55 results found
Pickles M, Cori A, Probert WJM, et al., 2021, PopART-IBM, a highly efficient stochastic individual-based simulation model of generalised HIV epidemics developed in the context of the HPTN 071 (PopART) trial., PLoS Comput Biol, Vol: 17
Mathematical models are powerful tools in HIV epidemiology, producing quantitative projections of key indicators such as HIV incidence and prevalence. In order to improve the accuracy of predictions, such models need to incorporate a number of behavioural and biological heterogeneities, especially those related to the sexual network within which HIV transmission occurs. An individual-based model, which explicitly models sexual partnerships, is thus often the most natural type of model to choose. In this paper we present PopART-IBM, a computationally efficient individual-based model capable of simulating 50 years of an HIV epidemic in a large, high-prevalence community in under a minute. We show how the model calibrates within a Bayesian inference framework to detailed age- and sex-stratified data from multiple sources on HIV prevalence, awareness of HIV status, ART status, and viral suppression for an HPTN 071 (PopART) study community in Zambia, and present future projections of HIV prevalence and incidence for this community in the absence of trial intervention.
Thomas R, Probert W, Sauter R, et al., 2021, Cost and cost-effectiveness of a universal HIV testing and treatment intervention in Zambia and South Africa: evidence and projections from the HPTN 071 (PopART) trial, The Lancet Global Health, Vol: 9, Pages: e668-e680, ISSN: 2214-109X
BackgroundThe HPTN 071 (PopART) trial showed that a combination HIV prevention package including universal HIV testing and treatment (UTT) reduced population-level incidence of HIV compared with standard care. However, evidence is scarce on the costs and cost-effectiveness of such an intervention.MethodsUsing an individual-based model, we simulated the PopART intervention and standard care with antiretroviral therapy (ART) provided according to national guidelines for the 21 trial communities in Zambia and South Africa (for all individuals aged >14 years), with model parameters and primary cost data collected during the PopART trial and from published sources. Two intervention scenarios were modelled: annual rounds of PopART from 2014 to 2030 (PopART 2014–30; as the UNAIDS Fast-Track target year) and three rounds of PopART throughout the trial intervention period (PopART 2014–17). For each country, we calculated incremental cost-effectiveness ratios (ICERs) as the cost per disability-adjusted life-year (DALY) and cost per HIV infection averted. Cost-effectiveness acceptability curves were used to indicate the probability of PopART being cost-effective compared with standard care at different thresholds of cost per DALY averted. We also assessed budget impact by projecting undiscounted costs of the intervention compared with standard care up to 2030.FindingsDuring 2014–17, the mean cost per person per year of delivering home-based HIV counselling and testing, linkage to care, promotion of ART adherence, and voluntary medical male circumcision via community HIV care providers for the simulated population was US$6·53 (SD 0·29) in Zambia and US$7·93 (0·16) in South Africa. In the PopART 2014–30 scenario, median ICERs for PopART delivered annually until 2030 were $2111 (95% credible interval [CrI] 1827–2462) per HIV infection averted in Zambia and $3248 (2472–3963) per HIV infection averted in South Afric
Amiri L, Torabi M, Deardon R, et al., 2021, Spatial modeling of individual-level infectious disease transmission: Tuberculosis data in Manitoba, Canada., Stat Med, Vol: 40, Pages: 1678-1704
Geographically dependent individual level models (GD-ILMs) are a class of statistical models that can be used to study the spread of infectious disease through a population in discrete-time in which covariates can be measured both at individual and area levels. The typical ILMs to illustrate spatial data are based on the distance between susceptible and infectious individuals. A key feature of GD-ILMs is that they take into account the spatial location of the individuals in addition to the distance between susceptible and infectious individuals. As a motivation of this article, we consider tuberculosis (TB) data which is an infectious disease which can be transmitted through individuals. It is also known that certain areas/demographics/communities have higher prevalent of TB (see Section 4 for more details). It is also of interest of policy makers to identify those areas with higher infectivity rate of TB for possible preventions. Therefore, we need to analyze this data properly to address those concerns. In this article, the expectation conditional maximization algorithm is proposed for estimating the parameters of GD-ILMs to be able to predict the areas with the highest average infectivity rates of TB. We also evaluate the performance of our proposed approach through some simulations. Our simulation results indicate that the proposed method provides reliable estimates of parameters which confirms accuracy of the infectivity rates.
