Advancing HIV Prevention: A Comprehensive Analysis Of PrEP's Efficacy, Adherence Dynamics, And Implementation Challenges

Manav Kumar, Kajal Kumari , Nahida Khatun, Sapna Kumari, Laxman Kumar Mahto, Divya Roshni Panna, Bina Kumari, Priyanka Kumari, Archana Rani, Alok Kumar, Suman Kumari, Shweta Kumari,

doi:10.5281/zenodo.13834930

Review Paper | Open Access
Volume 02 | Issue 09 | Article Id IJPS/240209108

Advancing HIV Prevention: A Comprehensive Analysis Of PrEP's Efficacy, Adherence Dynamics, And Implementation Challenges
Manav Kumar* Kajal Kumari Nahida Khatun Sapna Kumari Laxman Kumar Mahto Divya Roshni Panna Bina Kumari Priyanka Kumari Archana Rani Alok Kumar Suman Kumari Shweta Kumari
¹Student, Department of Pharmacy, Sai Nath University, Ranchi, Jharkhand 835219, India
²Student, Department of Pharmacy, Faculty of Medical Science and Research, Sai Nath University, Ranchi, Jharkhand 835219, India.

Abstract

Pre-Exposure Prophylaxis (PrEP) has transformed HIV prevention by providing substantial defense against transmission. This review extensively examines the various facets of PrEP, including its effectiveness, difficulties with adherence, and strategies for implementation. We examine the pharmacokinetic thresholds, steady-state drug levels, and adherence patterns that impact the effectiveness of PrEP. Furthermore, we investigate the critical importance of counseling in promoting adherence and discuss techniques for incorporating PrEP into medical facilities. The review also discusses challenges in implementation such as testing methods, coverage, and the potential influence of behavioral disinhibition. Additionally, we examine the psychosocial elements that impact the adoption of PrEP, including risk assessment, knowledge, and discrimination. This review aims to inform healthcare providers, policymakers, and individuals about the potential benefits and challenges of PrEP by giving a thorough overview, ultimately helping with its effective implementation and utilization.

Keywords

Pre-Exposure Prophylaxis (PrEP), HIV prevention, adherence, pharmacokinetics, counseling, implementation challenges, psychosocial factors, risk perception, stigma, healthcare systems.

Introduction

Over the past decade, the introduction of innovative biomedical methods has revolutionized HIV (Human immunodeficiency virus) prevention, reshaping the trajectory of the epidemic [1,2]. PrEP (Pre-Exposure Prophylaxis) involves the use of antiretroviral medication to significantly reduce the likelihood of HIV infection [3]. Daily oral Pre-Exposure Prophylaxis (PrEP) has emerged as a ground breaking strategy in HIV prevention, showing remarkable success in curbing transmission and becoming a widely adopted measure in diverse environments [4,5]. We concentrate on preventing HIV transmission through sexual activity, as the effectiveness of PrEP [6]. We Covers Drug level at the time of Exposure, Prevention of HIV Through PrEP During Steady- State Drug level Concentration, Effective Counseling for Adhering to PrEP in HIV Prevention, and Measuring Program Success Through Effective Adherence to Prevention Strategies [7,8,9]. We Highlight making a Health System and setting PrEP-Friendly, Overcoming Personal Challenges and New Options for PrEP. Navigating Pregnancy and Contraception with PrEP, Overcoming Challenges in PrEP Access for Women [10,11,12]. Central Focus on Different Challenges in HIV Risk Assessment for Women: Consequences for PrEP Use and Risk Stratification The devices Several Techniques for Measuring Adherence to PrEP: Managing Methodological Issues and New Technologies in HIV Prevention [13,14,15]. HIV Pre-Exposure Prophylaxis: Tissue-Specific Considerations and Exposure Risk Windows for Pharmacokinetic Thresholds and Dosage Dynamics [16,17]. Core Area is The implications on dosage adherence and tissue-specific kinetics in pharmacodynamic equilibrium in HIV PrEP [18]. The section called "Implementation Challenges" covers the difficulties in putting PrEP programs into practice, including methods for testing, coverage, and adherence obstacles [19]. and all of the components associated with the acceptance and execution of PrEP, such as willingness, awareness, perception of risk, and stigma [20,21].

