HIV Prevention: Digital Health Interventions to Improve Adherence to HIV Pre-Exposure Prophylaxis

The CPSTF finding is based on evidence from a systematic review of 7 studies (search period January 2000 to September 2021). Eligible studies were identified through a three-step process: CDC librarians identified eligible studies through a three-step process. First, they conducted searches and compiled a database of publications relevant to PrEP. Next, they performed queries within this database for publications relevant to digital health interventions to improve PrEP adherence. And finally, they conducted a PubMed search to identify more recent publications potentially relevant to PrEP.

The systematic review was conducted on behalf of the CPSTF by a team of specialists in systematic review methods, and in research, practice, and policy related to HIV prevention, treatment, and care.

Ending the HIV Epidemic in the United States is the operational plan developed by agencies across the U.S. Department of Health and Human Services (HHS) to pursue the goal of reducing new HIV infections by 75% by 2025 and 90% by 2030. HHS identified four key strategies to achieve these goals in the United States: diagnose people living with HIV as early as possible after infection, treat people with HIV rapidly and effectively to reach sustained viral suppression, prevent new HIV transmission through evidence-based interventions such as PrEP, and respond quickly to potential HIV outbreaks. The HIV National Strategic Plan (2021-2025) is closely aligned with, and complements, Ending the HIV Epidemic. This plan aims to integrate coordinated efforts that address the HIV epidemic among all partners and stakeholders, prevent new HIV infections, improve health outcomes of people with HIV, and reduce HIV-related disparities and health inequities.

The U.S. Preventive Services Task Force (USPSTF) recommends that clinicians offer PrEP to persons who are at higher risk of HIV acquisition (USPSTF 2019). When taken daily as prescribed, PrEP reduces the risk of getting HIV from sex by 99% and from injection drug use by at least 74% (CDC HIV). There is a strong connection between adherence to PrEP and its effectiveness in preventing HIV acquisition; reduced adherence is associated with marked declines in effectiveness (USPSTF 2019).

The systematic review included 7 studies.

Adherence:

• Interventions increased “good adherence” to PrEP (defined as taking four or more doses of PrEP per week) by a median of 10.0 percentage points or a median of 11.1% when compared with standard care (5 studies).
• Interventions increased “excellent adherence” to PrEP (defined as taking seven doses of PrEP per week) by a median of 13.6 percentage points or a median of 65.4% when compared with standard care (3 studies).
• One study found adding visualized feedback to an app increased the number of participants achieving excellent adherence but did not reduce the number of participants with “poor adherence” (defined as less than four doses per week).
• One study reported the intervention group missed fewer doses of PrEP when compared with the control group.

Retention:

• One study found the intervention improved retention in PrEP care, measured as the proportion of participants who attended all of their clinic visits.

A systematic review of economic evidence has not been conducted.

Based on results from the systematic review, the CPSTF finding should be applicable to younger gay and bisexual men and other men who have sex with men (collectively referred to as MSM) in urban U.S. settings independent of socioeconomic status, race, or ethnicity, or substance use.

CPSTF identified several areas that have limited information. Additional research and evaluation could help answer the following questions and fill remaining gaps in the evidence base. (What are evidence gaps?)

Setting:

• How effective are digital health interventions for rural areas?

Population characteristics:

• How effective are these interventions for the following populations?
  • Older adults
  • Females and transgender persons
  • People in racial or ethnic minority groups
  • People with mental health issues
  • People who engage in excessive alcohol use or drug use (including injection drug use)

Intervention characteristics:

• Does intervention effectiveness change by offering participants the following?
  • All or part of the necessary equipment, such as mobile phones or data plans
  • Materials and communications in languages other than English
  • In-person services

• Included studies were conducted in the United States (6 studies) and The Netherlands (1 study).
• Studies evaluated a digital app only (2 studies), an app plus text messaging (1 study), text messaging only (1 study), or text messaging plus email, phone, or internet communication (3 studies).
• Digital health services included medication reminders (5 studies), information and education (4 studies), adherence tracking (2 studies), support groups (2 studies), and counseling (1 study).
• Interventions communicated with participants daily (2 studies), weekly (3 studies), or monthly (1 study).
• Participants received feedback in one or more of the following ways: unidirectional communication (pre-set messages; 3 studies), automated bidirectional communication (questions were answered by pre-set messages; 3 studies), or personalized bidirectional communication (questions were answered by support person in real time; 2 studies).

