Publications
69 results found
Wong NS, Chan KCW, Wong BCK, et al., 2019, Latent tuberculosis infection testing strategies for HIV-positive individuals in Hong Kong., JAMA Network Open, Vol: 2, Pages: 1-12, ISSN: 2574-3805
Importance: With immune recovery following early initiation of antiretroviral therapy (ART), the risk of tuberculosis (TB) reactivation among individuals with HIV could be reduced. The current strategy of annual latent TB infection (LTBI) testing should be revisited to increase cost-effectiveness and reduce the intensity of testing for individuals. Objective: To analyze the cost-effectiveness of LTBI testing strategies for individuals in Hong Kong with HIV who had negative LTBI test results at baseline. Design, Setting, and Participants: This decision analytical model study using a cost-effectiveness analysis included 3130 individuals with HIV in Hong Kong, China, which has an intermediate TB burden and a low incidence of HIV-TB coinfection. A system dynamics model of individuals with HIV attending a major HIV specialist clinic in Hong Kong was developed and parameterized by longitudinal clinical and LTBI testing records of patients during a 15-year period. The study population was stratified by age group, CD4 lymphocyte level, ART status, and right of abode. Alternative strategies for LTBI testing after a baseline test were compared with annual testing under different coverages of ART, LTBI testing, and LTBI treatment scenarios in the model. An annual discounting rate of 3.5% was used in cost-effectiveness analysis. Main Outcomes and Measures: Proportion of new TB cases averted above base case scenario, discounted quality-adjusted life-years gained (QALYG), incremental cost, and incremental cost-effectiveness ratios in 2017 to 2023. Results: A total of 3130 patients with HIV (2740 [87.5%] male and 2800 [89.5%] younger than 50 years at HIV diagnosis) with 16 630 person-years of follow-up data from 2002 to 2017 were analyzed. Of these, 94 patients (0.67 [95% CI, 0.51-0.91] per 100 person-years) developed TB. Model estimates of cumulative number of TB cases would reach 146 by 2023, with the annual number of new TB diagnoses ranging from 6 to 8. For patients who had ne
Shacklett BL, Blanco J, Hightow-Weidman L, et al., 2019, HIV Research for Prevention 2018: From research to impact: Conference summary and highlights, AIDS Research and Human Retroviruses, Vol: 35, Pages: 598-607, ISSN: 0889-2229
The HIV Research for Prevention (HIVR4P) conference is dedicated to advancing HIV prevention research, responding to a growing consensus that effective and durable prevention will require a combination of approaches as well as unprecedented collaboration among scientists, practitioners, and community workers from different fields and geographic areas. The conference theme in 2018, “From Research to Impact,” acknowledged an increasing focus on translation of promising research findings into practical, accessible, and affordable HIV prevention options for those who need them worldwide. HIVR4P 2018 was held in Madrid, Spain, on 21–25 October, with >1,400 participants from 52 countries around the globe, representing all aspects of HIV prevention research and implementation. The program included 137 oral and 610 poster presentations. This article presents a brief summary of highlights from the conference. More detailed information, complete abstracts as well as webcasts and daily Rapporteur summaries may be found on the conference website.
