Planning for pre-exposure prophylaxis to prevent HIV transmission: challenges and opportunities.
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ABSTRACT:
SUBMITTER: Kim SC
PROVIDER: S-EPMC2914050 | biostudies-literature | 2010 Jul
REPOSITORIES: biostudies-literature
Publications
Planning for pre-exposure prophylaxis to prevent HIV transmission: challenges and opportunities.
Kim Susan C SC Becker Stephen S Dieffenbach Carl C Hanewall Blair S BS Hankins Catherine C Lo Ying-Ru YR Mellors John W JW O'Reilly Kevin K Paxton Lynn L Roffenbender Jason S JS Warren Mitchell M Piot Peter P Dybul Mark R MR
Journal of the International AIDS Society 20100712
There are currently several ongoing or planned trials evaluating the efficacy of pre-exposure prophylaxis (PrEP) as a preventative approach to reducing the transmission of HIV. PrEP may prove ineffective, demonstrate partial efficacy, or show high efficacy and have the potential to reduce HIV infection in a significant way. However, in addition to the trial results, it is important that issues related to delivery, implementation and further research are also discussed. As a part of the ongoing d ...[more]
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Project description:There are 34 million people living with human immunodeficiency virus (HIV) worldwide and each year this number increases. Until a vaccine is discovered, the prevention of new HIV infections remains an urgent priority. Several trials studying the use of oral and topical agents for the prevention of HIV infection have already been completed. Adherence has proved to be a major challenge in achieving product efficacy.To provide the clinical pharmacist with an understanding of the oral pre-exposure prophylaxis (PrEP) and topical microbicide product pipeline whilst emphasizing the critical importance of adherence to these drugs to avert HIV infection.PubMed/Medline and the web-based clinical trials registry (ClinTrials.gov) were searched using appropriate key words. For the time period 1992-2013--all phase II and phase III safety and effectiveness studies--testing agents for prevention of HIV infection were included in the review. Efficacy estimates, adherence estimates and reported challenges with adherence were extracted.Twenty-four phase II and III clinical trials were found during review. Of these, 20 trials have been completed, and six trials show effectiveness in preventing HIV infection. The majority of the successful trials were to oral PrEP and to date only one microbicide trial of a vaginal antiretroviral microbicide gel has showed effectiveness. Adherence to study product played a major role in trial outcomes and there are several reasons for non-adherence. These include high on-trial pregnancy rates, low trial retention rates, low participant perception of risk, participant characteristics such as age <25 years, single status, migratory partners and trial fatigue. Study product characteristics such as dosage form, dosing interval, as well as associated adverse events may also influence adherence.Moderate to high adherence is critical to demonstrate efficacy of drugs for HIV prevention. For topical agents, intermittent use associated with coitus is more effective than daily use, particularly if sex is infrequent or partners migrant. For oral agents, daily use is effective but the motivation to use the drug and high risk perception is important. In serodiscordant couples, early initiation of highly active antiretroviral therapy in the infected partner affords almost complete protection to the negative partner. Drugs need to be tailored to the population at risk and availability of multiple drug options are important.
| S-EPMC3947256 | biostudies-other
Project description:The US Food and Drug Administration (FDA) approved oral daily tenofovir/emtricitabine (Truvada) for pre-exposure prophylaxis of human immunodeficiency virus (HIV) infection in 2012 on the basis of two randomized controlled trials (RCTs), one in men who have sex with men (MSM) and another in HIV serodiscordant heterosexual couples. Subsequently, even greater efficacy has been demonstrated in MSM with rapid population-level incidence reductions in some locations. In contrast, studies of antiretroviral pre-exposure prophylaxis (PrEP) in heterosexual women showed only modest or no efficacy, largely attributed to low adherence. The mixed results of antiretroviral-based PrEP bear witness to unique drug development challenges at this complicated intersection of sexual behavior, public health, and drug development. Multiple innovative methods and formulation strategies followed to address unmet medical needs of persons struggling with daily oral PrEP adherence or preference for nonsystemic PrEP options. Clinical pharmacology plays essential roles throughout this PrEP development process, especially in early product development and through pharmacologically informed enhancement and interpretation of clinical trials.
