Public health benefits of shifting from hospital-focused to ambulatory TB care in Eastern Europe: Optimising TB investments in Belarus, the Republic of Moldova, and Romania.

High rates of drug-resistant tuberculosis (DR-TB) continue to threaten public health, especially in Eastern Europe. Costs for treating DR-TB are substantially higher than treating drug-susceptible TB, and higher yet if DR-TB services are delivered in hospital. The WHO recommends that multidrug-resistant (MDR) TB be treated using mainly ambulatory care, shown to have non-inferior health outcomes, however, there has been a delay to transition away from hospital-focused MDR-TB care in certain Eastern European countries. Allocative efficiency analyses were conducted for three countries in Eastern Europe, Belarus, the Republic of Moldova, and Romania, to minimise a combination of TB incidence, prevalence, and mortality by 2035. A primary focus of these studies was to determine the health benefits and financial savings that could be realised if DR-TB service delivery shifted from hospital-focused to ambulatory care. Here we provide a comprehensive assessment of findings from these studies to demonstrate the collective benefit of transitioning from hospital-focused to ambulatory TB care, and to address common regional considerations. We highlight that transitioning from hospital-focused to ambulatory TB care could reduce treatment costs by 20% in Romania, 24% in Moldova, and by as much as 40% in Belarus or almost 35 million US dollars across these three countries by 2035 without affecting quality of care. Improved TB outcomes could be achieved, however, without additional spending by reinvesting these savings in higher-impact TB diagnosis and more efficacious DR-TB treatment regimens. We found commonalities in the large portion of TB cases treated in hospital across these three regional countries, and similar obstacles to transitioning to ambulatory care. National governments in the Eastern European region should examine barriers delaying adoption of ambulatory DR-TB care and consider lost opportunities caused by delays in switching to more efficient treatment modes.

How to do (or not to do) health resource allocations using constrained mathematical optimization.

Despite the push towards evidence-based health policy, decisions about how to allocate health resources are all too often made on the basis of political forces or a continuation of the status quo. This results in wastage in health systems and loss of potential population health. However, if health systems are to serve people best, then they must operate efficiently and equitably, and appropriate valuation methods are needed to determine how to do this. With the advances in computing power over the past few decades, advanced mathematical optimization algorithms can now be run on personal computers and can be used to provide comprehensive, evidence-based recommendations for policymakers on how to prioritize health spending considering policy objectives, interactions of interventions, real-world system constraints and budget envelopes. Such methods provide an invaluable complement to traditional or extended cost-effectiveness analyses or league tables. In this paper, we describe how such methods work, how policymakers and programme managers can access them and implement their recommendations and how they have changed health spending in the world to date.

The global HIV response at 40.

It is helpful to divide the global HIV response into three phases: The first, from about 1980 to 2000, represents "Calamity". The second, from roughly 2000 to 2015 represents "Hope." The third, from 2015, is unfolding and may be termed "Choices" - and these choices may be severely constrained by COVID, so "Constrained Choices in an era of COVID" may prove more apt. As we take stock of HIV at 40, there are positive lessons for the wider health response - and challenging reflections for the wider impact of the global HIV response. The positive lessons include: (1) the importance of activism; (2) the role of scientific progress and innovation; (3) the impact of evidence in concentrating resources on proven approaches; (4) the importance of surveillance to understanding transmission dynamics; (5) the use of epidemic intelligence to guide precision implementation; (6) the focus on implementation cascades (diagnosis, linkage, adherence, disease suppression); and finally (7) an overarching execution and results focus.Given this remarkable legacy, it seems churlish to ask whether the HIV response could have achieved more. Yet, consider these approximate figures. Development assistance for HIV totals about 100 billion dollars, 70 billion from the USA matched by roughly 100 billion in domestic resources. For 200 billion dollars, should we not have achieved more than 23 million people initiating treatment (very crudely, 10 000 dollars per person on treatment)? Much of the hundred billion dollars of development assistance (roughly half) focused on about a dozen priority countries in eastern and southern African. The larger PEPFAR recipients, with populations of roughly 50 million, each received 5 billion dollars or more cumulatively. And there are further Global Fund contributions of an additional billion dollars in many of these countries. For 6 billion dollars per country, should we have expected more?The World Bank Human Capital Project posits that to maximize human capital formation, countries must ensure that their children survive, are well nourished and stimulated, learn skills and live long, productive lives. Using the Human Capital Index (a composite index based on these factors), South Africa - the largest HIV financing recipient - ranks 126th of 157 countries, below Haiti, Ghana, the Congo Republic, Senegal and Benin. Consider how many recipients of major HIV development finance fall into the bottom fifth: Namibia, Botswana, Eswatini (formerly Swaziland), Malawi, South Africa, Tanzania, Zambia, Uganda, Lesotho, Ethiopia, Mozambique, Cote D'Ivoire and Nigeria. Of course, causality is unresolved and there are several possible explanations: (1) low human capital formation may increase HIV transmission; (2) the HIV epidemic may have intergenerational impacts; (3) the all-consuming focus on HIV may have displaced other health, education and development priorities. Yet, it remains hard to see these data and to argue that successful HIV responses among the largest HIV financing recipients strengthened their wider health sector and human development outcomes.A plausible principle emerges. Narrowly targeted disease-specific emergency responses may lead to disease-specific gains but do not improve governance or national systems capacity or wider disease or development outcomes. This is not to undermine the emergency origins of the HIV response; 2021 is not 2000 and it is unlikely that we would have 23 million people initiating treatment without an emergency response. Yet, there are reasons (intensified by COVID), to suggest that we must pivot towards long-term, integrated, developmental, nationally owned and financed, systems-orientated responses - particularly when both development assistance and national budgets are likely to be constrained in an era of COVID.

