Numerical approaches for the rapid analysis of prophylactic efficacy against HIV with arbitrary drug-dosing schemes

Pre-exposure prophylaxis (PrEP) is an important pillar to prevent HIV transmission. Because of experimental and clinical shortcomings, mathematical models that integrate pharmacological, viral- and host factors are frequently used to quantify clinical efficacy of PrEP. Stochastic simulations of these models provides sample statistics from which the clinical efficacy is approximated. However, many stochastic simulations are needed to reduce the associated sampling error. To remedy the shortcomings of stochastic simulation, we developed a numerical method that allows predicting the efficacy of arbitrary prophylactic regimen directly from a viral dynamics model, without sampling. We apply the method to various hypothetical dolutegravir (DTG) prophylaxis scenarios. The approach is verified against state-of-the-art stochastic simulation. While the method is more accurate than stochastic simulation, it is superior in terms of computational performance. For example, a continuous 6-month prophylactic profile is computed within a few seconds on a laptop computer. The method’s computational performance, therefore, substantially expands the horizon of feasible analysis in the context of PrEP, and possibly other applications.

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Numerical approaches for the rapid analysis of prophylactic efficacy against HIV with arbitrary drug-dosing schemes

10.1101/2021.07.22.453374 ◽

2021 ◽

Author(s):

Lanxin Zhang ◽

Junyu Wang ◽

Max von Kleist

Keyword(s):

Stochastic Simulation ◽

Clinical Efficacy ◽

Hiv Transmission ◽

Sampling Error ◽

Stochastic Simulations ◽

Laptop Computer ◽

Prophylactic Regimen ◽

Drug Dosing ◽

Computational Performance ◽

Exposure Prophylaxis

Pre-exposure prophylaxis (PrEP) is an important pillar to prevent HIV transmission. Because of experimental and clinical shortcomings, mathematical models that integrate pharmacological, viral- and host factors are frequently used to quantify clinical efficacy of PrEP. Stochastic simulations of these models provides sample statistics from which the clinical efficacy is approximated. However, many stochastic simulations are needed to reduce the associated sampling error. To remedy the shortcomings of stochastic simulation, we developed three numerical methods that allow predicting the efficacy of arbitrary prophylactic regimen directly from a viral dynamics model, without sampling. We apply the methods to various hypothetical dolutegravir (DTG) prophylaxis scenarios. The approaches are verified against one another, as well as state-of-the-art stochastic simulation. While the methods are more accurate than stochastic simulation, they are superior in terms of computational performance. For example, a continuous 6-month prophylactic profile is computed within a few seconds on a laptop computer. The methods' computational performance, therefore, substantially expands the horizon of feasible analysis in the context of PrEP, and possibly other applications.

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986. Improvement in Administration of HIV Post-Exposure Prophylaxis in the Emergency Department Following Sexual Assault

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1172 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S521-S522

Author(s):

Jennifer R Silva-Nash ◽

Stacie Bordelon ◽

Ryan K Dare ◽

Sherrie Searcy

Keyword(s):

Emergency Department ◽

Sexual Assault ◽

Hiv Transmission ◽

Post Exposure Prophylaxis ◽

Intervention Period ◽

Post Intervention ◽

Post Exposure ◽

Assault Victims ◽

Exposure Prophylaxis

Abstract Background Nonoccupational post exposure prophylaxis (nPEP) following sexual assault can prevent HIV transmission. A standardized Emergency Department (ED) protocol for evaluation, treatment, and follow up for post assault victims was implemented to improve compliance with CDC nPEP guidelines. Methods A single-center observational study of post sexual assault patients before/after implementation of an ED nPEP protocol was conducted by comparing the appropriateness of prescriptions, labs, and necessary follow up. A standardized order-set based on CDC nPEP guidelines, with involvement of an HIV pharmacist and ID clinic, was implemented during the 2018-2019 academic year. Clinical data from pre-intervention period (07/2016-06/2017) was compared to post-intervention period (07/2018-08/2019) following a 1-year washout period. Results During the study, 147 post-sexual assault patients (59 Pre, 88 Post) were included. One hundred thirty-three (90.4%) were female, 68 (46.6%) were African American and 133 (90.4%) were candidates for nPEP. Median time to presentation following assault was 12.6 hours. nPEP was offered to 40 (67.8%) and 84 (95.5%) patients (P< 0.001) and ultimately prescribed to 29 (49.2%) and 71 (80.7%) patients (P< 0.001) in pre and post periods respectively. Renal function (37.3% vs 88.6%; P< 0.001), pregnancy (39.0% vs 79.6%; P< 0.001), syphilis (3.4% vs 89.8%; P< 0.001), hepatitis B (15.3% vs 95.5%; P< 0.001) and hepatitis C (27.1% vs 94.3%) screening occurred more frequently during the post period. Labratory, nPEP Prescription and Follow up Details for Patients Prescribed nPEP Conclusion The standardization of an nPEP ED protocol for sexual assault victims resulted in increased nPEP administration, appropriateness of prescription, screening for other sexually transmitted infectious and scheduling follow up care. While guideline compliance dramatically improved, further interventions are likely warranted in this vulnerable population. Disclosures Ryan K. Dare, MD, MS, Accelerate Diagnostics, Inc (Research Grant or Support)

