Public Health Implications of Adapting HIV Pre-exposure Prophylaxis Programs for Virtual Service Delivery in the Context of the COVID-19 Pandemic: Systematic Review

Introduction

The novel coronavirus disease COVID-19 caused by SARS-CoV-2 threatens to disrupt global progress toward HIV elimination [1]. In response to the COVID-19 pandemic, many countries have employed nonpharmacologic interventions such as lockdowns, social distancing, and restrictions on gatherings to control the spread of SARS-CoV-2. However, other countries with a high burden of COVID-19 have not successfully and universally instituted these mitigation measures at a national level [2]. Countries with limited uptake of mitigation measures are seeing their health care infrastructure overwhelmed with the pandemic due to widespread community transmission, and are thus struggling to provide comprehensive clinical care for COVID-19 and for chronic diseases, including HIV [1,2]. Recent gains in HIV epidemic control may be lost if HIV prevention and treatment services are not maintained. Additionally, the morbidity and mortality of COVID-19 might be increased in the face of uncontrolled chronic diseases and HIV, although there have been conflicting reports among persons living with HIV [3,4].

COVID-19 and HIV both disproportionally affect socially disadvantaged and hard-to-reach populations [4]. Opportunities exist to leverage ongoing public health responses to mitigate the impacts of COVID-19 on HIV services, and novel approaches to care provision might help address both epidemics. For example, the US Ending the HIV Epidemic (EHE) initiative aims to overcome existing social and economic disparities by increasing access to HIV services for vulnerable populations in the United States [5]. In this regard, the aims of EHE to increase services for vulnerable populations align with approaches for controlling the COVID-19 pandemic, which has also exacerbated health inequities [6]. Globally, the public and private sectors have collaborated for years to address the HIV crisis using a public health approach. This has resulted in platforms for service delivery, a health workforce trained in HIV care and treatment, supply chains, and collaboration across a diverse group of stakeholders, including community leaders and governments, to ensure that marginalized populations receive the services they need. Efforts should be made to identify best practices and lessons learned from HIV prevention to lessen the impacts of COVID-19 on HIV programs [7]. The HIV community can sustain progress toward HIV epidemic control by rapidly employing innovations to maintain and extend HIV programming during the COVID-19 pandemic [8]. Additionally, COVID-19–specific education, testing, and vaccination could be integrated into HIV prevention programs, considering that these service delivery platforms are designed to reach vulnerable persons at risk of HIV and the general population.

To ensure that HIV prevention programs are improved to deliver services in the context of limited mobility and strained health systems, we reviewed the literature for adaptations of pre-exposure prophylaxis (PrEP) programs for HIV prevention both prior to and in the time of COVID-19. PrEP is vital to achieving HIV epidemic control and should be prioritized in the context of COVID-19 along with HIV treatment. We describe technological innovations for HIV prevention and PrEP service delivery, and propose a model for virtual PrEP service delivery to ensure HIV prevention interventions reach those most vulnerable during the implementation of COVID-19 mitigation measures.

Methods

Literature Search and Review

We performed a review of the literature to identify published peer-reviewed articles about virtual service delivery and related adaptations such as telemedicine (see Multimedia Appendix 1 for the detailed search strategy). PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) was used as a guide for this systematic review [9]. We searched the OVID/Medline, Scopus, Cochrane Library, CINAHL, PsycINFO, and Embase databases to identify human studies published between January 1, 2010, and October 26, 2021, to reflect the time period during which innovative technologies for health were introduced. Search terms included “telemedicine,” “telehealth,” “mobile health,” “eHealth,” “mHealth,” “telecommunication,” “social media,” “mobile device,” and “internet,” among others (see Multimedia Appendix 1). The search was limited to articles published in English. We used EndNote X8 (Clarivate Analytics) to compile, clean, categorize, and assess citations. We assessed for risk of bias in a randomized controlled trial (RCT) using the Cochrane risk of bias tool [10].

