doi: 10.56294/saludcyt2024.1085

 

REVIEW

 

Adherence and Compliance with Oral Pre-Exposure Prophylaxis (PrEP) for HIV Prevention

 

Adherencia y cumplimiento de la Profilaxis Pre Exposición (PrEP) para la prevención del VIH

 

Moisés Jaurégui¹  *, María Candia¹  *, Víctor Pedrero¹  *, Camilo Silva^1,2  *, Lúcia Alves da Silva Lara³  *, Ana Katherine Gonçalves⁴  *, Ricardo Arcêncio⁵  *, Denisse Cartagena-Ramos¹  *

 

¹Universidad Andrés Bello, Facultad de Enfermería. Santiago, Chile.

²Universidad Católica Silva Henríquez, Facultad de Ciencias de la Salud, Escuela de Enfermería. Santiago, Chile.

³Universidade de São Paulo, Faculdade de Medicina. Ribeirão Preto, Brasil.

⁴Universidade Federal do Rio Grande do Norte, Faculdade de Medicina. Natal, Brasil.

⁵Universidade de São Paulo, Escola de Enfermagem, Ribeirão Preto, Brasil.

 

Cite as: Jaúregui M, Candia M, Pedrero V, Silva C, da Silva Lara LA, Gonçalves AK, et al. Adherence and Compliance with Oral Pre-Exposure Prophylaxis (PrEP) for HIV Prevention. Salud, Ciencia y Tecnología. 2024; 4:1085. https://doi.org/10.56294/saludcyt20241085

 

Submitted: 09-02-2024                       Revised: 05-05-2024                                       Accepted: 12-08-2024                       Published: 13-08-2024

 

Editor: Dr. William Castillo-González

 

ABSTRACT

 

Introduction: men who have sex with men (MSM), transgender people, sex workers, people who inject drugs, individuals in prisons and other closed settings have been considered key populations because they are at high risk of contracting HIV. The World Health Organization (WHO) has recommended Oral Pre-Exposure Prophylaxis (PrEP) because of its protective effect against HIV in this population. This study aims to analyze the factors that influence adherence and compliance with oral PrEP for HIV prevention.

Method: this systematic review was conducted the databases used were the PubMed, CINAHL Complete, and EMBASE. For search keywords, MeSH, CINAHL Subjects, and Emtree terms were combined with AND and OR Boolean operators. Studies selected encompassed quantitative, qualitative, mixed, and multimethod designs, between from 2015 to 2022, in English, Spanish, and Portuguese language. All references were imported and exported through EndNote for data collection. Methodological quality was evaluated using the MMAT checklist. We used deductive thematic analysis based on Taylor there are six categories that influence adherence and compliance to oral PrEP.

Results: out of 526 articles retrieved, 314 duplicates were eliminated and 26 were incorporated. Various factors affect adherence and compliance with oral PrEP.

Conclusions: based on the findings, PrEP’s effectiveness and the perceived high risk of HIV infection served as motivators for PrEP utilization, while negative sentiments regarding PrEP, side effects, and stigma acted as hurdles to its use. Readiness facilitated PrEP adoption. Healthcare team support was viewed as an effective attribute for those administering oral PrEP.

 

Keywords: Adult; Human Immunodeficiency Virus; Pre-Exposure Prophylaxis; Treatment Adherence and Compliance; Systematic Review.

 

RESUMEN

 

Introducción: los hombres que tienen relaciones sexuales con hombres (HSH), las personas transexuales, trabajadores sexuales, las personas que se inyectan drogas, los individuos privados de libertad y otros entornos cerrados se han considerado poblaciones clave por su alto riesgo de contraer el VIH. La Organización Mundial de la Salud (OMS) ha recomendado la PrEP por su efecto protector frente al VIH en esta población. Este estudio pretende analizar los factores que influyen en la adherencia y el cumplimiento de la Profilaxis Pre Exposición (PrEP) oral para la prevención del VIH.

Método: se realizó esta revisión sistemática las bases de datos utilizadas fueron PubMed, CINAHL Complete y EMBASE. Para la búsqueda de palabras clave, se combinaron los términos MeSH, CINAHL Subjects y Emtree con los operadores booleanos AND y OR. Los estudios seleccionados abarcaron diseños cuantitativos, cualitativos, mixtos y multi método, entre 2015 y 2022, en idioma inglés, español y portugués. Todas las referencias fueron importadas y exportadas a través de EndNote para la recolección de datos. La calidad metodológica se evaluó mediante la lista de verificación MMAT. Se utilizó un análisis temático deductivo basado en Taylor hay seis categorías que influyen en la adherencia y el cumplimiento de la PrEP oral.