Bhattacharjee P, Ma H, Musyoki H, et al., 2020, Prevalence and patterns of gender-based violence across adolescent girls and young women in Mombasa, Kenya, BMC Women's Health, Vol: 20, ISSN: 1472-6874
Background We sought to estimate the prevalence and describe heterogeneity in experiences of gender-based violence (GBV) across subgroups of adolescent girls and young women (AGYW). MethodsWe used data from a cross-sectional bio-behavioural survey among 1299 AGYW aged 14-24 in Mombasa, Kenya in 2015. Respondents were recruited from hotspots associated with sex work, and self-selected into one of three subgroups: young women engaged in casual sex (YCS), young women engaged in transactional sex (YTS), and young women engaged in sex work (YSW). We compared overall and across subgroups: prevalence of lifetime and recent (within previous year) self-reported experience of physical, sexual, and police violence; patterns and perpetrators of first and most recent episode of physical and sexual violence; and factors associated with physical and sexual violence. ResultsThe prevalences of lifetime and recent physical violence were 18.0% and 10.7% respectively. Lifetime and recent sexual violence respectively were reported by 20.5% and 9.8% of respondents. Prevalence of lifetime and recent experience of police violence were 34.7% and 25.8% respectively. All forms of violence were most frequently reported by YSW, followed by YTS and then YCS. 62%/81% of respondents reported having sex during the first episode of physical/sexual violence, and 48%/62% of those sex acts at first episode of physical/sexual violence were condomless. In the most recent episode of violence when sex took place levels of condom use remained low at 53-61%. The main perpetrators of violence were intimate partners for YCS, and both intimate partners and regular non-client partners for YTS. For YSW, first-time and regular paying clients were the main perpetrators of physical and sexual violence. Alcohol use, ever being pregnant and regular source of income were associated with physical and sexual violence though it differed by subgroup and type of violence. ConclusionsAGYW in these settings experience high vu
Foss AM, Prudden HJ, Mitchell KM, et al., 2020, Using data from 'visible' populations to estimate the size and importance of 'hidden' populations in an epidemic: A modelling technique., Infectious Disease Modelling, Vol: 5, Pages: 798-813, ISSN: 2468-2152
We used reported behavioural data from cisgender men who have sex with men and transgender women (MSM/TGW) in Bangalore, mainly collected from 'hot-spot' locations that attract MSM/TGW, to illustrate a technique to deal with potential issues with the representativeness of this sample. A deterministic dynamic model of HIV transmission was developed, incorporating three subgroups of MSM/TGW, grouped according to their reported predominant sexual role (insertive, receptive or versatile). Using mathematical modelling and data triangulation for 'balancing' numbers of partners and role preferences, we compared three different approaches to determine if our technique could be useful for inferring characteristics of a more 'hidden' insertive MSM subpopulation, and explored their potential importance for the HIV epidemic. Projections for 2009 across all three approaches suggest that HIV prevalence among insertive MSM was likely to be less than half that recorded in the surveys (4.5-6.5% versus 13.1%), but that the relative size of this subgroup was over four times larger (61-69% of all MSM/TGW versus 15%). We infer that the insertive MSM accounted for 10-20% of all prevalent HIV infections among urban males aged 15-49. Mathematical modelling can be used with data on 'visible' MSM/TGW to provide insights into the characteristics of 'hidden' MSM. A greater understanding of the sexual behaviour of all MSM/TGW is important for effective HIV programming. More broadly, a hidden subgroup with a lower infectious disease prevalence than more visible subgroups, has the potential to contain more infections, if the hidden subgroup is considerably larger in size.
Hogan A, Jewell B, Sherrard-Smith E, et al., 2020, Potential impact of the COVID-19 pandemic on HIV, TB and malaria in low- and middle-income countries: a modelling study, The Lancet Global Health, Vol: 8, Pages: e1132-e1141, ISSN: 2214-109X
Background: COVID-19 has the potential to cause substantial disruptions to health services, including by cases overburdening the health system or response measures limiting usual programmatic activities. We aimed to quantify the extent to which disruptions in services for human immunodeficiency virus (HIV), tuberculosis (TB) and malaria in low- and middle-income countries with high burdens of those disease could lead to additional loss of life. Methods: We constructed plausible scenarios for the disruptions that could be incurred during the COVID-19 pandemic and used established transmission models for each disease to estimate the additional impact on health that could be caused in selected settings.Findings: In high burden settings, HIV-, TB- and malaria-related deaths over five years may increase by up to 10%, 20% and 36%, respectively, compared to if there were no COVID-19 pandemic. We estimate the greatest impact on HIV to be from interruption to antiretroviral therapy, which may occur during a period of high health system demand. For TB, we estimate the greatest impact is from reductions in timely diagnosis and treatment of new cases, which may result from any prolonged period of COVID-19 suppression interventions. We estimate that the greatest impact on malaria burden could come from interruption of planned net campaigns. These disruptions could lead to loss of life-years over five years that is of the same order of magnitude as the direct impact from COVID-19 in places with a high burden of malaria and large HIV/TB epidemics.Interpretation: Maintaining the most critical prevention activities and healthcare services for HIV, TB and malaria could significantly reduce the overall impact of the COVID-19 pandemic.Funding: Bill & Melinda Gates Foundation, The Wellcome Trust, DFID, MRC
Skovdal M, Pickles MR, Hallett TB, et al., 2020, Complexities to consider when communicating risk of COVID-19, Public Health, Vol: 186, Pages: 283-285, ISSN: 0033-3506
Bhattacharjee P, Isac S, Musyoki H, et al., 2020, HIV prevalence, testing and treatment among men who have sex with men through engagement in virtual sexual networks in Kenya: a cross-sectional bio-behavioural study, Journal of the International AIDS Society, Vol: 23, ISSN: 1758-2652
