PrEP Adherence Intervention for HIV Prevention

(PRIME Trial)

Overseen By Vanessa McMahan, PhD

Age: 18+

Sex: Male

Trial Phase: Phase 4

Sponsor: San Francisco Department of Public Health

Must be taking: PrEP

Disqualifiers: PrEP >6 months, Hepatitis B, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 7

Duration: 24 weeks

140 Participants Needed

Trial Summary

What is the purpose of this trial?

In this study, "PrEP Intervention for people who Inject Substances and Use Methamphetamine" (PRIME), we propose to assess if using video directly observed therapy with real-time contingency management (VDOT-CM) may help people assigned male sex at birth who inject methamphetamine adhere to PrEP. We will randomize 140 adults who use methamphetamine, are HIV-negative, and have recently engaged in a sexual HIV risk behavior to VDOT-CM or counseling alone for 24 weeks. The study aims are to (1) determine the efficacy of VDOT-CM compared to counseling alone for PrEP adherence, (2) evaluate the acceptability of PrEP and adherence support strategies among the cohort, and (3) compare injection or chemsex and sexual HIV risk behavior before and during PrEP use. We hypothesize that participants randomized to VDOT-CM will have superior adherence to PrEP. We also hypothesize that participants will describe barriers to and facilitators of PrEP adherence, and those who are randomized to VDOT-CM will consider it an acceptable PrEP adherence support strategy. Finally, we do not expect to find increased injection, chemsex, or sexual risk behaviors for HIV among study participants after they begin taking PrEP.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify whether you need to stop taking your current medications. However, it focuses on adherence to PrEP, so you may need to continue taking PrEP if you are already on it.

What data supports the effectiveness of the treatment Integrated Next-Step Counseling, Video directly observed therapy with contingency management, VDOT-CM, Video Directly Observed Therapy with Contingency Management for HIV prevention?

Research shows that using video directly observed therapy (VDOT) and contingency management (rewards for taking medication) can help people stick to their HIV treatment plans. For example, a study found that people using a smartphone-based version of this approach submitted valid medication videos 81% of the time and showed improved adherence to their treatment. ^{1 2 3 4 5}

Is the PrEP Adherence Intervention for HIV Prevention safe for humans?

The available research does not provide specific safety data for the PrEP Adherence Intervention methods like Integrated Next-Step Counseling or Video Directly Observed Therapy with Contingency Management. However, these methods focus on improving adherence to PrEP, which is generally considered safe when taken as prescribed. ^{6 7 8 9 10}

How is the VDOT-CM treatment for PrEP adherence different from other treatments?

The VDOT-CM treatment is unique because it combines video directly observed therapy, where patients record themselves taking their medication to ensure adherence, with contingency management, which provides rewards for consistent medication use. This approach specifically targets improving adherence, a critical factor in the effectiveness of PrEP for HIV prevention, by using technology and incentives to support patients. ^{8 11 12 13 14}

Research Team

Phillip Coffin, MD, MIA

Principal Investigator

San Francisco Department of Public Health

Eligibility Criteria

This trial is for males aged 18-65 who inject substances, use methamphetamine, and are at risk of HIV. They must be HIV-negative with recent risky sexual behavior and have access to a computer. It's not for those on PrEP over 6 months or with certain health conditions like kidney issues or hepatitis B.

Inclusion Criteria

Proficient in English

Reliable access to a computer to complete study visits, if participating remotely

≥ 1 positive methamphetamine urine toxicology

Exclusion Criteria

I am not willing to use a video app to record myself taking medication.

I cannot take medications containing tenofovir or emtricitabine.

I have been taking PrEP for over 6 months.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Enrollment

Participants are randomized to receive either Integrated Next Step Counseling (iNSC) or iNSC with video directly observed therapy (VDOT) and contingency management (CM)

1 week

1 visit (in-person)

Treatment

Participants receive PrEP adherence support through iNSC or VDOT-CM for 24 weeks

24 weeks

5 visits (in-person) at weeks 6, 12, 18, and 24

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Integrated Next-Step Counseling
• Video directly observed therapy with contingency management

Trial Overview The study tests if video observed therapy with rewards (VDOT-CM) improves adherence to PrEP medication compared to counseling alone in preventing HIV. Participants will either receive VDOT-CM or just counseling for six months and their adherence and attitudes towards PrEP will be monitored.

Participant Groups

Group I: Video directly observed therapy with contingency management Experimental Treatment 2 Interventions

Video directly observed therapy with contingency management, in addition to Integrated Next-Step Counseling.

Group II: Integrated Next-Step Counseling Placebo Group 1 Intervention

Who Is Running the Clinical Trial?

San Francisco Department of Public Health

Lead Sponsor

Trials

38

Recruited

36,000+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

Findings from Research

The VITAL Start video intervention was highly acceptable among HIV-positive pregnant women, with 100% completion and 96.5% recommending it, indicating strong engagement and potential for widespread use.