Multifaceted Challenges in HIV Risk Assessment for Women: Implications for PrEP Uptake and Risk Stratification Tools

HIV risk perception Women at risk for HIV infection may not be fully conscious of their partner's HIV risk, which can lead to an underestimation of their own risk and a reduction in motivation to start and/or strictly adhere to PrEP [22,23,24]. This presents a difficulty for the adoption of methods for preventing HIV in women. Additionally, inadequate HIV risk assessment among women can affect healthcare providers' recommendations and PrEP advising trends [25,26]. Risk factors for HIV acquisition in women might be indirect (partner's risk behavior, HIV density of sexual networks, excessive sexual activity, personal substance use, genital illnesses) in addition to direct (i.e., difficult to spot) [27,28]. Women might not be aware of their own HIV risk, might feel guilty or humiliated for revealing their actual risk [29]. They might not fully comprehend the risk behaviors of their partners, or they could believe that talking about these risks is inappropriate (e.g., in the context of intimate partner abuse) [30]. Tools taking into consideration factors including age, partner HIV viral load, marital status, drug usage, unprotected sex, and so on [31,32]. Risk stratification is an inexpensive method of evaluating who most needs PrEP. To reliably predict HIV risk among women, these techniques must be modified for the setting and incorporate population-specific data, such as local HIV prevalence [33,34].

Multifaceted Approaches to Quantifying PrEP Adherence: Navigating Methodological Limitations and Emerging Technologies in HIV Prevention

Quantifying PrEP use is the next stage in evaluating prevention-effective adherence [35]. There isn't a single ideal method for assessing medication-taking behavior; each approach has pros and cons. Understanding adherence behavior requires a context-appropriate combination of several measures, since individual adherence measures are not flawless [36,37]. Crucially, in multiple PrEP clinical trials, self-report was mainly uninformative due to over reporting of adherence, and it did not correlate with dosage regimens [38]. As was previously mentioned in relation to self-reported risk behavior, and/or questions that have been verified by objective PrEP adherence metrics may help to increase self-reported adherence [39]. In the event that there are no repercussions for reporting socially undesirable behaviour (such as onerous intervention components when have been reports of condom-free sex or non-adherence) [40, 41]. Remarkably, there is a higher likelihood of accuracy in reporting nonadherence than in reporting adherence [42]. Pharmacy refill data offer a methodical technique that has been successful in anticipating viral suppression in antiretroviral therapy programs and could be workable for regular clinical use with PrEP. Electronic adherence monitoring is only available for research studies due to cost concerns, but it is the only approach that provides dose-by-dose measurement for evaluating adherence patterns, which are essential for comprehending prevention-effective adherence [43,44,45]. Therefore, it should be thought of implementing electronic monitoring in at least a portion of participants in demonstration programs [46]. This is also wireless electronic monitoring, which can deliver data instantly, lower the chance of data loss, and require less personnel to collect data in geographically separated environments [47,48]. Drug levels are not practicable for normal use, but they were essential for reliably documenting the administration of medicines in the PrEP clinical studies [49]. For demonstration projects, stored samples for selective testing present an possible economical option [50].

Pharmacokinetic Thresholds and Dosage Dynamics in HIV Pre-Exposure Prophylaxis: Tissue-Specific Considerations and Exposure Risk Windows

The drugs level at the point of risk exposure must be sufficient to stop HIV replication for the adherence pattern to be protective [51, 52]. Two weekly doses on average may offer 76?ficacy in modeling studies based on MSM, four weekly doses may offer 96% protection, and seven weekly doses may offer 99?ficacy [53, 54]. However, vaginal tissue may require a higher average oral dosage for maintaining drug levels in a safe range since rectal tissue has substantially greater tenofovir concentrations than vaginal tissue [55, 56]. Furthermore, it is difficult to determine the exact moment at which the risk resulting from an exposure has subsided because it is not known how long it takes for HIV to entirely leave the body. PEP offers useful guidance from which recommendations might be made [57, 58].

Pharmacodynamic Equilibrium in HIV PrEP: Tissue-Specific Kinetics and Dosage Adherence Implications

The majority of oral PrEP trials' success has been linked to tenofovir blood concentrations [59]. The majority of estimations suggest that steady-state treatment concentrations in blood mononuclear cells can be achieved with about seven oral dosages per day [60]. There aren't as many data to determine when steady-state concentrations in vaginal and rectal tissue are reached, but the data typically match blood concentrations, so it's reasonable to recommend employing PrEP for seven days before gaining protection [61, 62]. When steady state is still not reached, the effects of doses not taken on efficacy may have more severe consequences (i.e., there is probably less "forgiveness" for missed doses) [63]. These issues need to be taken into account at all times when using PrEP, not just at beginnings, since its usage may be intermittent.