Mitchell KM, Hoots B, German D, et al., 2019, Improvements in the HIV care continuum needed to meaningfully reduce HIV incidence among men who have sex with men in Baltimore, US: a modelling study for HPTN 078, Journal of the International AIDS Society, Vol: 22, ISSN: 1758-2652
Introduction HIV prevalence is high among men who have sex with men (MSM) in Baltimore, Maryland, United States, and levels of viral suppression among HIV-positive MSM are relatively low. The HIV Prevention Trials Network (HPTN) 078 trial seeks to increase levels of viral suppression among US MSM by increasing rates of diagnosis and linkage to care and treatment. We estimated the increases in viral suppression needed to reach different HIV incidence reduction targets, and the impact of meeting diagnosis and treatment targets.Methods: We used a mathematical model of HIV transmission among MSM from Baltimore, US, parameterised with behavioural data and fitted to HIV prevalence and care continuum data for Baltimore wherever possible, to project increases in viral suppression needed to reduce the HIV incidence rate among Baltimore MSM by 10, 20, 30, or 50% after 2, 5, and 10 years. We also projected HIV incidence reductions achieved if US national targets – 90% of people living with HIV (PLHIV) know their HIV serostatus, 90% of those diagnosed are retained in HIV medical care and 80% of those diagnosed are virally suppressed - or UNAIDS 90-90-90 targets (90% of PLHIV know their status, 90% of those diagnosed receive antiretroviral therapy (ART), 90% of those receiving ART are virally suppressed) are each met by 2020.Results: To reduce the HIV incidence rate by 20% and 50% after 5 years (compared with the base-case at the same time point), the proportion of all HIV-positive MSM who are virally suppressed must increase above 2015 levels by a median 13 percentage points (95% uncertainty interval 9-16 percentage points) from median 49% to 60%, and 27 percentage points (22-35) from 49% to 75%, respectively. Meeting all three US or 90-90-90 UNAIDS targets results in a 48% (31-63%) and 51% (38-65%) HIV incidence rate reduction in 2020, respectively. Conclusions: Substantial improvements in levels of viral suppression will be needed to achieve significant incidence reduct
Silhol R, Boily M-C, Dimitrov D, et al., 2018, Understanding HIV Transmission Dynamics and the Impact of Past HIV Interventions Among MSM in Baltimore: A Modelling Study for HPTN 078, HIV Research for Prevention Meeting (HIVR4P) - AIDS Vaccine, Microbicide and ARV-Based Prevention Science, Publisher: MARY ANN LIEBERT, INC, Pages: 283-283, ISSN: 0889-2229
Stannah J, Dale E, Elmes J, et al., 2018, Sub-optimal Engagement of African MSM in the HIV Treatment Cascade: A Systematic Review and Meta-analysis, HIV Research for Prevention Meeting (HIVR4P) - AIDS Vaccine, Microbicide and ARV-Based Prevention Science, Publisher: MARY ANN LIEBERT, INC, Pages: 404-404, ISSN: 0889-2229
Mitchell K, Elmes J, Dimitrov D, et al., 2018, Potential Impact of Increased ART and PrEP Coverage on the HIV Epidemic Among MSM in Atlanta: Mathematical Modelling for HPTN 078, HIV Research for Prevention Meeting (HIVR4P) - AIDS Vaccine, Microbicide and ARV-Based Prevention Science, Publisher: MARY ANN LIEBERT, INC, Pages: 81-81, ISSN: 0889-2229
Dale E, Stannah J, Elmes J, et al., 2018, Increases Over Time in HIV Testing Among MSM in Africa: A Systematic Review and Meta-analysis, HIV Research for Prevention Meeting (HIVR4P) - AIDS Vaccine, Microbicide and ARV-Based Prevention Science, Publisher: MARY ANN LIEBERT, INC, Pages: 403-403, ISSN: 0889-2229
Tang W, Wei C, Cao B, et al., 2018, Crowdsourcing to expand HIV testing among men who have sex with men in China: A closed cohort stepped wedge cluster randomized controlled trial, PLOS MEDICINE, Vol: 15, ISSN: 1549-1676
BackgroundHIV testing rates are suboptimal among at-risk men. Crowdsourcing may be a useful tool for designing innovative, community-based HIV testing strategies to increase HIV testing. The purpose of this study was to use a stepped wedge cluster randomized controlled trial (RCT) to evaluate the effect of a crowdsourced HIV intervention on HIV testing uptake among men who have sex with men (MSM) in eight Chinese cities.Methods and findingsAn HIV testing intervention was developed through a national image contest, a regional strategy designathon, and local message contests. The final intervention included a multimedia HIV testing campaign, an online HIV testing service, and local testing promotion campaigns tailored for MSM. This intervention was evaluated using a closed cohort stepped wedge cluster RCT in eight Chinese cities (Guangzhou, Shenzhen, Zhuhai, and Jiangmen in Guangdong province; Jinan, Qingdao, Yantai, and Jining in Shandong province) from August 2016 to August 2017. MSM were recruited through Blued, a social networking mobile application for MSM, from July 29 to August 21 of 2016. The primary outcome was self-reported HIV testing in the past 3 months. Secondary outcomes included HIV self-testing, facility-based HIV testing, condom use, and syphilis testing. Generalized linear mixed models (GLMMs) were used to analyze primary and secondary outcomes. We enrolled a total of 1,381 MSM. Most were ≤30 years old (82%), unmarried (86%), and had a college degree or higher (65%). The proportion of individuals receiving an HIV test during the intervention periods within a city was 8.9% (95% confidence interval [CI] 2.2–15.5) greater than during the control periods. In addition, the intention-to-treat analysis showed a higher probability of receiving an HIV test during the intervention periods as compared to the control periods (estimated risk ratio [RR] = 1.43, 95% CI 1.19–1.73). The intervention also increased HIV self-testing (RR = 1.89, 95% CI 1
