NCT00108862

Brief Summary

The purpose of this study is to determine the best time to begin anti-HIV treatment in individuals who have HIV and tuberculosis (TB). Study hypothesis: Immediate antiretroviral therapy (ART), initiated after approximately 2 weeks of TB treatment, will reduce the frequency of other AIDS-defining illnesses and death in HIV-infected participants being treated for TB by at least 40% at week 48 when compared to deferred ART, initiated at after 8-12 weeks of TB treatment.

Trial Health

98
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
809

participants targeted

Target at P75+ for phase_4

Timeline
Completed

Started Aug 2006

Longer than P75 for phase_4

Geographic Reach
12 countries

25 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

April 19, 2005

Completed
1 day until next milestone

First Posted

Study publicly available on registry

April 20, 2005

Completed
1.3 years until next milestone

Study Start

First participant enrolled

August 1, 2006

Completed
3.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 1, 2010

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

July 1, 2010

Completed
1.3 years until next milestone

Results Posted

Study results publicly available

November 2, 2011

Completed
Last Updated

October 11, 2018

Status Verified

September 1, 2018

Enrollment Period

3.9 years

First QC Date

April 19, 2005

Results QC Date

September 27, 2011

Last Update Submit

September 11, 2018

Conditions

HIV InfectionTuberculosis

Keywords

Treatment NaiveTBHIVAntiretroviral AgentsStrategy Study

Outcome Measures

Primary Outcomes (1)

  • Percent of Participants Who Survived Without AIDS Progression.

    As this was a study of the strategy of providing antiretroviral therapy (ART) during the initial treatment of TB versus deferring ART until TB was treated for 8-12 weeks, all eligible participants randomized were followed for 48 weeks, whether they started ART as scheduled, whether they started ART at all, or even if the participant did not have TB and discontinued TB treatment. The percent surviving without a new AIDS-defining illness was calculated using a Kaplan-Meier estimator with an associated standard error.

    Through week 48

Secondary Outcomes (9)

  • Percent of Participants Reporting a Grade 3 or 4 Adverse Event or Laboratory Abnormality

    Through week 48

  • Time to First New AIDS-defining Illness or Death.

    Through week 48

  • Percent of Participants With Culture-confirmed Tuberculosis (TB) Who Survived Without AIDS Progression.

    Through week 48

  • Percent of Participants Who Interrupted or Discontinued at Least One Tuberculosis (TB) Medication Due to Toxicity.

    Through week 48

  • Percent of Participants With Confirmed or Probable Tuberculosis (TB) Whose TB Resolved, or Who Required TB Treatment Through the End of Follow-up, or Died, or Were Lost to Follow-up.

    Through week 48

  • +4 more secondary outcomes

Other Outcomes (2)

  • Percent of Participants in the Less Than 50 Cells/mm^3 CD4 Stratum Who Survived Without AIDS Progression.

    Through week 48

  • Percent of Participants in the Greater Than or Equal to 50 Cells/mm^3 CD4 Stratum Who Survived Without AIDS Progression.

    Through week 48

Study Arms (2)

Immediate ART

EXPERIMENTAL

The intervention is the strategy of initiating antiretroviral therapy (ART) after approximately 2 weeks of tuberculosis (TB) treatment.

Other: Strategy: Immediate ART

Deferred ART

ACTIVE COMPARATOR

The intervention is the strategy of initiating ART after 8 to 12 weeks of TB treatment.

Other: Strategy: Deferred ART

Interventions

Strategy: Immediate ARTOTHER

The intervention is the strategy of initiating antiretroviral therapy (ART) after approximately 2 weeks of rifampin (RIF)- or other rifamycin-based TB treatment according to in-country national TB treatment guidelines. The study-provided ART is efavirenz (EFV) 600 mg (1 tablet orally), emtricitabine (FTC) 200 mg (1 capsule orally), and tenofovir disoproxil fumarate (TDF) 300 mg (1 tablet orally) daily. Substitutions with other locally available U.S. Food and Drug Administration (FDA)-approved or tentatively approved antiretrovirals that are compatible with TB treatment may be used at the discretion of the site investigator. The TB treatment will be supplied and monitored by the host country TB control program.

Immediate ART
Strategy: Deferred ARTOTHER

The intervention is the strategy of initiating ART either after 8-12 weeks of RIF- or other rifamycin-based TB treatment according to in-country national TB treatment guidelines. The study-provided ART is EFV 600 mg (1 tablet orally), FTC 200 mg (1 capsule orally), and TDF 300 mg (1 tablet orally) daily. Initiation outside of these windows, on a case by case basis, is permitted at the discretion of the site investigator. Substitutions with other locally available U.S. FDA-approved or tentatively approved antiretrovirals that are compatible with TB treatment may be used at the discretion of the site investigator. The TB treatment will be supplied and monitored by the host country TB control program.

Also known as: Early ART
Deferred ART

Eligibility Criteria

Age13 Years+
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • HIV-infected.
  • Confirmed or probable TB (more information on the criterion can be found in the protocol).
  • Chest x-ray within 30 days prior to study entry.
  • Receipt of 1-14 cumulative days of rifampin- or other rifamycin-based TB treatment that was initiated within 28 days prior to study entry.
  • CD4 count less than 250 cells/mm\^3 within 30 days prior to study entry.
  • Willing to use acceptable methods of contraception while on study drugs and for 6 weeks after stopping these drugs.
  • Able to swallow oral medications.
  • Parent of guardian willing to provide informed consent, if applicable.
  • Karnofsky performance score =\>20 at time of study entry.