Participants in the VITAL Start group showed significant improvements in HIV/ART knowledge and self-reported adherence compared to the standard of care, suggesting that video-based education can enhance treatment engagement, although it did not significantly impact retention or pill count within the one-month follow-up.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

VITAL Start: Video-Based Intervention to Inspire Treatment Adherence for Life-Pilot of a Novel Video-Based Approach to HIV Counseling for Pregnant Women Living with HIV. Kim, MH., Ahmed, S., Tembo, T., et al.[2020]

Modified directly observed therapy (mDOT) has proven effective in helping patients adhere to complex antiretroviral therapy (ART), but existing studies lack detailed guidance for implementation.

Based on insights from 10 federally funded research projects, mDOT can be tailored to various settings and populations, emphasizing the importance of flexibility in design and delivery to meet specific needs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modified directly observed therapy for antiretroviral therapy: a primer from the field. Goggin, K., Liston, RJ., Mitty, JA.[2023]

Modified directly observed therapy (MDOT) was found to be feasible and effective in improving medication adherence among 31 HIV-positive African American substance users over a 6-month period, with more participants achieving viral loads below 400 copies per milliliter.

Participants reported significant reductions in depressive symptoms and high acceptability of the MDOT intervention, with 95% enjoying the outreach visits and 100% acknowledging that MDOT helped them take their medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The feasibility of modified directly observed therapy for HIV-seropositive African American substance users. Ma, M., Brown, BR., Coleman, M., et al.[2022]

A smartphone-based intervention using contingency management showed high usability, with participants submitting 75% of required video selfies for medication adherence, and 81% of those meeting validity criteria.

The intervention demonstrated promise in promoting adherence to antiretroviral therapy among HIV+ individuals with substance use disorders, although significant effects on adherence measures were not consistently maintained after adjusting for other variables.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Smartphone-based incentives for promoting adherence to antiretroviral therapy: A randomized controlled trial. DeFulio, A., Devoto, A., Traxler, H., et al.[2021]

In a proof-of-concept study involving 5 out of 8 eligible youth living with HIV, video directly observed therapy (VDOT) showed promise in improving medication adherence, with all participants achieving virologic suppression one month after starting the intervention.

Participants reported high satisfaction with VDOT, suggesting it could be an effective method for enhancing adherence to antiretroviral therapy, although healthcare providers noted it could be burdensome at times, indicating a need for larger studies to further evaluate its effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Video directly observed therapy to improve adherence of human immunodeficiency virus infected adolescents to combination antiretroviral therapy: a proof-of-concept study. Kordy, F., Nashid, N., Khan, S., et al.[2023]

The VOICE Adherence Strengthening Program (VASP) was implemented to enhance counseling for participants in a trial of tenofovir-based PrEP, with staff reporting a preference for this new approach, suggesting it may improve counseling quality.

Despite positive feedback from staff about VASP, there were no significant changes in reported product use or drug detection among participants, indicating that the new counseling strategy did not translate into increased adherence to PrEP.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perceptions and Experiences with the VOICE Adherence Strengthening Program (VASP) in the MTN-003 Trial. van der Straten, A., Mayo, A., Brown, ER., et al.[2022]

A significant portion of participants (35%) faced challenges in accessing PrEP due to providers being unwilling to prescribe it, despite 65% starting the medication within 1-3 months of learning about it.

Urine monitoring for tenofovir (TFV) was well-accepted by participants and could serve as an effective method for objectively tracking adherence to PrEP, addressing the primary barrier of remembering to take the medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Challenges to PrEP use and perceptions of urine tenofovir adherence monitoring reported by individuals on PrEP. Hunt, T., Lalley-Chareczko, L., Daughtridge, G., et al.[2020]

A study involving 103 gay and bisexual men revealed that most participants (84.3%) used multiple strategies to maintain high adherence to HIV pre-exposure prophylaxis (PrEP), which is crucial for its effectiveness.

Participants reported an average of only 1.6 missed doses in the past 30 days, attributing their adherence to strategies like integrating PrEP into daily routines, using pillboxes, and setting smartphone reminders, suggesting that healthcare providers should recommend these strategies to improve adherence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gay and Bisexual Men's Strategies to Maintain Daily Adherence to Their HIV Pre-exposure Prophylaxis (PrEP) Medication: Results from a Qualitative Study. Grov, C., Flynn, AWP., D'Angelo, AB., et al.[2020]

In a study involving 3065 high-risk HIV-negative adults, the incidence of HIV-1 was very low at 1.1 cases per 1000 person-years, showing that both daily and on-demand PrEP are effective in preventing HIV infection.

There was no significant difference in HIV-1 incidence between those using daily PrEP and those using on-demand PrEP, indicating that on-demand PrEP is a valid alternative, providing flexibility for men who have sex with men (MSM) in their HIV prevention strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daily and on-demand HIV pre-exposure prophylaxis with emtricitabine and tenofovir disoproxil (ANRS PREVENIR): a prospective observational cohort study. Molina, JM., Ghosn, J., Assoumou, L., et al.[2022]

Real-time, objective measurement of adherence to PrEP, such as drug level monitoring through methods like dried blood spots (DBS) and urine tests, can significantly improve adherence rates and reduce the risk of HIV infection among users.