Mitchell KM, Dimitrov D, Hughes J, et al., 2018, In what circumstances could non-daily pre-exposure prophylaxis for HIV substantially reduce program costs?, AIDS, Vol: 32, Pages: 809-818, ISSN: 0269-9370
Objectives:To review the main factors influencing the costs of nondaily oral pre-exposure prophylaxis (PrEP) with tenofovir ( emtricitabine). To estimate the costreductions possible with nondaily PrEP compared with daily PrEP for different popula-tions (MSM and heterosexual populations).Design:Systematic review and data triangulation.Methods:We estimated the required number of tablets/person/week for dosing regi-mens used in the HPTN 067/ADAPT (daily/time-driven/event-driven) and IPERGAY (on-demand) trials for different patterns of sexual intercourse. Using trial data, andbehavioural and cost data obtained through systematic literature reviews, we estimatedcost savings resulting from tablet reductions for nondaily versus daily oral PrEP,assuming 100% adherence.Results:Among different populations being prioritized for PrEP, the median reportednumber of days of sexual activity varied between 0 and 2days/week (0–1.5days/weekfor MSM, 1–2days/week for heterosexual populations). With 100% adherence and twoor fewer sex-days/week, HPTN 067/ADAPT nondaily regimens reduced the number oftablets/week by more than 40% compared with daily PrEP. PrEP program costs werereduced the most in settings with high drug costs, for example, by 66–69% with event-driven PrEP for French/US populations reporting on average one sex-day/week.Conclusion:Nondaily oral PrEP could lower costs substantially (>50%) compared withdaily PrEP, particularly in high-income countries. Adherence and efficacy data areneeded to determine cost-effectiveness.
Sucharitakul K, Boily MC, Dimitrov D, et al., 2018, Influence of model assumptions about HIV disease progression after initiating or stopping treatment on estimates of infections and deaths averted by scaling up antiretroviral therapy, PLoS ONE, Vol: 13, ISSN: 1932-6203
BackgroundMany mathematical models have investigated the population-level impact of expanding antiretroviral therapy (ART), using different assumptions about HIV disease progression on ART and among ART dropouts. We evaluated the influence of these assumptions on model projections of the number of infections and deaths prevented by expanded ART.MethodsA new dynamic model of HIV transmission among men who have sex with men (MSM) was developed, which incorporated each of four alternative assumptions about disease progression used in previous models: (A) ART slows disease progression; (B) ART halts disease progression; (C) ART reverses disease progression by increasing CD4 count; (D) ART reverses disease progression, but disease progresses rapidly once treatment is stopped. The model was independently calibrated to HIV prevalence and ART coverage data from the United States under each progression assumption in turn. New HIV infections and HIV-related deaths averted over 10 years were compared for fixed ART coverage increases.ResultsLittle absolute difference (<7 percentage points (pp)) in HIV infections averted over 10 years was seen between progression assumptions for the same increases in ART coverage (varied between 33% and 90%) if ART dropouts reinitiated ART at the same rate as ART-naïve MSM. Larger differences in the predicted fraction of HIV-related deaths averted were observed (up to 15pp). However, if ART dropouts could only reinitiate ART at CD4<200 cells/μl, assumption C predicted substantially larger fractions of HIV infections and deaths averted than other assumptions (up to 20pp and 37pp larger, respectively).ConclusionDifferent disease progression assumptions on and post-ART interruption did not affect the fraction of HIV infections averted with expanded ART, unless ART dropouts only re-initiated ART at low CD4 counts. Different disease progression assumptions had a larger influence on the fraction of HIV-related deaths averted with expande
de Montigny S, Boily M, Masse BM, et al., 2018, Assessing the utility of the tipping point ratio to monitor HIV treatment programmes in the era of universal access to ART., Infectious Disease Modelling, Vol: 3, Pages: 85-96, ISSN: 2468-0427
