The Adult Antiretroviral Treatment and Resistance Study (Tshepo)

Study Overview
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Brief Summary
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The Adult Antiretroviral Treatment and Resistance Study, hereafter referred to as The Tshepo Study, is the first large-scale research study of antiretroviral therapy to treat AIDS and HIV infection in Botswana. The Tshepo Study is an open-label, randomized study comparing: (1) the rate of development and specific types of drug resistance mutations with various antiretroviral combination therapies to HIV-1C, the subtype of HIV found in southern Africa, and (2) the short and long-term effectiveness of two operational modifications of Directly Observed Therapy (DOT) medication adherence strategies for antiretroviral therapy. Specifically, treatment follow-up via the Standard of Care, the national standard of care as it evolves in Botswana, with intensive clinic-based follow up including regular adherence education sessions, will be compared to Community-Based Directly Observed Therapy (Com-DOT). Com-DOT involves the SOC with added community or family-based DOT. This Com-DOT component would involve a trained, community or family-based Medication Partner (mopati) who observes the patient take his or medications daily.

Official Title
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The Adult Antiretroviral Treatment and Resistance Study (Tshepo)

Conditions
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AIDS, HIV Infection

Intervention / Treatment
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* Drug: (A) zidovudine, lamivudine and nevirapine
* Drug: (B) zidovudine, lamivudine and efavirenz
* Drug: (C) zidovudine, didanosine, and nevirapine
* Drug: (D) zidovudine, didanosine, and efavirenz
* Drug: (E) stavudine, lamivudine, and nevirapine
* Drug: (F) stavudine, lamivudine and efavirenz
* Procedure: Adherence Strategy Standard of Care (SOC)
* Procedure: Adherence Strategy Community-Based DOT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria:(1) HIV infection indicated by (a) positive ELISA in two separate blood samples, the second no more than eight weeks prior to randomization), (b) CD4 cell count of less than 200 cells/ml OR CD4 cell count between 201-350 with plasma HIV-1 RNA level of greater than 55,000 copies/ml, (c) Karnofsky (performance) score greater than or equal to 50; (2) no history of previous antiretroviral therapy, except for zidovudine and/or single-dose nevirapine administered during pregnancy to prevent mother-to-child HIV transmission of HIV-1; (3) baseline hemoglobin of greater than or equal to 8.0 g/dl (4) baseline absolute neutrophil count greater than or equal to 1000 cells/mm3 (5) baseline serum creatinine level less than 200 micromol/L (6) baseline SGPT(ALT) less than 205 U/L and SGOT (AST) less than 170 U/L (7) baseline alkaline phosphatase level less than or equal to 330 U/L etc.

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

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


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: (A) zidovudine, lamivudine and nevirapine|nan|
|Drug: (B) zidovudine, lamivudine and efavirenz|nan|
|Drug: (C) zidovudine, didanosine, and nevirapine|nan|
|Drug: (D) zidovudine, didanosine, and efavirenz|nan|
|Drug: (E) stavudine, lamivudine, and nevirapine|nan|
|Drug: (F) stavudine, lamivudine and efavirenz|nan|
|Procedure: Adherence Strategy Standard of Care (SOC)|nan|
|Procedure: Adherence Strategy Community-Based DOT|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Virological failure, time to grade 3 or higher toxicity. |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to drug resistance, rates of point mutations at virological failure, adherence to study medication. |  |  |