Figure no 1 "PK/PD Modeling" (Pharmacokinetic/Pharmacodynamic) brings in the critical scientific evaluation of drug behavior and effects in the body.

Expanding PrEP Access and Addressing Implementation Challenges.

Since the approach may work just as well for men, pre-exposure prophylaxis (PrEP), looks to be a prospective new option to close the gender gap in female-controlled prevention [64]. The concept of utilizing antiretroviral drugs (ARV), as a preventative therapy has been studied and shown to be effective in preventing HIV transmission from mother to child [65, 66]. More importantly, post-exposure prophylaxis, or PEP, is an expected practice for healthcare workers follow an incidental HIV exposure and has been shown to prevent 80% of HIV infections carried on by needle mishaps [67, 68]. Some worry that using PrEP People on PrEP can feel less vulnerable to HIV infection and as a result use fewer condoms [69]. Behavioral disinhibition has the potential to substantially mitigate or even reverse the impact of PrEP, especially in those conditions once its coverage and effectiveness are poor people [70]. Exact assessments of PrEP's impact on populations could aid leaders and aid in the design of PrEP applications for HIVcontrol efforts [71]. Due to the several clinical trials that showed the effectiveness of tenofovir or tenofovir/FTC against HIV transmission, there is currently a demand for the implementation of such programs. Only those who have not been infected start receiving PrEP. Either Provider-Initiated Testing and Counselling (PITC) or Client-Initiated Testing and Training (CITC, formerly known as Voluntary Counselling and Testing) can be used to detect people without HIV . PrEP coverage relies on people without HIV who are using PrEP. Some will cease taking prescription drugs (non-adherence) [72, 73]. We also modeled an intervention with led to a rise in the usage of contraceptives in client-sex worker contacts in order to look into alternatives to PrEP [74].

Addressing Individual-Level Barriers to PrEP Uptake and Adherence.

PrEP cascades akin to the HIV testing and treatment cascade, individual-level barriers to PrEP uptake and persistence have been discovered [75, 76]. While the details and ordering of these obstacles vary, the phases in the cascades tend to be the same. First, local efforts that boost demand for PrEP are closely correlated with and require awareness of the program [77]. High levels of information among all population members in important populations—not just those who are currently eligible for PrEP—should be goal. In spite of recognizing that risk is dynamic and that a person who is not at risk now might become one in the future, this also helps to foster community support for the use of PrEP. Second, using PrEP is a necessity and may help to clarify non-use among particular high-risk individuals who are aware about PrEP [78, 79], concerns about side effects, attitudes toward medications in general, and readiness to participate in the necessary clinical procedures are all aspects that can contribute to a person's willingness to use PrEP. Disentangling and addressing these components depending on specific people and environments is necessary [80, 81]. Third, the decision to start PrEP relies on an individual's awareness of potential risk, and it has been found that a significant factor in persons who are at risk choosing not to start PrEP is the discrepancy between their perceptions of risk and their actual risks [82,83]. Some experts think that it can be counterproductive to employ risk and risk-avoidance principles when advertising PrEP because such messages is not economical for those who believe that they're in risk [84]. It has been documented by research that it is frequently preferred to frame PrEP in terms of positive results, such as reduced anxiety and improved pleasure or affection [85]. In addition to this so-called "gain-framing" messaging, it might be crucial to simplify risk messaging and concentrate it on specific behaviors [86]. Given that the stigma associated with PrEP and the belief of stigma is a significant barrier to PrEP uptake, this adjustment must be made without stigmatizing these behaviors [87]. Furthermore, those who feel that their episodes of potential risk are not frequent enough to justify daily

CONCLUSION:

The many challenges that women must overcome in order to obtain and use Pre-Exposure Prophylaxis (PrEP) for HIV prevention are brought to light in this review. Inadequate assessment of risk, together with cultural elements and personal challenges, substantially hinders the adoption and conformity of PrEP. To tackle these obstacles, a comprehensive strategy is needed, involving refining risk assessment tools, increasing healthcare professional education, and tackling the stigma that the public associated with HIV and PrEP. To further maximize PrEP's efficiency on decreasing HIV transmission among women, it must be expanded into varied contexts and effective counseling strategies need to be carried out. By addressing these critical issues, we can empower women to make informed decisions about their health and reduce their risk of HIV infection.

