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A modeling study of the Danish HIV epidemic in men who have sex with men: travel, pre-exposure prophylaxis and elimination.

ABSTRACT: UNAIDS has identified the Danish HIV epidemic in men who have sex with men (MSM) as a priority for elimination. Incidence is close to the elimination threshold of one new infection per year per 1,000 individuals. However, surveillance data show that HIV strains are being imported into Denmark, mainly due to travel. We use a transmission model to predict (from 2018 to 2030) the impact of pre-exposure prophylaxis (PrEP) on incidence. Our model reflects the current epidemic and diagnosis rates in the Danish MSM community. We conduct a sensitivity analysis based on 20,000 simulations, and assume that PrEP coverage could range from zero to 50% and diagnosis rates increase up to three-fold. We predict that incidence will fall below the elimination threshold, even without the introduction of PrEP, reaching 0.87 (median, 95% Confidence Interval: 0.65-1.23) new infections per 1,000 MSM by 2030. PrEP could reduce incidence to well below the threshold, if it results in a significant increase in diagnosis rates and reduces the number of infections occurring abroad. The Danish Medicine Agency and Danish Health Authority have recommended introducing PrEP. Our study provides strong support for this recommendation, and shows the importance of Danish MSM using PrEP when abroad.

SUBMITTER: Palk L

PROVIDER: S-EPMC6207710 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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A modeling study of the Danish HIV epidemic in men who have sex with men: travel, pre-exposure prophylaxis and elimination.

Palk Laurence L Gerstoft Jan J Obel Niels N Blower Sally S

Scientific reports 20181030 1

UNAIDS has identified the Danish HIV epidemic in men who have sex with men (MSM) as a priority for elimination. Incidence is close to the elimination threshold of one new infection per year per 1,000 individuals. However, surveillance data show that HIV strains are being imported into Denmark, mainly due to travel. We use a transmission model to predict (from 2018 to 2030) the impact of pre-exposure prophylaxis (PrEP) on incidence. Our model reflects the current epidemic and diagnosis rates in t ...[more]

PMID: 30375426

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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:BackgroundRoutine HIV pre-exposure prophylaxis (PrEP) and HIV care appointments provide opportunities for screening men who have sex with men (MSM) for hepatitis C virus infection (HCV). However, levels of screening required for achieving the WHO elimination target of reducing HCV incidence by 90% by 2030 among all MSM are unknown.MethodsAn HCV/HIV transmission model was calibrated to UK prevalence of HIV among MSM (4·7%) and chronic HCV infection among HIV-positive MSM (9·9%) and HIV-negative MSM (1.2%). Assuming 12·5% coverage of PrEP among HIV-negative MSM, we evaluated the relative reduction in overall HCV incidence by 2030 (compared to 2018 levels) of HCV screening every 12/6-months (alongside completing direct acting antiviral treatment within 6-months of diagnosis) in PrEP users and/or HIV-diagnosed MSM. We estimated the additional screening required among HIV-negative non-PrEP users to reduce overall incidence by 90% by 2030. The effect of 50% reduction in condom use among PrEP users (risk compensation) was estimated.ResultsScreening and treating PrEP users for HCV every 12 or 6-months decreases HCV incidence by 67·3% (uncertainty range 52·7-79·2%) or 70·2% (57·1-80·8%), respectively, increasing to 75·4% (59·0-88·6%) or 78·8% (63·9-90·4%) if HIV-diagnosed MSM are also screened at same frequencies. Risk compensation reduces these latter projections by <10%. To reduce HCV incidence by 90% by 2030 without risk compensation, HIV-negative non-PrEP users require screening every 5·6 (3·8-9·2) years if MSM on PrEP and HIV-diagnosed MSM are screened every 6-months, shortening to 4·4 (3·1-6·6) years with risk compensation. For 25·0% PrEP coverage, the HCV elimination target can be reached without screening HIV-negative MSM not on PrEP, irrespective of risk compensation.InterpretationAt low PrEP coverage, increased screening of all MSM is required to achieve the WHO HCV-elimination targets for MSM in the UK, whereas at higher PrEP coverage this is possible through just screening HIV-diagnosed MSM and PrEP users.

Dataset Information

A modeling study of the Danish HIV epidemic in men who have sex with men: travel, pre-exposure prophylaxis and elimination.

Publications

A modeling study of the Danish HIV epidemic in men who have sex with men: travel, pre-exposure prophylaxis and elimination.

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