INTRODUCTION: In Kenya, men who have sex with men (MSM) are increasingly using virtual sites, including web-based apps, to meet sex partners. We examined HIV testing, HIV prevalence, awareness of HIV-positive status and linkage to antiretroviral therapy (ART), for HIV-positive MSM who solely met partners via physical sites (PMSM), compared with those who did so in virtual sites (either solely via virtual sites (VMSM), or via both virtual and physical sites (DMSM)). METHODS: We conducted a cross-sectional bio-behavioural survey of 1200 MSM, 15 years and above, in three counties in Kenya between May and July 2019, using random sampling of physical and virtual sites. We classified participants as PMSM, DMSM and VMSM, based on where they met sex partners, and compared the following between groups using chi-square tests: (i) proportion tested; (ii) HIV prevalence and (iii) HIV care continuum among MSM living with HIV. We then performed multivariable logistic regression to measure independent associations between network engagement and HIV status. RESULTS: 177 (14.7%), 768 (64.0%) and 255 (21.2%), of participants were classified as PMSM, DMSM and VMSM respectively. 68.4%, 70.4% and 78.5% of PMSM, DMSM and VMSM, respectively, reported an HIV test in the previous six months. HIV prevalence was 8.5% (PMSM), 15.4% (DMSM) and 26.7% (VMSM), p < 0.001. Among those living with HIV, 46.7% (PMSM), 41.5% (DMSM) and 29.4% (VMSM) were diagnosed and aware of their status; and 40.0%, 35.6% and 26.5% were on antiretroviral treatment. After adjustment for other predictors, MSM engaged in virtual networks remained at a two to threefold higher risk of prevalent HIV: VMSM versus PMSM (adjusted odds ratio 3.88 (95% confidence interval (CI) 1.84 to 8.17) p < 0.001); DMSM versus PMSM (2.00 (95% CI 1.03 to 3.87), p = 0.040). CONCLUSIONS: Engagement in virtual networks is associated with elevated HIV risk, irrespective of individual-level risk factors. Und
Mellan T, Hoeltgebaum H, Mishra S, et al., 2020, Report 21: Estimating COVID-19 cases and reproduction number in Brazil
Brazil is an epicentre for COVID-19 in Latin America. In this report we describe the Brazilian epidemicusing three epidemiological measures: the number of infections, the number of deaths and the reproduction number. Our modelling framework requires sufficient death data to estimate trends, and wetherefore limit our analysis to 16 states that have experienced a total of more than fifty deaths. Thedistribution of deaths among states is highly heterogeneous, with 5 states—São Paulo, Rio de Janeiro,Ceará, Pernambuco and Amazonas—accounting for 81% of deaths reported to date. In these states, weestimate that the percentage of people that have been infected with SARS-CoV-2 ranges from 3.3% (95%CI: 2.8%-3.7%) in São Paulo to 10.6% (95% CI: 8.8%-12.1%) in Amazonas. The reproduction number (ameasure of transmission intensity) at the start of the epidemic meant that an infected individual wouldinfect three or four others on average. Following non-pharmaceutical interventions such as school closures and decreases in population mobility, we show that the reproduction number has dropped substantially in each state. However, for all 16 states we study, we estimate with high confidence that thereproduction number remains above 1. A reproduction number above 1 means that the epidemic isnot yet controlled and will continue to grow. These trends are in stark contrast to other major COVID19 epidemics in Europe and Asia where enforced lockdowns have successfully driven the reproductionnumber below 1. While the Brazilian epidemic is still relatively nascent on a national scale, our resultssuggest that further action is needed to limit spread and prevent health system overload.
Vollmer M, Mishra S, Unwin H, et al., 2020, Report 20: A sub-national analysis of the rate of transmission of Covid-19 in Italy
Italy was the first European country to experience sustained local transmission of COVID-19. As of 1st May 2020, the Italian health authorities reported 28; 238 deaths nationally. To control the epidemic, the Italian government implemented a suite of non-pharmaceutical interventions (NPIs), including school and university closures, social distancing and full lockdown involving banning of public gatherings and non essential movement. In this report, we model the effect of NPIs on transmission using data on average mobility. We estimate that the average reproduction number (a measure of transmission intensity) is currently below one for all Italian regions, and significantly so for the majority of the regions. Despite the large number of deaths, the proportion of population that has been infected by SARS-CoV-2 (the attack rate) is far from the herd immunity threshold in all Italian regions, with the highest attack rate observed in Lombardy (13.18% [10.66%-16.70%]). Italy is set to relax the currently implemented NPIs from 4th May 2020. Given the control achieved by NPIs, we consider three scenarios for the next 8 weeks: a scenario in which mobility remains the same as during the lockdown, a scenario in which mobility returns to pre-lockdown levels by 20%, and a scenario in which mobility returns to pre-lockdown levels by 40%. The scenarios explored assume that mobility is scaled evenly across all dimensions, that behaviour stays the same as before NPIs were implemented, that no pharmaceutical interventions are introduced, and it does not include transmission reduction from contact tracing, testing and the isolation of confirmed or suspected cases. We find that, in the absence of additional interventions, even a 20% return to pre-lockdown mobility could lead to a resurgence in the number of deaths far greater than experienced in the current wave in several regions. Future increases in the number of deaths will lag behind the increase in transmission intensity and so a
The World Health Organization has called for increased molecular testing in response to the COVID-19 pandemic, but different countries have taken very different approaches. We used a simple mathematical model to investigate the potential effectiveness of alternative testing strategies for COVID-19 control. Weekly screening of healthcare workers (HCWs) and other at-risk groups using PCR or point-of-care tests for infection irrespective of symptoms is estimated to reduce their contribution to transmission by 25-33%, on top of reductions achieved by self-isolation following symptoms. Widespread PCR testing in the general population is unlikely to limit transmission more than contact-tracing and quarantine based on symptoms alone, but could allow earlier release of contacts from quarantine. Immunity passports based on tests for antibody or infection could support return to work but face significant technical, legal and ethical challenges. Testing is essential for pandemic surveillance but its direct contribution to the prevention of transmission is likely to be limited to patients, HCWs and other high-risk groups.