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Couples Living with HIV

Journal of the International Association of Providers of AIDS Care (JIAPAC) ◽

10.1177/2325957415612127 ◽

2016 ◽

Vol 16 (2) ◽

pp. 133-139 ◽

Cited By ~ 6

Author(s):

Violeta J. Rodriguez ◽

Andrew Spence ◽

Mallory Monda ◽

JoNell Potter ◽

Deborah Jones

Keyword(s):

Perceived Risk ◽

Hiv Transmission ◽

Horizontal Transmission ◽

Hiv Status ◽

Safer Conception ◽

Reproductive Intentions ◽

Hiv Prevention Strategies ◽

Exposure Prophylaxis ◽

Living With Hiv ◽

Men’S Involvement

Background: Desires to have children are not lessened by a woman’s HIV status. Couples may lack information to conceive safely, and men may be especially uninformed. This study examined reproductive intentions, practices, and attitudes among men in HIV-infected couples, including attitudes regarding the perceived risk of vertical and horizontal transmission, safer conception, and preconception planning. Methods: Men ( n = 12) in HIV-infected couples were interviewed regarding reproductive intentions, attitudes, and knowledge and qualitative assessments were coded for dominant themes. Results: Themes primarily addressed concerns about the health of the baby, men’s involvement in pregnancy, safer conception, concerns about HIV transmission and antiretroviral therapy, and HIV infection. Men lacked information on safer conception and newer HIV prevention strategies, such as pre-exposure prophylaxis (PrEP). Discussion: Gaps in knowledge regarding preconception practices among men in HIV-infected couples were identified. Results highlight men’s desire for involvement in preconception planning, and opportunities for providers to facilitate this practice and to increase patient education and the use of PrEP are discussed.

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Deviation from Hardy–Weinberg proportions in finite populations

Genetics Research ◽

10.1017/s0016672300034224 ◽

1996 ◽

Vol 68 (3) ◽

pp. 249-257 ◽

Cited By ~ 13

Author(s):

Jinliang Wang

Keyword(s):

Sampling Error ◽

Random Mating ◽

Random Selection ◽

Stochastic Simulations ◽

Gene Frequencies ◽

Dioecious Species ◽

Male And Female ◽

Census Size ◽

Genotype Frequencies ◽

Gene Frequency Difference

SummaryFor a finite diploid population with no mutation, migration and selection, equations for the deviation of observed genotype frequencies from Hardy–Weinberg proportions are derived in this paper for monoecious species and for autosomal and sex-linked loci in dioecious species. It is shown that the genotype frequency deviation in finite random-mating populations results from the difference between the gene frequencies of male and female gametes, which is determined by two independent causes: the gene frequency difference between male and female parents and the sampling error due to the finite number of offspring. Previous studies have considered only one of the causes and the equations derived by previous authors are applicable only in the special case of random selection. The general equations derived here for both causes incorporate the variances and covariances of family size and thus they reduce to previous equations for random selection. Stochastic simulations are run to check the predictions from different formulae. Non-random mating and variation in census size are considered and the applications of the derived formulae are exemplified.

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Is pre-exposure prophylaxis effective and feasible for preventing HIV transmission in adolescent males?

Evidence-Based Practice ◽

10.1097/ebp.0000000000001397 ◽

2021 ◽

Vol Publish Ahead of Print ◽

Author(s):

Herman Tang ◽

Bachir Tazkarji

Keyword(s):

Hiv Transmission ◽

Adolescent Males ◽

Exposure Prophylaxis

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1701. Added Benefits of Pre-exposure Prophylaxis Use on HIV Incidence with Minimal Changes in Efficiency in the Context of High Treatment Engagement among Men Who Have Sex with Men

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1879 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S833-S833

Author(s):

Alyson L Singleton ◽

Brandon D Marshall ◽

Xiao Zang ◽

Amy S Nunn ◽

William C Goedel

Keyword(s):

