Dataset Information

Impact along the HIV pre-exposure prophylaxis "cascade of prevention" in western Kenya: a mathematical modelling study.

ABSTRACT:

Introduction

Over one hundred implementation studies of HIV pre-exposure prophylaxis (PrEP) are completed, underway or planned. We synthesized evidence from these studies to inform mathematical modelling of the prevention cascade for oral and long-acting PrEP in the setting of western Kenya, one of the world's most heavily HIV-affected regions.

Methods

We incorporated steps of the PrEP prevention cascade - uptake, adherence, retention and re-engagement after discontinuation - into EMOD-HIV, an open-source transmission model calibrated to the demography and HIV epidemic patterns of western Kenya. Early PrEP implementation research from East Africa was used to parameterize prevention cascades for oral PrEP as currently implemented, delivery innovations for oral PrEP, and future long-acting PrEP. We compared infections averted by PrEP at the population level for different cascade assumptions and sub-populations on PrEP. Analyses were conducted over the 2020 to 2040 time horizon, with additional sensitivity analyses for the time horizon of analysis and the time when long-acting PrEP becomes available.

Results

The maximum impact of oral PrEP diminished by over 98% across all prevention cascades, with the exception of long-acting PrEP under optimistic assumptions about uptake and re-engagement after discontinuation. Long-acting PrEP had the highest population-level impact, even after accounting for possible delays in product availability, primarily because its effectiveness does not depend on drug adherence. Retention was the most significant cascade step reducing the potential impact of long-acting PrEP. These results were robust to assumptions about the sub-populations receiving PrEP, but were highly influenced by assumptions about re-initiation of PrEP after discontinuation, about which evidence was sparse.

Conclusions

Implementation challenges along the prevention cascade compound to diminish the population-level impact of oral PrEP. Long-acting PrEP is expected to be less impacted by user uptake and adherence, but it is instead dependent on product availability in the short term and retention in the long term. To maximize the impact of long-acting PrEP, ensuring timely product approval and rollout is critical. Research is needed on strategies to improve retention and patterns of PrEP re-initiation.

SUBMITTER: Bershteyn A

PROVIDER: S-EPMC7325506 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Impact along the HIV pre-exposure prophylaxis "cascade of prevention" in western Kenya: a mathematical modelling study.

Bershteyn Anna A Sharma Monisha M Akullian Adam N AN Peebles Kathryn K Sarkar Supriya S Braithwaite R Scott RS Mudimu Edinah E

Journal of the International AIDS Society 20200601

<h4>Introduction</h4>Over one hundred implementation studies of HIV pre-exposure prophylaxis (PrEP) are completed, underway or planned. We synthesized evidence from these studies to inform mathematical modelling of the prevention cascade for oral and long-acting PrEP in the setting of western Kenya, one of the world's most heavily HIV-affected regions.<h4>Methods</h4>We incorporated steps of the PrEP prevention cascade - uptake, adherence, retention and re-engagement after discontinuation - into ...[more]

PMID: 32602669

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Project description:ObjectivesHIV pre-exposure prophylaxis (PrEP) may change serosorting patterns. We examined the influence of serosorting on the population-level HIV transmission impact of PrEP, and how impact could change if PrEP users stopped serosorting.DesignWe developed a compartmental HIV transmission model parameterized with bio-behavioural and HIV surveillance data among MSM in Canada.MethodsWe separately fit the model with serosorting and without serosorting [counterfactual; sero-proportionate mixing (random partner-selection proportional to availability by HIV status)], and reproduced stable HIV epidemics with HIV-prevalence 10.3-24.8%, undiagnosed fraction 4.9-15.8% and treatment coverage 82.5-88.4%. We simulated PrEP-intervention reaching stable pre-specified coverage by year-one and compared absolute difference in relative HIV-incidence reduction 10 years post-intervention (PrEP-impact) between models with serosorting vs. sero-proportionate mixing; and counterfactual scenarios when PrEP users immediately stopped vs. continued serosorting. We examined sensitivity of results to PrEP-effectiveness (44-99%; reflecting varying dosing or adherence levels) and coverage (10-50%).ResultsModels with serosorting predicted a larger PrEP-impact than models with sero-proportionate mixing under all PrEP-effectiveness and coverage assumptions [median (interquartile range): 8.1% (5.5-11.6%)]. PrEP users' stopping serosorting reduced PrEP-impact compared with when PrEP users continued serosorting: reductions in PrEP-impact were minimal [2.1% (1.4-3.4%)] under high PrEP-effectiveness (86-99%); however, could be considerable [10.9% (8.2-14.1%)] under low PrEP effectiveness (44%) and high coverage (30-50%).ConclusionModels assuming sero-proportionate mixing may underestimate population-level HIV-incidence reductions due to PrEP. PrEP-mediated changes in serosorting could lead to programmatically important reductions in PrEP-impact under low PrEP-effectiveness. Our findings suggest the need to monitor sexual mixing patterns to inform PrEP implementation and evaluation.