Resultados: de los 526 artículos recuperados, se eliminaron 314 duplicados y se incorporaron 26. Diversos factores influyen en la adherencia y el cumplimiento de la PrEP oral.

Conclusiones: según los resultados, la eficacia de la PrEP y el alto riesgo percibido de infección por VIH sirvieron como motivadores para la utilización de la PrEP, mientras que los sentimientos negativos respecto a la PrEP, los efectos secundarios y el estigma actuaron como obstáculos para su uso. La disposición facilitó la adopción de la PrEP. El apoyo del equipo sanitario se consideró un atributo eficaz para quienes administran la PrEP oral.

 

Palabras clave: Adulto; Virus de Inmunodeficiencia Humana; Profilaxis Pre-Exposición; Adherencia y Cumplimiento del Tratamiento; Revisión Sistemática.

 

 

 

INTRODUCTION

Human Immunodeficiency Virus (HIV) infection is a significant public health concern worldwide. In 2022, the Joint United Nations Programme on HIV/AIDS reported 38,4 million individuals living with HIV globally along with 1,5 million new HIV infections, concentrated in key populations. In 2019, there was a surge in new HIV infections, amounting to 62 % ⁽¹⁾ globally and 21 % in Latin America among key populations.⁽²⁾

According to the World Health Organization (WHO), key populations are groups that are at a higher risk of HIV infection and include men who have sex with men (MSM), people who inject drugs (PWID), people in detention and other closed settings, sex workers, and transgender people.⁽³⁾

To combat the spread of HIV, the global response recommends combination prevention,⁽⁴⁾ a strategy that employs multiple interventions, including oral pre-exposure prophylaxis (PrEP). The PrEP is a prevention strategy that uses the antiretroviral combination of tenofovir disoproxil fumarate and emtricitabine or lamivudine and consists of daily consumption of this drug prior to sexual activity. One study showed that daily use of PrEP prevents HIV acquisition⁽⁵⁾ or taking four or more doses of PrEP per week reduces the risk of infection by 99 % ^(4,6), particularly in key populations.^{(7,8,9,10,11)} According to WHO, in 2015 this intervention was suggested for this population⁽⁵⁾ and by 2023, a total of 60 countries have incorporated PrEP in their health system.⁽¹²⁾

Adherence is defined as the behavior of the person to follow a given treatment and compliance as the coincidence between the patient’s behavior and the medical prescription. As a worldwide strategy, oral PrEP monitoring has been recommended.⁽¹²⁾ Currently, adherence and compliance can be assessed and measured by means of self-report questionnaires.⁽¹³⁾ There are other adherence metrics including pharmacological (hair, urine), electronic adherence monitors, pharmacy refills, electronic pill intake and pill counts, however, self-reporting has been shown to have some advantages as a tool for use in professional care and cost-effectiveness.⁽¹⁴⁾

According to Taylor et al. there are six categories that influence adherence and compliance to oral PrEP in the patient such as: 1) motivations to use PrEP, 2) barriers to PrEP use, 3) facilitators to PrEP use, 4) sexual decision making in the context of PrEP, 5) prospective content of PrEP education, and 6) perceived effective characteristics of the staff administering oral PrEP.⁽¹⁵⁾

Adherence and compliance are relevant aspects in the effectiveness and efficiency of the treatment planned by the health professional. Despite the above, some studies have shown adherence levels ranging from 40 to 60 % in countries such as the United States, Uganda, and Brazil, respectively,^(16,17,18) the latter showing 60 % adherence among MSM and transgender women.⁽¹⁴⁾

Since 2015, systematic reviews have been developed, however, with focus on MSM,^{(19,20,21,22)} people who use injectable drugs,⁽²³⁾ transgender,⁽²⁴⁾ more than one key population,⁽²⁵⁾ only one review addressed MSM, people who use injectable drugs, transgender, people deprived of liberty and sex workers, but dates from 2018, which represents that adherence and compliance should be studied again due to lack of updated evidence. In this context, it is relevant to analyze the aspects that influence adherence and adherence to oral PrEP for HIV prevention.