Bhattacharjee P, Rego D, Musyoki H, et al., 2019, Evaluation of community-based HIV self-testing delivery strategies on reducing undiagnosed HIV infection, and improving linkage to prevention and treatment services, among men who have sex with men in Kenya: a programme science study protocol, BMC Public Health, Vol: 19, Pages: 1-13, ISSN: 1471-2458
BackgroundHIV prevalence among men having sex with men (MSM) in Kenya is 18.2%. Despite scale-up of HIV testing services, many MSM remain unaware of their HIV status and thus do not benefit from accessing HIV treatment or prevention services. HIV self-testing (HIVST) may help address this gap. However, evidence is limited on how, when, and in what contexts the delivery of HIVST to MSM could increase awareness of HIV status and lead to early linkage to HIV treatment and prevention.MethodsThe study will be embedded within existing MSM-focused community-based HIV prevention and treatment programmes in 3 counties in Kenya (Kisumu, Mombasa, Kiambu). The study is designed to assess three HIV testing outcomes among MSM, namely a) coverage b) frequency of testing and c) early uptake of testing. The study will adopt a mixed methods programme science approach to the implementation and evaluation of HIVST strategies via: (i) a baseline and endline bio-behavioural survey with 1400 MSM; (ii) a socio-sexual network study with 351 MSM; (iii) a longitudinal qualitative cohort study with 72 MSM; (iv) routine programme monitoring in three sites; (v) a programme-specific costing exercise; and (vi) mathematical modelling. This protocol evaluates the impact of community-based implementation of HIV self-testing delivery strategies among MSM in Kenya on reducing the undiagnosed MSM population, and time for linkage to prevention, treatment and care following HIV self-testing. Baseline data collection started in April 2019 and the endline data collection will start in July 2020.DiscussionThis study is one of the first programme science studies in Sub-Saharan Africa exploring the effectiveness of integrating HIVST interventions within already existing HIV prevention and treatment programmes for MSM in Kenya at scale. Findings from this study will inform national best approaches to scale up HIVST among MSM in Kenya.
Becker M, Balakireva O, Pavlova D, et al., 2019, Assessing the influence of conflict on the dynamics of sex work and the HIV and HCV epidemics in Ukraine: protocol for an observational, ethnographic, and mathematical modeling study., BMC Int Health Hum Rights, Vol: 19
BACKGROUND: Armed conflict erupted in eastern Ukraine in 2014 and still continues. This conflict has resulted in an intensification of poverty, displacement and migration, and has weakened the local health system. Ukraine has some of the highest rates of HIV and Hepatitis C (HCV) in Europe. Whether and how the current conflict, and its consequences, will lead to changes in the HIV and HCV epidemic in Ukraine is unclear. Our study aims to characterize how the armed conflict in eastern Ukraine and its consequences influence the pattern, practice, and experience of sex work and how this affects HIV and HCV rates among female sex workers (FSWs) and their clients. METHODS: We are implementing a 5-year mixed methods study in Dnipro, eastern Ukraine. Serial mapping and size estimation of FSWs and clients will be conducted followed by bio-behavioral cross-sectional surveys among FSWs and their clients. The qualitative component of the study will include in-depth interviews with FSWs and other key stakeholders and participant diaries will be implemented with FSWs. We will also conduct an archival review over the course of the project. Finally, we will use these data to develop and structure a mathematical model with which to estimate the potential influence of changes due to conflict on the trajectory of HIV and HCV epidemics among FSW and clients. DISCUSSION: The limited data that exists on the effect of conflict on disease transmission provides mixed results. Our study will provide rigorous, timely and context-specific data on HIV and HCV transmission in the setting of conflict. This information can be used to inform the design and delivery of HIV and HCV prevention and care services.
Cheuk E, Isac S, Musyoki H, et al., 2019, Informing HIV prevention programs for adolescent girls and young women: a modified approach to programmatic mapping and key population size estimation, JMIR Public Health and Surveillance, Vol: 5, Pages: 242-255, ISSN: 2369-2960
Background: Standard programmatic mapping involves identifying locations where key populations meet, profiling of these locations (hotspots), and estimating the key population size. Information gained from this method has been used for HIV programming—resource allocation, program planning, service delivery, and monitoring and evaluation—for people who inject drugs, men who have sex with men, and female sex workers (FSWs). With an increasing focus on adolescent girls and young women (AGYW) as a priority population for HIV prevention, programs need to know the location of and how to effectively reach individuals who are at increased risk for HIV but were conventionally considered part of the general population. We hypothesize that AGYW who engage in transactional and casual sex also congregate at sex work hotspots to meet sex partners. Therefore, we adapted the standard programmatic mapping approach to understand the geographic distribution and population size of AGYW at increased HIV risk in Mombasa County, Kenya.Objectives: The objectives are several-fold: (1) detail and compare the modified programmatic mapping approach used in this study to the standard approach, (2) estimate the number of young FSWs, (3) estimate the number of AGYW who congregate in sex work hotspots to meet sex partners other than clients, (4) estimate the overlap in sexual network in hotspots, (5) describe the distribution of sex work hotspots across Mombasa and its four subcounties, and (6) compare the distribution of hotspots that were known to the local HIV prevention program prior to this study and those newly identified.Methods: The standard programmatic mapping approach was modified to estimate the population of young women aged 14 to 24 years who visit sex work hotspots in Mombasa to meet partners for commercial, transactional, and casual sex.Results: We estimated that there were 11,777 FSWs (range 9265 to 14,290) in Mombasa in 2014 among whom 6127 (52.02%) were 14 to 24 year
Becker ML, Bhattacharjee P, Blanchard JF, et al., 2018, Vulnerabilities at First Sex and Their Association With Lifetime Gender-Based Violence and HIV Prevalence Among Adolescent Girls and Young Women Engaged in Sex Work, Transactional Sex, and Casual Sex in Kenya, JAIDS: Journal of Acquired Immune Deficiency Syndromes, Vol: 79, Pages: 296-304, ISSN: 1525-4135
BACKGROUND:Adolescent girls and young women (AGYW) experience high rates of HIV early in their sexual life course. We estimated the prevalence of HIV-associated vulnerabilities at first sex, and their association with lifetime gender-based violence (GBV) and HIV. METHODS:We conducted a cross-sectional biobehavioral survey among AGYW (14-24 years) in Mombasa, Kenya in 2015. We compared the prevalence of first sex vulnerabilities across AGYW who self-identified as engaging in sex work (N = 408), transactional sex (N = 177), or casual sex (N = 714) and used logistic regression to identify age-adjusted associations between first sex vulnerabilities and outcomes (GBV after first sex; HIV). RESULTS:The median age at first sex was 16 years (interquartile range 14-18). A total of 43.6% received gifts or money at first sex; 41.2% and 11.2% experienced a coerced and forced first sex, respectively. First sex vulnerabilities were generally more common among AGYW in sex work. GBV (prevalence 23.8%) and HIV (prevalence 5.6%) were associated with first sex before age 15 [GBV adjusted odds ratio (AOR) 1.4, 95% confidence interval (CI): 1.0 to 1.9; HIV AOR 1.9, 95% CI: 1.1 to 1.3]; before or within 1 year of menarche (GBV AOR 1.3, 95% CI: 1.0 to 1.7; HIV AOR 2.1, 95% CI: 1.3 to 3.6); and receipt of money (GBV AOR 1.9, 95% CI: 1.4 to 2.5; HIV AOR 2.0, 95% CI: 1.2 to 3.4). CONCLUSIONS:HIV-associated vulnerabilities begin at first sex and potentially mediate an AGYW's trajectory of risk. HIV prevention programs should include structural interventions that reach AGYW early, and screening for a history of first sex vulnerabilities could help identify AGYW at risk of ongoing GBV and HIV.
Thomas RA, Burger R, Harper A, et al., 2017, Differences in health-related quality of life between HIV-positive and HIV-negative people in Zambia and South Africa: a cross-sectional baseline survey of the HPTN 071 (PopART) trial, The Lancet Global Health, Vol: 5, Pages: e1133-e1141, ISSN: 2214-109X
BackgroundThe life expectancy of HIV-positive individuals receiving antiretroviral therapy (ART) is approaching that of HIV-negative people. However, little is known about how these populations compare in terms of health-related quality of life (HRQoL). We aimed to compare HRQoL between HIV-positive and HIV-negative people in Zambia and South Africa.MethodsAs part of the HPTN 071 (PopART) study, data from adults aged 18–44 years were gathered between Nov 28, 2013, and March 31, 2015, in large cross-sectional surveys of random samples of the general population in 21 communities in Zambia and South Africa. HRQoL data were collected with a standardised generic measure of health across five domains. We used β-distributed multivariable models to analyse differences in HRQoL scores between HIV-negative and HIV-positive individuals who were unaware of their status; aware, but not in HIV care; in HIV care, but who had not initiated ART; on ART for less than 5 years; and on ART for 5 years or more. We included controls for sociodemographic variables, herpes simplex virus type-2 status, and recreational drug use.FindingsWe obtained data for 19 750 respondents in Zambia and 18 941 respondents in South Africa. Laboratory-confirmed HIV status was available for 19 330 respondents in Zambia and 18 004 respondents in South Africa; 4128 (21%) of these 19 330 respondents in Zambia and 4012 (22%) of 18 004 respondents in South Africa had laboratory-confirmed HIV. We obtained complete HRQoL information for 19 637 respondents in Zambia and 18 429 respondents in South Africa. HRQoL scores did not differ significantly between individuals who had initiated ART more than 5 years previously and HIV-negative individuals, neither in Zambia (change in mean score −0·002, 95% CI −0·01 to 0·001; p=0·219) nor in South Africa (0·000, −0·002 to 0·003; p=0·939). However, scores did differ between HIV-positive individu
Ratmann O, Hodcroft EB, Pickles M, et al., 2017, Phylogenetic tools for generalized HIV-1 epidemics: findings from the PANGEA-HIV methods comparison, Molecular Biology and Evolution, Vol: 34, Pages: 185-203, ISSN: 1537-1719
Viral phylogenetic methods contribute to understanding how HIV spreads in populations, and thereby help guide the design of prevention interventions. So far, most analyses have been applied to well-sampled concentrated HIV-1 epidemics in wealthy countries. To direct the use of phylogenetic tools to where the impact of HIV-1 is greatest, the Phylogenetics And Networks for Generalized HIV Epidemics in Africa (PANGEA-HIV) consortium generates full-genome viral sequences from across sub-Saharan Africa. Analyzing these data presents new challenges, since epidemics are principally driven by heterosexual transmission and a smaller fraction of cases is sampled. Here, we show that viral phylogenetic tools can be adapted and used to estimate epidemiological quantities of central importance to HIV-1 prevention in sub-Saharan Africa. We used a community-wide methods comparison exercise on simulated data, where participants were blinded to the true dynamics they were inferring. Two distinct simulations captured generalized HIV-1 epidemics, before and after a large community-level intervention that reduced infection levels. Five research groups participated. Structured coalescent modeling approaches were most successful: phylogenetic estimates of HIV-1 incidence, incidence reductions, and the proportion of transmissions from individuals in their first 3 months of infection correlated with the true values (Pearson correlation > 90%), with small bias. However, on some simulations, true values were markedly outside reported confidence or credibility intervals. The blinded comparison revealed current limits and strengths in using HIV phylogenetics in challenging settings, provided benchmarks for future methods’ development, and supports using the latest generation of phylogenetic tools to advance HIV surveillance and prevention.