Impacts of COVID-19-related service disruptions on TB incidence and deaths in Indonesia, Kyrgyzstan, Malawi, Mozambique, and Peru: Implications for national TB responses.

Initial global-level estimates reported in June 2020 by the World Health Organization suggested that levels of disruption to TB service delivery could be as high as 25%-50% and result in an additional 6·3 million cases of tuberculosis (TB) and an additional 1·4 million TB-related deaths attributable to COVID-19 between 2020 and 2025. Quarterly epidemiological estimates and programmatic TB data capturing disruption levels to each TB service were collected by National TB Programmes in Indonesia, Kyrgyzstan, Malawi, Mozambique, and Peru. Data from 2019, for a pre-COVID-19 baseline, and throughout 2020, together with the NTP's COVID-19 response plans, were used within Optima TB models to project TB incidence and deaths over five years because of COVID-19-related disruptions, and the extent to which those impacts may be mitigated through proposed catch-up strategies in each country. Countries reported disruptions of up to 64% to demand-driven TB diagnosis. However, TB service availability disruptions were shorter and less severe, with TB treatment experiencing levels of disruption of up to 21%. We predicted that under the worse-case scenario cumulative new latent TB infections, new active TB infections, and TB-related deaths could increase by up to 23%, 11%, and 20%, respectively, by 2024. However, three of the five countries were on track to mitigate these increases to 3% or less by maintaining TB services in 2021 and 2022 and by implementing proposed catch-up strategies. Indonesia was already experiencing the worse-case scenario, which could lead to 270,000 additional active TB infections and 36,000 additional TB-related deaths by the end of 2024. The COVID-19 pandemic is projected to negatively affect progress towards 2035 End TB targets, especially in countries already off-track. Findings highlight both successful TB service delivery adaptions in 2020 and the need to proactively maintain TB service availability despite potential future waves of more transmissible COVID-19 variants.

Adherence to HIV post-exposure prophylaxis for children/adolescents who have been sexually assaulted: A systematic review of barriers, enablers, and interventions.

Post-exposure prophylaxis (PEP) is a key intervention for preventing HIV acquisition, including following sexual assault. However, uptake and completion rates for HIV PEP are lowest following sexual assault, with only 40% reporting completing the 28-day course. We undertook a systematic review to assess barriers and enablers to adherence to PEP in children and adolescents following sexual assault and identify potential interventions. Five databases and one conference abstract library were searched using adapted search strategies to identify quantitative and qualitative studies reporting patient-reported barriers and enablers to PEP and randomized trials assessing interventions to improve PEP adherence and completion rates. All searches were conducted up to October 2016; the search was updated in PubMed up to 31 July 2018. 14 studies reported barriers and enablers to PEP adherence. The most commonly cited patient/caregiver reported barriers to PEP adherence/completion included side effects, forgetting, stigma/blame, being busy, poor knowledge, and mental health problems. The most commonly reported factors associated with PEP adherence/completion (reported across 7 studies) included health provider encouragement to take PEP (type of encouragement not described), perpetrator known to be HIV-positive, monetary support for transport, the victim of assault attending counseling, being reminded by family/peers to take PEP, and "one-stop" services offering both HIV testing and PEP at initial consultation. Three randomized trials provided limited evidence supporting the potential benefit of enhanced adherence support for HIV PEP; however, data for children were lacking. Despite low completion rates, there is limited research into causes of and interventions to improve adherence to PEP following sexual assault, and no direct evidence for children.

Opportunities for improved HIV prevention and treatment through budget optimization in Eswatini.

INTRODUCTION: Eswatini achieved a 44% decrease in new HIV infections from 2014 to 2019 through substantial scale-up of testing and treatment. However, it still has one of the highest rates of HIV incidence in the world, with 14 infections per 1,000 adults 15-49 years estimated for 2017. The Government of Eswatini has called for an 85% reduction in new infections by 2023 over 2017 levels. To make further progress towards this target and to achieve maximum health gains, this study aims to model optimized investments of available HIV resources. METHODS: The Optima HIV model was applied to estimate the impact of efficiency strategies to accelerate prevention of HIV infections and HIV-related deaths. We estimated the number of infections and deaths that could be prevented by optimizing HIV investments. We optimize across HIV programs, then across service delivery modalities for voluntary medical male circumcision (VMMC), HIV testing, and antiretroviral refill, as well as switching to a lower cost antiretroviral regimen. FINDINGS: Under an optimized budget, prioritising HIV testing for the general population followed by key preventative interventions may result in approximately 1,000 more new infections (2% more) being averted by 2023. More infections could be averted with further optimization between service delivery modalities across the HIV cascade. Scaling-up index and self-testing could lead to 100,000 more people getting tested for HIV (25% more tests) with the same budget. By prioritizing Fast-Track, community-based, and facility-based antiretroviral refill options, an estimated 30,000 more people could receive treatment, 17% more than baseline or US$5.5 million could be saved, 4% of the total budget. Finally, switching non-pregnant HIV-positive adults to a Dolutegravir-based antiretroviral therapy regimen and concentrating delivery of VMMC to existing fixed facilities over mobile clinics, US$4.5 million (7% of total budget) and US$6.6 million (10% of total budget) could be saved, respectively. SIGNIFICANCE: With a relatively short five-year timeframe, even under a substantially increased and optimized budget, Eswatini is unlikely to reach their ambitious national prevention target by 2023. However, by optimizing investment of the same budget towards highly cost-effective VMMC, testing, and treatment modalities, further reductions in HIV incidence and cost savings could be realized.

Diabetes care cascade in Ukraine: an analysis of breakpoints and opportunities for improved diabetes outcomes.

BACKGROUND: Diabetes is one of the leading causes of poor health and high care costs in Ukraine. To prevent diabetes complications and alleviate the financial burden of diabetes care on patients, the Ukrainian government reimburses diabetes medication and provides glucose monitoring, but there are significant gaps in the care continuum. We estimate the costs of providing diabetes care and the most cost-effective ways to address these gaps in the Poltava region of Ukraine. METHODS: We gathered data on the unit costs of diabetes interventions in Poltava and estimated expenditure on diabetes care. We estimated the optimal combination of facility-based and outreach screening and investigated how additional funding could best be allocated to improve glucose control outcomes. RESULTS: Of the ~ 40,000 adults in diabetes care, only ~ 25% achieved sustained glucose control. Monitoring costs were higher for those who did not: by 10% for patients receiving non-pharmacological treatment, by 61% for insulin patients, and twice as high for patients prescribed oral treatment. Initiatives to improve treatment adherence (e.g. medication copayment schemes, enhanced adherence counseling) would address barriers along the care continuum and we estimate such expenditures may be recouped by reductions in patient monitoring costs. Improvements in case detection are also needed, with only around two-thirds of estimated cases having been diagnosed. Outreach screening campaigns could play a significant role: depending on how well-targeted and scalable such campaigns are, we estimate that 10-46% of all screening could be conducted via outreach, at a cost per positive patient identified of US$7.12-9.63. CONCLUSIONS: Investments to improve case detection and treatment adherence are the most efficient interventions for improved diabetes control in Poltava. Quantitative tools provide essential decision support for targeting investment to close the gaps in care.

What Proportion of Female Sex Workers Practise anal Intercourse and How Frequently? A Systematic Review and Meta-analysis.

