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

11. září 2018 aktualizováno: 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.

Přehled studie

Postavení

Ukončeno

Podmínky

Intervence / Léčba

Detailní popis

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.

Typ studie

Intervenční

Zápis (Aktuální)

130

Fáze

  • Fáze 2

Kontakty a umístění

Tato část poskytuje kontaktní údaje pro ty, kteří studii provádějí, a informace o tom, kde se tato studie provádí.

Studijní místa

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

Kritéria účasti

Výzkumníci hledají lidi, kteří odpovídají určitému popisu, kterému se říká kritéria způsobilosti. Některé příklady těchto kritérií jsou celkový zdravotní stav osoby nebo předchozí léčba.

Kritéria způsobilosti

Věk způsobilý ke studiu

18 let a starší (Dospělý, Starší dospělý)

Přijímá zdravé dobrovolníky

Ne

Pohlaví způsobilá ke studiu

Všechno

Popis

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.

Studijní plán

Tato část poskytuje podrobnosti o studijním plánu, včetně toho, jak je studie navržena a co studie měří.

Jak je studie koncipována?

Detaily designu

  • Primární účel: Léčba
  • Přidělení: Randomizované
  • Intervenční model: Paralelní přiřazení
  • Maskování: Žádné (otevřený štítek)

Zbraně a zásahy

Skupina účastníků / Arm
Intervence / Léčba
Aktivní komparátor: IT arm
IT (immediate treatment) arm participants received emtricitabine/tenofovir disoproxil fumarate once daily and lopinavir/ritonavir twice daily
Lék: Emtricitabine/ tenofovir disoproxil fumarate
once daily
Lék: Lopinavir/Ritonavir
twice daily
Žádný zásah: DT arm
DT (deferred treatment) arm participants received no treatment

Co je měření studie?

Primární výstupní opatření

Měření výsledku
Popis opatření
Časové okno
Ranked Log10 HIV-1 RNA Viral Load (log10 Copies/mL) Averaged at 72 and 76 Weeks for the IT Arm and DT Arm
Časové okno: 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
Časové okno: 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%.
Časové okno: 96 weeks since randomization
96 weeks since randomization

Sekundární výstupní opatření

Měření výsledku
Popis opatření
Časové okno
Change in CD4 Counts Cells/mm^3 From Week 36 for IT Arm and From Week 0 for DT Arm
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 5 years since randomization
5th, 10th, 25th, 50th and 75th percentiles in weeks from randomization to treatment initiation or death
5 years since randomization

Spolupracovníci a vyšetřovatelé

Zde najdete lidi a organizace zapojené do této studie.

Sponzor

AIDS Clinical Trials Group

Spolupracovníci

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

Vyšetřovatelé

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

Publikace a užitečné odkazy

Osoba odpovědná za zadávání informací o studiu tyto publikace poskytuje dobrovolně. Mohou se týkat čehokoli, co souvisí se studiem.

Obecné publikace

Užitečné odkazy

Termíny studijních záznamů

Tato data sledují průběh záznamů studie a předkládání souhrnných výsledků na ClinicalTrials.gov. Záznamy ze studií a hlášené výsledky jsou před zveřejněním na veřejné webové stránce přezkoumány Národní lékařskou knihovnou (NLM), aby se ujistily, že splňují specifické standardy kontroly kvality.

Hlavní termíny studia

Začátek studia

1. ledna 2005

Primární dokončení (Aktuální)

1. července 2009

Dokončení studie (Aktuální)

1. května 2011

Termíny zápisu do studia

První předloženo

3. září 2004

První předloženo, které splnilo kritéria kontroly kvality

3. září 2004

První zveřejněno (Odhad)

6. září 2004

Aktualizace studijních záznamů

Poslední zveřejněná aktualizace (Aktuální)

11. října 2018

Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality

11. září 2018

Naposledy ověřeno

1. září 2018

Více informací

Termíny související s touto studií

Klíčová slova

Další relevantní podmínky MeSH

Další identifikační čísla studie

  • ACTG A5217
  • 1U01AI068636 (Grant/smlouva NIH USA)
  • AIEDRP AIN503

Informace o lécích a zařízeních, studijní dokumenty

Studuje lékový produkt regulovaný americkým FDA

Ne

Studuje produkt zařízení regulovaný americkým úřadem FDA

Ne

produkt vyrobený a vyvážený z USA

Ne

Tyto informace byly beze změn načteny přímo z webu clinicaltrials.gov. Máte-li jakékoli požadavky na změnu, odstranění nebo aktualizaci podrobností studie, kontaktujte prosím register@clinicaltrials.gov. Jakmile bude změna implementována na clinicaltrials.gov, bude automaticky aktualizována i na našem webu .

Klinické studie na HIV infekce

Klinické studie na Emtricitabine/ tenofovir disoproxil fumarate

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Zdravotní podmínky

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Podmínky

Vzácné nemoci

Drogové intervence

Doplňky stravy

Sponzor / Spolupracovníci

Místa

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