The purpose of this study is to determine the effectiveness of several anti-HIV treatment strategies in resource-poor South African communities. These strategies include using specially trained doctors or nurses to administer therapy, providing patients with a support group and adherence counseling, and having community members observe patients taking their medications.

Condition

Intervention

HIV Infections

Behavior: Monitoring by an HIV-trained medical doctor  Behavior: Monitoring by an HIV-trained primary care nurse  Behavior: Monitoring by a clinic-based treatment support group plus adherence counseling  Behavior: Monitoring by trained community member plus directly observed therapy (DOT)  Drug: Didanosine  Drug: Efavirenz  Drug: Lamivudine  Drug: Lopinavir/ritonavir  Drug: Nevirapine  Drug: Stavudine

Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcomes: Cumulative virologic failure, defined by viral load decline of less than 1.5 log after 12 weeks of treatment or 2 viral load measures of greater than 1000 copies/ml on 2 consecutive occasions more than 4 weeks apart after 24 weeks of treatment; cumulative treatment failure, defined as a composite endpoint consisting of virologic failure, toxicity failure, withdrawn consent, defaulting clinic schedule, loss to follow-up, disease progression, and death; adherence, defined by pills or measured drug solution not taken by participant; drug resistance HIV mutations, defined by demonstration of virologic failure; HIV disease progression or death, defined as a composite endpoint consisting of progression to a new CDC Category C (AIDS-defining) illness after 12 weeks of treatment or death
Expected Total Enrollment:  1340

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, is 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. The first phase of 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. The second phase of this study will evaluate the effectiveness of ART with the support of a clinic-based treatment support group and adherence counseling, compared to ART with a trained community member and directly observed therapy (DOT). Participants in this study will be recruited from resource-poor communities outside Johannesburg and Cape Town, South Africa.

This study will last 5 years and consists of 2 phases. HIV infected people 16 years of age and older and other HIV infected members of their household (including children) will be enrolled in Phase 1. Study participants in Phase 1 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. Phase 1 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 will enter Phase 2 of the study if their Phase 1 treatment fails. Adults and children who are not receiving treatment for active tuberculosis (TB) will receive didanosine (ddI) daily, LPV/r twice daily, and zidovudine (ZDV) twice daily. Women of childbearing potential whose LPV/r-containing Phase 1 regimen failed will receive EFV daily, ddI daily, and ZDV twice daily. Women of childbearing potential whose LPV/r-containing Phase 1 regimen failed and who are unwilling to use acceptable forms of contraception will receive ddI daily; NVP daily for 2 weeks, then twice daily; and ZDV twice daily. Children who received LPV/r as part of first-line ART in Phase 1 will not be eligible to enter Phase 2. Phase 2 participants will be randomly assigned to one of two arms. Arm 1 will receive ART with the support of a clinic-based treatment support group and adherence counseling. Arm 2 will receive ART with the support of a trained community member and DOT; Arm 2 participants will be observed taking their medications at least one dose daily, five days a week, either at home or at their place of work.

Study visits for Phase 1 will occur at study entry, Weeks 2, 4, 8, and 12, and every 12 weeks thereafter. A physical exam, measurement of height and weight, 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 16 years old and older in Phase 2 will occur at phase entry, Weeks 2 and 4 of Phase 2, every 4 weeks until Week 48 of Phase 2, 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. Participants in the DOT arm will have a home visit with a DOT counselor at Week 2 of Phase 2. Phase 2 pediatric participants aged 3 to 16 years of age will have study visits at phase entry and every 12 weeks thereafter. A complete physical exam, measurement of height and weight, TB infection screening, blood collection, pill counts, and compliance/adherence and resource utilization counseling will occur at all visits.

Ages Eligible for Study:  3 Years and above,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria for Adult Participants in Phase 1:

• 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
• ART 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

Inclusion Criteria for Pediatric Participants in Phase 1:

• HIV-1 infected
• Member of household of the randomized adult participant
• 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 percentage less than 20% within 6 months prior to study entry
• ART 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.
• Parent or guardian willing to provide informed consent
• Have primary caregiver willing and able to administer ART

Exclusion Criteria for All Participants of Phase 1:

• 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 seven 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

Please refer to this study by ClinicalTrials.gov identifier  NCT00255840

Study chairs or principal investigators

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

Study ID Numbers:  CIPRA-ZA Project 1; CIPRA; Project 1; 3-U19-AI053217-03S1; 3-U19-AI053217-04S1; 3-U19-AI053217-04
Last Updated:  December 8, 2005
Record first received:  November 16, 2005
ClinicalTrials.gov Identifier:  NCT00255840
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2006-01-10