BackgroundThe epidemiological tipping point ratio (TPR) has been suggested as a useful indicator to monitor the scale-up of antiretroviral treatment (ART) programmes and determine when scale-up is sufficient to control the epidemic. TPR has been defined as the ratio of yearly number of new HIV infections to the yearly number of new ART initiations or to the yearly net increase in the number of people on ART. It has been used to rank the progress of treatment programmes across countries, with the objective of reaching a TPR value under 1. Our study aims to assess if TPR alone can be used as an indicator of ART success across settings by comparing the expected changes in HIV incidence and ART coverage when TPR is maintained constant over time. In particular, we focus on the effect of ART initiation timing (emphasis on ART being initiated early or late during HIV progression) on the interpretation of the TPR.MethodsWe used a dynamic model of HIV transmission in South Africa representing ART rollout leading to universal treatment in 2017. The model is calibrated to HIV incidence, HIV prevalence and ART coverage in 2012 in South Africa, and 1000 simulations are selected for the base-case scenario. To measure the effect of TPR, we simulate TPR-preserving interventions, maintaining TPR (yearly number of new ART initiations denominator) at the value observed in 2019 (between 0.65 and 1.25) for 15 years. We compare ART coverage and HIV incidence across TPR values and across strategies in which ART access is prioritized differently. In a secondary analysis, we illustrate the sensitivity of new ART initiations to ART retention, and we compare both definitions of the TPR.ResultsOur analysis shows that HIV incidence reduction is weakly correlated to TPR: the same reduction in HIV incidence (15%) can be achieved by implementing the same strategy with a wide range of TPR maintained (0.65–1.12). Assuming high retention in ART, TPR-preserving strategies prioritizing early ART
Tucker JD, Wei C, Li H, et al., 2017, Crowdsourcing to promote HIV testing among MSM in China: study protocol for a stepped wedge randomized controlled trial, TRIALS, Vol: 18, ISSN: 1745-6215
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Mitchell KM, Hoots B, Dimitrov D, et al., 2016, Potential Impact on HIV Incidence of Increasing Viral Suppression among HIV-positive MSM in Baltimore: Mathematical Modelling for HPTN 078, Conference on HIV Research for Prevention (HIV R4P), Publisher: Mary Ann Liebert, Pages: 64-64, ISSN: 1931-8405
Dimitrov D, Wood D, Mitchell KM, et al., 2016, Predicted Effectiveness of Daily and Non-daily PrEP Based on Sex Coverage Data from HPTN 067 ADAPT Sites in South Africa, Thailand and US, Conference on HIV Research for Prevention (HIV R4P), Publisher: MARY ANN LIEBERT, INC, Pages: 298-298, ISSN: 0889-2229
Mitchell KM, Prudden HJ, Washington R, et al., 2016, Potential impact of pre-exposure prophylaxis for female sex workers and men who have sex with men in Bangalore, India: a mathematical modelling study, Journal of the International AIDS Society, Vol: 19, ISSN: 1758-2652
Introduction: In 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 prioritising PrEP to female sex workers and/or men who have sex with men in Bangalore.Methods: A mathematical model of HIV transmission and treatment for female sex workers, clients, men who have sex with men and low-risk groups was parameterised 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 prioritisation 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. Results: Population 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 prioritised. 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
Mukandavire Z, Mitchell KM, Vickerman P, 2015, Comparing the impact of increasing condom use or HIV pre-exposure prophylaxis (PrEP) use among female sex workers, Epidemics, Vol: 14, Pages: 62-70, ISSN: 1878-0067
In many settings, interventions targeting female sex workers (FSWs) could significantly reduce the overall transmission of HIV. To understand the role HIV pre-exposure prophylaxis (PrEP) could play in controlling HIV transmission amongst FSWs, it is important to understand how its impact compares with scaling-up condom use—one of the proven HIV prevention strategies for FSWs. It is important to remember that condoms also have other benefits such as reducing the incidence of sexually transmitted infections and preventing pregnancy. A dynamic deterministic model of HIV transmission amongst FSWs, their clients and other male partners (termed ‘pimps’) was used to compare the protection provided by PrEP for HIV-negative FSWs with FSWs increasing their condom use with clients and/or pimps. For different HIV prevalence scenarios, levels of pimp interaction, and baseline condom use, we estimated the coverage of PrEP that gives the same reduction in endemic FSW HIV prevalence or HIV infections averted as different increases in condom use. To achieve the same impact on FSW HIV prevalence as increasing condom use by 1%, the coverage of PrEP has to increase by >2%. The relative impact of PrEP increases for scenarios where pimps contribute to HIV transmission, but not greatly, and decreases with higher baseline condom use. In terms of HIV infections averted over 10 years, the relative impact of PrEP compared to condoms was reduced, with a >3% increase in PrEP coverage achieving the same impact as a 1% increase in condom use. Condom promotion interventions should remain the mainstay HIV prevention strategy for FSWs, with PrEP only being implemented once condom interventions have been maximised or to fill prevention gaps where condoms cannot be used.
