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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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HIV Infections, Tuberculosis

Intervention / Treatment
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* Drug: Efavirenz
* Drug: Lamivudine/Zidovudine


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br>Randomly assigned group who will start an ART regimen of 3TC/ZDV and EFV twice daily at study entry | Drug: Efavirenz<br>* Non-nucleoside reverse transcriptase inhibitor dosed at 600mg taken by mouth every 24 hours at bedtime<br>* Other names: EFV;Drug: Lamivudine/Zidovudine<br>* Nucleoside reverse transcriptase inhibitor dosed at 150mg/300mg fixed dose combination taken by mouth every 12 hours<br>* Other names: 3TC/AZT;|
| Active Comparator: B<br>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<br>* Non-nucleoside reverse transcriptase inhibitor dosed at 600mg taken by mouth every 24 hours at bedtime<br>* Other names: EFV;Drug: Lamivudine/Zidovudine<br>* Nucleoside reverse transcriptase inhibitor dosed at 150mg/300mg fixed dose combination taken by mouth every 12 hours<br>* Other names: 3TC/AZT;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival |  | At 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| Adherence based on self-report questionnaires and dosage count |  | Throughout study | 
| Cost of therapy |  | Throughout study | 
| Plasma HIV-1 RNA below limits of quantitation after initiating ART |  | Every 6 months throughout study | 
| Absolute CD4 cell count change from baseline in subjects who initiate ART |  | Every 6 months throughout study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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TB, Treatment Naive