| S-EPMC6925668 | biostudies-literature
Project description:Following US Food and Drugs Administration approval in July 2012 of daily oral tenofovir and emtricitabine for pre-exposure prophylaxis (PrEP) to prevent HIV infection in high-risk individuals in the USA, there has been much controversy about the implementation of this PrEP regimen in other countries throughout the world, and in Europe in particular. In this review, we focus on the challenges and opportunities of a daily oral PrEP regimen to curb the rising incidence of HIV infection in high-risk groups, and particularly in men who have sex with men. A number of issues would need to be addressed before PrEP could be implemented, including assessing the real effectiveness and cost-effectiveness of daily PrEP, the sustainability of daily adherence, the risk of selecting resistance, the long-term safety, and the risk of change in sexual behavior that might offset the benefit of PrEP. Alternatives to a daily oral PrEP regimen are being explored.
| S-EPMC3751938 | biostudies-other
Project description:Preventing new HIV infections remains a global challenge. Young women continue to bear a disproportionate burden of infection. Oral pre-exposure prophylaxis (PrEP), offers a novel women-initiated prevention technology and PrEP trials completed to date underscore the importance of their inclusion early in trials evaluating new HIV PrEP technologies. Data from completed topical and systemic PrEP trials highlight the role of gender specific physiological and social factors that impact PrEP uptake, adherence and efficacy. Here we review the past and current developments of HIV-1 prevention options for women with special focus on PrEP considering the diverse factors that can impact PrEP efficacy. Furthermore, we highlight the importance of inclusion of female scientists, clinicians, and community advocates in scientific efforts to further improve HIV prevention strategies.
| S-EPMC9763292 | biostudies-literature
Project description:Pre-exposure prophylaxis (PrEP) has emerged as a promising strategy for preventing the transmission of HIV. Although only one formulation is currently approved for PrEP, research into both new compounds and new delivery systems for PrEP regimens offer intriguing challenges from the perspective of pharmacokinetic and pharmacodynamic modeling. This review aims to provide an overview the current modeling landscape for HIV PrEP, focused on PK/PD and QSP models relating to antiretroviral agents. Both current PrEP treatments and new compounds that show promise as PrEP agents are highlighted, as well as models of uncommon administration routes, predictions based on models of mechanism of action and viral dynamics, and issues related to adherence to therapy. The spread of human immunodeficiency virus (HIV) remains one of the foremost global health concerns. In the absence of a vaccine, other prophylactic strategies have been developed to prevent HIV transmission. One approach, known as pre-exposure prophylaxis (PrEP), allows HIV-negative individuals who are at high risk of exposure to the virus, be it through an HIV-positive sexual partner or through the shared use of drug injection equipment, to substantially reduce the risk of developing an HIV infection. PrEP is a relatively recent approach to combating the HIV epidemic, with the only currently approved treatment being Truvada, a daily oral antiretroviral (ARV) therapy initially indicated in the treatment of active HIV-1 infections, but approved for HIV PrEP in 2012. Although PrEP therapy has consistently demonstrated high efficacy in preventing HIV infection, this efficacy is dependent on patient adherence to the prescribed treatment regimen. This can present a significant problem in low- and middle-income countries, which may lack the infrastructure to provide sufficient access to PrEP medication to maintain daily dosing regimens. Furthermore, while the conventional approach has generally been to advocate for continuous administration akin to regimens used for viral suppression in infected patients, there has been some discussion of whether a better treatment paradigm might be to push for PrEP therapy primarily during those known periods of heightened exposure risk, while relying on post-exposure prophylaxis regimens to prevent infection after unanticipated exposures during low-risk periods. These considerations have led to a push for the development of long-duration and on-demand PrEP formulations, including subdermal and subcutaneous implants, slow-release intramuscular depot injections, vaginal and rectal antimicrobial gels, and intravaginal rings and dissolving films. PrEP therapy is a quickly evolving field, with a variety of antiretroviral compounds and formulations under investigation. This review aims to report on notable drugs and formulations from a pharmacokinetic/pharmacodynamic (PK/PD) modeling perspective. Given the nature of PrEP as a preventive therapy designed for long-term use, clinical trials for PrEP therapies can last for months or even years, particularly in the case of long-duration formulations. Furthermore, in contrast to antiretroviral trials in infected patients, pharmacodynamic endpoints in PrEP therapies are difficult to quantify, as the primary endpoint for efficacy is generally the rate of seroconversion. Computational modeling approaches offer flexible and powerful tools to provide insight into drug behavior in clinical settings, and can ultimately reduce the time, expense, and patient burden incurred in the development of PrEP therapies.
