Evaluation of Two Anti-HIV Treatment Strategies in Resource-Limited South African Communities

Study Overview
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Brief Summary
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The purpose of this study is to determine the effectiveness of several anti-HIV treatment strategies in resource-poor South African communities. The strategies being studied are using specially trained doctors or nurses to administer HIV care.

Detailed Description
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The introduction of antiretroviral therapy (ART) for the treatment of HIV has dramatically improved morbidity and mortality for HIV infected people in the developed world. However, research data on the efficacy of ART regimens in developing countries, such as South Africa, are limited. There are an estimated 4.7 million HIV infected individuals in the South African population of about 40 million inhabitants. The greatest social impact may be achieved by treating an entire household affected by HIV to ensure maximum adherence to prescribed ART regimens and to minimize the sharing of antiretroviral drugs. This study will evaluate the effectiveness of ART given by an HIV-trained doctor compared to ART given by an HIV-trained primary health care nurse. Participants failing first-line therapy will receive a second-line regimen based on what medications are available at the clinic, with approval by the clinical safety team. Participants in this study will be recruited from resource-poor communities outside Johannesburg and Cape Town, South Africa. This study will last 5 years. HIV infected people and other HIV infected members of their household 16 years of age and older will be enrolled. Study participants will receive first-line ART consisting of efavirenz (EFV) once daily, lamivudine (3TC) twice daily, and stavudine (d4T) twice daily. Women of childbearing potential who are unwilling to use acceptable forms of contraception and who have CD4 counts less than 250 cells/mm3 will receive 3TC twice daily; nevirapine (NVP) daily for 2 weeks, then twice daily; and d4T twice daily. Women who are pregnant at baseline, who become pregnant on study treatment, or who are unwilling to use acceptable methods of contraception and have CD4 counts of 250 cells/mm3 or more, or children who were previously exposed to NVP will receive 3TC twice daily, lopinavir/ritonavir (LPV/r) twice daily, and d4T twice daily. Participants will be randomly assigned to one of two arms. Arm 1 will receive ART under the monitoring care of an HIV-trained medical doctor, while Arm 2 will receive ART under the monitoring care of an HIV-trained primary health care nurse with training in HIV diagnosis and treatment. Participants who fail their first-line regimen will receive a second-line regimen but will remain in their treatment arms. Study visits will occur at study entry; Weeks 2, 4, 8, and 12; and every 12 weeks thereafter. A physical exam, measurement of height and weight, tuberculosis (TB) and hepatitis B infection screening, blood collection, pill counts, and compliance/adherence and resource utilization counseling will occur at most visits. Participants will also be asked to complete quality of life and household cost questionnaires at selected visits. Study visits for participants who fail first-line treatment will occur at treatment failure, between Days 15 and 30, Week 4 post-treatment failure, every 4 weeks until Week 48 post-treatment failure, and every 12 weeks thereafter. A targeted physical exam, measurement of height and weight, TB infection screening, blood collection, pill counts, and compliance/adherence and resource utilization counseling will occur at most visits. Participants will also be asked to complete quality of life and household cost questionnaires at selected visits.

Official Title
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Safeguard the Household - A Study of HIV Antiretroviral Therapy Treatment Strategies Appropriate for a Resource Poor Country