Lamberton PH, Mitchell K, Gower CM, et al., 2015, HOTSPOTS OF <i>SCHISTOSOMA MANSONI</i> TRANSMISSION TEN YEARS INTO A MASS DRUG ADMINISTRATION PROGRAM, Publisher: AMER SOC TROP MED & HYGIENE, Pages: 558-558, ISSN: 0002-9637
Mitchell KM, Lépine A, Terris-Prestholt F, et al., 2015, Modelling the impact and cost-effectiveness of combination prevention amongst HIV serodiscordant couples in Nigeria, AIDS, Vol: 29, Pages: 2035-2044, ISSN: 0269-9370
Objective: To estimate the impact and cost-effectiveness of treatment as prevention(TasP), pre-exposure prophylaxis (PrEP) and condom promotion for serodiscordantcouples in Nigeria.Design: Mathematical and cost modelling.Methods: A deterministic model of HIV-1 transmission within a cohort of serodiscordantcouples and to/from external partners was parameterized using data from Nigeriaand other African settings. The impact and cost-effectiveness were estimated forcondom promotion, PrEP and/or TasP, compared with a baseline where antiretroviraltherapy (ART) was offered according to 2010 national guidelines (CD4þ <350 cells/ml)to all HIV-positive partners. The impact was additionally compared with a baseline ofcurrent ART coverage (35% of those with CD4þ <350 cells/ml). Full costs (in US $2012)of programme introduction and implementation were estimated from a providerperspective.Results: Substantial benefits came from scaling up ART to all HIV-positive partnersaccording to 2010 national guidelines, with additional smaller benefits of providingTasP, PrEP or condom promotion. Compared with a baseline of offering ART to all HIVpositivepartners at the 2010 national guidelines, condom promotion was the most costeffectivestrategy [US $1206/disability-adjusted-life-year (DALY)], the next most costeffectiveintervention was to additionally give TasP to HIV-positive partners (incrementalcost-effectiveness ratio US $1607/DALY), followed by additionally giving PrEPto HIV-negative partners until their HIV-positive partners initiate ART (US $7870/DALY). When impact was measured in terms of infections averted, PrEP with condompromotion prevented double the number of infections as condom promotion alone.Conclusions: The first priority intervention for serodiscordant couples in Nigeria shouldbe scaled up ART access for HIV-positive partners. Subsequent incremental benefits aregreatest with condom promotion and TasP, followed by PrEP
Fukushige M, Mitchell KM, Bourke CD, et al., 2015, A meta-analysis of experimental studies of attenuated <i>Schistosoma</i> <i>mansoni</i> vaccines in the mouse model, FRONTIERS IN IMMUNOLOGY, Vol: 6, ISSN: 1664-3224
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- Citations: 8
Mitchell KM, Foss AM, Ramesh BM, et al., 2014, Relationship between exposure to the Avahan intervention and levels of reported condom use among men who have sex with men in southern India, BMC Public Health, Vol: 14, ISSN: 1471-2458
BackgroundThe Avahan intervention promotes consistent (100%) condom use amongst men who have sex with men in southern India. We assessed how condom use varies with intervention exposure for men who have sex with men in Bangalore.MethodsSelf-reported condom use and intervention exposure data were derived from a cross-sectional survey. Consistent condom use and condom use at last sex act with all, main, and casual male sex partners were assessed. Binary and continuous variables reflecting intervention exposure (including contact(s) with intervention staff, receiving condoms and seeing condom demonstrations) were used. Multivariable logistic regression was employed to assess the relationship between condom use with each type of partner and each exposure variable independently, controlling for socio-demographic and behavioural factors associated with condom use or intervention exposure.ResultsCondom use with all partners was higher among those who had ever been contacted by, received condoms from, or seen a condom demonstration by intervention staff (adjusted odds ratio >2, p < 0.02 for all). Consistent condom use with all types of partner increased with the number of condom demonstrations seen in the last month (adjusted odds ratio = 2.1 per demonstration, p < 0.025), while condom use at last sex act with a casual (but not main) partner increased with the number of condoms received from the intervention (adjusted odds ratio = 1.4 per condom, p = 0.04).ConclusionsDirect contact with Avahan program staff is associated with increased reported condom use among men who have sex with men in Bangalore. Reported consistent condom use and condom use at last sex act are associated with contacts involving demonstrations of correct condom use, and with receiving condoms, respectively.Keywords: Consistent condom use; Condom use at last sex act; Condom demonstration; Key population; Bangalore; Cross-secti