HIV is more efficiently acquired during receptive anal intercourse (AI) compared to vaginal intercourse (VI) and may contribute substantially to female sex workers' (FSW) high HIV burden. We aim to determine how common and frequent AI is among FSW globally. We searched PubMed, Embase and PsycINFO for studies reporting the proportion of FSW practising AI (prevalence) and/or the number of AI acts (frequency) worldwide from 01/1980 to 10/2018. We assessed the influence of participant and study characteristics on AI prevalence (e.g. continent, study year and interview method) through sub-group analysis. Of 15,830 identified studies, 131 were included. Nearly all (N = 128) reported AI prevalence and few frequency (N = 13), over various recall periods. Most studies used face-to-face interviews (N = 111). Pooled prevalences varied little by recall period (lifetime: 15.7% 95%CI 12.2-19.3%, N = 30, I2 = 99%; past month: 16.2% 95%CI 10.8-21.6%, N = 18, I2 = 99%). The pooled proportion of FSW reporting < 100% condom use tended to be non-significantly higher during AI compared to during VI (e.g. any unprotected VI: 19.1% 95%CI 1.7-36.4, N = 5 and any unprotected AI: 46.4% 95%CI 9.1-83.6, N = 5 in the past week). Across all study participants, between 2.4 and 15.9% (N = 6) of all intercourse acts (AI and VI) were anal. Neither AI prevalence nor frequency varied substantially by any participant or study characteristics. Although varied, AI among FSW is generally common, inconsistently protected with condoms and practiced sufficiently frequently to contribute substantially to HIV acquisition in this risk group. Interventions to address barriers to condom use are needed.

HIV viral resuppression following an elevated viral load: a systematic review and meta-analysis.

INTRODUCTION: Guidelines for antiretroviral therapy recommend enhanced adherence counselling be provided to individuals with an initial elevated viral load before making a decision whether to switch antiretroviral regimen. We undertook this systematic review to estimate the proportion of patients with an initial elevated viral load who resuppress following enhanced adherence counselling. METHODS: Two databases and two conference abstract sites were searched from January 2012 to October 2019 for studies reporting the number of patients with an elevated viral load whose viral load was undetectable when subsequently assessed. Data were pooled using random effects meta-analysis. RESULTS: Fifty-eight studies reported outcomes of 45,720 viraemic patients, mostly from Africa (48 studies), and among patients on first-line antiretroviral therapy (43 studies). Almost half (46.1%, 95% CI 42.6% to 49.5%) of patients with an initial elevated viral load resuppressed following an enhanced adherence intervention. Of those on first-line ART with confirmed virological failure (6280 patients, 21 studies), only 53.4% (40.1% to 66.8%) were appropriately switched to a different regimen. Resuppression was higher among studies that provided details of adherence support. The proportion resuppressing was lower among children (31.2%, 21.1% to 41.3%) and adolescents (40.4%, 15.7% to 65.2%) compared to adults (50.4%, 42.6% to 58.3%). No important differences were observed by date of study publication, gender, viral failure threshold, publication status, time between viral loads or treatment regimen. Information on resistance testing among people with an elevated viral load was inconsistently reported. CONCLUSIONS: The findings of this review suggest that in settings with limited resources, current guideline recommendations to provide enhanced adherence counselling can result in resuppression of a substantial number of these patients, avoiding unnecessary drug regimen changes. Appropriate action on viral load results is limited across a range of settings, highlighting the importance of viral load cascade analyses to identify gaps and focus quality improvement to ensure that action is taken on the results of viral load testing.

CD4 count recovery and associated factors among individuals enrolled in the South African antiretroviral therapy programme: An analysis of national laboratory based data.

BACKGROUND: We describe CD4 count recovery among HIV positive individuals who initiated antiretroviral therapy (ART) with and without severe immune suppression using complete laboratory data from South Africa's national HIV treatment programme between 2010 and 2014 and discuss implications for CD4 count monitoring. METHODS: Retrospective analysis of routinely collected laboratory data from South Africa's National Health Laboratory Service (NHLS). A probabilistic record linkage algorithm was used to create a cohort of HIV positive individuals who initiated ART between 2010 and 2014 based on timing of CD4 count and viral load measurements. A CD4 count < 50 copies/µl at ART initiation was considered severe immunosuppression. A multivariable piecewise mixed-effects linear regression model adjusting for age, gender, year of starting ART, viral suppression in follow up and province was used to predict CD4 counts during follow up. RESULTS: 1,070,900 individuals had evidence of starting ART during 2010-2014 and met the criteria for inclusion in the cohort -46.6% starting ART with CD4 < 200 cells/µl and 10.1% with CD4 < 50 cells/ µl. For individuals with CD4 counts < 200 cells/µl, predicted CD4 counts > 200 cells/µl, >350 cells/µl and >500 cells/µl corresponded with mean follow up durations of 1.5 years (standard deviation [s.d] 1.1), 1.9years (s.d 1.2) and 2.1 years (s.d 1.3 years). For those with CD4 counts < 50 cells/µl, predicted CD4 count above these threshold corresponded with mean follow up durations of 2.5 years (s.d 0.9 years), 4.4 years (s.d 0.4 years) and 5.0 years (s.d 0.1years) for recovery to the same thresholds. CD4 count recovery varied mostly with duration on ART, CD4 count at the start of ART and gender. CONCLUSION: For individuals starting with ART with severe immunosuppression, CD4 recovery to 200cells/µl did not occur or took longer than 12 month for significant proportions. CD4 monitoring and interventions recommended for advanced HIV disease should continue until full recovery.

