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HIV-1 self-testing to improve the efficiency of pre-exposure prophylaxis delivery: a randomized trial in Kenya.

ABSTRACT: BACKGROUND:The introduction of pre-exposure prophylaxis (PrEP) for human immunodeficiency virus-1 (HIV-1) prevention in Africa presents new challenges for health systems that are already overburdened because PrEP delivery requires frequent clinic visits (generally every 3 months) for HIV-1 testing and PrEP refills. HIV-1 self-testing (HIVST) has the potential to improve the efficiency of PrEP delivery by decreasing the number of clinic visits. Here, we describe the rationale and design of a randomized, noninferiority trial designed to test the effectiveness and safety of using HIVST to support PrEP delivery in Kenya. METHODS:The JiPime-JiPrEP (Kiswahili for 'Test Yourself, PrEP Yourself') study is a three-arm randomized trial taking place in Thika, Kenya. Participants (n =?495) are eligible for enrollment if they are at least 18?years old, HIV-1 seronegative, and have been taking PrEP for 1 month. Three distinct participant types will be enrolled: men (n =?165) and women (n =?165) who are in mutually disclosed HIV-1 serodiscordant relationships, and women (n =?165) who are at HIV-1 risk and not in a known serodiscordant relationship. Participants in each of these subpopulations will be 1:1:1 randomized to: 1) the standard of care, with quarterly clinic visits; 2) oral HIVST, with biannual clinic visits plus oral HIVSTs to use at the quarters between those visits; or 3) blood-based HIVST, with biannual clinic visits plus blood-based HIVSTs. All participants will complete quantitative surveys and provide blood samples for the objective measurement of PrEP adherence at baseline, 6?months, and 12?months. The primary outcomes are PrEP adherence, PrEP continuation, and HIV-1 testing, measured at 6?months and secondarily at 12?months. DISCUSSION:The findings from this trial can help to understand how HIVST-a new HIV-1 testing technology-can support health systems in sub-Saharan Africa. Additionally, the findings can inform policy aimed at improving the efficiency of PrEP implementation and scale-up in Kenya. TRIAL REGISTRATION:ClinicalTrials.gov, NCT03593629 . Retrospectively registered on 20 July 2018.

SUBMITTER: Ortblad KF

PROVIDER: S-EPMC6610957 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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HIV-1 self-testing to improve the efficiency of pre-exposure prophylaxis delivery: a randomized trial in Kenya.

Ortblad Katrina F KF Kearney John E JE Mugwanya Kenneth K Irungu Elizabeth M EM Haberer Jessica E JE Barnabas Ruanne V RV Donnell Deborah D Mugo Nelly Rwamba NR Baeten Jared M JM Ngure Kenneth K

Trials 20190704 1

<h4>Background</h4>The introduction of pre-exposure prophylaxis (PrEP) for human immunodeficiency virus-1 (HIV-1) prevention in Africa presents new challenges for health systems that are already overburdened because PrEP delivery requires frequent clinic visits (generally every 3 months) for HIV-1 testing and PrEP refills. HIV-1 self-testing (HIVST) has the potential to improve the efficiency of PrEP delivery by decreasing the number of clinic visits. Here, we describe the rationale and design o ...[more]

PMID: 31272495

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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.

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.

