Dataset Information

Mathematical modelling of the influence of serosorting on the population-level HIV transmission impact of pre-exposure prophylaxis.

ABSTRACT:

Objectives

HIV 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.

Design

We developed a compartmental HIV transmission model parameterized with bio-behavioural and HIV surveillance data among MSM in Canada.

Methods

We 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%).

Results

Models 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%).

Conclusion

Models 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.

SUBMITTER: Wang L

PROVIDER: S-EPMC8183492 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Mathematical modelling of the influence of serosorting on the population-level HIV transmission impact of pre-exposure prophylaxis.

Wang Linwei L Moqueet Nasheed N Simkin Anna A Knight Jesse J Ma Huiting H Lachowsky Nathan J NJ Armstrong Heather L HL Tan Darrell H S DHS Burchell Ann N AN Hart Trevor A TA Moore David M DM Adam Barry D BD Macfadden Derek R DR Baral Stefan S Mishra Sharmistha S

AIDS (London, England) 20210601 7

<h4>Objectives</h4>HIV 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.<h4>Design</h4>We developed a compartmental HIV transmission model parameterized with bio-behavioural and HIV surveillance data among MSM in Canada.<h4>Methods</h4>We separately fit the model with serosorting and without serosorting [counterfactual; se ...[more]

PMID: 33534205

Similar Datasets

Project description:IntroductionOver 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.MethodsWe 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.ResultsThe 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.ConclusionsImplementation 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.

Project description:IntroductionAffordable HIV prevention tools are needed in Eastern and Southern Africa (ESA). Several promising long-acting pre-exposure prophylaxis (LA-PrEP) products are available or in development. However, ESA settings face severe healthcare resource constraints. We aimed to estimate the threshold price at which LA-PrEP products could be cost-effective in three ESA settings.MethodsWe adapted an agent-based model, EMOD-HIV, to simulate LA-PrEP (monthly oral, 2- and 6-monthly injectable) rollout in South Africa, Zimbabwe and Kenya. Due to uncertainties about LA-PrEP use, we examined a range of coverages (5%-20% of HIV-negative sexually active adults) and extents to which LA-PrEP use will be concentrated among those most at risk (prioritized rollout from higher- to lower-risk groups vs. uniform rollout among sexually active adults). To evaluate a 20-year commitment to LA-PrEP delivery, we assumed LA-PrEP was scaled up to target coverage from 2025 to 2030 and maintained at target levels before ending in 2045. We estimated maximum per-dose and per-year LA-PrEP costs that achieve cost-effectiveness (<US$500 per disability-adjusted life-year averted) over 35 years (until 2060), compared to a scenario of daily oral PrEP only. Sensitivity analyses varied PrEP scale-up speeds and eligible populations.ResultsRisk-prioritized LA-PrEP for 5% of adults was projected to avert 11-21% of HIV acquisitions across settings, with 3-5 times more HIV acquisitions averted and 3-5 times higher maximum cost compared to non-prioritized rollout. Six-monthly injectable PrEP supported the highest per-dose cost: in the scenario with the most cost-effective LA-PrEP use (5% risk-prioritized rollout), the maximum per-dose price in South Africa was $52.99 (95% CI: $48.82-$57.21), in Zimbabwe $14.64 (95% CI: $12.04-$17.38) and in western Kenya $7.50 (95% CI: $6.73-$8.27). For monthly oral PrEP, corresponding per-dose costs were $5.02 (95% CI: $4.67-$5.37), $1.45 (95% CI: $1.10-$1.79) and $0.87 (95% CI: $0.80-$0.93). Results were sensitive to eligible population and prioritization, and moderately sensitive to scale-up speed and product effectiveness.ConclusionsLA-PrEP is likely to require reduced pricing and/or risk-prioritized rollout to be cost-effective in ESA.

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:IntroductionHIV pre-exposure prophylaxis (PrEP) has been recommended and partly subsidized in Québec, Canada, since 2013. We evaluated the population-level impact of PrEP on HIV transmission among men who have sex with men (MSM) in Montréal, Québec's largest city, over 2013-2021.MethodsWe used an agent-based mathematical model of sexual HIV transmission to estimate the fraction of HIV acquisitions averted by PrEP compared to a counterfactual scenario without PrEP. The model was calibrated to local MSM survey, surveillance, and cohort data and accounted for COVID-19 pandemic impacts on sexual activity, HIV prevention, and care. PrEP was modelled from 2013 onwards, assuming 86% individual-level effectiveness. The PrEP eligibility criteria were: any anal sex unprotected by condoms (past 6 months) and either multiple partnerships (past 6 months) or multiple uses of post-exposure prophylaxis (lifetime). To assess potential optimization strategies, we modelled hypothetical scenarios prioritizing PrEP to MSM with high sexual activity (≥11 anal sex partners annually) or aged ⩽45 years, increasing coverage to levels achieved in Vancouver, Canada (where PrEP is free-of-charge), and improving retention.ResultsOver 2013-2021, the estimated annual HIV incidence decreased from 0.4 (90% credible interval [CrI]: 0.3-0.6) to 0.2 (90% CrI: 0.1-0.2) per 100 person-years. PrEP coverage among HIV-negative MSM remained low until 2015 (<1%). Afterwards, coverage increased to a maximum of 10% of all HIV-negative MSM, or about 16% of the 62% PrEP-eligible HIV-negative MSM in 2020. Over 2015-2021, PrEP averted an estimated 20% (90% CrI: 11%-30%) of cumulative HIV acquisitions. The hypothetical scenarios modelled showed that, at the same coverage level, prioritizing PrEP to high sexual activity MSM could have averted 30% (90% CrI: 19%-42%) of HIV acquisitions from 2015-2021. Even larger impacts could have resulted from higher coverage. Under the provincial eligibility criteria, reaching 10% coverage among HIV-negative MSM in 2015 and 30% in 2019, like attained in Vancouver, could have averted up to 63% (90% CrI: 54%-70%) of HIV acquisitions from 2015 to 2021.ConclusionsPrEP reduced population-level HIV transmission among Montréal MSM. However, our study suggests missed prevention opportunities and adds support for public policies that reduce PrEP barriers, financial or otherwise, to MSM at risk of HIV acquisition.

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.

Dataset Information

Mathematical modelling of the influence of serosorting on the population-level HIV transmission impact of pre-exposure prophylaxis.

Objectives

Design

Methods

Results

Conclusion

Publications

Mathematical modelling of the influence of serosorting on the population-level HIV transmission impact of pre-exposure prophylaxis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets