Search

Background The SEARCH study provided community-based HIV and multi-disease testing and antiretroviral therapy (ART) to 32 communities in East Africa and reported no statistically significant difference in three-year HIV incidence. We used mathematical modelling to estimate the effect of control arm viral suppression and community mixing on SEARCH trial outcomes. Setting Uganda and Kenya. Methods Using the individual-based HIV modeling software EMOD-HIV, we configured a new model of SEARCH communities. The model was parameterized using demographic, HIV prevalence, male circumcision, and viral suppression data, and calibrated to HIV prevalence, ART coverage, and population size. Using assumptions about ART scale-up in the control arm, degree of community mixing, and effect of baseline testing, we estimated comparative HIV incidence under multiple scenarios. Results Prior to the trial results, we predicted that SEARCH would report a 4-40% reduction between arms, depending on control arm ART linkage rates and community mixing. With universal baseline testing followed by rapidly expanded ART eligibility and uptake, modelled effect sizes were smaller than the study was powered to detect. Using interim viral suppression data, we estimated three-year cumulative incidence would have been reduced by up to 27% in the control arm and 43% in the intervention arm compared to a counterfactual without universal baseline testing. Conclusions Our model suggests that the active control arm substantially reduced expected effect size and power of the SEARCH study. However, compared to a counterfactual "true control" without increased ART linkage due to baseline testing, SEARCH reduced HIV incidence by up to 43%.

Summary Background COVID-19 has the potential to cause substantial disruptions to health services, due to cases overburdening the health system or response measures limiting usual programmatic activities. We aimed to quantify the extent to which disruptions to services for HIV, tuberculosis, and malaria in low-income and middle-income countries with high burdens of these diseases could lead to additional loss of life over the next 5 years. Methods Assuming a basic reproduction number of 3·0, we constructed four scenarios for possible responses to the COVID-19 pandemic: no action, mitigation for 6 months, suppression for 2 months, or suppression for 1 year. We used established transmission models of HIV, tuberculosis, and malaria to estimate the additional impact on health that could be caused in selected settings, either due to COVID-19 interventions limiting activities, or due to the high demand on the health system due to the COVID-19 pandemic. Findings In high-burden settings, deaths due to HIV, tuberculosis, and malaria over 5 years could increase by up to 10%, 20%, and 36%, respectively, compared with if there was no COVID-19 pandemic. The greatest impact on HIV was estimated to be from interruption to antiretroviral therapy, which could occur during a period of high health system demand. For tuberculosis, the greatest impact would be from reductions in timely diagnosis and treatment of new cases, which could result from any prolonged period of COVID-19 suppression interventions. The greatest impact on malaria burden could be as a result of interruption of planned net campaigns. These disruptions could lead to a loss of life-years over 5 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 and tuberculosis epidemics. Interpretation Maintaining the most critical prevention activities and health-care services for HIV, tuberculosis, and malaria could substantially reduce the overall impact of the COVID-19 pandemic. Funding Bill & Melinda Gates Foundation, Wellcome Trust, UK Department for International Development, and Medical Research Council.

Summary Background The COVID-19 pandemic could lead to disruptions to provision of HIV services for people living with HIV and those at risk of acquiring HIV in sub-Saharan Africa, where UNAIDS estimated that more than two-thirds of the approximately 38 million people living with HIV resided in 2018. We aimed to predict the potential effects of such disruptions on HIV-related deaths and new infections in sub-Saharan Africa. Methods In this modelling study, we used five well described models of HIV epidemics (Goals, Optima HIV, HIV Synthesis, an Imperial College London model, and Epidemiological MODeling software [EMOD]) to estimate the effect of various potential disruptions to HIV prevention, testing, and treatment services on HIV-related deaths and new infections in sub-Saharan Africa lasting 6 months over 1 year from April 1, 2020. We considered scenarios in which disruptions affected 20%, 50%, and 100% of the population. Findings A 6-month interruption of supply of antiretroviral therapy (ART) drugs across 50% of the population of people living with HIV who are on treatment would be expected to lead to a 1·63 times (median across models; range 1·39–1·87) increase in HIV-related deaths over a 1-year period compared with no disruption. In sub-Saharan Africa, this increase amounts to a median excess of HIV deaths, across all model estimates, of 296 000 (range 229 023–420 000) if such a high level of disruption occurred. Interruption of ART would increase mother-to-child transmission of HIV by approximately 1·6 times. Although an interruption in the supply of ART drugs would have the largest impact of any potential disruptions, effects of poorer clinical care due to overstretched health facilities, interruptions of supply of other drugs such as co-trimoxazole, and suspension of HIV testing would all have a substantial effect on population-level mortality (up to a 1·06 times increase in HIV-related deaths over a 1-year period due to disruptions affecting 50% of the population compared with no disruption). Interruption to condom supplies and peer education would make populations more susceptible to increases in HIV incidence, although physical distancing measures could lead to reductions in risky sexual behaviour (up to 1·19 times increase in new HIV infections over a 1-year period if 50% of people are affected). Interpretation During the COVID-19 pandemic, the primary priority for governments, donors, suppliers, and communities should focus on maintaining uninterrupted supply of ART drugs for people with HIV to avoid additional HIV-related deaths. The provision of other HIV prevention measures is also important to prevent any increase in HIV incidence. Funding Bill & Melinda Gates Foundation.

The Institute for Health Metrics and Evaluation model for predicting the course of the coronavirus disease 2019 pandemic has attracted considerable attention, including from the U.S. government. The appearance of certainty of model estimates is seductive when the world is desperate to know what lies ahead, but caution is warranted regarding the validity and usefulness of the model projections for policymakers.

SummaryThe numbers of deaths caused by HIV could increase substantially if the COVID-19 epidemic leads to interruptions in the availability of HIV services. We compare publicly available scenarios for COVID-19 mortality with predicted additional HIV-related mortality based on assumptions about possible interruptions in HIV programs. An interruption in the supply of ART for 40% of those on ART for 3 months could cause a number of deaths on the same order of magnitude as the number that are anticipated to be saved from COVID-19 through social distancing measures. In contrast, if the disruption can be managed such that the supply and usage of ART is maintained, the increase in AIDS deaths would be limited to 1% over five years, although this could still be accompanied by substantial increases in new HIV infections if there are reductions in VMMC, oral PrEP use, and condom availability.

BackgroundThe United States is now the country reporting the highest number of 2019 coronavirus disease (COVID-19) cases and deaths. However, little is known about the epidemiology and burden of severe COVID-19 to inform planning within healthcare systems and modeling of intervention impact.MethodsWe assessed incidence, duration of hospitalization, and clinical outcomes of acute COVID-19 inpatient admissions in a prospectively-followed cohort of 9,596,321 individuals enrolled in comprehensive, integrated healthcare delivery plans from Kaiser Permanente in California and Washington state. We also estimated the effective reproductive number (RE) describing transmission in the study populations.ResultsData covered 1277 hospitalized patients with laboratory- or clinically-confirmed COVID-19 diagnosis by April 9, 2020. Cumulative incidence of first COVID-19 acute inpatient admission was 10.6-12.4 per 100,000 cohort members across the study regions. Mean censoring-adjusted duration of hospitalization was 10.7 days (2.5-97.5%iles: 0.8-30.1) among survivors and 13.7 days (2.5-97.5%iles: 1.7-34.6) among non-survivors. Among all hospitalized confirmed cases, censoring-adjusted probabilities of ICU admission and mortality were 41.9% (95% confidence interval: 34.1-51.4%) and 17.8% (14.3-22.2%), respectively, and higher among men than women. We estimated RE was 1.43 (1.17-1.73), 2.09 (1.63-2.69), and 1.47 (0.07-2.59) in Northern California, Southern California, and Washington, respectively, for infections acquired March 1, 2020. RE declined to 0.98 (0.76-1.27), 0.89 (0.74-1.06), and 0.92 (0.05-1.55) respectively, for infections acquired March 20, 2020.ConclusionsWe identify high probability of ICU admission, long durations of stay, and considerable mortality risk among hospitalized COVID-19 cases in the western United States. Reductions in RE have occurred in conjunction with implementation of non-pharmaceutical interventions.

Western Kenya suffers a highly endemic and also very heterogeneous epidemic of human immunodeficiency virus (HIV). Although female sex workers (FSW) and their male clients are known to be at high risk for HIV, HIV prevalence across regions in Western Kenya is not strongly correlated with the fraction of women engaged in commercial sex. An agent-based network model of HIV transmission, geographically stratified at the county level, was fit to the HIV epidemic, scale-up of interventions, and populations of FSW in Western Kenya under two assumptions about the potential mobility of FSW clients. In the first, all clients were assumed to be resident in the same geographies as their interactions with FSW. In the second, some clients were considered non-resident and engaged only in interactions with FSW, but not in longer-term non-FSW partnerships in these geographies. Under both assumptions, the model successfully reconciled disparate geographic patterns of FSW and HIV prevalence. Transmission patterns in the model suggest a greater role for FSW in local transmission when clients were resident to the counties, with 30.0% of local HIV transmissions attributable to current and former FSW and clients, compared to 21.9% when mobility of clients was included. Nonetheless, the overall epidemic drivers remained similar, with risky behavior in the general population dominating transmission in high-prevalence counties. Our modeling suggests that co-location of high-risk populations and generalized epidemics can further amplify the spread of HIV, but that large numbers of formal FSW and clients are not required to observe or mechanistically explain high HIV prevalence in the general population.

Assessment of the extent of civilian casualties during times of conflict presents significant challenges in data collection, quantitative methods, interpretation, and presentation. In this article, we briefly consider the motivation and use of casualty accounting and review historical approaches to these questions with illustrative comments on the US Civil War, World War I, World War II, and other conflicts. We provide an overview of several accounting methodologies including excess mortality, epidemiologic surveys, direct and indirect counts, multiple list estimation, and crowdsourcing. We reflect on the evolution toward modern approaches to casualty assessments, permitted by both a deeper understanding of human rights and by contemporaneous technological advances in data collection techniques. Our goal is to introduce several areas of research that deserve attention from social science historians and statisticians.

Author(s): Mayer, Christopher M; Owaraganise, Asiphas; Kabami, Jane; Kwarisiima, Dalsone; Koss, Catherine A; Charlebois, Edwin D; Kamya, Moses R; Petersen, Maya L; Havlir, Diane V; Jewell, Britta L | Abstract: IntroductionGeographic and transportation barriers are associated with poorer HIV-related health outcomes in sub-Saharan Africa, but data on the impact of these barriers on prevention interventions are limited. We estimated the association between distance to clinic and other transportation-related barriers on pre-exposure prophylaxis (PrEP) uptake and initial clinic visit attendance in a rural community in southwestern Uganda enrolled in the ongoing SEARCH study (NCT01864603).MethodsCommunity-wide HIV testing was conducted and offered to adult (≥15nyears) participants in Ruhoko. Participants were eligible for PrEP based on an empiric risk score, having an HIV-discordant partner, or self-referral at either the community health campaign or during home-based testing from March to April 2017. We collected data from PrEP-eligible households on GPS-measured distance to clinic, walking time to clinic and road difficulty. A sample of participants was also asked to identify their primary barriers to PrEP use with a semi-quantitative questionnaire. We used multivariable logistic regression to evaluate the association between transportation barriers and (1) PrEP uptake among PrEP-eligible individuals and (2) four-week clinic visit attendance among PrEP initiators.ResultsOf the 701 PrEP-eligible participants, 272 (39%) started PrEP within four weeks; of these, 45 (17%) were retained at four weeks. Participants with a distance to clinic of ≥2nkm were less likely to start PrEP (aOR 0.34; 95% CI 0.15 to 0.79, pn=n0.012) and less likely to be retained on PrEP once initiated (aOR 0.29; 95% CI 0.10 to 0.84; pn=n0.024). Participants who were deemed eligible during home-based testing and did not have the option of same-day PrEP start were also substantially less likely to initiate PrEP (aOR 0.16, 95% CI 0.07 to 0.37, pnln0.001). Of participants asked to name barriers to PrEP use (Nn=n98), the most frequently cited were "needing to take PrEP every day" (Nn=n18) and "low/no risk of getting HIV" (Nn=n18). Transportation-related barriers, including "clinic is too far away" (Nn=n6) and "travel away from home" (Nn=n4) were also reported.ConclusionsDistance to clinic is a significant predictor of PrEP uptake and four-week follow-up visit attendance in a community in rural Uganda. Interventions that address geographic and transportation barriers may improve PrEP uptake and retention in sub-Saharan Africa.