Project description:BACKGROUND:Antiretroviral-based interventions for HIV-1 prevention, including antiretroviral therapy (ART) to reduce the infectiousness of HIV-1 infected persons and pre-exposure prophylaxis (PrEP) to reduce the susceptibility of HIV-1 uninfected persons, showed high efficacy for HIV-1 protection in randomized clinical trials. We conducted a prospective implementation study to understand the feasibility and effectiveness of these interventions in delivery settings. METHODS AND FINDINGS:Between November 5, 2012, and January 5, 2015, we enrolled and followed 1,013 heterosexual HIV-1-serodiscordant couples in Kenya and Uganda in a prospective implementation study. ART and PrEP were offered through a pragmatic strategy, with ART promoted for all couples and PrEP offered until 6 mo after ART initiation by the HIV-1 infected partner, permitting time to achieve virologic suppression. One thousand thirteen couples were enrolled, 78% of partnerships initiated ART, and 97% used PrEP, during a median follow-up of 0.9 years. Objective measures of adherence to both prevention strategies demonstrated high use (?85%). Given the low HIV-1 incidence observed in the study, an additional analysis was added to compare observed incidence to incidence estimated under a simulated counterfactual model constructed using data from a prior prospective study of HIV-1-serodiscordant couples. Counterfactual simulations predicted 39.7 HIV-1 infections would be expected in the population at an incidence of 5.2 per 100 person-years (95% CI 3.7-6.9). However, only two incident HIV-1 infections were observed, at an incidence of 0.2 per 100 person-years (95% CI 0.0-0.9, p < 0.0001 versus predicted). The use of a non-concurrent comparison of HIV-1 incidence is a potential limitation of this approach; however, it would not have been ethical to enroll a contemporaneous population not provided access to ART and PrEP. CONCLUSIONS:Integrated delivery of time-limited PrEP until sustained ART use in African HIV-1-serodiscordant couples was feasible, demonstrated high uptake and adherence, and resulted in near elimination of HIV-1 transmission, with an observed HIV incidence of <0.5% per year compared to an expected incidence of >5% per year.

Project description:IntroductionIn public clinics in Kenya, separate, sequential delivery of the component services of pre-exposure prophylaxis (PrEP) (e.g. HIV testing, counselling, and dispensing) creates long wait times that hinder clients' ability and desire to access and continue PrEP. We conducted a mixed methods study in four public clinics in western Kenya to identify strategies for operationalizing a one-stop shop (OSS) model and evaluate whether this model could improve client wait time and care acceptability among clients and providers without negatively impacting uptake or continuation.MethodsFrom January 2020 through November 2020, we collected and analysed 47 time-and-motion observations using Mann-Whitney U tests, 29 provider and client interviews, 68 technical assistance reports, and clinic flow maps from intervention clinics. We used controlled interrupted time series (cITS) to compare trends in PrEP initiation and on-time returns from a 12-month pre-intervention period (January-December 2019) to an 8-month post-period (January-November 2020, excluding a 3-month COVID-19 wash-out period) at intervention and control clinics.ResultsFrom the pre- to post-period, median client wait time at intervention clinics dropped significantly from 31 to 6 minutes (p = 0.02), while median provider contact time remained around 23 minutes (p = 0.4). Intervention clinics achieved efficiency gains by moving PrEP delivery to lower volume departments, moving steps closer together (e.g. relocating supplies; cross-training and task-shifting), and differentiating clients based on the subset of services needed. Clients and providers found the OSS model highly acceptable and additionally identified increased privacy, reduced stigma, and higher quality client-provider interactions as benefits of the model. From the pre- to post-period, average monthly initiations at intervention and control clinics increased by 6 and 2.3, respectively, and percent of expected follow-up visits occurring on time decreased by 18% and 26%, respectively; cITS analysis of PrEP initiations (n = 1227) and follow-up visits (n = 2696) revealed no significant difference between intervention and control clinics in terms of trends in PrEP initiation and on-time returns (all p>0.05).ConclusionsAn OSS model significantly improved client wait time and care acceptability without negatively impacting initiations or continuations, thus highlighting opportunities to improve the efficiency of PrEP delivery efficiency and client-centredness.

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.

