HIV Infections
Conditions
Keywords
Treatment Naive
Brief summary
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
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.
Interventions
BEHAVIORALMonitoring by an HIV-trained medical doctor
Participants will receive care from an HIV-trained medical doctor
BEHAVIORALMonitoring by an HIV-trained primary care nurse
Participants will receive care from an HIV-trained primary care nurse
DRUGEfavirenz
600 mg tablet taken orally daily
DRUGLamivudine
150 mg tablet taken orally daily
DRUGLopinavir/Ritonavir
400 mg lopinavir/100mg ritonavir tablet taken orally twice daily
DRUGNevirapine
200 mg tablet taken orally for 14 days before taking a 200 mg tablet orally twice daily
DRUGStavudine
Tablet taken orally daily. Dosage depends on weight.
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
CIPRA SA
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
16 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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). | 96 weeks | Cumulative treatment failure is a composite endpoint made up of death, virological failure, toxicity failure and protocol-defined loss to follow-up failure. |
Secondary
| Measure | Time frame |
|---|---|
| Drug Resistance HIV Mutations, Defined by Demonstration of Virologic Failure | Throughout the study |
| To Compare Subject Adherence to First Line Antiretroviral Treatment as Measured by Pill Count, Between the Two Primary Health Care Monitoring Models. | Throughout 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 |
Participant flow
Recruitment details
HIV-positive adult participants were recruited from February 2005 to December 2007 from two primary health care clinics, one in Masiphumelele, Cape Town and the other in Soweto, Johannesburg.
Participants by arm
| Arm | Count |
|---|---|
| Antiretroviral Therapy Monitored by Medical Officer First line antiretroviral regimen monitored by a HIV-trained medical doctor:
1. Stavudine (\>60 kg: 40 mg twice daily and \<60 kg: 30 mg twice daily)
2. Lamivudine (150mg twice daily) and
3. Efavirenz (600mg daily). For women of child bearing potential with a CD4+ count \<250 cells/mm3, Nevirapine (200 mg daily x 14 days, then 200 mg twice daily) and for women with a CD4+ count \> 250 cells/mm3, Lopinavir/ritonavir (400/100mg twice daily). | 408 |
| Antiretroviral Therapy Managed by Primary Health Care Nurse First line antiretroviral regimen monitored by HIV-trained primary health care nurse:
1. Stavudine (\>60 kg: 40 mg twice daily and \<60 kg: 30 mg twice daily)
2. Lamivudine (150mg twice daily) and
3. Efavirenz (600mg daily). For women of child bearing potential with a CD4+ count \<250 cells/mm3, Nevirapine (200 mg daily x 14 days, then 200 mg twice daily) and for women with a CD4+ count \> 250 cells/mm3, Lopinavir/ritonavir (400/100mg twice daily). | 404 |
| Total | 812 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Discontinued intervention | 53 | 56 |
| Overall Study | Lost to Follow-up | 10 | 14 |
Baseline characteristics
| Characteristic | Total | Antiretroviral Therapy Monitored by Medical Officer | Antiretroviral Therapy Managed by Primary Health Care Nurse |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 812 Participants | 408 Participants | 404 Participants |
| Age Continuous | 33.12 years STANDARD_DEVIATION 7.29 | 33.2612388 years STANDARD_DEVIATION 7.1934154 | 32.9739630 years STANDARD_DEVIATION 7.3921786 |
| Region of Enrollment South Africa | 812 participants | 408 participants | 404 participants |
| Sex: Female, Male Female | 573 Participants | 276 Participants | 297 Participants |
| Sex: Female, Male Male | 239 Participants | 132 Participants | 107 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 194 / 408 | 119 / 404 |
| serious Total, serious adverse events | 126 / 408 | 153 / 404 |
Outcome results
Primary
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.
Time frame: 96 weeks
Population: The primary analysis was an intention-to-treat analysis of any treatment failure with use of Cox proportional hazards regression.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Antiretroviral Therapy Monitored by Medical Officer | 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). | 44 Percentage of participants |
| Antiretroviral Therapy Managed by Primary Health Care Nurse | 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). | 48 Percentage of participants |
Secondary
Drug Resistance HIV Mutations, Defined by Demonstration of Virologic Failure
Time frame: Throughout the study
Secondary
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
Secondary
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
Secondary
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