Background: There is concern that the COVID-19 pandemic could severely disrupt HIV services in sub-Saharan Africa. However, it is difficult to determine priorities for maintaining different elements of existing HIV services given widespread uncertainty. Methods: We explore the impact of disruptions on HIV outcomes in South Africa, Malawi, Zimbabwe, and Uganda using a mathematical model, examine how impact is affected by model assumptions, and compare potential HIV deaths to those that may be caused by COVID-19 in the same settings. Findings: The most important determinant of HIV-related mortality is an interruption to antiretroviral treatment (ART) supply. A three-month interruption for 40% of those on ART could cause a similar number of additional deaths as those that might be saved from COVID-19 through social distancing. An interruption for more than 6–90% of individuals on ART for nine months could cause the number of HIV deaths to exceed the number of COVID-19 deaths, depending on the COVID-19 projection. However, if ART supply is maintained, but new treatment, voluntary medical male circumcision, and pre-exposure prophylaxis initiations cease for 3 months and condom use is reduced, increases in HIV deaths would be limited to

ObjectiveTo understand the epidemiology and burden of severe coronavirus disease 2019 (covid-19) during the first epidemic wave on the west coast of the United States.DesignProspective cohort study.SettingKaiser Permanente integrated healthcare delivery systems serving populations in northern California, southern California, and Washington state.Participants1840 people with a first acute hospital admission for confirmed covid-19 by 22 April 2020, among 9 596 321 healthcare plan enrollees. Analyses of hospital length of stay and clinical outcomes included 1328 people admitted by 9 April 2020 (534 in northern California, 711 in southern California, and 83 in Washington).Main outcome measuresCumulative incidence of first acute hospital admission for confirmed covid-19, and subsequent probabilities of admission to an intensive care unit (ICU) and mortality, as well as duration of hospital stay and ICU stay. The effective reproduction number (RE) describing transmission dynamics was estimated for each region.ResultsAs of 22 April 2020, cumulative incidences of a first acute hospital admission for covid-19 were 15.6 per 100 000 cohort members in northern California, 23.3 per 100 000 in southern California, and 14.7 per 100 000 in Washington. Accounting for censoring of incomplete hospital stays among those admitted by 9 April 2020, the estimated median duration of stay among survivors was 9.3 days (with 95% staying 0.8 to 32.9 days) and among non-survivors was 12.7 days (1.6 to 37.7 days). The censoring adjusted probability of ICU admission for male patients was 48.5% (95% confidence interval 41.8% to 56.3%) and for female patients was 32.0% (26.6% to 38.4%). For patients requiring critical care, the median duration of ICU stay was 10.6 days (with 95% staying 1.3 to 30.8 days). The censoring adjusted case fatality ratio was 23.5% (95% confidence interval 19.6% to 28.2%) among male inpatients and 14.9% (11.8% to 18.6%) among female inpatients; mortality risk increased with age for both male and female patients. Reductions in RE were identified over the study period within each region.ConclusionsAmong residents of California and Washington state enrolled in Kaiser Permanente healthcare plans who were admitted to hospital with covid-19, the probabilities of ICU admission, of long hospital stay, and of mortality were identified to be high. Incidence rates of new hospital admissions have stabilized or declined in conjunction with implementation of social distancing interventions.

President Trump is not alone in mistaking death “estimates” for death “counts”, write Michael Spagat, Britta Jewell and Nicholas Jewell