African American ◽

Hiv Infection ◽

Hiv Transmission ◽

Treatment Engagement ◽

Hiv Incidence ◽

Black African ◽

African American Msm ◽

Sex With Men ◽

Exposure Prophylaxis ◽

High Treatment

Abstract Background Although there is ongoing debate over the need for substantial increases in PrEP use when antiretroviral treatment confers the dual benefits of reducing HIV-related morbidity and mortality and the risk of HIV transmission, no studies to date have quantified the potential added benefits of PrEP use in settings with high treatment engagement across variable sub-epidemics in the United States. Methods We used a previously published agent-based network model to simulate HIV transmission in a dynamic network of 17,440 Black/African American and White MSM in Atlanta, Georgia from 2015 to 2024 to understand how the magnitude of reductions in HIV incidence attributable to varying levels of PrEP use (0–90%) changes in potential futures where high levels of treatment engagement (i.e. the UNAIDS ‘90-90-90’ goals and eventual ‘95-95-95’ goals) are achieved and maintained, as compared to current levels of treatment engagement in Atlanta (Figure 1). Model inputs related to HIV treatment engagement among Black/African American and White men who have sex with men in Atlanta. A comparison of current levels of treatment engagement (Panel A) to treatment engagement at ‘90-90-90’ (Panel B) and ‘95-95-95’ goals (Panel C). Results Even at achievement and maintenance of ‘90-90-90’ goals, 75% PrEP coverage reduced incidence rates by an additional 67.9% and 74.2% to 1.53 (SI: 1.39, 1.70) and 0.355 (SI: 0.316, 0.391) per 100 person-years for Black/African American and White MSM, respectively (Figure 2), compared to the same scenario with no PrEP use. Additionally, an increase from 15% PrEP coverage to 75% under ‘90-90-90’ goals only increased person-years of PrEP use per HIV infection averted, a measure of efficiency of PrEP, by 8.1% and 10.5% to 26.7 (SI: 25.6, 28.0) and 73.3 (SI: 70.6, 75.7) among Black/African American MSM and White MSM, respectively (Figure 3). Overall (Panel A) and race-stratified (Panel B and Panel C) marginal changes in HIV incidence over ten years among Black/African American and White men who have sex with men in Atlanta across scenarios of varied levels of treatment engagement among agents living with HIV infection and levels of pre-exposure prophylaxis use among HIV-uninfected agents. Note: All changes are calculated within each set of treatment scenarios relative to a scenario where no agents use pre-exposure prophylaxis. Person-years of pre-exposure prophylaxis use per HIV infection averted among Black/African American (Panel A) and White (Panel B) men who have sex with men in Atlanta across scenarios of varied levels of treatment engagement among agents living with HIV infection and levels of pre-exposure prophylaxis use among HIV-uninfected agents. Note: The number of HIV infections averted is calculated within each set of treatment scenarios relative to a scenario where no agents use pre-exposure prophylaxis. Conclusion Even in the context of high treatment engagement, substantial expansion of PrEP use still contributes to meaningful decreases in HIV incidence among MSM with minimal changes in person-years of PrEP use per HIV infection averted, particularly for Black/African American MSM. Disclosures All Authors: No reported disclosures

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Development and Initial Validation of a Stochastic Discrete Event Simulation to Assess Disaster Preparedness

Prehospital and Disaster Medicine ◽

10.1017/s1049023x19002528 ◽

2019 ◽

Vol 34 (s1) ◽

pp. s118-s118

Author(s):

Mattias Lantz Cronqvist ◽

Carl-Oscar Jonson ◽

Erik Prytz

Keyword(s):

Stochastic Simulation ◽

Emergency Preparedness ◽

Disaster Preparedness ◽

Discrete Event ◽

Geographical Location ◽

Simulation System ◽

Simulation Software ◽

Stochastic Simulations ◽

Preventable Death ◽

Analog Simulation

Introduction:Assessing disaster preparedness in a given region is a complex problem. Current methods are often resource-intensive and may lack generalizability beyond a specific scenario. Computer-based stochastic simulations may be an additional method but would require systems that are valid, flexible, and easy to use. Emergo Train System (ETS) is an analog simulation system used for disaster preparedness assessments.Aim:To digitalize the ETS model and develop stochastic simulation software for improved disaster preparedness assessments.Methods:A simulation software was developed in C#. The simulation model was based on ETS. Preliminary verification and validation (V&V) tests were performed, including unit and integration testing, trace validation, and a comparison to a prior analog ETS disaster preparedness assessment exercise.Results:The software contains medically validated patients from ETS and is capable of automatically running disaster scenarios with stochastic variations in the injury panorama, available resources, geographical location, and other variables. It consists of two main programs: an editor where scenarios can be constructed and a simulation system to evaluate the outcome. Initial V&V testing showed that the software is reliable and internally consistent. The comparison to the analog exercise showed a general high agreement in terms of patient outcome. The analog exercise featured a train derailment with 397 injured, of which 45 patients suffered preventable death. In comparison, the computer simulation ran 100 iterations of the same scenario and indicated that a median of 41 patients (IQR 31 to 44) would suffer a preventable death.Discussion:Stochastic simulation methods can be a powerful complement to traditional capability assessments methods. The developed simulation software can be used for both assessing emergency preparedness with some validity and as a complement to analog capability assessment exercises, both as input and to validate results. Future work includes comparing the simulation to real disaster outcomes.

