HIV Infections
Conditions
Keywords
Directly Observed Therapy, DOT
Brief summary
Three or more anti-HIV drugs are taken in combination as part of a treatment regimen. These drug regimens must be closely followed in order to be successful. Having a support person watch a patient take his or her anti-HIV drugs each day may help a patient follow his or her regimen. This study will see if patient-chosen treatment supporters help patients take HIV medicines correctly and improve their health. Study hypothesis: The mean change in CD4 count at 12 and 24 months will be significantly higher in the directly observed therapy-highly active antiretroviral therapy (DOT-HAART) arm as compared to the self-administered arm.
Detailed description
South Africa has one of the worst and fastest growing HIV epidemics in the world. Highly active antiretroviral therapy (HAART) has been shown both at the individual and public health levels to reduce morbidity, mortality, and vertical and possibly horizontal HIV transmission. However, expenses, feasibility, long-term adherence, and effective delivery of HAART remain formidable barriers, particularly in developing nations. Recently, international initiatives have provided hope for widespread use of HAART at affordable cost in sub-Saharan Africa. Simplified, once-daily HAART regimens with directly observed therapy (DOT) may help to achieve high levels of treatment adherence, a key component for long-term viral suppression and treatment success. Peer advocates have been used to improve adherence with medical therapies in a variety of settings. This study will evaluate the effectiveness and feasibility of DOT using patient-nominated peer supervisors to improve adherence to HAART in HIV infected adults in South Africa. Participants will be randomly assigned to either Peer-DOT-HAART or self-administration of a once-daily combination of the Western Cape Province ART program medications for 24 months. Study measures will include CD4 cell count and HIV viral load, adherence questionnaires, genotypic HAART resistance testing, and incidence of new or recurrent opportunistic infections.
Interventions
BEHAVIORALDirectly Observed Therapy
Use of a patient nominated peer supporter who will observe the morning dose of ARVs
Sponsors
University of Cape Town
Johns Hopkins University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* HIV infected * Viral load greater than 1000 copies/ml * CD4 count of 200 cells/mm3 or less, or World Health Organization Stage 4 disease * Living in the area of the study site * Had a known address for more than 3 months * Willing to nominate a treatment supervisor (a close family member, sexual partner, friend, or community volunteer) to observe daily ingestion of tablets * Willing to disclose HIV status to a treatment supervisor and ready to commit to long-term antiretroviral therapy * Acceptable methods of contraception
Exclusion criteria
* Pregnant
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Impact of DOT Compared to Self-administered Treatment as Measured by HIV Viral Load at 12 Months of Treatment | at 12 and 24 months of treatment | Proportion of Patients with HIV RNA Levels of \<400 at 12 Months - Intention-to-treat |
| Impact of DOT Compared to Self-administered Treatment as Measured by HIV Viral Load at 24 Months of Treatment | 24 months | Proportion of Patients with HIV RNA Levels of \<400 Copies/mL at 24 Months \[Intention-to-treat (ITT) |
| Immunological Response: Median CD4 (IQR) Cell Count Increase From Baseline at 12 Months by Study Arm | 12 months | — |
| Immunological Response: Median CD4 (IQR) Cell Count Increase From Baseline at 24 Months by Study Arm | 24 months | — |
Countries
South Africa
Participant flow
Recruitment details
The study site was a public sector ART clinic at the GF Jooste Hospital, a secondary level facility in Cape Town, Western Cape province of South Africa, serving several peri-urban townships. Enrollment began February 13, 2005, and ended on July 7, 2007, with the last follow-up occurring on July 25, 2008.