| S-EPMC7005100 | biostudies-literature
Project description:IntroductionOral pre-exposure prophylaxis (PrEP) is increasingly being implemented in sub-Saharan Africa. Adolescent girls and young women (AGYW) in Kenya contribute more than half of all new infections among young people aged 15-24 years, highlighting the need for evidence on the cost of PrEP in real-world implementation to inform the budget impact, cost-effectiveness, and financial sustainability of PrEP programs.MethodsWe estimated the cost of delivering PrEP to AGYW enrolled in a PrEP implementation study in two family planning clinics in Kisumu county, located in western Kenya. We derived total annual costs and the average cost per client-month of PrEP by input type (variable or fixed) and visit type (initiation or follow-up). We estimated all costs as implemented in the study, and under implementation by the Kenyan Ministry of Health (MoH), both at the program volume observed and if the facilities were delivering PrEP at full capacity (scaled-MoH).ResultsFor the costing period between March 2018 and March 2019, 615 HIV-negative women contributed 1,128 (502 initiation and 626 follow-up) visits. The average cost per client-month of PrEP dispensed per study protocol and per the MoH scenario was $28.92 and $14.52, respectively. If the MoH scaled the program so that facilities could see PrEP clients at capacity, the average cost per client-month of PrEP was $10.88. Medication costs accounted for the largest proportion of the total annual costs (48% in MoH scenario and 65% in the scaled-MoH scenario).ConclusionsUsing data from a PrEP implementation program, we found that the cost per client-month of PrEP dispensed is reduced by 62% if PrEP delivery at the two clinics is scaled up by the MoH. Our findings are valuable for informing local resource allocation and budgetary cost projections for scale-up of PrEP delivery to AGYW. Additionally, previous cost-effectiveness studies have been limited by the use of fixed assumptions of the cost of PrEP per person-month. Our study provides cost estimates from practical data which will better inform cost-effectiveness and budget impact analyses.
| S-EPMC8049260 | biostudies-literature
Project description:Clinical trials have recently demonstrated the effectiveness of Pre-Exposure Prophylaxis (PrEP) in preventing HIV infection. Consequently, PrEP may soon be used for epidemic control. We model the dynamic interactions that will occur between treatment programs and potential PrEP interventions in resource-constrained countries. We determine the consequences for HIV transmission and drug resistance. We use response hypersurface modeling to predict the effect of PrEP on decreasing transmission as a function of effectiveness, adherence and coverage. We predict PrEP will increase need for second-line therapies (SLT) for treatment-naïve individuals, but could significantly decrease need for SLT for treatment-experienced individuals. If the rollout of PrEP is carefully planned it could increase the sustainability of treatment programs. If not, need for SLT could increase and the sustainability of treatment programs could be compromised. Our results show the optimal strategy for rolling out PrEP in resource-constrained countries is to begin around the "worst" treatment programs.