Panovska-Griffiths J, Vassall A, Prudden HJ, et al., 2014, Optimal allocation of resources in female sex worker targeted HIV prevention interventions: Model insights from Avahan in South India, PLOS One, Vol: 9, ISSN: 1932-6203
BackgroundThe Avahan programme has provided HIV prevention activities, including condom promotion, to female sex workers (FSWs) in southern India since 2004. Evidence suggests Avahan averted 202,000 HIV infections over 4 years. For replicating this intervention elsewhere, it is essential to understand how the intervention’s impact could have been optimised for different budget levels.MethodsBehavioural data were used to determine how condom use varied for FSWs with different levels of intervention intensity. Cost data from 64 Avahan districts quantified how district-level costs related to intervention scale and intensity. A deterministic model for HIV transmission amongst FSWs and clients projected the impact and cost of intervention strategies for different scale and intensity, and identified the optimal strategies that maximise impact for different budget levels.ResultsAs budget levels increase, the optimal intervention strategy is to first increase intervention intensity which achieves little impact, then scale-up coverage to high levels for large increases in impact, and lastly increase intensity further for small additional gains. The cost-effectiveness of these optimal strategies generally improves with increasing resources, while straying from these strategies can triple costs for the same impact. Projections suggest Avahan was close to being optimal, and moderate budget reductions (≥20%) would have reduced impact considerably (>40%).DiscussionOur analysis suggests that tailoring the design of HIV prevention programmes for FSWs can improve impact, and that a certain level of resources are required to achieve demonstrable impact. These insights are critical for optimising the use of limited resources for preventing HIV.
Mitchell KM, Foss AM, Prudden HJ, et al., 2014, Who mixes with whom among men who have sex with men? Implications for modelling the HIV epidemic in southern India, Journal of Theoretical Biology, Vol: 355, Pages: 140-150, ISSN: 1095-8541
In India, the identity of men who have sex with men (MSM) is closely related to the role taken in anal sex(insertive, receptive or both), but little is known about sexual mixing between identity groups. Both rolesegregation (taking only the insertive or receptive role) and the extent of assortative (within-group)mixing are known to affect HIV epidemic size in other settings and populations. This study explores howdifferent possible mixing scenarios, consistent with behavioural data collected in Bangalore, south India,affect both the HIV epidemic, and the impact of a targeted intervention. Deterministic models describingHIV transmission between three MSM identity groups (mostly insertive Panthis/Bisexuals, mostlyreceptive Kothis/Hijras and versatile Double Deckers), were parameterised with behavioural data fromBangalore. We extended previous models of MSM role segregation to allow each of the identity groups tohave both insertive and receptive acts, in differing ratios, in line with field data. The models were used toexplore four different mixing scenarios ranging from assortative (maximising within-group mixing) todisassortative (minimising within-group mixing). A simple model was used to obtain insights into therelationship between the degree of within-group mixing, R0 and equilibrium HIV prevalence underdifferent mixing scenarios. A more complex, extended version of the model was used to compare the predicted HIV prevalence trends and impact of an HIV intervention when fitted to data from Bangalore.With the simple model, mixing scenarios with increased amounts of assortative (within-group) mixingtended to give rise to a higher R0 and increased the likelihood that an epidemic would occur. When thecomplex model was fit to HIV prevalence data, large differences in the level of assortative mixing wereseen between the fits identified using different mixing scenarios, but little difference was projected infuture HIV prevalence trends. An oral pre-exposure prophylaxis (P
Mitchell KM, Mutapi F, Mduluza T, et al., 2014, Predicted impact of mass drug administration on the development of protective immunity against Schistosoma haematobium, PLOS Neglected Tropical Diseases, Vol: 8, ISSN: 1935-2735