Effectiveness Review

• Logic Model – Effectiveness Review [PDF (Print Only) – 134 KB]
• Text Description – Effectiveness Review [PDF – 56 KB]

When starting an effectiveness review, the systematic review team develops an analytic framework. The analytic framework illustrates how the intervention approach is thought to affect public health. It guides the search for evidence and may be used to summarize the evidence collected. The analytic framework often includes intermediate outcomes, potential effect modifiers, potential harms, and potential additional benefits.

Effectiveness Review

• Summary Evidence Table – Effectiveness Review [PDF – 218 KB]

The number of studies and publications do not always correspond (e.g., a publication may include several studies, or one study may be explained in several publications).

Effectiveness Review

Colson P, Franks J, Wu Y, et al. Adherence to pre-exposure prophylaxis in black men who have sex with men and transgender women in a community setting in Harlem, NY. AIDS and Behavior 2020;24(12):3436-55.

Fuchs JD, Stojanovski K, Vittinghoff E, et al. A mobile health strategy to support adherence to antiretroviral preexposure prophylaxis. AIDS Patient Care and STDs 2018;32(3):104-11.

Liu AY, Vittinghoff E, von Felten P, et al. Randomized controlled trial of a mobile health intervention to promote retention and adherence to preexposure prophylaxis among young people at risk for human immunodeficiency virus: The EPIC study. Clinical Infectious Diseases 2019;68(12):2010-7.

Mitchell JT, LeGrand S, Hightow-Weidman LB, et al. Smartphone-based contingency management intervention to improve pre-exposure prophylaxis adherence: pilot trial. JMIR mHealth and uHealth 2018;6(9):e10456.

Moore DJ, Jain S, Dubé MP, et al. Randomized controlled trial of daily text messages to support adherence to preexposure prophylaxis in individuals at risk for human immunodeficiency virus: the TAPIR study. Clinical Infectious Diseases 2018;66(10):1566-72.

van den Elshout MAM, Hoornenborg E, Achterbergh RCA, et al. Improving adherence to daily preexposure prophylaxis among MSM in Amsterdam by providing feedback via a mobile application. AIDS 2021;35(11):1823-34.

Whiteley L, Craker L, Haubrick KK, et al. The impact of a mobile gaming intervention to increase adherence to pre-exposure prophylaxis. AIDS and Behavior 2021;25(6):1884-9.

The Federal government has tips and resources to support the use of PrEP:

• Information on PrEP use from CDC: PrEP | HIV Basics | HIV/AIDS | CDC
• Data for HIV incidence, diagnosis, and linkage to medical care, America’s HIV Epidemic Analysis Dashboard: Homepage | AHEAD (hiv.gov)
• Resources on how to pay for PrEP: https://www.cdc.gov/stophivtogether/library/hiv-prevention-resources/fact-sheets/cdc-lsht-factsheet-paying-for-prep.pdf [PDF – 441 KB]

Effectiveness Review

Librarians from the Division of HIV Prevention established a database with all publications relevant to PrEP and performed queries within the established database for publications relevant to digital health interventions to improve PrEP adherence.

• Establishing the overall database:
  • Searches were conducted in the following databases: MEDLINE, EMBASE, PsycINFO, and CINAHL.
  • Search period was January 2000 to June 2021.
  • Search terms used were HIV infection AND PrEP.
• Searching for review specific citations: established database was searched for publications relevant to digital health interventions to improve adherence to HIV PrEP
  • Query terms were PrEP treatment adherence/compliance.
• Hand search for more recent publications:
  • A desktop search was performed using PubMed
  • Search period was conducted on 9/15/2021 with search period of January 2021 to September 2021
  • Search terms used were PrEP, adherence, dhealth, mhealth, telehealth.