 

METHOD

Study design

This was a systematic review of the aspects that influence adherence and compliance to oral PrEP and was conducted following the “preferred reporting items for systematic review and meta-analyses” PRISMA: 1) formulation of the research question; 2) search strategy; 3) eligibility criteria; 4) selection of articles, 5) evaluation of the methodological quality of the studies and 6) synthesis and levels of evidence and reported by means of the Prisma Checklist.⁽²⁶⁾

 

Formulation of the research question

The research question was what are the aspects that influence adherence and compliance to oral pre-exposure prophylaxis for HIV prevention? and formulated using the acronym PICO, where P: Population, I: Intervention, C: Comparison, O: Outcome.

 

Search strategy

The electronic databases US National Library of Medicine National Institutes of Health (PubMed), CINAHL Complete and Excerpta Medica Database (EMBASE) were used for the search, according to the recommendation of the Cochrane Collaboration,⁽²⁷⁾ as they represent the largest databases of peer-reviewed articles.

The strategy used for the PubMed database was a combination of Medical Subject Headings (MESH) descriptors, keywords, and Boolean operators. The search is shown in table 1:

 

 

Eligibility Criteria

Quantitative, qualitative, mixed, and multi-method primary studies, published between 2015 to 2022, in English, Portuguese and Spanish language, about oral PrEP (tenofovir disoproxil fumarate and emtricitabine or lamivudine) were included.

 

Article selection

All references were imported into the EndNote bibliographic manager, likewise duplicates were eliminated by this manager and the literature was exported in RTF format to an Excel spreadsheet for the selection process that included reading title, abstract and complete. Discrepancies were discussed by one author.

 

Evaluation of the methodological quality of the included studies

The methodological quality of the included studies was assessed using the criteria of the Mixed Methods Appraisal Tool (MMAT) checklist,^(28,29,30) which is a tool designed to simultaneously assess and describe the methodological quality of qualitative, quantitative (randomized, nonrandomized, and descriptive) and mixed methods studies.^(28,29,30)

For the evaluation of the studies, the information of the articles to be evaluated must be entered, answer the questions to assess the eligibility of the articles, select the appropriate category of studies according to design (qualitative study, randomized clinical studies, non-randomized studies, descriptive quantitative studies, mixed methods studies) and finally score the studies according to the criteria “Yes” or “No” and “Can´t tell”, the latter meaning that the document does not provide adequate information to answer “Yes” or “No”, or that they report unclear information related to the criterion.^(28,29,30)

 

Synthesis and level of evidence

For the synthesis of the information, the following data were extracted: author, country, participant inclusion criteria, sample size or number of participants, type of study, type of design, measurement instrument, findings, aspects that influence adherence and compliance.

Finally, the descriptive analysis was performed by means of percentages of the variables studied. The deductive thematic analysis was performed by means of the following stages: 1) familiarization with the data, 2) generation of initial codes, 3) search by themes, 4) review of themes, 5) definition of themes, and 6) articulation of themes with literature in the area and production of the final analysis.⁽³¹⁾ The categories identified were grouped according to 1) motivations for using PrEP, 2) barriers to PrEP use, 3) facilitators to PrEP use, 4) sexual decision making in the context of PrEP, 5) prospective content of PrEP education, and 6) perceived effective characteristics of personnel administering PrEP.⁽¹⁵⁾

 

RESULTS

From a total of 526 articles identified, 59 were selected by title, 36 by title/abstract, 33 by full reading, and 26 were included.

 

Figure 1. Flowchart on item selection process according to Prisma

 

 

 

 

Characteristics of included studies

According to type of study, 53,8 % corresponded to quantitative studies,^{(32,33,34,35,36,37,38,39,40,41,42,43)} 38,4 % to qualitative studies^{(44,45,46,47,48,49,50,51,52,53,54,55)} and 7,7 % to mixed studies.^(56,57)

Fifty percent corresponded to studies conducted in the United States^{(32,34,36,38,41,46,47,48,50,51,54,55)}, the remaining 50 % to countries such as Spain (4,2 %),⁽³³⁾ Thailand (4,2 %),⁽⁵³⁾ Malaysia (4,2 %),⁽³⁸⁾ China (8,2 %),^(41,43,44) Australia (4,2 %),⁽⁵⁰⁾ Mexico (4,2 %),⁽⁴⁰⁾ Peru (4,2 %) ⁽⁴⁵⁾ and Kenya and Uganda (8,2 %),^(36,57) Kenya (4,2 %),⁽⁴⁶⁾ Uganda (4,2 %).⁽⁵⁶⁾ Studies included more than one key population ^{(32,36,39,40,42,45,46,48–50,52,54,55,56,57)} and one key population.^{(33,34,35,37,38,41,43,44,51,53)} According to the methodological evaluation of the studies, 11 of them presented more than 80 % of the MMAT criteria.^{(31,32,33,38,39,42,45,45,48,49,51,52)}

