HIV pre-exposure prophylaxis and health and community systems in the Global South: Thailand case study.
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SUBMITTER: Colby D
PROVIDER: S-EPMC4509899 | biostudies-other | 2015
REPOSITORIES: biostudies-other
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HIV pre-exposure prophylaxis and health and community systems in the Global South: Thailand case study.
Colby Donn D Srithanaviboonchai Kriengkrai K Vanichseni Suphak S Ongwandee Sumet S Phanuphak Nittaya N Martin Michael M Choopanya Kachit K Chariyalertsak Suwat S van Griensven Frits F
Journal of the International AIDS Society 20150720 4 Suppl 3
<h4>Introduction</h4>Pre-exposure prophylaxis (PrEP) is recommended by the World Health Organization as an effective method of HIV prevention for individuals at risk for infection. In this paper, we describe the unique role that Thailand has played in the global effort to combat the HIV epidemic, including its role in proving the efficacy of PrEP, and discuss the opportunities and challenges of implementing PrEP in a middle-income country.<h4>Discussion</h4>Thailand was one of the first countrie ...[more]
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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:BackgroundRapid easy-to-use HIV tests offer opportunities to increase HIV testing among populations at risk of infection. We used the OraQuick Rapid HIV-1/2 antibody test (OraQuick) in the Bangkok Tenofovir Study, an HIV pre-exposure prophylaxis trial among people who inject drugs.MethodsThe Bangkok Tenofovir Study was a randomized, double-blind, placebo-controlled trial. We tested participants' oral fluid for HIV using OraQuick monthly and blood using a nucleic-acid amplification test (NAAT) every 3 months. We used Kaplan-Meier methods to estimate the duration from a positive HIV NAAT until the mid-point between the last non-reactive and first reactive oral fluid test and proportional hazards to examine factors associated with the time until the test was reactive.ResultsWe screened 3678 people for HIV using OraQuick. Among 447 with reactive results, 436 (97.5%) were confirmed HIV-infected, 10 (2.2%) HIV-uninfected, and one (0.2%) had indeterminate results. Two participants with non-reactive OraQuick results were, in fact, HIV-infected at screening yielding 99.5% sensitivity, 99.7% specificity, a 97.8% positive predictive value, and a 99.9% negative predictive value. Participants receiving tenofovir took longer to develop a reactive OraQuick (191.8 days) than participants receiving placebo (16.8 days) (p = 0.02) and participants infected with HIV CRF01_AE developed a reactive OraQuick earlier than participants infected with other subtypes (p = 0.04).DiscussionThe oral fluid HIV test performed well at screening, suggesting it can be used when rapid results and non-invasive tools are preferred. However, participants receiving tenofovir took longer to develop a reactive oral fluid test result than those receiving placebo. Thus, among people using pre-exposure prophylaxis, a blood-based HIV test may be an appropriate choice.Trial registrationClinicalTrials.gov NCT00119106.
| S-EPMC4696659 | biostudies-literature
Project description:The year 2016 will mark an important milestone - the 35th anniversary of the first reported cases of HIV/AIDS. Antiretroviral Therapy (ART) including Highly Active Antiretroviral Therapy (HAART) drug regimens is widely considered to be one of the greatest achievements in therapeutic drug research having transformed HIV infection into a chronically managed disease. Unfortunately, the lack of widespread preventive measures and the inability to eradicate HIV from infected cells highlight the significant challenges remaining today. Moving forward there are at least three high priority goals for anti-HIV drug delivery (DD) research: (1) to prevent new HIV infections from occurring, (2) to facilitate a functional cure, i.e., when HIV is present but the body controls it without drugs and (3) to eradicate established infection. Pre-exposure Prophylaxis (PrEP) represents a significant step forward in preventing the establishment of chronic HIV infection. However, the ultimate success of PrEP will depend on achieving sustained antiretroviral (ARV) tissue concentrations and will require strict patient adherence to the regimen. While first generation long acting/extended release (LA/ER) DD Systems (DDS) currently in development show considerable promise, significant DD treatment and prevention challenges persist. First, there is a critical need to improve cell specificity through targeting in order to selectively achieve efficacious drug concentrations in HIV reservoir sites to control/eradicate HIV as well as mitigate systemic side effects. In addition, approaches for reducing cellular efflux and metabolism of ARV drugs to prolong effective concentrations in target cells need to be developed. Finally, given the current understanding of HIV pathogenesis, next generation anti-HIV DDS need to address selective DD to the gut mucosa and lymph nodes. The current review focuses on the DDS technologies, critical challenges, opportunities, strategies, and approaches by which novel delivery systems will help iterate towards prevention, functional cure and eventually the eradication of HIV infection.