Two team members independently screened each paper for all searches to determine eligibility. Uncertainties and disagreements were resolved by consensus among review team members.

Search Overview

• Establishing the overall database Time Period: 1/1/2000 – 6/29/2021
• Databases (platforms) included:
  • MEDLINE (Ovid)
  • EMBASE (Ovid)
  • PsycINFO (Ovid)
  • CINAHL (EBSCOhost)
• Hand Search: 27 journals quarterly
• Total number of unique citations: 6,155
• Hand search for more recent publications PubMed Keyword Search
  • Terms Searched: PrEP, Adherence, dhealth, mhealth, telehealth
  • Last date search 9/15/2021
  • 1 citation found

Searches Implemented

Database: MEDLINE (Ovid)

Ovid Search Syntax: / for index term, ti for title, ab for abstract, $ for truncation

HIV, AIDS or STD index terms and keywords

1. HIV infections/ OR AIDS/ OR Sexually Transmitted Diseases/ OR HIV seropositivity/ OR HIV seronegativity/ OR AIDS serodiagnosis/ OR Hepatitis C/

2. ((HIV OR (AIDS not hearing) OR Hepatitis C OR HCV OR Sexually transmitted disease$ OR Sexually transmitted infection$ OR STD OR STDs OR STI OR STIs)).ti,ab

3. 1 OR 2

Pre-exposure prophylaxis index terms and keywords

4. Pre-Exposure Prophylaxis/ OR Chemoprevention/

5. (Pre exposure prophylaxis OR Preexposure prophylaxis OR PrEP OR Chemoprophylaxis or Chemo prophylaxis OR chemoprevention).ti,ab

6. 4 OR 5

7. 3 AND 6

Database: EMBASE (OVID)

HIV, AIDS or STD index terms and keywords

1. Human Immunodeficiency Virus Infection/ OR Acquired Immune Deficiency Syndrome/ OR Sexually Transmitted Diseases/ OR Serodiagnosis/ OR Hepatitis C virus/

2. ((HIV OR (AIDS not hearing) OR Hepatitis C OR HCV OR Sexually transmitted disease$ OR Sexually transmitted infection$ OR STD OR STDs OR STI OR STIs)).ti,ab

3. 1 OR 2

Pre-exposure prophylaxis index terms and keywords

4. Pre-Exposure Prophylaxis/

5. (Pre exposure prophylaxis OR Preexposure prophylaxis OR PrEP OR Chemoprophylaxis or Chemo prophylaxis OR chemoprevention).ti,ab

6. 4 OR 5

7. 3 AND 6

8. 7 NOT (Conference Abstract or Conference Paper or Conference Proceeding or Conference Review).pt

Database: PsycINFO (Ovid)

HIV OR AIDS OR STD INDEX TERMS AND KEYWORDS

1. HIV/ OR AIDS/ OR AIDS Prevention/ OR Sexually Transmitted Diseases/ OR Hepatitis/

2. ((HIV OR (AIDS not hearing) OR Hepatitis C OR HCV OR Sexually transmitted disease$ OR Sexually transmitted infection$ OR STD OR STDs OR STI OR STIs)).ti,ab

3. 1 OR 2

Pre-exposure prophylaxis keywords (Note no index terms available)

4. (Pre exposure prophylaxis OR Preexposure prophylaxis OR PrEP OR Chemoprophylaxis or Chemo prophylaxis OR chemoprevention).ti,ab

5. 3 AND 4

Database: CINAHL (EBSCOhost)

EBSCOhost search syntax: MH for CINAHL heading, TI for title, AB for abstract, * for truncation

Pre-exposure prophylaxis index terms and keywords

1. (MH “HIV Infections”) OR (MH “Acquired Immunodeficiency Syndrome”) OR (MH “Sexually Transmitted Diseases”) OR (MH “HIV Seropositivity”) OR (MH “HIV Seronegativity”) OR (MH “AIDS Serodiagnosis”) OR (MH “Hepatitis C”)

2. TI ((HIV OR ( (AIDS not hearing) ) OR Sexually transmitted disease* OR Sexually transmitted infection* OR STD OR STDs OR STI OR STIs OR Hepatitis C OR HCV))