Aspects influencing adherence and compliance to oral PrEP were categorized according to 1) motivations to use PrEP, 2) barriers to PrEP use, 3) facilitators to PrEP use, 4) sexual decision making in the context of PrEP, 5) prospective content of PrEP education, and 6) perceived effective characteristics of personnel administering PrEP.⁽¹⁵⁾

 

Motivations for using PrEP

PrEP effectiveness,^{(34,42,43,44,46,49,50)} sexual well-being,^(38,46,49) and perceived high risk of HIV infection ^{(36,38,41,44,45,48,49,50,56)} were identified motivations for improved adherence and compliance.

 

Barriers to PrEP Use

Low access,^(45,50,53) low socioeconomic status,^(41,45,54) low schooling,^(32,36) young adult and/or adolescent age group ⁽³⁶⁾ and PrEP drug dosage were considered as barriers to PrEP use.^{(48,50,52,53,56)} Likewise, negative feelings towards PrEP,^{(32,41,44,45,48,56)} stigma^{(48,50,52,53,55)} were presented as barriers. Additionally, side effects of PrEP,^{(32,44,48,51,54,56)} low risk perception^(44,53) were identified as barriers. Also, four studies evidenced dissatisfaction with medical care,^{(48,51,52,54)} perception of low protection of oral PrEP against Sexually Transmitted Infections (STIs) as barriers to oral PrEP use.^(35,51)

 

Facilitators for PrEP use

Three studies distinguished migration/ethnicity,^(36,38,41) marital status ^(36,43) as facilitators. Also, willingness to use PrEP,^{(33,44,45,47,51,53)} perceived ease of PrEP,^(33,50,53) economic incentive,⁽³⁷⁾ and knowledge about PrEP ^{(33,38,51,52)} were facilitators for its use.

 

Sexual decision making in the PrEP context

Drug and/or alcohol use ^(36,48,49) and partner type (serodiscordant, plus 2 anal sex partners, and stable partners), ^(36,38,42) were decisions participants made when using PrEP.

 

Prospective Oral PrEP Education content

No PrEP educational content delivered by health care personnel was identified.

 

Perceived effective characteristics of staff administering oral PrEP.

Six studies identified health care team support,^{(34,35,47,50,57)} PrEP drug cost coverage,⁽¹⁴⁾ and intervention follow-up by hair testing in PrEP users ⁽⁴⁰⁾ were characteristics perceived as effective by health care personnel providing care to key populations.

 

DISCUSSION

Motivations for PrEP use highlighted PrEP effectiveness and perceived high risk of HIV infection. The effectiveness of oral PrEP was shown to be one of the motivations influencing adherence and compliance.^{(34,42,43,44,46,49,50)}. Similar results were identified in the literature, as one study found effectiveness to be a predictor for oral PrEP adoption ORa:2,48; (95 % CI: 1,89-3,25), p<0,001.⁽³⁴⁾ In addition, another study showed that once-daily consumption of Truvada® can reduce the risk of HIV infection by more than 90 % ^(5,58) and its implementation as a public health strategy is cost-effective.^(7,8,9)

In addition, the perception of high HIV risk ^{(36,37,38,41,44,45,48,50,56)}, was another motivation that influences the use of PrEP. Similar results were identified in the literature, a study in France identified that patients with higher perceived risk of contracting HIV have higher adherence to oral PrEP (p < 0,001) ⁽⁵⁹⁾ and another in the United States, corroborated that risk perception is a predictor for PrEP adoption ORa:1,04; (CI: 1,02-1,07), p < 0,01.⁽³⁴⁾

In relation to barriers to PrEP use, negative feelings about PrEP, stigma and side effects of PrEP stood out. Negative feelings about PrEP were shown to be a barrier to PrEP use ^{(32,41,44,45,56)}. Likewise, a study in the United States corroborated those negative feelings about PrEP is a barrier to discontinuation of PrEP.⁽⁶⁰⁾

Stigma was identified as a second barrier to PrEP use.^{(48,50,52,53,55)} These findings were corroborated by a study which showed that high levels of stigma were associated with low adherence to treatment ORa = 2,74, (95 % CI: 1,13-6,61) p<0,01.⁽⁶¹⁾

Side effects were identified as a third barrier to PrEP use.^{(32,44,48,51,54,56)} These findings were like a study in Germany, which showed an association between side effects and low adherence to the drug (p=0,015).⁽⁶²⁾ Likewise, another study in the United States showed that the presence of side effects to the use of the drug is a barrier that leads to discontinuation of PrEP.⁽⁶⁰⁾