| S-EPMC4879940 | biostudies-literature
Project description:BackgroundMultiple prevention measures have the possibility of impacting HIV incidence in South Korea, including early diagnosis, early treatment, and pre-exposure prophylaxis (PrEP). We investigated how each of these interventions could impact the local HIV epidemic, especially among men who have sex with men (MSM), who have become the major risk group in South Korea. A mathematical model was used to estimate the effects of each these interventions on the HIV epidemic in South Korea over the next 40 years, as compared to the current situation.MethodsWe constructed a mathematical model of HIV infection among MSM in South Korea, dividing the MSM population into seven groups, and simulated the effects of early antiretroviral therapy (ART), early diagnosis, PrEP, and combination interventions on the incidence and prevalence of HIV infection, as compared to the current situation that would be expected without any new prevention measures.ResultsOverall, the model suggested that the most effective prevention measure would be PrEP. Even though PrEP effectiveness could be lessened by increased unsafe sex behavior, PrEP use was still more beneficial than the current situation. In the model, early diagnosis of HIV infection was also effectively decreased HIV incidence. However, early ART did not show considerable effectiveness. As expected, it would be most effective if all interventions (PrEP, early diagnosis and early treatment) were implemented together.ConclusionsThis model suggests that PrEP and early diagnosis could be a very effective way to reduce HIV incidence in South Korea among MSM.
| S-EPMC3963840 | 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
Project description:Tenofovir diphosphate (TFV-DP) concentrations measured with dried blood spots (DBS) can be used to classify adherence to emtricitabine/tenofovir disoproxil fumarate (F/TDF) for HIV pre-exposure prophylaxis (PrEP). A TFV-DP of 700 fmol/punch was previously associated with high PrEP efficacy, and was estimated to represent ≥4 doses/week on average. However, interindividual variability in TFV-DP concentrations may lead to adherence misclassification and decrease the precision of adherence-efficacy relationships. The purpose of this analysis was to evaluate sources of TFV-DP variability to improve the precision of TFV-DP for adherence assessments by incorporating individual characteristics. Data and samples from a 36-week study of TFV-DP in DBS, collected biweekly, among 48 HIV-negative volunteers (25 Females/26 Caucasian/10 African American/14 Hispanic) receiving F/TDF at 33%, 67%, and 100% of daily dosing under directly observed therapy were used for analysis. The simplest pharmacokinetic model to describe TFV-DP accumulation with acceptable performance was a one-compartment constant input model. Covariates, including laboratory values and demographics were ranked in importance of their association with post hoc pharmacokinetic (PK) parameters using random forest analyses. Weight and platelet count were included in the final model and simulations were conducted to generate benchmarks for <2, 2-3, 4-5, and 6-7 doses/week. Based on these simulations, the previously established protective TFV-DP concentration of ≥700 fmol/punch was observed in those taking 2-3 (in individuals ≤110 kg) and ≥4 (in individuals >110 kg) doses/week, amounting to a much lower rate of misspecification (17% vs. 30%) with this individualized model versus previous interpretations. Incorporating body weight and platelet count improved the precision of TFV-DP concentrations for adherence assessments. Previous benchmarks were conservative, indicating that the pharmacological forgiveness of F/TDF may be higher than currently recognized and supports continued investigation of intermittent PrEP dosing regimens. Clinical Trial Registration number, NCT02022657.
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Project description:Women experiencing incarceration (WEI) in the United States are disproportionately impacted by HIV, yet HIV pre-exposure prophylaxis (PrEP) is underutilized by women in the United States. In order to inform an intervention to promote PrEP initiation during incarceration and facilitate linkage to PrEP care following release from incarceration, we conducted individual, semistructured qualitative interviews with WEI (N = 21) and key stakeholders (N = 14). While WEI had little or no previous knowledge about PrEP, they viewed it as something that would benefit women involved in the criminal justice system. Participants stated that HIV-related stigma and underestimation of HIV risk might serve as barriers to PrEP initiation during incarceration. Participants reported that competing priorities, difficulty scheduling an appointment, and lack of motivation could interfere with linkage to PrEP care in the community. Further, cost, substance use, and difficulty remembering to take the medication were cited most commonly as likely barriers to adherence.