Conditions
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HIV Infections

Intervention / Treatment
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* Behavioral: Monitoring by an HIV-trained medical doctor
* Behavioral: Monitoring by an HIV-trained primary care nurse
* Drug: Efavirenz
* Drug: Lamivudine
* Drug: Lopinavir/Ritonavir
* Drug: Nevirapine
* Drug: Stavudine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HIV-1 infected Current severe CDC Category B AIDS-defining illness (with the exception of a single episode of bacterial sepsis or a single episode of zoster), OR history of a severe CDC Category B or C AIDS-defining illness, OR one CD4 count less than 350 cells/mm3 within 6 months prior to study entry Antiretroviral naive. A participant who previously received 6 weeks or less of post-exposure prophylaxis or short course therapy for the prevention of mother-to-child transmission are not excluded. More information on this criterion can be found in the protocol. Willing to use acceptable forms of contraception Parent or guardian willing to provide informed consent, if applicable Exclusion Criteria: Current newly diagnosed CDC Category C AIDS-defining opportunistic infection or condition requiring acute therapy at the time of study entry. More information on this criterion can be found in the protocol. Therapy with agents with significant systemic myelosuppressive, neurotoxic, pancreatotoxic, hepatotoxic, or cytotoxic potential within 30 days prior to study entry Require certain medications Current alcohol or substance abuse that, in the opinion of the investigator, may interfere with the study Uncontrolled diarrhea (more than 6 stools per day for 7 consecutive days) within 30 days prior to study entry Diagnosis of or suspected acute hepatitis within 30 days prior to study entry Signs or symptoms of bilateral peripheral neuropathy of Grade 2 or greater at screening Inability to tolerate oral medication Any other clinical condition that, in the opinion of the investigator, may interfere with the study In the first trimester of pregnancy

Ages Eligible for Study
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Minimum Age: 16 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 |
| --- | --- |
| Active Comparator: A<br>Study-specified Antiretroviral regimen under care of HIV-trained medical doctor | Behavioral: Monitoring by an HIV-trained medical doctor<br>* Participants will receive care from an HIV-trained medical doctor<br>Drug: Efavirenz<br>* 600 mg tablet taken orally daily<br>* Other names: EFV;Drug: Lamivudine<br>* 150 mg tablet taken orally daily<br>* Other names: 3TC;Drug: Lopinavir/Ritonavir<br>* 400 mg lopinavir/100mg ritonavir tablet taken orally twice daily<br>* Other names: LPV/RTV;Drug: Nevirapine<br>* 200 mg tablet taken orally for 14 days before taking a 200 mg tablet orally twice daily<br>* Other names: NVP;Drug: Stavudine<br>* Tablet taken orally daily. Dosage depends on weight.<br>* Other names: d4T;|
| Active Comparator: B<br>Study-specified Antiretroviral regimen under care of HIV-trained primary care nurse | Behavioral: Monitoring by an HIV-trained primary care nurse<br>* Participants will receive care from an HIV-trained primary care nurse<br>Drug: Efavirenz<br>* 600 mg tablet taken orally daily<br>* Other names: EFV;Drug: Lamivudine<br>* 150 mg tablet taken orally daily<br>* Other names: 3TC;Drug: Lopinavir/Ritonavir<br>* 400 mg lopinavir/100mg ritonavir tablet taken orally twice daily<br>* Other names: LPV/RTV;Drug: Nevirapine<br>* 200 mg tablet taken orally for 14 days before taking a 200 mg tablet orally twice daily<br>* Other names: NVP;Drug: Stavudine<br>* Tablet taken orally daily. Dosage depends on weight.<br>* Other names: d4T;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cumulative Treatment Failure Rate of Participants on First Line Antiretroviral Therapy Monitored by Primary Health Care Nurses (Investigative Arm)is Not Inferior to the Cumulative Treatment Failure Rate of Participants Monitored by Doctors (Control Arm). | Cumulative treatment failure is a composite endpoint made up of death, virological failure, toxicity failure and protocol-defined loss to follow-up failure. | 96 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To Compare Subject Adherence to First Line Antiretroviral Treatment as Measured by Pill Count, Between the Two Primary Health Care Monitoring Models. |  | Throughout study | 
| Drug Resistance HIV Mutations, Defined by Demonstration of Virologic Failure |  | Throughout the study | 
| To Compare the Overall Clinical Safety of Antiretroviral Therapy, as Measured by the Occurrence of Clinical and Laboratory Grade 3 and 4 Adverse Events, Between Primary Health Care Monitoring Arms. |  | Throughout study | 
| To Estimate the Total and Incremental Costs, From the Provider and Societal Perspectives, of the Two Approaches (the Primary Health Care Sister and Doctor) to the Provision of Antiretrovirals in Primary Health Care Services in Each Study Site. |  | Throughout study | 

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