Early Versus Standard Start of Anti-HIV Therapy for Treatment-Naive Adults in Haiti

NCT00120510 | Completed DMC

• 3 other identifiers: CIPRA HT 0015K24AI051966-0310403
• Study Type: interventional
• Target: 816
• Locations: 1 country
• Sites: 1

Brief Summary

Anti-HIV treatment consisting of lamivudine/zidovudine (3TC/ZDV) and efavirenz (EFV) is the current standard of care for initial treatment of HIV in most areas of the world. The purpose of this study is to determine the best time to start this anti-HIV treatment in treatment-naive adults in Haiti.

Conditions

HIV Infections; Tuberculosis

Keywords

Treatment Naive; TB

Outcome Measures

Primary Outcomes (1)

• Survival

  At 36 months

Secondary Outcomes (9)

• Safety and drug-associated side effects and toxicities of the study drugs

  Throughout study

• Pattern and frequency of antiretroviral drug resistance during ART

  Throughout study

• Occurrence and clinical outcome of opportunistic infections, viral coinfections, and immune reconstitution syndromes observed during ART

  Throughout study

• TB treatment outcomes in patients with active pulmonary TB at enrollment

  Throughout study

• Quality of life scores based on self-report questionnaires

  Throughout study

Study Arms (2)

A

EXPERIMENTAL

Randomly assigned group who will start an ART regimen of 3TC/ZDV and EFV twice daily at study entry

Drug: Efavirenz; Drug: Lamivudine/Zidovudine

B

ACTIVE COMPARATOR

Randomly assigned group who will delay beginning ART regimen of 3TC/ZDV and EFC twice daily until they develop clinical AIDS or their CD4 count drops below 200 cells/mm3

Drug: Efavirenz; Drug: Lamivudine/Zidovudine

Interventions

Efavirenz DRUG

Non-nucleoside reverse transcriptase inhibitor dosed at 600mg taken by mouth every 24 hours at bedtime

Also known as: EFV

A; B

Lamivudine/Zidovudine DRUG

Nucleoside reverse transcriptase inhibitor dosed at 150mg/300mg fixed dose combination taken by mouth every 12 hours

Also known as: 3TC/ZDV, 3TC/AZT

A; B

Eligibility Criteria

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

You may qualify if:

• HIV-infected
• Received pre- and post-test counseling at the GHESKIO Centers
• CD4 count between 200 and 350 cells/mm3
• World Health Organization (WHO) Stage I, II, or III HIV disease
• Willing to use acceptable forms of contraception

You may not qualify if:

• WHO Stage IV HIV disease (AIDS)
• or more days of cumulative ART prior to study entry OR on ART at time of study entry
• Active TB, if diagnostic work-up for TB is incomplete OR if decision to treat TB has not been made. More information on this criterion can be found in the protocol.
• Recurrent active TB OR history of interrupted or incomplete TB therapy. More information on this criterion can be found in the protocol.
• Has not been evaluated for latent TB and decision to treat latent TB with isoniazid has not been made. More information on this criterion can be found in the protocol.
• Requires ART in the next 3 months, in the opinion of the investigator
• Other serious medical illness requiring chronic maintenance therapy (e.g., hypertension, diabetes) UNLESS the individual has completed at least 14 days of therapy prior to study enrollment AND is clinically stable
• Any psychological condition (e.g., severe depression, schizophrenia) that, in the opinion of the investigator, may interfere with the study
• Any social condition (e.g., pending emigration, pending incarceration) that, in the opinion of the investigator, may interfere with the study
• Active drug or alcohol use that, in the opinion of the investigator, may interfere with the study
• Current inflammation of the pancreas
• Allergy/sensitivity to any of study drugs or their formulations
• Requires certain medications
• Enrolled in another therapeutic or interventional clinical trial
• Pregnant or breastfeeding

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

Les Centres GHESKIO CIPRA CRS

Port-au-Prince, HT-6110, Haiti

Location

Related Publications (10)

• Blankson JN. Primary HIV-1 infection: to treat or not to treat? AIDS Read. 2005 May;15(5):245-6, 249-51.

  PMID: 15900634 BACKGROUND

• Duncombe C, Kerr SJ, Ruxrungtham K, Dore GJ, Law MG, Emery S, Lange JM, Phanuphak P, Cooper DA. HIV disease progression in a patient cohort treated via a clinical research network in a resource limited setting. AIDS. 2005 Jan 28;19(2):169-78. doi: 10.1097/00002030-200501280-00009.

