HIV Infections, Substance Use Disorders
Conditions
Brief summary
The fastest growing HIV epidemics globally are driven by injection drug use, but only a small percentage of HIV-positive people who inject drugs (PWID) have achieved viral suppression. The proposed project will adapt a couple-based antiretroviral therapy (ART) adherence intervention for PWID and assess the feasibility and acceptability of conducting dried blood spot testing to objectively measure ART adherence as part of an intervention in a clinical setting. This project advances HIV intervention science by providing an intervention that leverages social support within the dyad to improve ART adherence among PWID, which could lead to increased viral suppression, thus decreasing HIV transmission and HIV-related morbidity and mortality.
Detailed description
The purpose of this Mentored Research Scientist Development Award (K01) is to provide the candidate with the training and expertise needed to transition to research independence in the science of HIV prevention and intervention. The fastest growing HIV epidemics globally are driven by injection drug use. Central Asia has some of the highest rates of injection drug use and one of the fastest growing HIV epidemics in the world. HIV-positive people who inject drugs (PWID) face many barriers to antiretroviral therapy (ART) adherence, such as misperceptions about ART, stigma and substance use. Previous research among this population has shown that couple-based HIV interventions are highly efficacious at reducing risk behaviors, but there is currently no couple-based ART adherence intervention for PWID. The research aims of this proposal are to 1) identify core components of the SMART Couples intervention and other existing ART adherence intervention strategies and assess their appropriateness and feasibility as an integrated, couple-based ART adherence intervention for HIV+ PWID living in Kazakhstan (Phase 1); 2) adapt and refine SMART Couples and identify augmentative intervention strategies to create an integrated, couple-based ART adherence intervention for HIV+ PWID and their primary sex partners using results from Aim 1 (Phase 2); and 3a) pilot test the resulting couple-based intervention among 66 heterosexual PWID couples in Kazakhstan through a randomized control trial to assess the safety, feasibility, and acceptability of the intervention and obtain preliminary estimates of adherence outcomes in the intervention arm versus standard of care; and 3b) assess the feasibility and acceptability of conducting dried blood spot testing as part of an adherence intervention in a clinical setting (Phase 3). The proposed career development plan has been designed to augment the candidate's current training in epidemiology and enable her to 1) gain research skills in the design and adaptation of HIV interventions, with an emphasis on adherence among marginalized populations; 2) obtain methodological expertise in dyad and intensive longitudinal analysis and the triangulation of behavioral, biomedical, and technological data, particularly for the purposes of interpreting and analyzing these types of data to assess intervention efficacy and measure ART adherence; 3) acquire training in the conduct and analysis of qualitative in-depth interviews and focus groups, particularly for designing and adapting HIV interventions and assessing intervention feasibility and acceptability; and 4) increase professional skills for a successful independent research career. These training goals will be achieved through a combination of didactic courses, specialized workshops and seminars, hands-on research, and an interdisciplinary team of experts. The research findings and methodological skills to be gained from this K01 have wide applicability for disease research and high transferability across diverse research settings.
Interventions
The intervention will consist of 4 sessions with activities designed to strengthen communication and support within the couple to improve adherence to antiretroviral therapy and increase linkage to drug treatment services. The activities are based on cognitive-behavioral therapy. Participants' adherence will be monitored continuously through electronic monitoring devices and surveys completed at baseline and follow-up periods.
Standard of Care consists of an appointment with an AIDS Center nurse at baseline and two months later. Under current Standard of Care in Almaty, no behavioral intervention is provided. Participants obtain prescription refills and give blood for viral load and CD4 tests once every 6 months.