Ethics Considerations

This activity was reviewed by the US Centers for Disease Control and Prevention (CDC), and was conducted in compliance with applicable federal law and CDC policy. The activity was determined to meet the requirements of nonresearch and secondary data analysis for a public health response, as defined in 45 CFR 46.102(l). Thus, a protocol was not developed and registered.

Study Selection

Two authors (PP and MK) screened the titles and abstracts of articles identified from our database search for references to HIV, PrEP, and virtual service delivery using filters in EndNote. Next, the same two authors (PP and MK) reviewed the selected articles’ titles and abstracts to identify those reporting effective adaptations for virtual HIV service delivery, particularly related to PrEP, HIV prevention, and HIV testing, by reporting outcomes related to efficacy, feasibility, and/or acceptability. The full text of articles reporting relevant data and systematic reviews of virtual service delivery interventions were further reviewed. All systematic reviews about innovations of virtual HIV service delivery that focused on adherence and HIV testing were included because both have relevance to PrEP programs.

Studies of interventions were included if they focused on innovations for HIV prevention service delivery, particularly PrEP. We thus included intervention studies that described the use of technology such as apps, use of the internet, SMS text messaging, telemedicine/telehealth, mobile health (mHealth), and eHealth for PrEP. We also included all reviews and meta-analyses of technology innovations pertinent to HIV prevention service delivery, as these data would inform the virtual service delivery model that we aimed to propose. We excluded studies that did not focus on virtual service delivery, focused on prevention of vertical mother-to-child transmission, described protocols, were not in English, or were not accessible (Table 1).

Figure 1 details the study selection procedure. In addition, the references of papers that were selected were examined to identify other pertinent references. These selections and related data were confirmed by a second reviewer independent of the first reviewer. Studies with missing data were excluded.

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Other Considerations

The RCT was assessed for risk of bias using the Cochrane risk of bias tool [10] and some concerns were identified (Multimedia Appendix 2). Given the limited number of studies and the heterogeneity of studies and their outcomes, it was decided that we could not perform a robust meta-analysis of any given outcome. Thus, related analyses to explore causes of heterogeneity and certainty were not performed.

After reviewing the literature, we considered evidence-based interventions for PrEP service delivery in the time of COVID-19, and developed a virtual service delivery model for implementation to improve HIV prevention services now and in the future. We also suggest how to leverage this model for COVID-19 service delivery to maximize the use of vital health resources. All data and tools used are presented in this manuscript and are publicly available.

Results

Characteristics of Included Studies

Of the 6685 abstracts identified, 1888 were specific to virtual service delivery. Of those 1888 articles, 1259 focused on HIV, 120 of which were relevant for HIV prevention efforts; 48 pertained to PrEP and 19 of these focused on evaluations of interventions for virtual service delivery of PrEP; 16 were conducted in the United States and the other three were conducted in Kenya, India, and England [11-29]. One RCT was identified [19]. There were 16 systematic reviews related to virtual HIV care delivery [30-45], 3 of which were related to virtual PrEP delivery [30,42,45]. The remaining articles focused on aspects of care delivery, including telemedicine, use of SMS and the internet, mHealth, and eHealth. (Figure 1). These 16 papers were reviewed and examined for interventions that support virtual care delivery, which were evaluated for efficacy, feasibility, and/or acceptability and could be considered for PrEP service delivery in the time of COVID-19. Three systematic reviews provided pooled estimates [34,39,44].