  PMID: 15668542 BACKGROUND

• Pape JW. Tuberculosis and HIV in the Caribbean: approaches to diagnosis, treatment, and prophylaxis. Top HIV Med. 2004 Dec-2005 Jan;12(5):144-9.

  PMID: 15647610 BACKGROUND

• Teck R, Ascurra O, Gomani P, Manzi M, Pasulani O, Kusamale J, Salaniponi FM, Humblet P, Nunn P, Scano F, Harries AD, Zachariah R. WHO clinical staging of HIV infection and disease, tuberculosis and eligibility for antiretroviral treatment: relationship to CD4 lymphocyte counts. Int J Tuberc Lung Dis. 2005 Mar;9(3):258-62.

  PMID: 15786887 BACKGROUND

• Thorner A, Rosenberg E. Early versus delayed antiretroviral therapy in patients with HIV infection : a review of the current guidelines from an immunological perspective. Drugs. 2003;63(13):1325-37. doi: 10.2165/00003495-200363130-00001.

  PMID: 12825959 BACKGROUND

• Joseph Y, Yao Z, Dua A, Severe P, Collins SE, Bang H, Antoine Jean-Juste M, Ocheretina O, Apollon A, McNairy ML, Dupnik K, Cremieux E, Byrne A, Pape JW, Koenig SP. Long-term mortality after tuberculosis treatment among persons living with HIV in Haiti. J Int AIDS Soc. 2021 Jul;24(7):e25721. doi: 10.1002/jia2.25721.

  PMID: 34235862 DERIVED

• Collins SE, Jean Juste MA, Koenig SP, Secours R, Ocheretina O, Bernard D, Riviere C, Calnan M, Dunning A, Hurtado Rua SM, Johnson WD Jr, Pape JW, Fitzgerald DW, Severe P. CD4 deficit and tuberculosis risk persist with delayed antiretroviral therapy: 5-year data from CIPRA HT-001. Int J Tuberc Lung Dis. 2015 Jan;19(1):50-7. doi: 10.5588/ijtld.14.0217.

  PMID: 25519790 DERIVED

• Haas DW, Severe P, Jean Juste MA, Pape JW, Fitzgerald DW. Functional CYP2B6 variants and virologic response to an efavirenz-containing regimen in Port-au-Prince, Haiti. J Antimicrob Chemother. 2014 Aug;69(8):2187-90. doi: 10.1093/jac/dku088. Epub 2014 Apr 2.

  PMID: 24695352 DERIVED

• Koenig SP, Bang H, Severe P, Jean Juste MA, Ambroise A, Edwards A, Hippolyte J, Fitzgerald DW, McGreevy J, Riviere C, Marcelin S, Secours R, Johnson WD, Pape JW, Schackman BR. Cost-effectiveness of early versus standard antiretroviral therapy in HIV-infected adults in Haiti. PLoS Med. 2011 Sep;8(9):e1001095. doi: 10.1371/journal.pmed.1001095. Epub 2011 Sep 20.

  PMID: 21949643 DERIVED

• Severe P, Juste MA, Ambroise A, Eliacin L, Marchand C, Apollon S, Edwards A, Bang H, Nicotera J, Godfrey C, Gulick RM, Johnson WD Jr, Pape JW, Fitzgerald DW. Early versus standard antiretroviral therapy for HIV-infected adults in Haiti. N Engl J Med. 2010 Jul 15;363(3):257-65. doi: 10.1056/NEJMoa0910370.

  PMID: 20647201 DERIVED

MeSH Terms

Conditions

HIV Infections; Tuberculosis

Interventions

efavirenz; lamivudine, zidovudine drug combination

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; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses

Study Officials

• Jean William Pape, MD

  Cornell - GHESKIO, Institut de Laboratoire et de Recherches and Division of International Medicine and Infectious Diseases, Cornell University

  PRINCIPAL INVESTIGATOR

• Patrice Severe, MD

  Cornell - GHESKIO, Institut de Laboratoire et de Recherches

  STUDY DIRECTOR

• Daniel W. Fitzgerald, MD

  Division of International Medicine and Infectious Diseases, Cornell University

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 14, 2005
• First Posted: July 18, 2005
• Study Start: July 1, 2007
• Primary Completion: September 1, 2009
• Study Completion: September 1, 2009
• Last Updated: October 15, 2014

Record last verified: 2014-10

Locations

HA (1)