Project description:HIV pre-exposure prophylaxis (PrEP), the use of antiretroviral drugs by uninfected individuals to prevent HIV infection, has demonstrated effectiveness in preventing acquisition in a high-risk population of men who have sex with men (MSM). Consequently, there is a need to understand if and how PrEP can be used cost-effectively to prevent HIV infection in such populations.We developed a mathematical model representing the HIV epidemic among MSM and transwomen (male-to-female transgender individuals) in Lima, Peru, as a test case. PrEP effectiveness in the model is assumed to result from the combination of a "conditional efficacy" parameter and an adherence parameter. Annual operating costs from a health provider perspective were based on the US Centers for Disease Control and Prevention interim guidelines for PrEP use. The model was used to investigate the population-level impact, cost, and cost-effectiveness of PrEP under a range of implementation scenarios. The epidemiological impact of PrEP is largely driven by programme characteristics. For a modest PrEP coverage of 5%, over 8% of infections could be averted in a programme prioritising those at higher risk and attaining the adherence levels of the Pre-Exposure Prophylaxis Initiative study. Across all scenarios, the highest estimated cost per disability-adjusted life year averted (uniform strategy for a coverage level of 20%, US$1,036-US$4,254) is below the World Health Organization recommended threshold for cost-effective interventions, while only certain optimistic scenarios (low coverage of 5% and some or high prioritisation) are likely to be cost-effective using the World Bank threshold. The impact of PrEP is reduced if those on PrEP decrease condom use, but only extreme behaviour changes among non-adherers (over 80% reduction in condom use) and a low PrEP conditional efficacy (40%) would adversely impact the epidemic. However, PrEP will not arrest HIV transmission in isolation because of its incomplete effectiveness and dependence on adherence, and because the high cost of programmes limits the coverage levels that could potentially be attained.A strategic PrEP intervention could be a cost-effective addition to existing HIV prevention strategies for MSM populations. However, despite being cost-effective, a substantial expenditure would be required to generate significant reductions in incidence. Please see later in the article for the Editors' Summary.

Project description:BackgroundCost-effectiveness studies inform resource allocation, strategy, and policy development. However, due to their complexity, dependence on assumptions made, and inherent uncertainty, synthesising, and generalising the results can be difficult. We assess cost-effectiveness models evaluating expected health gains and costs of HIV pre-exposure prophylaxis (PrEP) interventions.Methods and findingsWe conducted a systematic review comparing epidemiological and economic assumptions of cost-effectiveness studies using various modelling approaches. The following databases were searched (until January 2013): PubMed/Medline, ISI Web of Knowledge, Centre for Reviews and Dissemination databases, EconLIT, and region-specific databases. We included modelling studies reporting both cost and expected impact of a PrEP roll-out. We explored five issues: prioritisation strategies, adherence, behaviour change, toxicity, and resistance. Of 961 studies retrieved, 13 were included. Studies modelled populations (heterosexual couples, men who have sex with men, people who inject drugs) in generalised and concentrated epidemics from Southern Africa (including South Africa), Ukraine, USA, and Peru. PrEP was found to have the potential to be a cost-effective addition to HIV prevention programmes in specific settings. The extent of the impact of PrEP depended upon assumptions made concerning cost, epidemic context, programme coverage, prioritisation strategies, and individual-level adherence. Delivery of PrEP to key populations at highest risk of HIV exposure appears the most cost-effective strategy. Limitations of this review include the partial geographical coverage, our inability to perform a meta-analysis, and the paucity of information available exploring trade-offs between early treatment and PrEP.ConclusionsOur review identifies the main considerations to address in assessing cost-effectiveness analyses of a PrEP intervention--cost, epidemic context, individual adherence level, PrEP programme coverage, and prioritisation strategy. Cost-effectiveness studies indicating where resources can be applied for greatest impact are essential to guide resource allocation decisions; however, the results of such analyses must be considered within the context of the underlying assumptions made. Please see later in the article for the Editors' Summary.