Summary of Pertinent Studies

We identified 19 papers [11-29] related to evaluations of interventions for PrEP virtual service delivery. These papers are summarized in Table 2. The primary aim of many of these interventions was to address barriers to PrEP delivery and uptake before the COVID-19 pandemic started in early 2020. For example, the interventions sought to reach people in rural areas or those who were not able to access facilities, as well as eliminating the stigma of PrEP and improving health literacy about many HIV prevention services, including HIV testing, condom use, PrEP, and testing for sexually transmitted infections (STIs). The data presented provide support for the use of social media, smartphone apps, text messaging, and the internet for service delivery and health communication. Two studies described successful PrEP initiation and monitoring using an online platform [17,27], and four studies found that telehealth for PrEP was feasible, acceptable, and effective [13,16,24,25]. Eight studies examined the use of apps [11,18,21,28] and SMS [15,19,22,26] for PrEP service delivery. Of note, only one study, the Enhancing PrEP in Community Settings (EPIC) study, presented results from an RCT [19]. One study described the successful use of the Extension for Community Healthcare Outcomes (ECHO) platform for training of PrEP providers [29]. ECHO, a distance telemonitoring program, has been extensively used to create communities of practice and deliver clinical mentorship to support remote health care provision, which has also been used for PrEP [29,41,46,47].

Of the 16 systematic reviews identified, three were specific to PrEP; one described successful PrEP delivery models, including community-based and home-based approaches [42], and two summarized novel interventions to use technology to improve PrEP availability, adherence, and uptake [41,45]. These include mobile apps that offer PrEP prescribing and preclude an in-person visit, distance mentorship of community PrEP providers, video teleconferencing for provider visits, electronic consults, and using text messaging and mobile/web platforms for PrEP initiation (Table 3) [41,45].

We also summarize systematic reviews that focus on technology innovations to improve HIV testing and adherence in Table 3, because these would also pertain to PrEP programs [30-45]. Most of these reviews focused on interventions to improve adherence to antiretroviral therapy (ART) [31-33,41,43,44]. Two studies reported pooled estimates for improved ART adherence, one for mHealth interventions (pooled odds ratio 2.15, 95% CI 1.18-3.91) and one for eHealth interventions (pooled Cohen d=0.25, 95% CI 0.05-0.46). All studies reported positive outcomes; however, the evaluation methods varied and thus have limited comparability.

PrEP Virtual Service Delivery Model

According to the evidence-based innovations identified from the literature review and those implemented during the COVID-19 pandemic, we suggest a comprehensive model for virtual PrEP service delivery (Figure 2) that includes a combination of interventions such as internet for demand creation and risk assessment, telehealth platforms for visits and training, multimonth dispensing and medication delivery, community-based and self-testing for HIV, and smartphone apps for follow-up reminders and adherence support groups [11-45,48-51]. Regarding monitoring and follow-up, quarterly PrEP monitoring is acceptable and preferred with in-person follow-up but also with telehealth [52].

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Leveraging Adaptations for COVID-19 Service Delivery

Although our primary goal was to consider how innovative PrEP program delivery methods could be used to mitigate the impact of COVID-19 on PrEP services, it is also clear that these PrEP delivery methods have the potential for COVID-19 prevention and control (Table 4). Examples include: (1) demand creation using traditional (radio, television) and social media platforms for HIV prevention and COVID-19 messaging; (2) service delivery with decentralized care, moving from facility to community, including home-based and mobile delivery (for HIV and/or COVID-19 testing and multimonth PrEP prescription refills); virtual platforms for follow-up appointments (telehealth), such as risk assessment, lab assessment, and adherence counseling for PrEP; mental health counseling; using apps (eg, WhatsApp) for support groups and mobile device SMS for adherence reminders; (3) training and education with the use of web-based platforms for education and training of health care workers about HIV prevention (and developments in COVID-19 prevention and management) to promote task-shifting (eg, ECHO project); (4) monitoring and evaluation, involving web-based and app-based data entry using tablets and/or mobile devices of PrEP core indicators; and (5) supply chain vulnerabilities, involving working with governments to enact policies that allow for continued manufacturing of commodities and novel procurement and distribution platforms (electronic prescriptions, mail order, direct drug delivery).