| S-EPMC8189628 | biostudies-literature
Project description:Adolescents are a critical population that is disproportionately impacted by the HIV epidemic. More than 2 million adolescents between the age group of 10 and 19 years are living with HIV, and millions are at risk of infection. HIV risks are considerably higher among girls, especially in high-prevalence settings such as eastern and southern Africa. In addition to girls, there are other vulnerable adolescent subgroups, such as teenagers, who use intravenous (IV) drugs, gay and bisexual boys, transgender youth, male sex workers, and people who fall into more than one of these categories. Pre-exposure prophylaxis (PrEP) is a new intervention for people at high risk for acquiring HIV, with an estimated HIV incidence of >3%. Recent data from trials show evidence of the efficacy of PrEP as a powerful HIV prevention tool in high-risk populations, including men who have sex with men, HIV-1-serodiscordant heterosexual couples, and IV drug users. The reported efficacy in those trials of the daily use of oral tenofovir, alone or in combination with emtricitabine, to prevent HIV infection ranged from 44% to 75% and was heavily dependent on adherence. Despite the proven efficacy of PrEP in adult trials, concerns remain about its feasibility in real-life scenarios due to stigma, cost, and limited clinician experience with PrEP delivery. Recent studies are attempting to expand the inquiry into the efficacy of such HIV prophylaxis approaches in adolescent populations, but there are still many gaps in knowledge, and no country has yet approved it for use with adolescents. The aim of this review was to identify and summarize the evidence from studies on PrEP for adolescents. We have compiled and reviewed published studies focusing on safety, feasibility, adherence to therapeutics, self-perception, and legal issues related to PrEP in people aged between 10 and 24 years.
| S-EPMC5716324 | biostudies-literature
Project description:BACKGROUND:There is now strong evidence that preventive oral antiretroviral therapy can moderately reduce likelihood of HIV infection. This concept is called HIV pre-exposure prophylaxis (PrEP). Premature closures of some previous PrEP clinical trials, secondary to ethical concerns, did not stop research. We aimed to appraise the extent of ethics considerations reporting in PrEP study documents. METHODS:We conducted a systematic quantitative ethics appraisal, grounded in PrEP literature and using eight principles proposed by Ezechiel Emanuel. We developed an a priori checklist of 101 evidence-based ethics items. We obtained protocols for eleven of nineteen clinical controlled studies identified. Two reviewers independently appraised study documents against the checklist. Ethics appraisal was synthesized using adjusted percentages of items reported. RESULTS:On average, 58% of the 101 ethics items were mentioned or addressed in documents, with variations noted both across studies and across principles. Considerations pertaining to social value were least reported (43% of checklist items, on average) whereas considerations related to informed consent and favorable risk-benefit ratio were most reported (75% of checklist items, on average). DISCUSSION:Some PrEP studies reportedly address more ethics considerations than others but, overall, ethics considerations reporting could be much improved. While this review does not allow us to comment on the actual execution of HIV PrEP trials, it is a reminder that optimism generated by potentially effective interventions should not overshadow the importance of ethics in research design and development. Improving ethics reporting might improve the perceived value of PrEP research and subsequent data.
| S-EPMC3151244 | biostudies-literature
Project description:When taken consistently, pre-exposure prophylaxis (PrEP) against human immunodeficiency virus (HIV) with once daily tenofovir disoproxil fumarate-emtricitabine (TDF-FTC) has been shown to safely reduce the incidence of HIV infection in high-risk individuals by more than 90%. Yet, according to the Centers for Disease Control and Prevention, there were about 2.1 million new cases of HIV reported worldwide in 2015. Undoubtedly, there is significant room for improvement to prevent the transmission of HIV. Research to date has been heavily focused on the high-risk men who have sex with men (MSM) population, yet, many women worldwide remain at high risk of HIV transmission. PrEP offers women a protection method that is discrete, does not require partner consent, and may be compatible with both contraception or conception as desired. However, women often remain under-represented in HIV prevention literature and are reported to have lower real-world uptake in comparison to men. Furthermore, clinical trials that do focus on the female population demonstrate mixed efficacy results that highlight the adherence challenges in this population. It is essential to identify factors that contribute to PrEP non-adherence as well as barriers to preventative treatment. This review will discuss the clinical evidence behind PrEP in women, current barriers to use afflicting this population, pharmacotherapy considerations for the female patient, alternative and future agents, and the current real-world application of PrEP.
| S-EPMC5595773 | biostudies-other