Preliminary data suggests that identifying non-adherence through biomarker testing, followed by enhanced support and counseling, leads to better adherence outcomes, highlighting the need for clinics to invest in these monitoring strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-Time Monitoring and Point-of-Care Testing: A Review of the Current Landscape of PrEP Adherence Monitoring. Hannaford, A., Arens, Y., Koenig, H.[2022]

In a study involving 1,147 HIV-uninfected participants from serodiscordant couples, high adherence to PrEP (99.1% by pill counts) was linked to a 100% efficacy in preventing HIV infections among those receiving the medication, highlighting the importance of adherence in PrEP effectiveness.

Factors such as younger age, heavy alcohol use, and sexual behavior were associated with lower adherence rates, while longer duration of PrEP use and polygamous marriage correlated with higher adherence, suggesting that targeted interventions could improve PrEP uptake.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adherence to antiretroviral prophylaxis for HIV prevention: a substudy cohort within a clinical trial of serodiscordant couples in East Africa. Haberer, JE., Baeten, JM., Campbell, J., et al.[2022]

Adherence to antiretroviral-based pre-exposure prophylaxis (PrEP) is crucial for preventing new HIV infections, and understanding how to support sustained adherence is essential for effective PrEP programs.

Key recommendations from four major PrEP trials emphasize the importance of participant-centered approaches, tailored strategies beyond just education, and addressing individual contexts to enhance adherence to PrEP.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adherence support approaches in biomedical HIV prevention trials: experiences, insights and future directions from four multisite prevention trials. Amico, KR., Mansoor, LE., Corneli, A., et al.[2023]

In a pilot study involving 61 adults interested in PrEP, those receiving strengths-based case management (SBCM) showed a higher rate of completing a provider visit (53.3%) compared to the control group (32.3%), suggesting that SBCM can effectively facilitate access to PrEP care.

Overall, 34% of participants initiated PrEP within 12 weeks, with no significant difference in the time to initiation between the SBCM and control groups, indicating that while SBCM helps with provider visits, it may not speed up the actual start of PrEP.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Randomized Study of Passive versus Active PrEP Patient Navigation for a Heterogeneous Population at Risk for HIV in South Florida. Doblecki-Lewis, S., Butts, S., Botero, V., et al.[2020]

Antiretroviral pre-exposure prophylaxis (PrEP) can help prevent HIV transmission, but its effectiveness is enhanced when combined with comprehensive support services, including risk-reduction counseling and regular HIV testing.

The authors propose a five-component framework for optimizing PrEP delivery, which includes drug provision, safety screening, behavioral interventions, long-term engagement strategies, and population-level monitoring to ensure successful implementation in clinical and community settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Packaging PrEP to Prevent HIV: An Integrated Framework to Plan for Pre-Exposure Prophylaxis Implementation in Clinical Practice. Underhill, K., Operario, D., Skeer, M., et al.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

VITAL Start: Video-Based Intervention to Inspire Treatment Adherence for Life-Pilot of a Novel Video-Based Approach to HIV Counseling for Pregnant Women Living with HIV. [2020]

2. United States pubmed.ncbi.nlm.nih.gov

Modified directly observed therapy for antiretroviral therapy: a primer from the field. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

The feasibility of modified directly observed therapy for HIV-seropositive African American substance users. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Smartphone-based incentives for promoting adherence to antiretroviral therapy: A randomized controlled trial. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Video directly observed therapy to improve adherence of human immunodeficiency virus infected adolescents to combination antiretroviral therapy: a proof-of-concept study. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Perceptions and Experiences with the VOICE Adherence Strengthening Program (VASP) in the MTN-003 Trial. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Challenges to PrEP use and perceptions of urine tenofovir adherence monitoring reported by individuals on PrEP. [2020]

8. United States pubmed.ncbi.nlm.nih.gov

Gay and Bisexual Men's Strategies to Maintain Daily Adherence to Their HIV Pre-exposure Prophylaxis (PrEP) Medication: Results from a Qualitative Study. [2020]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Daily and on-demand HIV pre-exposure prophylaxis with emtricitabine and tenofovir disoproxil (ANRS PREVENIR): a prospective observational cohort study. [2022]

10. New Zealand pubmed.ncbi.nlm.nih.gov

Real-Time Monitoring and Point-of-Care Testing: A Review of the Current Landscape of PrEP Adherence Monitoring. [2022]

11. United States pubmed.ncbi.nlm.nih.gov

Adherence to antiretroviral prophylaxis for HIV prevention: a substudy cohort within a clinical trial of serodiscordant couples in East Africa. [2022]

12. United States pubmed.ncbi.nlm.nih.gov

Adherence support approaches in biomedical HIV prevention trials: experiences, insights and future directions from four multisite prevention trials. [2023]

13. United States pubmed.ncbi.nlm.nih.gov

A Randomized Study of Passive versus Active PrEP Patient Navigation for a Heterogeneous Population at Risk for HIV in South Florida. [2020]

14. United States pubmed.ncbi.nlm.nih.gov

Packaging PrEP to Prevent HIV: An Integrated Framework to Plan for Pre-Exposure Prophylaxis Implementation in Clinical Practice. [2022]