IntroductionSEARCH is one of four randomized-controlled trials (RCTs) investigating the strategy of community-based treatment-as-prevention (TasP) for the reduction of HIV incidence in sub-Saharan Africa. SEARCH takes place among 32 pair-matched rural communities in three regions of East Africa and exceeded the UNAIDS 90-90-90 targets for HIV testing, linkage to care, and viral suppression in the intervention arm. We used mathematical modeling to estimate expected 3-year cumulative HIV incidence in both arms of the trial, using different assumptions about two main sources of uncertainty: scale-up of antiretroviral therapy (ART) in the control arm, and the degree of mixing between SEARCH residents and non-residents.MethodsWe used the HIV modelling software EMOD-HIV to configure and calibrate a new model of the SEARCH communities. The 32 trial communities were clustered into six nodes (three for the control arm and three for the intervention arm) using k-means clustering based on community HIV prevalence, male circumcision rates, mobility, and geographic region. The model was parameterized using data on demographics, HIV prevalence, male circumcision rates, and viral suppression data collected at trial baseline in 2013, and calibrated to nodespecific and age-specific HIV prevalence, ART coverage, and population size. Using data on ART scale-up in subsequent follow-up years in the trial, we varied linkage to ART in the control arm and the degree of external mixing between SEARCH residents and non-residents.ResultsIf no external mixing and no additional control arm ART linkage occurred, we estimate the trial would report a relative risk (RR) of 0.60 (95% CI 0.54-0.67, pConclusionThe SEARCH trial is predicted to show a 4-40% reduction in cumulative 3-year incidence, but between 18-72% of simulations were non-significant if either or both ART linkage in the control arm and external mixing are substantial. Despite achieving the 90-90-90 targets, our “best guess” is that the SEARCH trial has an equal probability of reporting a non-significant reduction in HIV incidence as it does a significant reduction.

The scientific breakthrough proving that antiretroviral therapy (ART) can halt heterosexual HIV transmission came in the form of a landmark clinical trial conducted among serodiscordant couples. Study findings immediately informed global recommendations for the use of treatment as prevention in serodiscordant couples. The extent to which these findings are generalizable to other key populations or to groups exposed to HIV through nonsexual transmission routes (i.e., anal intercourse or unsafe injection of drugs) has since driven a large body of research. This review explores the history of HIV research in serodiscordant couples, the implications for management of couples, subsequent research on treatment as prevention in other key populations, and challenges in community implementation of these strategies.

The scientific breakthrough proving that antiretroviral therapy (ART) can halt heterosexual HIV transmission came in the form of a landmark clinical trial conducted among serodiscordant couples. Study findings immediately informed global recommendations for the use of treatment as prevention in serodiscordant couples. The extent to which these findings are generalizable to other key populations or to groups exposed to HIV through nonsexual transmission routes (i.e., anal intercourse or unsafe injection of drugs) has since driven a large body of research. This review explores the history of HIV research in serodiscordant couples, the implications for management of couples, subsequent research on treatment as prevention in other key populations, and challenges in community implementation of these strategies.

Introduction : To be used most effectively, pre-exposure prophylaxis (PrEP) should be prioritized to those at high risk of acquisition and would ideally be aligned with time periods of increased exposure. Identifying such time periods is not always straightforward, however. Gaza Province in southern Mozambique is characterized by high levels of HIV transmission and circular labour migration to mines in South Africa. A strong seasonal pattern in births is observable, reflecting an increase in conception in December. Given the potential for increased HIV transmission between miners returning in December and their partners in Gaza Province, PrEP use by the latter would be a useful means of HIV prevention, especially for couples who wish to conceive. Methods : A mathematical model was used to represent population-level adult heterosexual HIV transmission in Gaza Province. Increased HIV acquisition among partners of miners in December, coinciding with the miners’ return from South Africa, is represented. In addition to a PrEP intervention, the scale-up of treatment and recent scale-up of male circumcision that have occurred in Gaza are represented. Results : Providing time-limited PrEP to the partners of migrant miners, as opposed to providing PrEP all year, would improve the cost per infection averted by 7.5-fold. For the cost per infection averted to be below US$3000, at least 85% of PrEP users would need to be good adherers and PrEP would need to be cheaper than US$115 per person per year. Uncertainty regarding incidence of HIV transmission among partners of miners each year in December has a strong influence on estimates of cost per infection averted. Conclusions : Providing time-limited PrEP to partners of migrant miners in Gaza Province during periods of increased exposure would be a novel strategy for providing PrEP. This strategy would allow for a better prioritized intervention, with the potential to improve the efficiency of a PrEP intervention considerably, as well as providing important reproductive health benefits. Keywords: HIV; pre-exposure prophylaxis; ARV-based prevention; cost-effectiveness; mathematical models To access the supplementary material to this article please see Supplementary Files under Article Tools online. (Published: 20 July 2015) Citation: Cremin I et al. Journal of the International AIDS Society 2015, 18 (Suppl 3):19946 http://www.jiasociety.org/index.php/jias/article/view/19946 | http://dx.doi.org/10.7448/IAS.18.4.19946

Objective To 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. Methods We 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. Results We 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. Conclusion After 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.