Discussion

Principal Findings

COVID-19 mitigation measures such as physical distancing and lockdowns have created significant challenges for HIV and PrEP programming [8]. This systematic review is unique in that it provides a comprehensive overview of specific technology-based interventions as well as differentiated service delivery models that may be critical to program adaptation during COVID-19. Our findings demonstrate that interventions developed before COVID-19, dating back to 2013, for successful adaptation of PrEP programs for virtual service delivery for HIV testing, ART adherence, and PrEP exist and are currently in use. Innovations such as telemedicine; using the internet and smartphone apps for demand creation, support groups, and follow-up reminders; and multimonth dispensing with mobile pharmacies are evidence-based interventions designed to address distance to services and improve convenience. These innovations might also be particularly impactful in the context of COVID-19 [11-29]. Our review also identified examples of models for virtual service delivery that use technology to support PrEP users, such as PrEPTECH, IowaTelePrEP, and telehealth-led PrEP service delivery [41,42,45]. However, these models address some but not all aspects of PrEP implementation, such as commodity procurement and the ability to purchase medications, which is challenging when countries are locked down and companies cannot supply and distribute drugs.

To build upon the current literature and suggest a practical application for innovative technological adaptations, we used findings from the literature review to develop an example of a model of virtual PrEP delivery, which incorporates innovations identified in our literature search. We identified evidence-based interventions that could adapt the current PrEP service delivery platform to provide decentralized, virtual care. This model would allow for continued PrEP service delivery in the face of COVID-19 mitigation strategies but also may improve our ability to engage hard-to-reach populations who do not access care at facilities. The model is also aligned with approaches already described in some countries. For example, in Brazil, at the initial teleconsultation, individuals are assessed for PrEP by phone and undergo HIV rapid testing. Individuals receive a digital prescription to retrieve a 120-day PrEP supply plus two HIV self-test kits, because home delivery was deemed unaffordable. Subsequent follow-up teleconsultations are performed remotely by phone call, including instructions for the HIV self-test performance and the results are shared by digital photo. This approach was successful in maintaining PrEP services, including uptake, as part of the Implementation PrEP Study (ImPrEP) project [48]. In addition, community pharmacists can deliver drugs and manage minor ailments, which supports the use of task-shifting [49]. Our model can be implemented in countries with widespread access to the internet and smartphones. However, implementation could be challenging in areas where such technologies are limited or unreliable.

Globally, differentiated service delivery models to improve the reach of PrEP and HIV programs, to decongest facilities, and to limit exposure to SARS-CoV-2 are recommended [53]. Our model of service delivery could help to maintain PrEP services in resource-poor settings in all countries, including the United States and Canada, and might improve the program’s ability to reach those most vulnerable by improving access to services and eliminating stigma associated with accessing facilities known to provide HIV services. Sexual and reproductive services could be leveraged to offer virtual HIV prevention services, particularly PrEP, as STI testing, condoms, and contraception should be offered with PrEP. Program evaluations are needed to understand the broader feasibility and impact of virtual service delivery models in low- and middle-income countries. To ensure that persons at substantial risk of HIV continue to benefit from PrEP, approaches to scale up virtual service delivery are underway in many countries [54]. HIV prevention services could also be leveraged for related prevention interventions such as STI testing, and to enhance the COVID-19 pandemic response.

Health care workers providing PrEP services can be trained virtually to deliver COVID-19 services, including education about mitigation measures and vaccination using online platforms [41,45]. The internet and smartphone apps can be used for service delivery such as intake assessments and appointment reminders or other public health communications such as contact-tracing programs alerting someone of exposure to SARS-CoV-2. COVID-19 testing can be offered through HIV testing platforms in the facility and community to create efficiencies. In addition, other prevention modalities for both HIV and COVID-19 could be delivered through the HIV prevention platform by leveraging the virtual service delivery of PrEP for COVID-19. For example, once COVID-19 vaccines [55] become widely available, PrEP service delivery could be leveraged for safe, widespread delivery by offering vaccination to clients who present for HIV testing.