Improving Linkage to and Retention in Care in Newly Diagnosed HIV-Positive Patients Using Smartphones in South Africa: Randomized Controlled Trial.

BACKGROUND: South Africa provides free antiretroviral therapy for almost 5 million people living with HIV, but only 71% of the eligible people are on treatment, representing a shortfall in the care cascade, especially among men and youth. Many developing countries have expanded access to smartphones; success in health apps raises the possibility of improving this cascade. OBJECTIVE: SmartLink is a health app for Android smartphones providing HIV-related laboratory results, information, support, and appointment reminders to engage and link patients to care. This study aimed to evaluate the ability of SmartLink to improve linkage to care for HIV-positive smartphone owners. METHODS: This study was a multisite randomized controlled trial in Johannesburg. The intervention arm received the app (along with referral to a treatment site) and the control arm received the standard of care (referral alone). Linkage to care was confirmed by an HIV-related blood test reported on the National Health Laboratory Service database between 2 weeks and 8 months after initiation. RESULTS: A total of 345 participants were recruited into the study; 64.9% (224/345) of the participants were female and 44.1% (152/345) were aged less than 30 years. In addition, 46.7% (161/345) were employed full time, 95.9% (331/345) had at least secondary school education, and 35.9% (124/345) were from Zimbabwe. Linkage to care between 2 weeks and 8 months was 48.6% (88/181) in the intervention arm versus 45.1% (74/164) in the control (P=.52) and increased to 64.1% (116/181) and 61.0% (100/164) (P=.55), respectively, after the initial 8-month period. Moreover, youth aged 18 to 30-years showed a statistically significant 20% increase in linkage to care for the intervention group. CONCLUSIONS: Youth aged less than 30 years have been historically difficult to reach with traditional interventions, and the SmartLink app provides a proof of concept that this population reacts to mobile health interventions that engage patients in HIV care. TRIAL REGISTRATION: ClinicalTrials.gov NCT02756949; https://clinicaltrials.gov/ct2/show/NCT02756949 (Archived by WebCite at http://www.webcitation.org/6z1GTJCNW).

Mapping and size estimates of female sex workers in Cameroon: Toward informed policy for design and implementation in the national HIV program.

BACKGROUND: Due to high HIV prevalence among Female Sex Workers (FSWs) in Cameroon (36.5%), this population is especially vulnerable to HIV acquisition and transmission nationwide. Though being prioritized in the national HIV response, it would be relevant to generate statistics on the number of FSWs in order to guide HIV interventions among FSWs. Our objective was to estimate the size of FSWs within hotspots of Cameroon. METHODS: A cross-sectional study was conducted from September-November 2015 in selected cities in Cameroon: Bafoussam, Bamenda, Bertoua, Buea, Douala, Kribi, Limbé, and Yaoundé. A programmatic mapping was used, consisting of interviews with secondary key informants (KI) to identify hotspots of FSWs and their respective estimated numbers. Validation of size estimates was done by interviews with FSW at each hotspot. Size estimations in the councils mapped were extended to others not mapped using a Poisson regression model. RESULTS: A total of 2,194 hotspots were identified: Douala (760), Yaoundé (622), Bamenda (263), Bafoussam (194), Kribi (154), Bertoua (140), Limbé (35), and Buea (26). The estimated total number (range) of FSWs was 21,124 (16,079-26,170), distributed per city as follows: Douala 7,557 (5,550-9,364), Yaoundé 6,596 (4,712-8,480), Bafoussam 2,458 (1,994-2,923), Bamenda 1,975 (1,605-2,345), Kribi 1,121 (832-1,408), Bertoua 1,044 (891-1,198), Buea 225 (185-266), and Limbé 148 (110-148). The variability of estimates among cities was also observed within the councils of each city. The national predicted estimate of FSW population was 112,580 (103,436-121,723), covering all councils of Cameroon. An estimate of 1.91% (112,580/5,881,526; 0.47%-3.36%) adult female population in Cameroon could be sex workers. CONCLUSION: There are considerable numbers of FSW in major cities in Cameroon. There is a need to prioritize interventions for HIV prevention toward this population in order to limit the burden of HIV sexual transmission nationwide.

