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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00120510
First received: July 14, 2005
Last updated: April 16, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention
HIV Infections
Tuberculosis
Drug: Efavirenz
Drug: Lamivudine/Zidovudine

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized Clinical Trial to Determine the Efficacy of Early Versus Standard Antiretroviral Therapy in HIV Infected Adults With CD4+ T Cell Counts Between 200 and 350 Cells/mm3

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:
  • Survival [ Time Frame: At 36 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Safety and drug-associated side effects and toxicities of the study drugs [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
  • Pattern and frequency of antiretroviral drug resistance during ART [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  • Occurrence and clinical outcome of opportunistic infections, viral coinfections, and immune reconstitution syndromes observed during ART [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  • TB treatment outcomes in patients with active pulmonary TB at enrollment [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  • Quality of life scores based on self-report questionnaires [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  • Adherence based on self-report questionnaires and dosage count [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  • Cost of therapy [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  • Plasma HIV-1 RNA below limits of quantitation after initiating ART [ Time Frame: Every 6 months throughout study ] [ Designated as safety issue: No ]
  • Absolute CD4 cell count change from baseline in subjects who initiate ART [ Time Frame: Every 6 months throughout study ] [ Designated as safety issue: No ]

Enrollment: 816
Study Start Date: July 2007
Study Completion Date: September 2009
Primary Completion Date: September 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A
Randomly assigned group who will start an ART regimen of 3TC/ZDV and EFV twice daily at study entry
Drug: Efavirenz
Non-nucleoside reverse transcriptase inhibitor dosed at 600mg taken by mouth every 24 hours at bedtime
Other Name: EFV
Drug: Lamivudine/Zidovudine
Nucleoside reverse transcriptase inhibitor dosed at 150mg/300mg fixed dose combination taken by mouth every 12 hours
Other Names:
  • 3TC/ZDV
  • 3TC/AZT
Active Comparator: B
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
Non-nucleoside reverse transcriptase inhibitor dosed at 600mg taken by mouth every 24 hours at bedtime
Other Name: EFV
Drug: Lamivudine/Zidovudine
Nucleoside reverse transcriptase inhibitor dosed at 150mg/300mg fixed dose combination taken by mouth every 12 hours
Other Names:
  • 3TC/ZDV
  • 3TC/AZT

Detailed Description:

In many parts of the world, initial standard of care for HIV includes 3TC/ZDV and the non-nucleoside reverse transcriptase inhibitor EFV. However, it is unclear if early (CD4 count less than 350 cells/mm3) or delayed (CD4 count less than 200 cells/mm3) therapy initiation leads to improved survival. This study will determine the most appropriate time to initiate ART in HIV infected individuals in Haiti. The study will enroll patients from the Haitian Study Group on Kaposi's Sarcoma and Opportunistic Infections (GHESKIO) Centers. Some participants in this study will have active pulmonary tuberculosis (TB).

This study will last at least 3 years. Participants will be randomly assigned to one of two groups at study entry. Group A participants will receive 3TC/ZDV twice daily and EFV once daily at study enrollment. Participants receiving TB therapy at the time of enrollment may be observed for 2 weeks prior to beginning early therapy. Dosage adjustment of EFV may be necessary for participants receiving rifampin as part of their TB therapy. Group B participants will receive 3TC/ZDV twice daily and EFV once daily when they develop clinical AIDS or their CD4 count drops below 200 cells/mm3 (WHO Stage IV). Directly observed therapy will be used for the first two months of treatment for every participant.

Group A participants will have 14 study visits after beginning treatment; the visits will occur at Months 1, 2, 3, and every 3 months thereafter. Medical and medication history, physical exams, and contraceptive counseling for women will occur at all visits. HIV counseling, blood collection, and HIV staging will occur at most visits. At some study visits, Group A participants will be asked to complete quality of life and adherence questionnaires. Group B participants will have 14 study visits after study entry and will begin treatment when they meet WHO criteria. Assessments will be the same as for Group A. Any participant who fails the first-line regimen during the study will switch to a second-line ART regimen.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • WHO Stage IV HIV disease (AIDS)
  • 7 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00120510

Locations
Haiti
Les Centres GHESKIO CIPRA CRS
Port au Prince, Haiti, HT-6110
Sponsors and Collaborators
Investigators
Principal Investigator: Jean William Pape, MD Cornell - GHESKIO, Institut de Laboratoire et de Recherches and Division of International Medicine and Infectious Diseases, Cornell University
Study Director: 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
  More Information

Additional Information:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00120510     History of Changes
Other Study ID Numbers: CIPRA HT 001, 5-K24-AI051966-03, 10403
Study First Received: July 14, 2005
Last Updated: April 16, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Treatment Naive
TB

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Tuberculosis
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Zidovudine
Lamivudine
Reverse Transcriptase Inhibitors
Efavirenz
Lamivudine, zidovudine drug combination
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on September 11, 2014