These adaptations should be instituted with engagement of governments, stakeholders, and community leaders. Community engagement is fundamental to the success of syndemic control; community leaders can be influential and are key for disseminating factual information. Efforts should be made to accurately forecast needs, in terms of funding, personnel, commodities, and others, and to allocate resources such that resources are not exhausted and are adequately redistributed as needed. Systems should be agile and adopt new advances in HIV prevention rapidly. Although our review was motivated by concern regarding service interruptions related to COVID-19, programs should be developed both for mitigating current service interruptions and for increasing efficiencies and creating more resilience to future causes of service interruptions. A recent study of HIV service disruption in sub-Saharan Africa highlighted that the most important priority to avoid additional deaths due to HIV during the COVID-19 pandemic was to maintain the supply of antiretroviral drugs for people living with HIV [56]. Provision of other HIV prevention interventions to prevent an increase in HIV incidence was also deemed necessary [56]. Therefore, our model of virtual service delivery might be relevant for maintaining and achieving low levels of HIV incidence.

Limitations

One important challenge that has not been addressed through our review and our model is the maintenance of supply chain and procurement mechanisms to ensure that HIV commodities such as drugs and tests remain available. National-level lockdowns have negatively impacted major pharmaceutical manufacturers, along with the global supply chain of drugs and medical commodities. Governments must ensure that HIV commodities procurement and delivery are maintained as essential services during pandemics that require lockdowns and quarantine for control. Governments should enact policies that allow for continued manufacturing of commodities and novel procurement and distribution platforms. Our literature review had other important limitations. We focused on HIV programs and may have missed relevant innovations used for other types of service delivery. We were not able to conduct meta-analyses for each PrEP intervention (Table 2) identified in our search given the small number of papers and the heterogeneity between studies, particularly of methodology. This limited our ability to conduct analyses related to syntheses of outcomes data. Lastly, as our search focused on service delivery, the review did not yield papers about policy needs related to virtual service delivery, which was outside the scope of our primary objectives.

Conclusions

Although vaccines are critical to effectively controlling the COVID-19 pandemic, there are ongoing threats to COVID-19 control (and therefore to sustaining HIV prevention and care programs); most notably, the identification of variant strains with increased transmissibility and immune escape from current vaccines poses a significant threat to infection control [57]. COVID-19 control measures may need to continue to limit the spread of SARS-CoV-2 infection due to these variants in some countries [57]. The COVID-19 pandemic has catalyzed a new reality of virtual care [58]. Virtual health service delivery could improve accessibility and affordability of health care, and might improve health inequities, especially for people who are not proximate to care facilities, during COVID-19. However, this requires further investigation. There are also other relevant and newer technologies that have not yet been studied in this context. For example, machine learning can be used to identify individuals who might benefit from HIV testing, PrEP, and other risk reduction strategies [59]. Wearable devices with biosensing capabilities could be updated to improve adherence to daily medications; to provide location information for testing and pharmacies services and/or facilitate contact tracing; and to provide notifications to maintain social distancing [60]. Further investigation is warranted to assess the feasibility, acceptability, and effectiveness of these new technologies and understand their role in public health and medicine.

Innovations in virtual service provision of PrEP occurred before COVID-19 but have new relevance in the COVID-19 pandemic. The United Nations Program on HIV and AIDS (UNAIDS) 2020 target of 3 million on PrEP was not achieved; without innovations and evolution of standard models of delivery, reaching the 2025 target of 95% of those at risk using effective combination prevention options may be similarly beyond reach. Substantial gains in HIV care and the intended acceleration toward global HIV epidemic control may be lost. The innovations we describe might strengthen HIV prevention service delivery in the long run by engaging traditionally hard-to-reach or remote populations, reducing stigma, and by also creating a more accessible health care platform. These are platforms that can be leveraged both to mitigate the impacts of the COVID-19 pandemic on HIV services, and to support interventions for the COVID-19 response and facilitate pandemic control directly now and in the future.