3. AB ((HIV OR ( (AIDS not hearing) ) OR Sexually transmitted disease* OR Sexually transmitted infection* OR STD OR STDs OR STI OR STIs OR Hepatitis C OR HCV))

4. 1 OR 2 OR 3

Pre-exposure prophylaxis index terms and keywords

5. (MH “Pre-Exposure Prophylaxis”) OR (MH “Chemoprevention”)

6. TI (Pre exposure prophylaxis OR Preexposure prophylaxis OR PrEP OR Chemoprophylaxis OR Chemo prophylaxis OR Chemoprevention)

7. AB (Pre exposure prophylaxis OR Preexposure prophylaxis OR PrEP OR Chemoprophylaxis OR Chemo prophylaxis OR Chemoprevention)

8. 5 OR 6 OR 7

9. 4 AND 8

Journals hand searched for more recent publications (27 journals)

1. AIDS
2. AIDS and Behavior
3. AIDS Care
4. AIDS Education and Prevention
5. AIDS Patient Care and STDs
6. American Journal of Public Health
7. BMC Infectious Diseases
8. BMJ Open
9. Clinical Infectious Diseases
10. Cochrane Database of Systematic Reviews
11. Current HIV/AIDS Reports
12. Current Opinion in HIV and AIDS
13. HIV Medicine
14. International Journal of STD & AIDS
15. JAIDS Journal of Acquired Immune Deficiency Syndromes
16. Journal of HIV/AIDS & Social Services
17. Journal of the Association of Nurses in AIDS Care
18. Journal of the International AIDS Society
19. Lancet HIV
20. Open Forum Infectious Diseases
21. PLoS Medicine
22. PLoS ONE
23. Public Health Reports
24. Sexual Health
25. Sexually Transmitted Diseases
26. Sexually Transmitted Infections
27. Systematic Review

The following considerations for implementation are drawn from studies included in the existing evidence review, the broader literature, and expert opinion from the CPSTF, as noted below.

• Digital interventions to improve adherence to daily-use HIV PrEP were highly accepted among study participants. Of the services offered, participants were most likely to use daily pill reminders and weekly check-ins.
• Although three studies included participants over 40 years of age, included studies recruited relatively young participants who were more likely to be comfortable with digital communication, and few reported difficulties sending and receiving messages.
• Interventions may need to be compliant with the Health Insurance Portability and Accountability Act (HIPAA). There are concerns around confidentiality when sending HIV-related text messages, and some interventions use innocuous language such as “time to take vitamin pills” to replace HIV-specific language. One study reported that their intervention was HIPAA compliant.
• Digital health interventions have technology and equipment requirements. In 2021, 85% of U.S. adults used a smartphone (Statista), 77% had high-speed broadband service at home (Pew Research Center), and 93% used the Internet (Pew Research Center), suggesting digital interventions could be widely implemented. The digital divide for smartphone ownership has diminished by race or ethnicity, but still exists for Americans with lower incomes, older adults, and people living in rural areas. It is important to consider participants’ income, age, and geographic location when implementing these interventions.
• Structural and financial barriers exist for PrEP access, including patients’ ability to get prescriptions and attend required clinic visits and testing appointments. These disparities in access lead to disparities in HIV care, morbidity, and mortality. Implementers may want to consider available ways to address some of these barriers. For example, most insurance plans and state Medicaid programs cover the cost of PrEP. The Ready, Set, PrEP program provides PrEP for free or at a reduced cost to those who qualify. Other programs include co-pay assistance programs that lower costs of PrEP medications and state PrEP assistance programs that cover costs for medication, clinical visits, and lab testing.

Healthy People 2030

Healthy People 2030 includes the following objectives related to this CPSTF recommendation.

• Reduce the number of new HIV infections — HIV‑01
• Increase knowledge of HIV status — HIV‑02
• Reduce the number of new HIV diagnoses — HIV‑03
• Increase linkage to HIV medical care — HIV‑04
• Increase viral suppression — HIV‑05