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

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.

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 preexposure 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:

AND
Treatment Adherence and Compliance.

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)or 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.Were not identified Were not identified

SSHS of 46 items
Were not identified Willingness to use PrEP (32,6 %) P e r c e i v e d ease of use of PrEP

Were not identified
Were

Were not identified
Were not identified 78 % of patients i n d i c a t e d that the text m e s s a g i n g service helped to remember to take PrEP

Were not identified
Were not identified S a l i n a s -Rodríguez et al. (40) México Older than 18    (52) U n i t e d States S e l f -i d e n t i f i e d cisgender gay or bisexual cisgender men (n=14) Qualitative Consensual

Semi-structured interview
Were not identified P a r t i c i p a n t s described having good knowledge about PrEP, prior to starting therapy and acquired through social networks, television, internet or other digital media

Were not identified
Were not identified Participants identified some obstacles to maintaining the required doses.Experiences of internalized homophobia and related stigma may affect the decision to take PrEP.Participants presented discomfort when discussing their sexual activity with the medical professional Cahill et al. (54) U n i t e d States T r a n s g e n d e r women, who have sex with men, HIV negative, having had at least one episode of insertive or receptive anal sex in the last three months (2 groups (n=11 and n=8).

Case study Focus group
Were not identified Were not identified Were not identified

Were not identified
Were

Were not identified
Were not identified

Were not identified
Were not identified

Future communication about PrEP adherence between patient and provider varied among participants
Salud, Ciencia y Tecnología.2024; 4:.1085 10

Were not identified
Were not identified

Were not identified
Were not identified Drug use (methamphetamine) and alcohol were the aspects that hinder the use of PrEP Vaccher et al. (50)   Is the statistical analysis appropriate to answer the research question?Ferrer et al. (33) Yes Yes Yes No Yes Kwan et al. (37) Yes Yes Yes Yes Yes Lim et al. (38) Yes Yes Yes Yes Yes Salinas-Rodríguez et al. (40)

Yes
No Yes No No Sun et al. (41) Yes Yes Yes Yes Yes Whiteley et al. (42) No  (32) Yes Yes Yes Yes Yes Martin et al. (39) Yes Is there coherence between qualitative data sources, collection, analyses and interpretation?Alt et al. (52) Yes Yes Yes Yes Yes Cahill et al. (54) Yes Yes Yes Yes Yes No No No No No Sevelius et al. (48) Yes Yes Yes Yes Yes Storholm et al. (49) Yes Yes Yes Yes Yes Vaccher et al. (50) No No No No No Watson et al. (51) Yes  (56) No No No No No

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)n 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)n 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)tigma 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)ide 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)ikewise, 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)ccording to the facilitators for the use of PrEP, willingness was identified. (33,44,45,47,51,53)These findings were Salud, Ciencia y Tecnología.2024; 4:.1085 14

Figure 1 .
Figure 1.Flowchart on item selection process according to Prisma

Table 1 .
Strategy search used for the PubMed database Human Immunodeficiency Viruses; Human T Cell Lymphotropic Virus Type III; Human T-Cell Lymphotropic Virus Type III; Human T-Cell Leukemia Virus Type III; Human T Cell Leukemia Virus Type III; LAV-HTLV-III; Lymphadenopathy-Associated Virus; Lymphadenopathy-Associated Virus; Lymphadenopathy-Associated Viruses, Virus; Lymphadenopathy-Associated, Viruses Lymphadenopathy-Associated, Human T Lymphotropic Virus Type III; Human T-Lymphotropic Virus Type III; AIDS Virus; AIDS Viruses, Virus; AIDS Viruses; AIDS Viruses; AIDS, Acquired Immune Deficiency Syndrome Virus; Acquired Immunodeficiency Syndrome Virus; HTLV-III.

Table 2 .
Characteristics of quantitative included studies not identified HIV= Human Immunodeficiency Virus; MSM= Men who have Sex with Men; CI= Confidence Interval; p: p-value; aOR= Adjusted Odds Ratio; OR: Odds Ratio; RRa= Adjusted Risk Ratio; WAS= Wilson Adherence Scale; PKQ=PrEP Knowledge Questionnaire; AQ=Attitude Questionnaire; PBBQ= Perception of Benefits and Barriers Questionnaire; TW= Transgender Woman; WGP= World Gay Pride; SSHS= Spanish Sexual Health Survey; STIs= Sexually Transmitted Infections; HK= Hong kong Dollar; USD= United States Dollar; BTS= Bangkok Project; CSES= Condom Use Self Efficacy Scale; CBSAMIS= Concealment Behavior Scale on American Men's Internet Survey; GSIBSI=Global Severity Index of the Brief Symptom Inventory; SRB= Sexual risk behavior, PKS= PrEP Knowlegde Scale; MBS= Motivation-Behavioral Skills; SSP= Social Support for PrEP; ICCCU= Importance of Condom and Confidence in Condom Use. https://doi.org/10.56294/saludcyt2024.1085

Table 3 .
Characteristics of the included qualitative studies

Table 4 .
Evaluation of the methodological quality of the included studies Q