS (101)
      • Boston, Massachusetts, Verenigde Staten, 02115
        • Brigham and Women's Hosp. ACTG CRS (107)
    • Missouri
      • Saint Louis, Missouri, Verenigde Staten, 63110
        • Washington University CRS (2101)
    • New York
      • New York, New York, Verenigde Staten, 10003
        • Beth Israel Medical Center
      • New York, New York, Verenigde Staten, 10032
        • HIV Prevention & Treatment CRS (30329)
      • Rochester, New York, Verenigde Staten, 14642
        • AIDS Care CRS (1108)
      • Rochester, New York, Verenigde Staten, 14642
        • University of Rochester ACTG CRS (1101)
    • North Carolina
      • Chapel Hill, North Carolina, Verenigde Staten, 27516
        • Unc Aids Crs (3201)
      • Greensboro, North Carolina, Verenigde Staten, 27401
        • Moses H. Cone Memorial Hospital CRS (3203)
      • Greensboro, North Carolina, Verenigde Staten, 27401
        • Regional Center for Infectious Disease, Wendover Medical Center CRS (3203)
    • Ohio
      • Columbus, Ohio, Verenigde Staten, 43210
        • The Ohio State Univ. AIDS CRS (2301)
    • Pennsylvania
      • Philadelphia, Pennsylvania, Verenigde Staten, 19104
        • Hosp. of the Univ. of Pennsylvania CRS (6201)
    • Rhode Island
      • Providence, Rhode Island, Verenigde Staten, 02906
        • The Miriam Hosp. ACTG CRS (2951)
    • Washington
      • Seattle, Washington, Verenigde Staten, 98104
        • University of Washington AIDS CRS (1401)
      • Seattle, Washington, Verenigde Staten, 98104
        • UW Primary Infection Clinic CRS (1404)

Deelname Criteria

Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.

Geschiktheidscriteria

Leeftijden die in aanmerking komen voor studie

18 jaar en ouder (Volwassen, Oudere volwassene)

Accepteert gezonde vrijwilligers

Nee

Geslachten die in aanmerking komen voor studie

Allemaal

Beschrijving

Inclusion Criteria for Step 1:

  • 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

Exclusion Criteria for Step 1:

  • 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

Inclusion Criteria for Step 2:

  • 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

      Exclusion Criteria for Step 2:

  • Pregnancy or breastfeeding

Inclusion Criteria for Step 3:

  • 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 for Step 3:

  • 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.

Studie plan

Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.

Hoe is de studie opgezet?

Ontwerpdetails

  • Primair doel: Behandeling
  • Toewijzing: Gerandomiseerd
  • Interventioneel model: Parallelle opdracht
  • Masker: Geen (open label)

Wapens en interventies

Deelnemersgroep / Arm
Interventie / Behandeling
Actieve vergelijker: IT arm
IT (immediate treatment) arm participants received emtricitabine/tenofovir disoproxil fumarate once daily and lopinavir/ritonavir twice daily
Geneesmiddel: Emtricitabine/ tenofovir disoproxil fumarate
once daily
Geneesmiddel: Lopinavir/Ritonavir
twice daily
Geen tussenkomst: DT arm
DT (deferred treatment) arm participants received no treatment

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Ranked Log10 HIV-1 RNA Viral Load (log10 Copies/mL) Averaged at 72 and 76 Weeks for the IT Arm and DT Arm
Tijdsspanne: At Weeks 72 and 76
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
Tijdsspanne: IT arm (weeks 72 and 76) and DT arm ( weeks 36 and 40)
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%.
Tijdsspanne: 96 weeks since randomization
96 weeks since randomization

Secundaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Change in CD4 Counts Cells/mm^3 From Week 36 for IT Arm and From Week 0 for DT Arm
Tijdsspanne: IT arm (weeks 36, 60, 72, 84 and 96) and DT arm (weeks 0, 24, 36, 48 and 60)
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
Tijdsspanne: 96 weeks since randomization
The clinical, virologic, or immunologic criteria for treatment initiation or re-initiation include CD4 count below 350 cells/mm^3 on two consecutive determinations at least 4 weeks apart, at least 12 weeks into the study or 12 weeks post-treatment discontinuation, (2) confirmed CD4 count below 200 cells/mm^3 or CD4 percent below 14% at any time on study, (3) confirmed HIV-1 RNA level above 750,000 copies/mL 4 weeks into the study or above 200,000 copies/mL 12 weeks or more into the study, or (4) CDC Category B or C diagnosis.
96 weeks since randomization
Number of Participants in IT Arm Off Treatment Before 36 Weeks
Tijdsspanne: At Week 36
The study provided fixed-dose combination emtricitabine/tenofovir DF 200/300 mg orally once daily and lopinavir/ritonavir 200/50 mg administered either as two tablets twice daily or four tablets once daily, for the first 36 weeks for individuals in the IT arm.
At Week 36
Time to Meeting the Clinical, Virologic, or Immunologic Criteria for Treatment Initiation or Re-initiation
Tijdsspanne: 96 weeks since randomization
5th, 10th, 25th, 50th, 75th and 90th percentiles in weeks from randomization to meeting the criteria for treatment initiation or re-initiation which include CD4 count below 350 cells/mm^3 on two consecutive measurements at least 4 weeks apart, at least 12 weeks into the study or 12 weeks post-treatment discontinuation, confirmed CD4 count below 200 cells/mm^3 or CD4 percent below 14% at any time on study, confirmed HIV-1 RNA level above 750,000 copies/mL 4 weeks into the study or above 200,000 copies/mL 12 weeks or more into the study, or CDC Category B or C diagnosis.
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
Tijdsspanne: 96 weeks since randomization
5th, 10th, 25th, 50th, 75th and 90th percentiles in weeks from randomization for DT arm or from week 36 for IT arm to meeting the criteria for treatment initiation or re-initiation which include two consecutive CD4 count below 350 cells/mm^3 at least 4 weeks apart, at least 12 weeks into the study or 12 weeks post-treatment discontinuation, confirmed CD4 count below 200 cells/mm^3 or CD4 percent below 14% at any time on study, confirmed HIV-1 RNA level above 750,000 copies/mL 4 weeks into the study or above 200,000 copies/mL 12 weeks or more into the study, or CDC Category B or C diagnosis.
96 weeks since randomization
Time to Treatment Initiation or Death
Tijdsspanne: 5 years since randomization
5th, 10th, 25th, 50th and 75th percentiles in weeks from randomization to treatment initiation or death
5 years since randomization

Medewerkers en onderzoekers

Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.

Sponsor

AIDS Clinical Trials Group

Medewerkers

National Institute of Allergy and Infectious Diseases (NIAID)
Adult AIDS Clinical Trials Group

Onderzoekers

  • Studie stoel: Christine Hogan, MD, Division of Infectious Diseases, Columbia University College of Physicians and Surgeons

Publicaties en nuttige links

De persoon die verantwoordelijk is voor het invoeren van informatie over het onderzoek stelt deze publicaties vrijwillig ter beschikking. Dit kan gaan over alles wat met het onderzoek te maken heeft.

Algemene publicaties

Nuttige links

Studie record data

Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.

Bestudeer belangrijke data

Studie start

1 januari 2005

Primaire voltooiing (Werkelijk)

1 juli 2009

Studie voltooiing (Werkelijk)

1 mei 2011

Studieregistratiedata

Eerst ingediend

3 september 2004

Eerst ingediend dat voldeed aan de QC-criteria

3 september 2004

Eerst geplaatst (Schatting)

6 september 2004

Updates van studierecords

Laatste update geplaatst (Werkelijk)

11 oktober 2018

Laatste update ingediend die voldeed aan QC-criteria

11 september 2018

Laatst geverifieerd

1 september 2018

Meer informatie

Termen gerelateerd aan deze studie

Trefwoorden

Aanvullende relevante MeSH-voorwaarden

Andere studie-ID-nummers

  • ACTG A5217
  • 1U01AI068636 (Subsidie/contract van de Amerikaanse NIH)
  • AIEDRP AIN503

Informatie over medicijnen en apparaten, studiedocumenten

Bestudeert een door de Amerikaanse FDA gereguleerd geneesmiddel

Nee

Bestudeert een door de Amerikaanse FDA gereguleerd apparaatproduct

Nee

product vervaardigd in en geëxporteerd uit de V.S.

Nee

Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .

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