According to the facilitators for the use of PrEP, willingness was identified.^{(33,44,45,47,51,53)} These findings were corroborated by a study in China, which found that willingness was associated with intention and adherence to PrEP and in turn with high level of schooling (postgraduate) ORa = 1,90, (95 % CI:1,11-3,26); p<0,001.⁽⁶¹⁾ Controversial outcomes were identified as socioeconomic factors, migration/ethnicity,^(39,40,55) marital status,^(36,63) these findings were corroborated by one study.⁽⁴³⁾

According to sexual decision making in the context of PrEP, the use of drugs and/or alcohol stood out.^(36,48,49) Similar results were found in a study in the United States, which showed that patients who consume any licit substance are more likely to adopt PrEP among the key population ORa: 2,27, (95 % CI: 0,92-5,56), p < 0,001.⁽³⁴⁾

According to prospective content of oral PrEP education, they were not identified as being delivered by health personnel. According to the characteristics perceived as effective of the personnel who administered oral PrEP, the support of the health team stood out.^{(34,35,47,48,50,57)} Similar results were identified.^(64,65)

The drug dose was considered a barrier,^{(48,50,52,53,56)} although some studies have corroborated this finding and show that it improves adherence and compliance to PrEP in other pharmacological presentations such as cervicovaginal ⁽⁶⁶⁾ and injectable ⁽⁶⁷⁾, there is other evidence that it has not been shown to be detrimental to adherence and compliance to PrEP.

The present review showed the aspects that influence adherence and compliance to PrEP in key populations. It is necessary to stimulate combination prevention, through interventions that detect and address these aspects for the improvement of adherence and compliance in the most vulnerable population.

 

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FINANCING

The authors did not receive financing for the development of this research.

 

CONFLICT OF INTEREST

The authors declare that there is no conflict of interest.

 

AUTHORSHIP CONTRIBUTION

Conceptualization: Moisés Jaurégui, María Candia, Víctor Pedrero, Denisse Cartagena-Ramos.

Data curation: Moisés Jaurégui, María Candia, Víctor Pedrero, Camilo Silva, Lúcia Alves da Silva Lara, Ana Katherine Gonçalves, Ricardo Arcêncio, Denisse Cartagena-Ramos.

Formal analysis: Moisés Jaurégui, María Candia, Víctor Pedrero, Camilo Silva, Lúcia Alves da Silva Lara, Ana Katherine Gonçalves, Ricardo Arcêncio, Denisse Cartagena-Ramos.

Research: Moisés Jaurégui, María Candia, Víctor Pedrero, Camilo Silva, Lúcia Alves da Silva Lara, Ana Katherine Gonçalves, Ricardo Arcêncio, Denisse Cartagena-Ramos.

Methodology: Moisés Jaurégui, María Candia, Víctor Pedrero, Camilo Silva, Lúcia Alves da Silva Lara, Ana Katherine Gonçalves, Ricardo Arcêncio, Denisse Cartagena-Ramos.

Project management: Moisés Jaurégui, María Candia, Víctor Pedrero, Denisse Cartagena-Ramos.

Resources: Víctor Pedrero, Denisse Cartagena-Ramos.

Software: Moisés Jaurégui, María Candia, Víctor Pedrero, Camilo Silva, Lúcia Alves da Silva Lara, Ana Katherine Gonçalves, Ricardo Arcêncio, Denisse Cartagena-Ramos.

Supervision: Víctor Pedrero, Denisse Cartagena-Ramos.

Validation: Víctor Pedrero, Camilo Silva, Lúcia Alves da Silva Lara, Ana Katherine Gonçalves, Ricardo Arcêncio, Denisse Cartagena-Ramos.

Visualization: Moisés Jaurégui, María Candia, Víctor Pedrero, Camilo Silva, Lúcia Alves da Silva Lara, Ana Katherine Gonçalves, Ricardo Arcêncio, Denisse Cartagena-Ramos.

Writing original draft: Moisés Jaurégui, María Candia, Víctor Pedrero, Camilo Silva, Lúcia Alves da Silva Lara, Ana Katherine Gonçalves, Ricardo Arcêncio, Denisse Cartagena-Ramos.

Writing - proofreading and editing: Moisés Jaurégui, María Candia, Víctor Pedrero, Camilo Silva, Lúcia Alves da Silva Lara, Ana Katherine Gonçalves, Ricardo Arcêncio, Denisse Cartagena-Ramos.