Project description:As pre-exposure prophylaxis (PrEP) effectiveness is strongly linked to adherence, we sought to determine if certain self-report measures could be used to inform objective PrEP adherence. We studied participants from the TAPIR study (a multicenter randomized study of daily text messages to support adherence to PrEP In At-Risk), a 48-week randomized controlled trial of HIV-uninfected men who have sex with men (MSM) randomized to receive text message to support adherence versus standard of care. Self-reported medication adherence was assessed using several validated measures modified for PrEP. Objective PrEP adherence was determined through dried blood spot (DBS) measurement of intracellular tenofovir diphosphate (TFV-DP) and emtricitabine triphosphate (FTC-TP). A summary of adherence was estimated using responses to the seven adherence items at weeks 12 and 48 using confirmatory factor analysis. Correlations between self-report questions and drug concentrations were estimated with Pearson's correlations for continuous outcomes and point-biserial correlations for dichotomous outcomes. Receiver operating characteristic (ROC) analyses were conducted to assess the performance of self-report measures in predicting protective or perfect TFV-DP concentrations. Of the 369 participants who completed week 12 or 48 visits, the mean age was 35 (standard deviation 9 years), with 79% White, 12% Black, and 29% Hispanic. Correlations between self-report measures of adherence (both individual items and the adherence factor) and quantifiable FTC-TP and continuous TFV-DP concentrations showed that all self-report measures were significantly associated with these objective measures. Compared to a summary measure of self-reported adherence, the 4-week percent taken question medication recall was the only self-report item similarly or more strongly associated with recent adherence and long-term protective and perfect adherence at weeks 12 and 48. ROC analysis also showed that 4-week percent taken question had a reasonable AUC (0.798 at week 12 and 0.758 at week 48) in predicting protective TFV-DP concentrations. All single-item self-report questions assessing PrEP adherence were significantly associated with biomarker quantification, with the 4-week percent taken question performing best. Therefore, in the absence of drug concentration measurements, a 4-week self-report percent taken question may be a good single-item measure of PrEP adherence.

Project description:PrEP awareness and uptake among men who have sex with men (MSM) and transgender women (TG) in Thailand remains low. Finding ways to increase HIV testing and PrEP uptake among high-risk groups is a critical priority. This study evaluates the effect of a novel Adam's Love Online-to-Offline (O2O) model on PrEP and HIV testing uptake among Thai MSM and TG and identifies factors associated with PrEP uptake.The O2O model was piloted by Adam's Love (www.adamslove.org) HIV educational and counselling website. MSM and TG reached online by PrEP promotions and interested in free PrEP and/or HIV testing services contacted Adam's Love online staff, received real-time PrEP eCounseling, and completed online bookings for receiving services at one of the four sites in Bangkok based on their preference. Auto-generated site- and service-specific e-tickets and Quick Response (QR) codes were sent to their mobile devices enabling monitoring and check-in by offline site staff. Service uptake and participant's socio-demographic and risk behaviour characteristics were analyzed. Factors associated with PrEP uptake were assessed using multiple logistic regression.Between January 10th and April 11th, 2016, Adam's Love reached 272,568 people online via the PrEP O2O promotions. 425 MSM and TG received eCounseling and e-tickets. There were 325 (76.5%) MSM and TG who checked-in at clinics and received HIV testing. Nine (2.8%) were diagnosed with HIV infection. Median (IQR) time between receiving the e-ticket and checking-in was 3 (0-7) days. Of 316 HIV-negative MSM and TG, 168 (53.2%) started PrEP. In a multivariate model, higher education (OR 2.30, 95%CI 1.14-4.66; p = 0.02), seeking sex partners online (OR 2.05, 95%CI 1.19-3.54; p = 0.009), being aware of sexual partners' HIV status (OR 2.37, 95%CI 1.29-4.35; p = 0.008), ever previously using post-exposure prophylaxis (PEP) (OR 2.46, 95%CI 1.19-5.09; p = 0.01), and enrolment at Adam's Love clinic compared to the other three sites (OR 3.79, 95%CI 2.06-6.95; p < 0.001) were independently associated with PrEP uptake.Adam's Love O2O model is highly effective in linking online at-risk MSM and TG to PrEP and HIV testing services, and has high potential to be replicated and scaled up in other settings with high Internet penetration among key populations.

Dataset Information

HIV-1 self-testing to improve the efficiency of pre-exposure prophylaxis delivery: a randomized trial in Kenya.

Publications

HIV-1 self-testing to improve the efficiency of pre-exposure prophylaxis delivery: a randomized trial in Kenya.

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