Adherence to Nucleos(t)ide Analogue Therapies for Chronic Hepatitis B Infection: A Systematic Review and Meta-Analysis.

Successful treatment outcomes for chronic hepatitis B virus (HBV) infection requires high levels of adherence to treatment. We searched three databases and abstracts from two conferences up to January 2018 for studies reporting the proportion of patients who were adherent to HBV antiviral therapy and pooled data using random effects meta-analysis. We included 30 studies, providing data for 23,823 patients. Overall, adherence to treatment was 74.6% (95% confidence interval [CI] 67.1%-82.1%). Adherence was similar in high-income settings (75.1%; 95% CI, 65.4%-85.0%) and in low-income and middle-income settings (72.9%; 95% CI, 57.8%-88.0%). Reported barriers to adherence included forgetting, limited understanding of the importance of adherence, and change to routine. Conclusion : There is a need to reinforce assessment and reporting of adherence as a routine part of HBV care and to assess the extent to which evidence-based interventions to improve adherence to medication for human immunodeficiency virus [HIV] and other chronic diseases are effective for HBV infection.

Improving Linkage to HIV Care Through Mobile Phone Apps: Randomized Controlled Trial.

BACKGROUND: In HIV treatment program, gaps in the "cascade of care" where patients are lost between diagnosis, laboratory evaluation, treatment initiation, and retention in HIV care, is a well-described challenge. Growing access to internet-enabled mobile phones has led to an interest in using the technology to improve patient engagement with health care. OBJECTIVE: The objectives of this trial were: (1) to assess whether a mobile phone-enabled app could provide HIV patients with laboratory test results, (2) to better understand the implementation of such an intervention, and (3) to determine app effectiveness in improving linkage to HIV care after diagnosis. METHODS: We developed and tested an app through a randomized controlled trial carried out in several primary health care facilities in Johannesburg. Newly diagnosed HIV-positive patients were screened, recruited, and randomized into the trial as they were giving a blood sample for initial CD4 staging. Trial eligibility included ownership of a phone compatible with the app and access to the internet. Trial participants were followed for a minimum of eight months to determine linkage to HIV care indicated by an HIV-related laboratory test result. RESULTS: The trial outcome results are being prepared for publication, but here we describe the significant operational and technological lessons provided by the implementation. Android was identified as the most suitable operating system for the app, due to Android functionality and communication characteristics. Android also had the most significant market share of all smartphone operating systems in South Africa. The app was successfully developed with laboratory results sent to personal smartphones. However, given the trial requirements and the app itself, only 10% of screened HIV patients successfully enrolled. We report on issues such as patient eligibility, app testing in a dynamic phone market, software installation and compatibility, safe identification of patients, linkage of laboratory results to patients lacking unique identifiers, and present lessons and potential solutions. CONCLUSIONS: The implementation challenges and lessons of this trial may assist future similar mHealth interventions to avoid some of the pitfalls. Ensuring sufficient expertise and understanding of the programmatic needs by the software developer, as well as in the implementation team, with adequate and rapid piloting within the target groups, could have led to better trial recruitment. However, the majority of screened patients were interested in the study, and the app was installed successfully in patients with suitable smartphones, suggesting that this may be a way to engage patients with their health care data in future. TRIAL REGISTRATION: ClinicalTrials.gov NCT02756949; https://clinicaltrials.gov/ct2/show/NCT02756949 (Archived by WebCite at http://www.webcitation.org/6z1GTJCNW).

How should HIV resources be allocated? Lessons learnt from applying Optima HIV in 23 countries.