You may not qualify if:

  • ART for longer than 7 cumulative days prior to study entry or treatment for any period of time with one or more antiretrovirals. Participants who have taken ART during pregnancy or for occupational exposure are not excluded.
  • Allergy or sensitivity to any of the study drugs or their formulations.
  • History of multidrug-resistant TB.
  • Receipt of any investigational therapy or chemotherapy within 30 days prior to study entry.
  • Certain medications.
  • Breastfeeding.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (26)

University of Southern California (1201)

Los Angeles, California, 90033-1079, United States

Location

University of California, San Diego, AVRC CRS (701)

San Diego, California, 92103, United States

Location

University of California, San Francisco AIDS CRS (801)

San Francisco, California, 94110, United States

Location

NY Univ. HIV/AIDS CRS (401)

New York, New York, 10016, United States

Location

Gaborone Prevention/Treatment Trials CRS (12701)

Gaborone, Botswana

Location

Molepolole Prevention/Treatment Trials CRS (12702)

Molepolole, Botswana

Location

Hospital Nossa Senhora da Conceicao CRS (12201)

Porto Alegre, Rio Grande do Sul, 9043010, Brazil

Location

Instituto de Pesquisa Clinica Evandro Chagas (12101)

Rio de Janeiro, 21045, Brazil

Location

Projecto Praca Onze/Hesfa CRS (30333)

Rio de Janeiro, Brazil

Location

Les Centres GHESKIO CRS (30022)

Bicentenaire, Port-au-Prince, HT-6110, Haiti

Location

National AIDS Research Institute Pune CRS (11601)

Pune, Maharashtra, 411026, India

Location

Y.R.G Ctr, for AIDS Research and Education (11701)

Chennai, India

Location

AMPATH at Moi Univ. Teaching Hosp. Eldoret CRS (12601)

Eldoret, 30100, Kenya

Location

Walter Reed Project - Kenya Med. Research Institute Kericho CRS (12501)

Kericho, 20200, Kenya

Location

College of Med. JHU CRS (30301)

Blantyre, Malawi

Location

University of North Carolina Lilongwe CRS (12001)

Lilongwe, Malawi

Location

Investigaciones Medicas en Salud (INMENSA) (11302)

San Isidro, Lima region, Peru

Location

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

Lima, 18 PE, Peru

Location

CAPRISA eThekwini CRS (31422)

Durban, KwaZulu-Natal, 4011, South Africa

Location

Durban Adult HIV CRS (11201)

Durban, 4013 SF, South Africa

Location

Soweto ACTG CRS (12301)

Johannesburg, South Africa

Location

Univ. of Witwatersrand CRS (11101)

Johannesburg, South Africa

Location

Chiang Mai University ACTG CRS (11501)

Chiang Mai, 50202, Thailand

Location

Joint Clinical Research Centre (JCRC) (12401)

Kampala, Uganda

Location

Kalingalinga Clinic CRS (12801)

Lusaka, Zambia

Location

UZ-Parirenyatwa CRS (30313)

Harare, Zimbabwe

Location

Related Publications (2)

  • Crump JA, Wu X, Kendall MA, Ive PD, Kumwenda JJ, Grinsztejn B, Jentsch U, Swindells S. Predictors and outcomes of Mycobacterium tuberculosis bacteremia among patients with HIV and tuberculosis co-infection enrolled in the ACTG A5221 STRIDE study. BMC Infect Dis. 2015 Jan 13;15:12. doi: 10.1186/s12879-014-0735-5.

    PMID: 25582793DERIVED

  • Havlir DV, Kendall MA, Ive P, Kumwenda J, Swindells S, Qasba SS, Luetkemeyer AF, Hogg E, Rooney JF, Wu X, Hosseinipour MC, Lalloo U, Veloso VG, Some FF, Kumarasamy N, Padayatchi N, Santos BR, Reid S, Hakim J, Mohapi L, Mugyenyi P, Sanchez J, Lama JR, Pape JW, Sanchez A, Asmelash A, Moko E, Sawe F, Andersen J, Sanne I; AIDS Clinical Trials Group Study A5221. Timing of antiretroviral therapy for HIV-1 infection and tuberculosis. N Engl J Med. 2011 Oct 20;365(16):1482-91. doi: 10.1056/NEJMoa1013607.

    PMID: 22010914DERIVED

MeSH Terms

Conditions

HIV InfectionsTuberculosis

Condition Hierarchy (Ancestors)

Blood-Borne InfectionsCommunicable DiseasesInfectionsSexually Transmitted Diseases, ViralSexually Transmitted DiseasesLentivirus InfectionsRetroviridae InfectionsRNA Virus InfectionsVirus DiseasesGenital DiseasesUrogenital DiseasesImmunologic Deficiency SyndromesImmune System DiseasesMycobacterium InfectionsActinomycetales InfectionsGram-Positive Bacterial InfectionsBacterial InfectionsBacterial Infections and Mycoses

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

  • Diane Havlir, MD

    San Francisco General Hospital and University of California, San Francisco

    STUDY CHAIR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
NETWORK
Responsible Party
SPONSOR

Study Record Dates

First Submitted

April 19, 2005

First Posted

April 20, 2005

Study Start

August 1, 2006

Primary Completion

July 1, 2010

Study Completion

July 1, 2010

Last Updated

October 11, 2018

Results First Posted

November 2, 2011

Record last verified: 2018-09

Locations

MA(2)US(4)BO(2)HA(1)TH(1)ZA(4)IN(2)ZI(1)BR(3)KE(2)PE(2)UG(1)