Previous studies suggest that protective immunity against Schistosoma haematobium is primarily stimulated by antigens from dying worms. Praziquantel treatment kills adult worms, boosting antigen exposure and protective antibody levels. Current schistosomiasis control efforts use repeated mass drug administration (MDA) of praziquantel to reduce morbidity, and may also reduce transmission. The long-term impact of MDA upon protective immunity, and subsequent effects on infection dynamics, are not known. A stochastic individual-based model describing levels of S. haematobium worm burden, egg output and protective parasite-specific antibody, which has previously been fitted to cross-sectional and short-term post-treatment egg count and antibody patterns, was used to predict dynamics of measured egg output and antibody during and after a 5-year MDA campaign. Different treatment schedules based on current World Health Organisation recommendations as well as different assumptions about reductions in transmission were investigated. We found that antibody levels were initially boosted by MDA, but declined below pre-intervention levels during or after MDA if protective immunity was short-lived. Following cessation of MDA, our models predicted that measured egg counts could sometimes overshoot pre-intervention levels, even if MDA had had no effect on transmission. With no reduction in transmission, this overshoot occurred if protective immunity was short-lived. This implies that disease burden may temporarily increase following discontinuation of treatment, even in the absence of any reduction in the overall transmission rate. If MDA was additionally assumed to reduce transmission, a larger overshoot was seen across a wide range of parameter combinations, including those with longer-lived protective immunity. MDA may reduce population levels of immunity to urogenital schistosomiasis in the long-term (3-10 years), particularly if transmission is reduced. If MDA is stopped while
Eaton JW, Menzies NA, Stover J, et al., 2014, Health benefits, costs, and cost-effectiveness of earlier eligibility for adult antiretroviral therapy and expanded treatment coverage: a combined analysis of 12 mathematical models, The Lancet Global Health, Vol: 2, Pages: E23-E34, ISSN: 2214-109X
BackgroundNew WHO guidelines recommend initiation of antiretroviral therapy for HIV-positive adults with CD4 counts of 500 cells per μL or less, a higher threshold than was previously recommended. Country decision makers have to decide whether to further expand eligibility for antiretroviral therapy accordingly. We aimed to assess the potential health benefits, costs, and cost-effectiveness of various eligibility criteria for adult antiretroviral therapy and expanded treatment coverage.MethodsWe used several independent mathematical models in four settings—South Africa (generalised epidemic, moderate antiretroviral therapy coverage), Zambia (generalised epidemic, high antiretroviral therapy coverage), India (concentrated epidemic, moderate antiretroviral therapy coverage), and Vietnam (concentrated epidemic, low antiretroviral therapy coverage)—to assess the potential health benefits, costs, and cost-effectiveness of various eligibility criteria for adult antiretroviral therapy under scenarios of existing and expanded treatment coverage, with results projected over 20 years. Analyses assessed the extension of eligibility to include individuals with CD4 counts of 500 cells per μL or less, or all HIV-positive adults, compared with the previous (2010) recommendation of initiation with CD4 counts of 350 cells per μL or less. We assessed costs from a health-system perspective, and calculated the incremental cost (in US$) per disability-adjusted life-year (DALY) averted to compare competing strategies. Strategies were regarded very cost effective if the cost per DALY averted was less than the country's 2012 per-head gross domestic product (GDP; South Africa: $8040; Zambia: $1425; India: $1489; Vietnam: $1407) and cost effective if the cost per DALY averted was less than three times the per-head GDP.FindingsIn South Africa, the cost per DALY averted of extending eligibility for antiretroviral therapy to adult patients with CD4 counts of 500 cells per &
Mitchell KM, Foss AM, Ramesh BM, et al., 2013, EFFECT OF INTERVENTION EXPOSURE ON SELF-REPORTED CONDOM USE AMONG MEN WHO HAVE SEX WITH MEN IN SOUTHERN INDIA, Publisher: BMJ PUBLISHING GROUP, Pages: A279-A279, ISSN: 1368-4973
Boily M-C, Pickles M, Lowndes CM, et al., 2013, Positive impact of a large-scale HIV prevention programme among female sex workers and clients in South India, AIDS, Vol: 27, Pages: 1449-1460, ISSN: 0269-9370