Ramachandran S, Mishra S, Condie N, et al., 2016, How do HIV-negative individuals in sub-Saharan Africa change their sexual risk behaviour upon learning their serostatus? A systematic review, Sexually Transmitted Infections, Vol: 92, Pages: 571-578, ISSN: 1472-3263
Objective: To determine whether, and how, sexual behaviour of HIV-negative individuals in Sub-Saharan Africa (SSA) changes upon learning their serostatus.Methods: We systematically reviewed the published literature using EMBASE and Medline to search for publications between 2004 and 2014. We included studies that quantified behaviour change (condom use, number of sexual partners or sex acts) following an HIV test in HIV-negative adults in SSA, and extracted relevant data including study characteristics and measurement type.Results: From 2185 unique citations, n=14 studies representing 22,390 participants met our inclusion criteria. We did not pool data due to marked heterogeneity in study outcome measures. The proportion of participants reporting consistent condom use (n=6) post-testing ranged from 7.6% greater, to 10.6% fewer, while “no condom use” (n=5) ranged from 40.0% less, to 0.7% more. Condom use in serodiscordant couples increased (n=3). Five studies measured the proportion reporting abstinence, finding an increase of 10.9% to a decrease of 5.3% post-testing. The post-testing change in the mean number of sex acts (n=3) ranged from a relative decrease of 15.7% to a relative increase of 9.4%. Two studies reported relative decreases in the mean number of sexual partners of 35.2% and 14.0%. Three studies examining serodiscordant primary relationships specifically all showed increases in extra-relational sex.Conclusions: With the exception of serodiscordant couples, there is variable evidence that awareness of one’s serostatus leads to substantial changes in risk behaviour among HIV-negative individuals. Further research is needed to estimate the behavioural impact of learning one’s serostatus in SSA.
Heffernan A, Barber E, Thomas R, et al., 2016, Impact and Cost-Effectiveness of Point-Of-Care CD4 Testing on the HIV Epidemic in South Africa., PLOS One, Vol: 11, ISSN: 1932-6203
Rapid diagnostic tools have been shown to improve linkage of patients to care. In the context of infectious diseases, assessing the impact and cost-effectiveness of such tools at the population level, accounting for both direct and indirect effects, is key to informing adoption of these tools. Point-of-care (POC) CD4 testing has been shown to be highly effective in increasing the proportion of HIV positive patients who initiate ART. We assess the impact and cost-effectiveness of introducing POC CD4 testing at the population level in South Africa in a range of care contexts, using a dynamic compartmental model of HIV transmission, calibrated to the South African HIV epidemic. We performed a meta-analysis to quantify the differences between POC and laboratory CD4 testing on the proportion linking to care following CD4 testing. Cumulative infections averted and incremental cost-effectiveness ratios (ICERs) were estimated over one and three years. We estimated that POC CD4 testing introduced in the current South African care context can prevent 1.7% (95% CI: 0.4% - 4.3%) of new HIV infections over 1 year. In that context, POC CD4 testing was cost-effective 99.8% of the time after 1 year with a median estimated ICER of US$4,468/DALY averted. In healthcare contexts with expanded HIV testing and improved retention in care, POC CD4 testing only became cost-effective after 3 years. The results were similar when, in addition, ART was offered irrespective of CD4 count, and CD4 testing was used for clinical assessment. Our findings suggest that even if ART is expanded to all HIV positive individuals and HIV testing efforts are increased in the near future, POC CD4 testing is a cost-effective tool, even within a short time horizon. Our study also illustrates the importance of evaluating the potential impact of such diagnostic technologies at the population level, so that indirect benefits and costs can be incorporated into estimations of cost-effectiveness.
Herbeck JT, Mittler JE, Gottlieb GS, et al., 2016, Evolution of HIV virulence in response to widespread scale up of antiretroviral therapy: a modeling study, Virus Evolution, Vol: 2, ISSN: 2057-1577
There are global increases in the use of HIV antiretroviral therapy (ART), guided by clinical benefits of early ART initiation and the efficacy of treatment as prevention of transmission. Separately, it has been shown theoretically and empirically that HIV virulence can evolve over time; observed virulence levels may reflect an adaptive balance between infected lifespan and per-contact transmission rate. However, the potential effects of widespread ART usage on HIV virulence are unknown. To predict these effects, we used an agent-based stochastic model to simulate evolutionary trends in HIV virulence, using set point viral load as a proxy for virulence. We calibrated our model to prevalence and incidence trends of South Africa. We explored two distinct ART scenarios: (1) ART initiation based on HIV-infected individuals reaching a CD4 count threshold; and (2) ART initiation based on individual time elapsed since HIV infection (a scenario that mimics “universal testing and treatment” (UTT) aspirations). In each case, we considered a range in population uptake of ART. We found that HIV virulence is generally unchanged in scenarios of CD4-based initiation. However, with ART initiation based on time since infection, virulence can increase moderately within several years of ART rollout, under high coverage levels and early treatment initiation (albeit within the context of epidemics that are rapidly decreasing in size). Sensitivity analyses suggested the impact of ART on virulence is relatively insensitive to model calibration. Our modeling study suggests that increasing HIV virulence driven by UTT is likely not a major public health concern, but should be monitored in sentinel surveillance, in a manner similar to transmitted resistance to antiretroviral drugs.