Sponsors
Study design
Eligibility
Inclusion criteria
Participant inclusion criteria for Phase 3: 66 couples (n=132) will participate in a randomized control trial of the adapted couple-based intervention. Couples are eligible to participate if: 1. both partners are ≥18 years old, 2. both identify each other as their primary sexual partner (e.g. spouse, girlfriend/boyfriend, regular sexual partner), 3. the relationship has existed at least 3 months, 4. both report feeling safe participating with their partner in the study, 5. neither reports any severe physical or sexual violence perpetrated by the other partner in the past year, 6. both are able to provide informed consent and follow study procedures, and 7. both are fluent in Russian. In addition, the index case (partner initially recruited from AIDS Center) must: (1) be confirmed HIV+ by the AIDS Center, (2) have been on ART at least 3 months, (3) not be virally suppressed according to the AIDS Center standard (\<500 copies/ml), and (4) report injecting any drug in the past year. Participant
Exclusion criteria
for Phase 3: Individuals who do not meet inclusion criteria or who meet any of the following criteria will be excluded from the study: 1. unable to provide informed consent, 2. unwilling or unable to participate in study procedures, 3. any condition that, in the opinion of the principal investigator and research staff, would make participation in the study unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving the study objectives.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adherence Rate to Antiretroviral Therapy | Day 1 to Day 180 (daily) | Adherence rate is defined as the number of days the electronic pill bottle was opened to take medication (out of a total of 180 days). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Stratified by Viral Load Suppression | 6 month follow-up | HIV viral load suppression was considered at ≤500 copies/ml in accordance with the Almaty AIDS Center testing standard. Participants were classified as virally suppressed or not based on their most recent viral load test result (at baseline and at the 6 month follow-up) obtained from electronic medical records at the AIDS Center. |
| Medication Adherence Rate (Self-Report Score) | 6 month follow-up | Self-reported; 3 item scale (Self-Report Measure for Medication Adherence by Wilson et al., AIDS & Behavior, 2016) asking participants how well they took their medication in the past 30 days (average score on a 0-100 scale). 0 = low adherence and 100 = high adherence. |
| Number of Subjects That Had Access to Substance Use Treatment | 6 month follow-up | Self-reported; participants reported if they were currently receiving methadone or opioid substitution therapy |
Countries
Kazakhstan
Participant flow
Recruitment details
Participants were recruited from the Almaty City AIDS Center from October 2020 to March 2023.
Pre-assignment details
Participants were randomized as a dyad to the intervention or standard of care arm. Numbers reported represent individual participants (not dyads).
Participants by arm
| Arm | Count |
|---|---|
| Intervention Subjects will receive an intervention based off of current evidence-based practices that will consist of activities designed to strengthen support within the couple to improve adherence to antiretroviral therapy.
SMART Couples 2: The intervention will consist of 3 sessions with activities designed to strengthen communication and support within the couple to improve adherence to antiretroviral therapy and increase linkage to drug treatment services. The activities are based on cognitive-behavioral therapy. Participants' adherence will be monitored continuously through electronic monitoring devices and surveys completed at baseline and follow-up periods. | 64 |
| Standard of Care Standard of Care is the comparison arm that consists of care currently provided at the AIDS Center. Subjects will receive a consultation with a healthcare provider every three months, prescription refills, and blood draws for viral load and CD4 testing.
Standard of Care: Standard of Care consists of an appointment with an AIDS Center nurse at baseline and two months later. Under current Standard of Care in Almaty, no behavioral intervention is provided. Participants obtain prescription refills and give blood for viral load and CD4 tests once every 6 months. | 68 |
| Total | 132 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 3 | 1 |
| Overall Study | Lost to Follow-up | 0 | 2 |
Baseline characteristics
| Characteristic | Standard of Care | Total | Intervention |
|---|---|---|---|
| Age, Continuous | 43.97 Years STANDARD_DEVIATION 9.59 | 45.01 Years STANDARD_DEVIATION 10.36 | 46.11 Years STANDARD_DEVIATION 11.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 68 Participants | 132 Participants | 64 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| HIV status HIV-negative | 18 Participants | 37 Participants | 19 Participants |
| HIV status HIV-positive | 50 Participants | 95 Participants | 45 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 23 Participants | 39 Participants | 16 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 45 Participants | 93 Participants | 48 Participants |
| Region of Enrollment Kazakhstan | 68 participants | 132 participants | 64 participants |
| Sex: Female, Male Female | 31 Participants | 59 Participants | 28 Participants |
| Sex: Female, Male Male | 37 Participants | 73 Participants | 36 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 3 / 64 | 1 / 68 |
| other Total, other adverse events | 3 / 64 | 0 / 68 |
| serious Total, serious adverse events | 4 / 64 | 3 / 68 |
Outcome results
Adherence Rate to Antiretroviral Therapy
Adherence rate is defined as the number of days the electronic pill bottle was opened to take medication (out of a total of 180 days).
