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

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
CIPRA SA
ClinicalTrials.gov Identifier:
NCT00255840
First received: November 16, 2005
Last updated: June 17, 2011
Last verified: June 2011
  Purpose

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.


Condition Intervention
HIV Infections
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

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: "Safeguard the Household" - A Study of HIV Antiretroviral Therapy Treatment Strategies Appropriate for a Resource Poor Country

Resource links provided by NLM:


Further study details as provided by CIPRA SA:

Primary Outcome Measures:
  • 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). [ Time Frame: 96 weeks ] [ Designated as safety issue: Yes ]
    Cumulative treatment failure is a composite endpoint made up of death, virological failure, toxicity failure and protocol-defined loss to follow-up failure.


Secondary Outcome Measures:
  • To Compare Subject Adherence to First Line Antiretroviral Treatment as Measured by Pill Count, Between the Two Primary Health Care Monitoring Models. [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  • Drug Resistance HIV Mutations, Defined by Demonstration of Virologic Failure [ Time Frame: Throughout the study ] [ Designated as safety issue: No ]
  • 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. [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
  • 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. [ Time Frame: Throughout study ] [ Designated as safety issue: No ]

Enrollment: 812
Study Start Date: July 2006
Study Completion Date: January 2009
Primary Completion Date: January 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: A
Study-specified Antiretroviral regimen under care of HIV-trained medical doctor
Behavioral: Monitoring by an HIV-trained medical doctor
Participants will receive care from an HIV-trained medical doctor
Drug: Efavirenz
600 mg tablet taken orally daily
Other Name: EFV
Drug: Lamivudine
150 mg tablet taken orally daily
Other Name: 3TC
Drug: Lopinavir/Ritonavir
400 mg lopinavir/100mg ritonavir tablet taken orally twice daily
Other Name: LPV/RTV
Drug: Nevirapine
200 mg tablet taken orally for 14 days before taking a 200 mg tablet orally twice daily
Other Name: NVP
Drug: Stavudine
Tablet taken orally daily. Dosage depends on weight.
Other Name: d4T
Active Comparator: B
Study-specified Antiretroviral regimen under care of HIV-trained primary care nurse
Behavioral: Monitoring by an HIV-trained primary care nurse
Participants will receive care from an HIV-trained primary care nurse
Drug: Efavirenz
600 mg tablet taken orally daily
Other Name: EFV
Drug: Lamivudine
150 mg tablet taken orally daily
Other Name: 3TC
Drug: Lopinavir/Ritonavir
400 mg lopinavir/100mg ritonavir tablet taken orally twice daily
Other Name: LPV/RTV
Drug: Nevirapine
200 mg tablet taken orally for 14 days before taking a 200 mg tablet orally twice daily
Other Name: NVP
Drug: Stavudine
Tablet taken orally daily. Dosage depends on weight.
Other Name: d4T

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   16 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  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: NCT00255840

Sponsors and Collaborators
CIPRA SA
Investigators
Principal Investigator: James McIntyre, MBChB, MRCOG Perinatal HIV Research Unit, Chris Hani Baragwanath Hospital
Principal Investigator: Ian Sanne, MBChB University of the Witwatersrand, Thembaletu Clinic, Helen Joseph Hospital
Principal Investigator: Robin Wood, MBChB, FCP (SA) Department of Medicine, University of Cape Town
  More Information

Additional Information:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: James McIntyre, CIPRA SA
ClinicalTrials.gov Identifier: NCT00255840     History of Changes
Other Study ID Numbers: CIPRA-SA Project 1, U19AI053217, 3-U19-AI053217-03S1, 3-U19-AI053217-04S1, 3-U19-AI053217-04
Study First Received: November 16, 2005
Results First Received: March 2, 2011
Last Updated: June 17, 2011
Health Authority: United States: Federal Government

Keywords provided by CIPRA SA:
Treatment Naive

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
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
Ritonavir
Lopinavir
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on September 16, 2014