Participants by arm
| Arm | Count |
|---|---|
| Peer Supporter Use of a patient nominated peer supporter who sill observe the morning dose of ARVs | 137 |
| Self Administration Self administration of ARVs | 137 |
| Total | 274 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 9 | 20 |
| Overall Study | Early study Closure | 32 | 32 |
| Overall Study | Lost to Follow-up | 9 | 9 |
| Overall Study | Withdrawal by Subject | 10 | 8 |
Baseline characteristics
| Characteristic | Self Administration | Peer Supporter | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 3 Participants | 4 Participants |
| Age, Categorical Between 18 and 65 years | 136 Participants | 134 Participants | 270 Participants |
| Age, Continuous | 36.7 years STANDARD_DEVIATION 9.2 | 35.7 years STANDARD_DEVIATION 9.7 | 36.2 years STANDARD_DEVIATION 9.1 |
| Region of Enrollment South Africa | 137 participants | 137 participants | 274 participants |
| Sex: Female, Male Female | 79 Participants | 79 Participants | 158 Participants |
| Sex: Female, Male Male | 58 Participants | 58 Participants | 116 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 71 / 137 | 89 / 137 |
| serious Total, serious adverse events | 19 / 137 | 29 / 137 |
Outcome results
Primary
Immunological Response: Median CD4 (IQR) Cell Count Increase From Baseline at 12 Months by Study Arm
Time frame: 12 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Peer Supporter | Immunological Response: Median CD4 (IQR) Cell Count Increase From Baseline at 12 Months by Study Arm | 185 cells/uL |
| Self Administration | Immunological Response: Median CD4 (IQR) Cell Count Increase From Baseline at 12 Months by Study Arm | 160 cells/uL |
Comparison: Unadjusted endpoint analyses were conducted on an intention-to-treat basis using all patients enrolled to compare outcomes in the DOT vs. Self-ART arm. For viral load analyses, missing values were considered detectable (missing¼failure analysis). As-treated analyses were also conducted using patients remaining in the study with available data.Crosssectional comparisons between study groups were conducted using two sample t-test,Wilcoxon rank-sum test,chi-squared orFisher's exact and Kaplan-Meierp-value: 0.14Wilcoxon (Mann-Whitney)
Primary
Immunological Response: Median CD4 (IQR) Cell Count Increase From Baseline at 24 Months by Study Arm
Time frame: 24 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Peer Supporter | Immunological Response: Median CD4 (IQR) Cell Count Increase From Baseline at 24 Months by Study Arm | 281 cells/uL |
| Self Administration | Immunological Response: Median CD4 (IQR) Cell Count Increase From Baseline at 24 Months by Study Arm | 262 cells/uL |
Comparison: Unadjusted endpoint analyses were conducted on an intention-to-treat basis using all patients enrolled to compare outcomes in the DOT vs. Self-ART arm. For viral load analyses, missing values were considered detectable (missing¼failure analysis). As-treated analyses were also conducted using patients remaining in the study with available data.Crosssectional comparisons between study groups were conducted using two sample t-test,Wilcoxon rank-sum test,chi-squared orFisher's exact and Kaplan-Meierp-value: 0.61Wilcoxon (Mann-Whitney)
Primary
Impact of DOT Compared to Self-administered Treatment as Measured by HIV Viral Load at 12 Months of Treatment
Proportion of Patients with HIV RNA Levels of \<400 at 12 Months - Intention-to-treat
Time frame: at 12 and 24 months of treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Peer Supporter | Impact of DOT Compared to Self-administered Treatment as Measured by HIV Viral Load at 12 Months of Treatment | 99 participants |
| Self Administration | Impact of DOT Compared to Self-administered Treatment as Measured by HIV Viral Load at 12 Months of Treatment | 93 participants |
Comparison: Unadjusted endpoint analyses were conducted on an intention-to-treat basis using all patients enrolled to compare outcomes in the DOT vs. Self-ART arm. For viral load analyses, missing values were considered detectable (missing¼failure analysis). As-treated analyses were also conducted using patients remaining in the study with available data.Crosssectional comparisons between study groups were conducted using two sample t-test,Wilcoxon rank-sum test,chi-squared orFisher's exact and Kaplan-Meierp-value: 0.42Chi-squared
Primary
Impact of DOT Compared to Self-administered Treatment as Measured by HIV Viral Load at 24 Months of Treatment
Proportion of Patients with HIV RNA Levels of \<400 Copies/mL at 24 Months \[Intention-to-treat (ITT)
Time frame: 24 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Peer Supporter | Impact of DOT Compared to Self-administered Treatment as Measured by HIV Viral Load at 24 Months of Treatment | 63 participants |
| Self Administration | Impact of DOT Compared to Self-administered Treatment as Measured by HIV Viral Load at 24 Months of Treatment | 62 participants |
Comparison: Unadjusted endpoint analyses were conducted on an intention-to-treat basis using all patients enrolled to compare outcomes in the DOT vs. Self-ART arm. For viral load analyses, missing values were considered detectable (missing¼failure analysis). As-treated analyses were also conducted using patients remaining in the study with available data.Crosssectional comparisons between study groups were conducted using two sample t-test,Wilcoxon rank-sum test,chi-squared orFisher's exact and Kaplan-Meierp-value: 0.89Chi-squared