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Weiss G, Smith DK, Newman S, Wiener J, Kitlas A, Hoover KW. PrEP implementation by local health departments in US cities and counties: Findings from a 2015 assessment of local health departments. PloS one. 2018 Jul 25;13(7):e0200338.
Frontières MS. Refugee health. An approach to emergency situations. 1997.
Seiffge-Krenke I. Adolescents' health: A developmental perspective. Psychology Press; 2019 Jan 22.
García M, Harris AL. PrEP awareness and decision-making for Latino MSM in San Antonio, Texas. PloS one. 2017 Sep 27;12(9):e0184014.
Gurwitz JH, Field TS, Harrold LR, Rothschild J, Debellis K, Seger AC, Cadoret C, Fish LS, Garber L, Kelleher M, Bates DW. Incidence and preventability of adverse drug events among older persons in the ambulatory setting. Jama. 2003 Mar 5;289(9):1107-16.
Grant RM, Anderson PL, McMahan V, Liu A, Amico KR, Mehrotra M, Hosek S, Mosquera C, Casapia M, Montoya O, Buchbinder S. Uptake of pre-exposure prophylaxis, sexual practices, and HIV incidence in men and transgender women who have sex with men: a cohort study. The Lancet infectious diseases. 2014 Sep 1;14(9):820-9.
Young LE, Schumm P, Alon L, Bouris A, Ferreira M, Hill B, Khanna AS, Valente TW, Schneider JA. PrEP Chicago: A randomized controlled peer change agent intervention to promote the adoption of pre-exposure prophylaxis for HIV prevention among young Black men who have sex with men. Clinical Trials. 2018 Feb;15(1):44-52.
Botnick MR. Reasonable trust: an analysis of sexual risk, trust, and intimacy among gay men (Doctoral dissertation, University of British Columbia).
Jada KS, van den Berg M. Identifying effective message-framing techniques in behaviour change communication for healthy diets: An experimental study of promoting biofortified maize adoption in Ethiopia. Appetite. 2022 Nov 1;178:106263.
Kim HK, Lee TK. Conditional effects of gain–loss-framed narratives among current smokers at different stages of change. Journal of Health Communication. 2017 Dec 2;22(12):990-8.
Calabrese SK. Understanding, contextualizing, and addressing PrEP stigma to enhance PrEP implementation. Current Hiv/Aids Reports. 2020 Dec;17:579-88.

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García M, Harris AL. PrEP awareness and decision-making for Latino MSM in San Antonio, Texas. PloS one. 2017 Sep 27;12(9):e0184014.
Gurwitz JH, Field TS, Harrold LR, Rothschild J, Debellis K, Seger AC, Cadoret C, Fish LS, Garber L, Kelleher M, Bates DW. Incidence and preventability of adverse drug events among older persons in the ambulatory setting. Jama. 2003 Mar 5;289(9):1107-16.
Grant RM, Anderson PL, McMahan V, Liu A, Amico KR, Mehrotra M, Hosek S, Mosquera C, Casapia M, Montoya O, Buchbinder S. Uptake of pre-exposure prophylaxis, sexual practices, and HIV incidence in men and transgender women who have sex with men: a cohort study. The Lancet infectious diseases. 2014 Sep 1;14(9):820-9.
Young LE, Schumm P, Alon L, Bouris A, Ferreira M, Hill B, Khanna AS, Valente TW, Schneider JA. PrEP Chicago: A randomized controlled peer change agent intervention to promote the adoption of pre-exposure prophylaxis for HIV prevention among young Black men who have sex with men. Clinical Trials. 2018 Feb;15(1):44-52.
Botnick MR. Reasonable trust: an analysis of sexual risk, trust, and intimacy among gay men (Doctoral dissertation, University of British Columbia).
Jada KS, van den Berg M. Identifying effective message-framing techniques in behaviour change communication for healthy diets: An experimental study of promoting biofortified maize adoption in Ethiopia. Appetite. 2022 Nov 1;178:106263.
Kim HK, Lee TK. Conditional effects of gain–loss-framed narratives among current smokers at different stages of change. Journal of Health Communication. 2017 Dec 2;22(12):990-8.
Calabrese SK. Understanding, contextualizing, and addressing PrEP stigma to enhance PrEP implementation. Current Hiv/Aids Reports. 2020 Dec;17:579-88.

Manav Kumar

Corresponding author

Student, Faculty of Medical Science and Research, Department of Pharmacy, Sai Nath University, Ranchi, Jharkhand 835219, India