Time frame: Day 1 to Day 180 (daily)
Population: Participants analyzed included only those who were HIV-positive and who used the electronic monitoring device: 35 out of 64 in the intervention arm and 45 out of 68 in the standard of care arm. Not all participants were able to collect evaluable data using the device since there were no in-person study visits during the pandemic to help with troubleshooting.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention | Adherence Rate to Antiretroviral Therapy | 10.49 Days | Standard Deviation 11.21 |
| Standard of Care | Adherence Rate to Antiretroviral Therapy | 14.02 Days | Standard Deviation 27.97 |
Medication Adherence Rate (Self-Report Score)
Self-reported; 3 item scale (Self-Report Measure for Medication Adherence by Wilson et al., AIDS & Behavior, 2016) asking participants how well they took their medication in the past 30 days (average score on a 0-100 scale). 0 = low adherence and 100 = high adherence.
Time frame: 6 month follow-up
Population: Only HIV-positive participants had outcome data in the analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Intervention | Medication Adherence Rate (Self-Report Score) | Baseline | 69.29 units on a scale | Standard Error 2.52 |
| Intervention | Medication Adherence Rate (Self-Report Score) | 6-month follow-up | 86.73 units on a scale | Standard Error 2.56 |
| Standard of Care | Medication Adherence Rate (Self-Report Score) | Baseline | 68.33 units on a scale | Standard Error 2.2 |
| Standard of Care | Medication Adherence Rate (Self-Report Score) | 6-month follow-up | 76.23 units on a scale | Standard Error 2.37 |
Number of Participants Stratified by Viral Load Suppression
HIV viral load suppression was considered at ≤500 copies/ml in accordance with the Almaty AIDS Center testing standard. Participants were classified as virally suppressed or not based on their most recent viral load test result (at baseline and at the 6 month follow-up) obtained from electronic medical records at the AIDS Center.
Time frame: 6 month follow-up
Population: Participants who had viral load testing data from the AIDS Center.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Intervention | Number of Participants Stratified by Viral Load Suppression | Detectable viral load (>500 copies/ml) at baseline decreased to virally suppressed at 6 months | 14 Participants |
| Intervention | Number of Participants Stratified by Viral Load Suppression | Viral load remained detectable (>500 copies/ml) at baseline and 6 months | 12 Participants |
| Intervention | Number of Participants Stratified by Viral Load Suppression | Viral load remained suppressed (≤500 copies/ml) at baseline and 6 months | 14 Participants |
| Standard of Care | Number of Participants Stratified by Viral Load Suppression | Detectable viral load (>500 copies/ml) at baseline decreased to virally suppressed at 6 months | 11 Participants |
| Standard of Care | Number of Participants Stratified by Viral Load Suppression | Viral load remained detectable (>500 copies/ml) at baseline and 6 months | 11 Participants |
| Standard of Care | Number of Participants Stratified by Viral Load Suppression | Viral load remained suppressed (≤500 copies/ml) at baseline and 6 months | 18 Participants |
Number of Subjects That Had Access to Substance Use Treatment
Self-reported; participants reported if they were currently receiving methadone or opioid substitution therapy
Time frame: 6 month follow-up
Population: Only participants who reported ever injecting drugs who completed the 6-month follow-up survey: 42 out of 64 in the intervention arm and 49 out of 68 in the standard of care arm.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Intervention | Number of Subjects That Had Access to Substance Use Treatment | 1 Participants |
| Standard of Care | Number of Subjects That Had Access to Substance Use Treatment | 3 Participants |