Dureau J, Kalogeropoulos K, Vickerman P, et al., 2016, A Bayesian approach to estimate changes in condom use from limited human immunodeficiency virus prevalence data, Journal of the Royal Statistical Society Series C - Applied Statistics, Vol: 65, Pages: 237-257, ISSN: 0035-9254
Evaluation of large-scale intervention programmes against human immunodeficiency virus (HIV) is becoming increasingly important, but impact estimates frequently hinge on knowledge of changes in behaviour such as the frequency of condom use over time, or other self-reported behaviour changes, for which we generally have limited or potentially biased data. We employ a Bayesian inference methodology that incorporates an HIV transmission dynamics model to estimate condom use time trends from HIV prevalence data. Estimation is implemented via particle Markov chain Monte Carlo methods, applied for the first time in this context. The preliminary choice of the formulation for the time varying parameter reflecting the proportion of condom use is critical in the context studied, because of the very limited amount of condom use and HIV data available. We consider various novel formulations to explore the trajectory of condom use over time, based on diffusion-driven trajectories and smooth sigmoid curves. Numerical simulations indicate that informative results can be obtained regarding the amplitude of the increase in condom use during an intervention, with good levels of sensitivity and specificity performance in effectively detecting changes. The application of this method to a real life problem demonstrates how it can help in evaluating HIV interventions based on a small number of prevalence estimates, and it opens the way to similar applications in different contexts.
Cori A, Pickles M, van Sighem A, et al., 2015, CD4+ cell dynamics in untreated HIV-1 infection: overall rates, and effects of age, viral load, sex and calendar time., AIDS, Vol: 29, Pages: 2435-2446, ISSN: 0269-9370
BACKGROUND: CD4 cell count is a key measure of HIV disease progression, and the basis of successive international guidelines for treatment initiation. CD4 cell dynamics are used in mathematical and econometric models for evaluating public health need and interventions. Here, we estimate rates of CD4 decline, stratified by relevant covariates, in a form that is clinically transparent and can be directly used in such models. METHODS: We analyse the AIDS Therapy Evaluation in the Netherlands cohort, including individuals with date of seroconversion estimated to be within 1 year and with intensive clinical follow-up prior to treatment initiation. Owing to the fact that CD4 cell counts are intrinsically noisy, we separate the analysis into long-term trends of smoothed CD4 cell counts and an observation model relating actual CD4 measurements to the underlying smoothed counts. We use a monotonic spline smoothing model to describe the decline of smoothed CD4 cell counts through categories CD4 above 500, 350-500, 200-350 and 200 cells/μl or less. We estimate the proportion of individuals starting in each category after seroconversion and the average time spent in each category. We examine individual-level cofactors which influence these parameters. RESULTS: Among untreated individuals, the time spent in each compartment was 3.32, 2.70, 5.50 and 5.06 years. Only 76% started in the CD4 cell count above 500 cells/μl compartment after seroconversion. Set-point viral load (SPVL) was an important factor: individuals with at least 5 log10 copies/ml took 5.37 years to reach CD4 cell count less than 200 cells/μl compared with 15.76 years for SPVL less than 4 log10 copies/ml. CONCLUSION: Many individuals already have CD4 cell count below 500 cells/μl after seroconversion. SPVL strongly influences the rate of CD4 decline. Treatment guidelines should consider measuring SPVL, whereas mathematical models should incorporate SPVL stratification.
Boily M-C, Pickles M, Alary M, et al., 2015, What Really Is a Concentrated HIV Epidemic and What Does It Mean for West and Central Africa? Insights From Mathematical Modeling, JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES, Vol: 68, Pages: S74-S82, ISSN: 1525-4135
Jewell BL, Cremin I, Pickles M, et al., 2015, Estimating the cost-effectiveness of pre-exposure prophylaxis to reduce HIV-1 and HSV-2 incidence in HIV-serodiscordant couples in South Africa, PLOS One, Vol: 10, ISSN: 1932-6203
ObjectiveTo estimate the cost-effectiveness of daily oral tenofovir-based PrEP, with a protective effect against HSV-2 as well as HIV-1, among HIV-1 serodiscordant couples in South Africa.MethodsWe incorporated HSV-2 acquisition, transmission, and interaction with HIV-1 into a microsimulation model of heterosexual HIV-1 serodiscordant couples in South Africa, with use of PrEP for the HIV-1 uninfected partner prior to ART initiation for the HIV-1 1infected partner, and for one year thereafter.ResultsWe estimate the cost per disability-adjusted life-year (DALY) averted for two scenarios, one in which PrEP has no effect on reducing HSV-2 acquisition, and one in which there is a 33% reduction. After a twenty-year intervention, the cost per DALY averted is estimated to be $10,383 and $9,757, respectively – a 6% reduction, given the additional benefit of reduced HSV-2 acquisition. If all couples are discordant for both HIV-1 and HSV-2, the cost per DALY averted falls to $1,445, which shows that the impact is limited by HSV-2 concordance in couples.ConclusionAfter a 20-year PrEP intervention, the cost per DALY averted with a reduction in HSV-2 is estimated to be modestly lower than without any effect, providing an increase of health benefits in addition to HIV-1 prevention at no extra cost. The small degree of the effect is in part due to a high prevalence of HSV-2 infection in HIV-1 serodiscordant couples in South Africa.