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Homo adhaerens: Risk and adherence in biomedical HIV prevention research

Social Studies of Science ◽

10.1177/0306312720933943 ◽

2020 ◽

Vol 50 (6) ◽

pp. 860-880

Author(s):

Clay Davis

Keyword(s):

Clinical Trials ◽

Hiv Prevention ◽

The United States ◽

Magic Bullet ◽

Prevention Research ◽

Prophylactic Regimen ◽

Hiv Therapy ◽

Making Sense ◽

Biomedical Hiv Prevention ◽

Exposure Prophylaxis

After the turn of the millennium, HIV clinical researchers pivoted from developing and testing new antiretrovirals (ARVs) for treatment, to reconfiguring the same molecules for pre-exposure prophylaxis (PrEP). In 2012, Truvada became the first HIV therapy to also be approved by the FDA for PrEP, regarded as a magic bullet that promised to end the epidemic. However, six years after its approval, it continues to be inaccessible to those who are most vulnerable. In this article, I critically analyze HIV PrEP clinical trials, dissecting the novel techniques researchers use to demonstrate efficacy. I argue that in making sense of the interplay between adherence to a prophylactic regimen and risk for HIV, biomedical HIV prevention research has revealed a new subject of biopolitics, Homo adhaerens. In the early 2000s, clinical researchers operating in the Global South identified Homo adhaerens as the ideal subject, one who embodies both high-risk behavior and diligent adherence to a daily oral regimen. I trace the construction of Homo adhaerens to the United States, where I listen closely to activists engaged with the ongoing DISCOVER trial of PrEP. Activists either aspire for Homo adhaerens as a standard, making the liberal argument that expanding access could make PrEP successful, or they rebuke the framework of clinical research that produces narrow understandings of adherence, efficacy, and universality. Ultimately, I argue that by failing to grapple with the social realities that underlie poor adherence, PrEP clinical trials produce knowledge that is not useful for those who are most vulnerable.

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What do patients consulting in a free STI center know about HIV transmission and prevention?

European Journal of Public Health ◽

10.1093/eurpub/ckz186.613 ◽

2019 ◽

Vol 29 (Supplement_4) ◽

Author(s):

C Duteil ◽

E de La Rochebrochard ◽

P Piron ◽

C Segouin ◽

P Troude

Keyword(s):

Hiv Prevention ◽

Screening Test ◽

Hiv Transmission ◽

Needle Exchange ◽

Treatment As Prevention ◽

False Beliefs ◽

Hiv Knowledge ◽

Unprotected Sexual Intercourse ◽

Prevention Messages ◽

Exposure Prophylaxis

Abstract Background Despite therapeutic progress, HIV remains a public health issue with about 6400 new HIV contaminations each year in France. HIV prevention relies on health education, early screening, treatment as prevention, post and pre-exposure prophylaxis. Patients’ visits to free sexually transmitted infections (STIs) screening centers (CeGIDD) are opportunities to spread prevention messages. This study aimed to assess level of HIV knowledge in a Parisian CeGIDD to improve prevention messages. Methods The study included patients older than 18 who came for STIs testing between August 2017 and August 2018 and who understand written French language. Data were collected by a self-administered electronic questionnaire filled in before medical consultation. It included sociodemographic data and knowledge regarding HIV transmission and prevention. Results The study included 2002 patients. The median age was 27 years and 66% were men. More than 96% of patients know that HIV transmission is possible through unprotected sexual intercourse and through needle exchange. However, some misconceptions persist: 20% of patients believe that HIV transmission is possible from using public toilets and 22% by mosquito bite. Prevention measures perceived as “absolutely or rather efficient” by patients were: using condom (97%), requesting a screening test from his partners (91%), getting screening tests regularly (90%), choosing his partners correctly (62%), having sex with few different partners (50%). Half of patients heard of post-exposure prophylaxis (51%). Conclusions Main modes of HIV transmission are well known (unprotected intercourse and needle exchange). However, false beliefs regarding prevention may lead to risk behavior (doing screening test regularly doesn’t protect against HIV) and need to be explored. Moreover, assessment of variation in level of HIV knowledge according to patient’s profile may help to target prevention message according to specific populations. Key messages Main modes of HIV transmission are well known. False beliefs regarding modes of prevention need to be explored to target HIV prevention messages.

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