INTRODUCTION: With limited funds available, meeting global health targets requires countries to both mobilize and prioritize their health spending. Within this context, countries have recognized the importance of allocating funds for HIV as efficiently as possible to maximize impact. Over the past six years, the governments of 23 countries in Africa, Asia, Eastern Europe and Latin America have used the Optima HIV tool to estimate the optimal allocation of HIV resources. METHODS: Each study commenced with a request by the national government for technical assistance in conducting an HIV allocative efficiency study using Optima HIV. Each study team validated the required data, calibrated the Optima HIV epidemic model to produce HIV epidemic projections, agreed on cost functions for interventions, and used the model to calculate the optimal allocation of available funds to best address national strategic plan targets. From a review and analysis of these 23 country studies, we extract common themes around the optimal allocation of HIV funding in different epidemiological contexts. RESULTS AND DISCUSSION: The optimal distribution of HIV resources depends on the amount of funding available and the characteristics of each country's epidemic, response and targets. Universally, the modelling results indicated that scaling up treatment coverage is an efficient use of resources. There is scope for efficiency gains by targeting the HIV response towards the populations and geographical regions where HIV incidence is highest. Across a range of countries, the model results indicate that a more efficient allocation of HIV resources could reduce cumulative new HIV infections by an average of 18% over the years to 2020 and 25% over the years to 2030, along with an approximately 25% reduction in deaths for both timelines. However, in most countries this would still not be sufficient to meet the targets of the national strategic plan, with modelling results indicating that budget increases of up to 185% would be required. CONCLUSIONS: Greater epidemiological impact would be possible through better targeting of existing resources, but additional resources would still be required to meet targets. Allocative efficiency models have proven valuable in improving the HIV planning and budgeting process.

CD4 Cell Count Threshold for Cryptococcal Antigen Screening of HIV-Infected Individuals: A Systematic Review and Meta-analysis.

Background: Current guidelines recommend screening all people living with human immunodeficiency virus (PLHIV) who have a CD4 count ≤100 cells/µL for cryptococcal antigen (CrAg) to identify those patients who could benefit from preemptive fluconazole treatment prior to the onset of meningitis. We conducted a systematic review to assess the prevalence of CrAg positivity at different CD4 cell counts. Methods: We searched 4 databases and abstracts from 3 conferences up to 1 September 2017 for studies reporting prevalence of CrAg positivity according to CD4 cell count strata. Prevalence estimates were pooled using random effects models. Results: Sixty studies met our inclusion criteria. The pooled prevalence of cryptococcal antigenemia was 6.5% (95% confidence interval [CI], 5.7%-7.3%; 54 studies) among patients with CD4 count ≤100 cells/µL and 2.0% (95% CI, 1.2%-2.7%; 21 studies) among patients with CD4 count 101-200 cells/µL. Twenty-one studies provided sufficient information to compare CrAg prevalence per strata; overall, 18.6% (95% CI, 15.4%-22.2%) of the CrAg-positive cases identified at ≤200 cells/µL (n = 11823) were identified among individuals with a CD4 count 101-200 cells/µL. CrAg prevalence was higher among inpatients (9.8% [95% CI, 4.0%-15.5%]) compared with outpatients (6.3% [95% CI, 5.3%-7.4%]). Conclusions: The findings of this review support current recommendations to screen all PLHIV who have a CD4 count ≤100 cells/µL for CrAg and suggest that screening may be considered at CD4 cell count ≤200 cells/µL.

Benefits and risks of rapid initiation of antiretroviral therapy.

BACKGROUND: Recent attention has focused on the question of how quickly antiretroviral therapy (ART) should be started once HIV diagnosis is confirmed. We assessed whether rapid ART initiation improves patient outcomes. METHODS: We searched five databases from inception up to August 2017. Rapid ART initiation was defined as initiation within 14 days of HIV diagnosis. Data were pooled using random effects meta-analysis. RESULTS: Across the randomized trials, ART start on the same day increased viral suppression at 12 months [three trials: relative risk (RR) 1.17, 95% confidence interval (CI) 1.07-1.27], retention in care at 12 months (RR 1.11, 95% CI 0.99-1.26), and the likelihood of starting ART within 90 days (four trials: RR 1.35, 95% CI 1.13-1.62) and 12 months after eligibility was established (three trials: RR 1.17, 95% CI 1.07-1.27). There was a nonsignificant trend toward reduced mortality (three trials: RR 0.53, 95% CI 0.24-1.08), as well as reduced loss to follow-up at 12 months (2 trials: RR 0.66, 95% CI 0.42-1.04). In the observational studies, offering accelerated ART initiation resulted in a greater likelihood of having started ART within 3 months (two studies: RR 1.53, 95% CI 1.11-2.10). There was a trend toward an increased risk of being lost to follow-up at 6 months (three studies: RR 1.85, 95% CI 0.96-3.55). CONCLUSION: Accelerated ART initiation can lead to improved clinical outcomes and is likely to be of particular benefit in those settings where extensive patient preparation prior to starting ART results in long delays. These findings informed a WHO recommendation supporting accelerated ART initiation, including same day ART start.

