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HIV InfectionsPhase 2NCT00090779

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

A Phase 2 study testing Emtricitabine/ tenofovir disoproxil fumarate and Lopinavir/Ritonavir in people with HIV Infections, run by Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections at 27 sites in 2 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
HIV Infections
What is being tested?
Emtricitabine/ tenofovir disoproxil fumarate and Lopinavir/Ritonavir
Could I receive a placebo?
No, everyone receives an active treatment
How many people
130 participants
Where
27 sitesin 2 countries
Study dates
Jan 2005to May 2011
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 24Show fewer
  • 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:
  • 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
  • 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
  • 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
  • Clinical progression to CDC category B or C disease
  • 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:
  • 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
  • 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
  • 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
  • Clinical progression to CDC category B or C disease
  • 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.

Who cannot join

  • 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
Show all 16Show fewer
  • 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.

Trial locations and contacts

27 sites in 2 countries.

27 sites in 2 countries

United States25 sites

  • The Ponce de Leon Center CRS

    Atlanta, Georgia, 30308

  • University of Colorado Hospital CRS (6101)

    Aurora, Colorado, 80045

  • IHV Baltimore Treatment CRS (4651)

    Baltimore, Maryland, 21201

  • Massachusetts General Hospital ACTG CRS (101)

    Boston, Massachusetts, 02114

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

    Boston, Massachusetts, 02115

  • Unc Aids Crs (3201)

    Chapel Hill, North Carolina, 27516

  • Northwestern University CRS (2701)

    Chicago, Illinois, 60611

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

    Chicago, Illinois, 60612

  • The Ohio State Univ. AIDS CRS (2301)

    Columbus, Ohio, 43210

  • Moses H. Cone Memorial Hospital CRS (3203)

    Greensboro, North Carolina, 27401

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

    Greensboro, North Carolina, 27401

  • Indiana University Hospital (2601)

    Indianapolis, Indiana, 46202-5250

  • University of Miami AIDS CRS (901)

    Miami, Florida, 33139

  • Beth Israel Medical Center

    New York, New York, 10003

  • HIV Prevention & Treatment CRS (30329)

    New York, New York, 10032

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

    Philadelphia, Pennsylvania, 19104

  • The Miriam Hosp. ACTG CRS (2951)

    Providence, Rhode Island, 02906

  • AIDS Care CRS (1108)

    Rochester, New York, 14642

  • University of Rochester ACTG CRS (1101)

    Rochester, New York, 14642

  • Ucsd, Avrc Crs (701)

    San Diego, California, 92103

  • Ucsf Aids Crs (801)

    San Francisco, California, 94110

  • University of Washington AIDS CRS (1401)

    Seattle, Washington, 98104

  • UW Primary Infection Clinic CRS (1404)

    Seattle, Washington, 98104

  • Washington University CRS (2101)

    St Louis, Missouri, 63110

  • Harbor-UCLA Med. Ctr. CRS (603)

    Torrance, California, 90502

Other trials in United States

Peru2 sites

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

    Lima, 18 PE

  • San Miguel CRS

    San Miguel, Lima region

Other trials in Peru

About this study

Official title: 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.

Read the detailed description

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
HIV Infections
Being tested
Emtricitabine/ tenofovir disoproxil fumarate, Lopinavir/Ritonavir
Keywords
Acute Infection, Treatment Naive
Medical subject headings
HIV Infections

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Emtricitabine/ tenofovir disoproxil fumarateDrug

    once daily

  • Lopinavir/RitonavirDrug

    twice daily

Study groups in NCT00090779
Study groupRoleWhat they receive
IT armActive comparatorIT (immediate treatment) arm participants received emtricitabine/tenofovir disoproxil fumarate once daily and lopinavir/ritonavir twice daily
Receives: Drug: Emtricitabine/ tenofovir disoproxil fumarate; Drug: Lopinavir/Ritonavir
DT armNo interventionDT (deferred treatment) arm participants received no treatment

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: At Weeks 72 and 76

  2. 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.

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

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

    Measured: 96 weeks since randomization

Secondary outcomes (6)

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

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

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

    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.

    Measured: 96 weeks since randomization

  3. Number of Participants in IT Arm Off Treatment Before 36 Weeks

    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.

    Measured: At Week 36

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

    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.

    Measured: 96 weeks since randomization

  5. 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

    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.

    Measured: 96 weeks since randomization

  6. Time to Treatment Initiation or Death

    5th, 10th, 25th, 50th and 75th percentiles in weeks from randomization to treatment initiation or death

    Measured: 5 years since randomization

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Sep 2004 (estimated)
  2. Study startJan 2005
  3. Primary completionJul 2009
  4. Study completionMay 2011

Why it stopped: The DSMB concluded that the findings regarding the primary analysis would persist and that no additional study goals would be achieved by continuing the study.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
130 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00090779
Sponsor's protocol ID
ACTG A5217
Other IDs
1U01AI068636, AIEDRP AIN503, ACTG A5217
Status last verified
Sep 2018
First submitted
3 Sep 2004
Last updated
11 Oct 2018
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 12370504

  • 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.

    PubMed 15156484

  • 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.

    PubMed 12167680

  • 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.

    PubMed 15057296

  • 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.

    PubMed 16962381

  • 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.

    PubMed 22180621

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Emtricitabine/ tenofovir disoproxil fumarate and Lopinavir/Ritonavir in people with HIV Infections, run by Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections at 27 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 24 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 11 Oct 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 27 sites in United States, Peru. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 18 Dec 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Ranked Log10 HIV-1 RNA Viral Load (log10 Copies/mL) Averaged at 72 and 76 Weeks for the IT Arm and DT Arm (time frame: At Weeks 72 and 76). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00090779, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Oct 2018.

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