Project description:IntroductionIn Bangalore, new HIV infections of female sex workers and men who have sex with men continue to occur, despite high condom use. Pre-exposure prophylaxis (PrEP) has high anti-HIV efficacy for men who have sex with men. PrEP demonstration projects are underway amongst Indian female sex workers. We estimated the impact and efficiency of prioritizing PrEP to female sex workers and/or men who have sex with men in Bangalore.MethodsA mathematical model of HIV transmission and treatment for female sex workers, clients, men who have sex with men and low-risk groups was parameterized and fitted to Bangalore data. The proportion of transmission attributable (population attributable fraction) to commercial sex and sex between men was calculated. PrEP impact (infections averted, life-years gained) and efficiency (life-years gained/infections averted per 100 person-years on PrEP) were estimated for different levels of PrEP adherence, coverage and prioritization strategies (female sex workers, high-risk men who have sex with men, both female sex workers and high-risk men who have sex with men, or female sex workers with lower condom use), under current conditions and in a scenario with lower baseline condom use amongst key populations.ResultsPopulation attributable fractions for commercial sex and sex between men have declined over time, and they are predicted to account for 19% of all new infections between 2016 and 2025. PrEP could prevent a substantial proportion of infections amongst female sex workers and men who have sex with men in this setting (23%/27% over 5/10 years, with 60% coverage and 50% adherence), which could avert 2.9%/4.3% of infections over 5/10 years in the whole Bangalore population. Impact and efficiency in the whole population was greater if female sex workers were prioritized. Efficiency increased, but impact decreased, if only female sex workers with lower condom use were given PrEP. Greater impact and efficiency was predicted for the scenario with lower condom use.ConclusionsPrEP could be beneficial for female sex workers and men who have sex with men in Bangalore, and give some benefits in the general population, especially in similar settings with lower condom use levels.

Project description:BACKGROUND:Oral pre-exposure prophylaxis (PrEP) prevents HIV infection in men who have sex with men (MSM); however, adherence is an ongoing concern. Long-acting injectable PrEP is being tested in phase 3 trials and could address challenges associated with adherence. We examined the potential effectiveness of long-acting injectable PrEP compared with oral PrEP in MSM. METHODS:We used an agent-based model to simulate HIV transmission in a dynamic network of 11?245 MSM in Atlanta, GA, USA. We used raw data from studies in macaque models and pharmacokinetic data from safety trials to estimate the time-varying efficacy of long-acting injectable PrEP. The effect of long-acting injectable PrEP on the cumulative number of new HIV infections over 10 years (2015-24) was compared with no PrEP and daily oral PrEP across a range of coverage levels. Sensitivity analyses were done with varying maximum efficacy and drug half-life values. FINDINGS:In the absence of PrEP, the model predicted 2374 new HIV infections (95% simulation interval [SI] 2345-2412) between 2015 and 2024. The cumulative number of new HIV infections was reduced in all scenarios in which MSM received long-acting injectable PrEP compared with oral PrEP. At a coverage level of 35%, compared with no PrEP, long-acting injectable PrEP led to a 44% reduction in new HIV infections (1044 new infections averted [95% SI 1018-1077]) versus 33% (792 infections averted [763-821]) for oral PrEP. The relative benefit of long-acting injectable PrEP was sensitive to the assumed efficacy of injections received every 8 weeks, discontinuation rates, and terminal drug half-life. INTERPRETATION:Long-acting injectable PrEP has the potential to produce larger reductions in HIV transmission in MSM than oral PrEP. However, the real-world, population-level impact of this approach will depend on uptake of this prevention method and its effectiveness, as well as retention of patients in clinical care. FUNDING:National Institute on Drug Abuse and National Institute of Mental Health.

Dataset Information

Impact along the HIV pre-exposure prophylaxis "cascade of prevention" in western Kenya: a mathematical modelling study.

Introduction

Methods

Results

Conclusions

Publications

Impact along the HIV pre-exposure prophylaxis "cascade of prevention" in western Kenya: a mathematical modelling study.

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