| S-EPMC3240958 | biostudies-literature
Project description:IntroductionGiven the synergistic relationship between HIV and sexually transmitted infections (STI), the integration of services has the potential to reduce the incidence of both HIV and STIs. We explored the extent to which STI testing has been offered within HIV pre-exposure prophylaxis (PrEP) programmes worldwide.MethodsWe conducted a systematic review of PrEP programmes implementing STI testing services in nine databases. We approached PrEP implementers for additional unpublished data and implementation details. Descriptive statistics were used to present the characteristics of STI testing within PrEP programmes. Content analysis of the input from PrEP implementers was conducted to summarize the barriers to and facilitators of STI testing.ResultsOf 9,161 citations, 91 studies conducted in 32 countries were included: 69% from high-income countries (HICs) and 64% from programmes targeting men who have sex with men (MSM) and transgender women (TGW) only. The majority of programmes (70%, 64/91) conducted STI testing before the initiation of PrEP. The most common STIs tested were gonorrhoea (86%, 78/91), chlamydia (84%, 76/91) and syphilis (84%, 76/91). The majority provided STI testing at three-month intervals (70%, 53/76, for syphilis; 70% 53/78, for chlamydia; 68%, 53/78, for gonorrhoea). Relative to low- and middle-income countries (LMICs), a higher proportion of PrEP programmes in HICs offered testing for gonorrhoea (92% vs. 71%, p < 0.05), chlamydia (92% vs. 64%, p < 0.01), syphilis (87% vs. 75%, p < 0.05), hepatitis A (18% vs. 4%, p < 0.05) and hepatitis C (43% vs. 21%, p < 0.05); offered testing for a higher number of STIs (mean 3.75 vs. 3.04, p < 0.05); and offered triple (throat, genital/urine and anorectal) anatomical site screening (54% vs. 18%, p < 0.001). Common implementation challenges included costs, access to STI diagnostics, programme logistics of integrating STI testing into PrEP delivery models and lack of capacity building for staff involved in PrEP provision.ConclusionsSignificant gaps and challenges remain in the provision of STI testing services within HIV PrEP programmes. We recommend more active integration of STI testing and management into PrEP programmes, supported by standardized practice guidelines, staff capacity building training and adequate funding. This could lead to improved sexual health and HIV outcomes in key populations.
| S-EPMC7893146 | biostudies-literature
Project description:IntroductionPoor or inconsistent adherence to daily oral pre-exposure prophylaxis (PrEP) has emerged as a key barrier to effective HIV prevention. The advent of potent long-acting (LA) antiretrovirals (ARVs) in conjunction with advances in controlled release technologies has enabled LA ARV drug delivery systems (DDS) capable of providing extended dosing intervals and overcome the challenge of suboptimal drug adherence with daily oral dosing.Areas coveredThis review discusses the current state of the LA PrEP field, recent advances, and emerging technologies, including ARV prodrug modifications and new DDS. Technological challenges, knowledge gaps, preclinical testing considerations, and future directions important in the context of clinical translation and implementation of LA HIV PrEP are discussed.Expert opinionThe HIV prevention field is evolving faster than ever and the bar for developing next-generation LA HIV prevention options continues to rise. The requirements for viable LA PrEP products to be implemented in resource-limited settings are challenging, necessitating proactive consideration and product modifications during the design and testing of promising new candidates. If successfully translated, next-generation LA PrEP that are safe, affordable, highly effective, and accepted by both end-users and key stakeholders will offer significant potential to curb the HIV pandemic.
| S-EPMC9639748 | biostudies-literature
Project description:There is increasing evidence that the use of antiretroviral agents (ARVs) can be a safe and effective means of preventing HIV infection. In fact, a combination of ARVs, tenofovir-emtricitabine, was recently approved by the US Food and Drug Administration (FDA) for use as "pre-exposure prophylaxis"(PrEP), and the US Centers for Disease Control and other regulatory authorities have issued guidance concerning PrEP use. Clinicians and policy makers are now faced with questions about the appropriateness of prescribing ARVs to healthy persons who are at risk of becoming infected with HIV, and those at risk of being infected must decide whether to use PrEP. In addition, researcher stakeholders must grapple with determining whether and how PrEP should be included in future HIV prevention research. In addressing such issues, it is important that their ethical dimensions are identified. When using PrEP, 2 broad ethical domains are of special relevance: well-being and justice. Ethical issues related to well-being include safety, parameters of use, risk behaviors, resistance, stigma, and diversion. Those related to justice include access and competing priorities. In research involving PrEP, ethical issues include determining the appropriate control arm and whether PrEP should be included as a part of the prevention package provided to all at risk participants. Although PrEP could play an important role in HIV prevention, understanding and addressing the related ethical issues is critical to its safe, effective, and appropriate use in practice and future research.
| S-EPMC3728665 | biostudies-other