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Mitchell KM, Cox AP, Mabey D, et al., 2013, The impact of syphilis screening among female sex workers in China: A modelling study, PLOS One, Vol: 8, ISSN: 1932-6203
BACKGROUND: In China, female sex workers (FSWs) are at high risk of syphilis infection, but are hard to reach for interventions. Point-of-care testing introduces opportunities for expanding syphilis control measures. Modelling is used to estimate the impact of using rapid tests to screen FSWs for syphilis. In other settings, modelling has predicted large rebounds in infectious syphilis following screening, which may undermine any impact achieved. METHODS: A deterministic syphilis transmission model among FSWs and clients was fitted to data from Yunnan Province (FSW syphilis prevalence = 7.5%), and used to estimate the impact of rapid syphilis testing and treatment for FSWs. Impact projections were compared for different model structures that included risk heterogeneity amongst FSWs, incoming syphilis infections amongst new FSWs and clients and re-infection from FSWs' regular non-commercial partners. The rebound in syphilis prevalence after screening ceased was explored. RESULTS: All model structures suggest yearly syphilis screening could substantially reduce (by 72-88%) syphilis prevalence amongst FSWs in this setting over five years. However, incoming syphilis infections amongst new FSWs and clients or re-infections from regular non-commercial partners of FSWs can considerably reduce (>30%) the proportion of infections averted. Including heterogeneity in risk amongst FSWs had little effect upon the proportion of infections averted. In this setting, the rebound in syphilis prevalence after screening ceased is predicted to be slight, but it could be large in high prevalence settings. CONCLUSIONS: Rapid test screening could dramatically reduce syphilis prevalence amongst hard-to-reach groups, but strategies to reduce re-infection from regular non-commercial partners are needed to maximise impact.
Bourke CD, Nausch N, Rujeni N, et al., 2012, Integrated analysis of innate, Th1, Th2, Th17, and regulatory cytokines identifies changes in immune polarisation following treatment of human schistosomiasis., Journal of Infectious Diseases, Vol: 208, Pages: 159-169, ISSN: 1537-6613
BACKGROUND: Schistosomiasis elicits cross-regulatory immune responses, but it is unclear how antihelminthic treatment affects this balance. This study integrates data on 13 cytokines elicited by 3 schistosome to examine how praziquantel treatment alters immune polarization and whether post-treatment cytokine profiles influence reinfection status. METHODS: Venous blood from 72 Schistosoma haematobium-exposed participants was cultured with schistosome egg, adult worm, and cercaria antigens pre- and 6 weeks post-praziquantel treatment. Innate inflammatory (tumor necrosis factor α [TNF-α], interleukin(IL-)-6, IL-8), Th1 (interferon γ [IFN-γ], IL-2, IL-12p70), Th2 (IL-4, IL-5, IL-13), Th17 (IL-17A, IL-21, IL-23p19), and regulatory (IL-10) cytokines were quantified via enzyme-linked immunosorbent assay. Cytokine data was integrated using nonmetric multidimensional scaling and factor analysis. RESULTS: Egg-specific cytokine phenotypes became more proinflammatory post-treatment due to increased TNF-α, IL-6, IL-8, IFN-γ, IL-12p70, and IL-23 levels. Post-treatment cercariae-specific responses were also more proinflammatory reflecting elevated IL-8. In contrast, post-treatment adult worm-specific responses were less inflammatory, reflecting lower post-treatment IL-6. A combination of egg-induced IL-6, IL-12p70, IL-21, and IL-23 and adult worm-induced IL-5 and IL-21 post-treatment was associated with reduced reinfection risk 18 months later. CONCLUSIONS: Praziquantel treatment markedly alters polarization of schistosome-specific cytokine responses, and these changes, particularly in response to egg-stage parasites, may promote resistance to reinfection.
Mitchell KM, Foss AM, Prudden HJ, et al., 2012, Sexual mixing patterns between men who have sex with men in southern India: implications for modelling the HIV epidemic and predicting the impact of targeted oral pre-exposure prophylaxis, Publisher: JOHN WILEY & SONS LTD, Pages: 106-107
Mitchell KM, Mutapi F, Savill NJ, et al., 2012, Protective immunity to <i>Schistosoma haematobium</i> infection is primarily an anti-fecundity response stimulated by the death of adult worms, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol: 109, Pages: 13347-13352, ISSN: 0027-8424
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