Shannon K, Strathdee SA, Goldenberg SM, et al., 2015, Global epidemiology of HIV among female sex workers: influence of structural determinants, LANCET, Vol: 385, Pages: 55-71, ISSN: 0140-6736
Vassall A, Chandrashekar S, Pickles M, et al., 2014, Community mobilisation and empowerment interventions as part of HIV prevention for female sex workers in southern India: a cost-effectiveness analysis, PLOS One, Vol: 9, ISSN: 1932-6203
BackgroundMost HIV prevention for female sex workers (FSWs) focuses on individual behaviour change involving peer educators, condom promotion and the provision of sexual health services. However, there is a growing recognition of the need to address broader societal, contextual and structural factors contributing to FSW risk behaviour. We assess the cost-effectiveness of adding community mobilisation (CM) and empowerment interventions (eg. community mobilisation, community involvement in programme management and services, violence reduction, and addressing legal policies and police practices), to core HIV prevention services delivered as part of Avahan in two districts (Bellary and Belgaum) of Karnataka state, Southern India.MethodsAn ingredients approach was used to estimate economic costs in US$ 2011 from an HIV programme perspective of CM and empowerment interventions over a seven year period (2004–2011). Incremental impact, in terms of HIV infections averted, was estimated using a two-stage process. An ‘exposure analysis’ explored whether exposure to CM was associated with FSW’s empowerment, risk behaviours and HIV/STI prevalence. Pathway analyses were then used to estimate the extent to which behaviour change may be attributable to CM and to inform a dynamic HIV transmission model.FindingsThe incremental costs of CM and empowerment were US$ 307,711 in Belgaum and US$ 592,903 in Bellary over seven years (2004–2011). Over a 7-year period (2004–2011) the mean (standard deviation, sd.) number of HIV infections averted through CM and empowerment is estimated to be 1257 (308) in Belgaum and 2775 (1260) in Bellary. This translates in a mean (sd.) incremental cost per disability adjusted life year (DALY) averted of US$ 14.12 (3.68) in Belgaum and US$ 13.48 (6.80) for Bellary - well below the World Health Organisation recommended willingness to pay threshold for India. When savings from ART are taken into account, investments in CM an
Mountain E, Pickles M, Mishra S, et al., 2014, The HIV care cascade and antiretroviral therapy in female sex workers: implications for HIV prevention, EXPERT REVIEW OF ANTI-INFECTIVE THERAPY, Vol: 12, Pages: 1203-1219, ISSN: 1478-7210
Mountain E, Mishra S, Vickerman P, et al., 2014, Antiretroviral therapy uptake, attrition, adherence and outcomes among HIB-infected female sex workers: a systematic review and meta-analysis, PLOS One, Vol: 9, ISSN: 1932-6203
PurposeWe aimed to characterize the antiretroviral therapy (ART) cascade among female sex workers (FSWs) globally.MethodsWe systematically searched PubMed, Embase and MEDLINE in March 2014 to identify studies reporting on ART uptake, attrition, adherence, and outcomes (viral suppression or CD4 count improvements) among HIV-infected FSWs globally. When possible, available estimates were pooled using random effects meta-analyses (with heterogeneity assessed using Cochran's Q test and I2 statistic).Results39 studies, reporting on 21 different FSW study populations in Asia, Africa, North America, South America, and Central America and the Caribbean, were included. Current ART use among HIV-infected FSWs was 38% (95% CI: 29%–48%, I2 = 96%, 15 studies), and estimates were similar between high-, and low- and middle-income countries. Ever ART use among HIV-infected FSWs was greater in high-income countries (80%; 95% CI: 48%–94%, I2 = 70%, 2 studies) compared to low- and middle-income countries (36%; 95% CI: 7%–81%, I2 = 99%, 3 studies). Loss to follow-up after ART initiation was 6% (95% CI: 3%–11%, I2 = 0%, 3 studies) and death after ART initiation was 6% (95% CI: 3%–11%, I2 = 0%, 3 studies). The fraction adherent to ≥95% of prescribed pills was 76% (95% CI: 68%–83%, I2 = 36%, 4 studies), and 57% (95% CI: 46%–68%, I2 = 82%, 4 studies) of FSWs on ART were virally suppressed. Median gains in CD4 count after 6 to 36 months on ART, ranged between 103 and 241 cells/mm3 (4 studies).ConclusionsDespite global increases in ART coverage, there is a concerning lack of published data on HIV treatment for FSWs. Available data suggest that FSWs can achieve levels of ART uptake, retention, adherence, and treatment response comparable to that seen among women in the general population, but these data are from only a few research settings. More routine programme data on HIV treatment among FSWs across settings should be collected and disseminated
Chandrashekar S, Guinness L, Pickles M, et al., 2014, The costs of scaling up HIV prevention for high risk groups: lessons learned from the Avahan programme in India, PLOS One, Vol: 9, ISSN: 1932-6203
OBJECTIVE: The study objective is to measure, analyse costs of scaling up HIV prevention for high-risk groups in India, in order to assist the design of future HIV prevention programmes in South Asia and beyond. DESIGN: Prospective costing study. METHODS: This study is one of the most comprehensive studies of the costs of HIV prevention for high-risk groups to date in both its scope and size. HIV prevention included outreach, sexually transmitted infections (STI) services, condom provision, expertise enhancement, community mobilisation and enabling environment activities. Economic costs were collected from 138 non-government organisations (NGOs) in 64 districts, four state level lead implementing partners (SLPs), and the national programme level (Bill and Melinda Gates Foundation (BMGF)) office over four years using a top down costing approach, presented in US$ 2011. RESULTS: Mean total unit costs (2004-08) per person reached at least once a year and per monthly contact were US$ 235(56-1864) and US$ 82(12-969) respectively. 35% of the cost was incurred by NGOs, 30% at the state level SLP and 35% at the national programme level. The proportion of total costs by activity were 34% for expertise enhancement, 37% for programme management (including support and supervision), 22% for core HIV prevention activities (outreach and STI services) and 7% for community mobilisation and enabling environment activities. Total unit cost per person reached fell sharply as the programme expanded due to declining unit costs above the service level (from US$ 477 per person reached in 2004 to US$ 145 per person reached in 2008). At the service level also unit costs decreased slightly over time from US$ 68 to US$ 64 per person reached. CONCLUSIONS: Scaling up HIV prevention for high risk groups requires significant investment in expertise enhancement and programme administration. However, unit costs decreased with programme expansion in spite of an increase in the scope of activities.
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