Efavirenz and Lamivudine/Zidovudine for Treatment-Naive HIV Infected Adults in Senegal

Study Overview
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Brief Summary
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The purpose of this study is to determine the safety and effectiveness of the anti-HIV drugs efavirenz and lamivudine/zidovudine given to treatment-naive HIV-infected people in Dakar, Senegal.

Detailed Description
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Despite a relatively low prevalence of HIV infection, all HIV subtypes have been documented in Senegal. Data on mutations that confer resistance to antiretroviral (ARV) drugs are limited to HIV subtype B; adherence data are also limited. The study will evaluate the safety and efficacy of an ARV regimen given to treatment-naive HIV infected adults and adolescents. The study will also examine the characteristics of virologic failure and adherence in this treatment group. Participants will be recruited at two sites in Dakar, Senegal. This study will last 96 weeks. At study entry, all participants will be given an ARV regimen of lamivudine/zidovudine twice daily and efavirenz once daily. If toxicity or treatment failure occurs, some participants may require changes in their ARV regimens. There will be 14 study visits during the study; a physical exam, blood collection, and sociodemographic and medication history assessments will occur at each visit. Participants will also be asked to complete quality-of-life and adherence questionnaires. An off-study visit will occur at approximately one month after Week 96, with assessments and procedures similar to visits during the study.

Official Title
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A Pilot Study of Safety, Effectiveness, and Adherence of Lamivudine/Zidovudine and Efavirenz (3TC/ZDV + EFV) to Treat HIV-1 Infection in Senegal

Conditions
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HIV Infections

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 Have never taken ARV drugs CD4 count of 200 cells/mm3 or less within 30 days of study entry if asymptomatic OR CD4 count of 350 cells/mm3 or less within 60 days of study entry if CDC Category A or B clinical condition present OR clinical diagnosis of AIDS, regardless of CD4 count Willing to stay in the study area for the duration of the study Willing to use acceptable forms of contraception Exclusion Criteria: HIV-2 infected Systemic chemotherapy (except interferon) within 6 months prior to study entry Current drug or alcohol abuse that, in the opinion of the investigator, may interfere with the study Serious illness, including any active AIDS-defining infection, active tuberculosis, malaria, or any illness requiring systemic treatment or hospitalization. People who have completed therapy or are clinically stable on therapy for at least 14 days prior to study entry are not excluded. Serious psychiatric problems within 60 days of study entry, including depression, suicidal thoughts or attempts, aggressive behavior, or psychosis-like symptoms Have taken certain medications within 30 days of study entry Pregnancy 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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>All participants will be given an ARV regimen of lamivudine/zidovudine and efavirenz at study entry. If toxicity or treatment failure occurs, some participants may require changes in their ARV regimens. | Drug: Efavirenz<br>* 600 mg tablet taken orally daily<br>* Other names: EFV;Drug: Lamivudine/zidovudine<br>* 150mg lamivudine/300mg zidovudine tablet taken orally twice daily<br>* Other names: 3TC/ZDV;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Virologic efficacy, defined as HIV-1 viral load less than 200 copies/ml |  | Through Week 24 | 
| Treatment-related toxicity of Grade 3 or higher as measured by development of drug-related toxicities severe enough to warrant dose modification, interruption, or permanent discontinuation |  | Through Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Virologic efficacy |  | At Weeks 48 and 96 | 
| Treatment related toxicity |  | At Weeks 48 and 96 | 
| Virologic failure, defined as HIV-1 viral load greater than 1,000 copies/ml |  | Throughout study | 
| CD4 counts and HIV-1 RNA viral load |  | Throughout study | 
| First new or recurrent AIDS-defining event (as defined by the CDC Expanded AIDS Surveillance Case definition) or death |  | Throughout study | 
| Treatment discontinuation, defined as premature discontinuation of participation in the study, failure to take ARV therapy for 8 or more consecutive weeks, or to switch to another ARV regimen for any reason during the full course of the study |  | Throughout study | 
| Genotypic resistance measured by at least 1 genotypic mutation associated with resistance among subjects with a confirmed virologic failure (as described previously) and evaluation of genotypic drug resistance patterns |  | At Weeks 24 and 96 | 
| Treatment adherence, defined by 95% or greater of prescribed pills taken |  | Throughout study | 
| Quality of life as measured by items and patterns of responses to the FAHI questionnaire |  | Throughout study | 
| HIV-1 DNA and RNA measurements |  | Throughout study | 

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