Patient-Reported Barriers to Adherence to Antiretroviral Therapy: A Systematic Review and Meta-Analysis.

BACKGROUND: Maintaining high levels of adherence to antiretroviral therapy (ART) is a challenge across settings and populations. Understanding the relative importance of different barriers to adherence will help inform the targeting of different interventions and future research priorities. METHODS AND FINDINGS: We searched MEDLINE via PubMed, Embase, Web of Science, and PsychINFO from 01 January 1997 to 31 March 2016 for studies reporting barriers to adherence to ART. We calculated pooled proportions of reported barriers to adherence per age group (adults, adolescents, and children). We included data from 125 studies that provided information about adherence barriers for 17,061 adults, 1,099 children, and 856 adolescents. We assessed differences according to geographical location and level of economic development. The most frequently reported individual barriers included forgetting (adults 41.4%, 95% CI 37.3%-45.4%; adolescents 63.1%, 95% CI 46.3%-80.0%; children/caregivers 29.2%, 95% CI 20.1%-38.4%), being away from home (adults 30.4%, 95% CI 25.5%-35.2%; adolescents 40.7%, 95% CI 25.7%-55.6%; children/caregivers 18.5%, 95% CI 10.3%-26.8%), and a change to daily routine (adults 28.0%, 95% CI 20.9%-35.0%; adolescents 32.4%, 95% CI 0%-75.0%; children/caregivers 26.3%, 95% CI 15.3%-37.4%). Depression was reported as a barrier to adherence by more than 15% of patients across all age categories (adults 15.5%, 95% CI 12.8%-18.3%; adolescents 25.7%, 95% CI 17.7%-33.6%; children 15.1%, 95% CI 3.9%-26.3%), while alcohol/substance misuse was commonly reported by adults (12.9%, 95% CI 9.7%-16.1%) and adolescents (28.8%, 95% CI 11.8%-45.8%). Secrecy/stigma was a commonly cited barrier to adherence, reported by more than 10% of adults and children across all regions (adults 13.6%, 95% CI 11.9%-15.3%; children/caregivers 22.3%, 95% CI 10.2%-34.5%). Among adults, feeling sick (15.9%, 95% CI 13.0%-18.8%) was a more commonly cited barrier to adherence than feeling well (9.3%, 95% CI 7.2%-11.4%). Health service-related barriers, including distance to clinic (adults 17.5%, 95% CI 13.0%-21.9%) and stock outs (adults 16.1%, 95% CI 11.7%-20.4%), were also frequently reported. Limitations of this review relate to the fact that included studies differed in approaches to assessing adherence barriers and included variable durations of follow up. Studies that report self-reported adherence will likely underestimate the frequency of non-adherence. For children, barriers were mainly reported by caregivers, which may not correspond to the most important barriers faced by children. CONCLUSIONS: Patients on ART face multiple barriers to adherence, and no single intervention will be sufficient to ensure that high levels of adherence to treatment and virological suppression are sustained. For maximum efficacy, health providers should consider a more triaged approach that first identifies patients at risk of poor adherence and then seeks to establish the support that is needed to overcome the most important barriers to adherence.

TB as a cause of hospitalization and in-hospital mortality among people living with HIV worldwide: a systematic review and meta-analysis.

INTRODUCTION: Despite significant progress in improving access to antiretroviral therapy over the past decade, substantial numbers of people living with HIV (PLHIV) in all regions continue to experience severe illness and require hospitalization. We undertook a global review assessing the proportion of hospitalizations and in-hospital deaths because of tuberculosis (TB) in PLHIV. METHODS: Seven databases were searched to identify studies reporting causes of hospitalizations among PLHIV from 1 January 2007 to 31 January 2015 irrespective of age, geographical region or language. The proportion of hospitalizations and in-hospital mortality attributable to TB was estimated using random effects meta-analysis. RESULTS: From an initial screen of 9049 records, 66 studies were identified, providing data on 35,845 adults and 2792 children across 42 countries. Overall, 17.7% (95% CI 16.0 to 20.2%) of all adult hospitalizations were because of TB, making it the leading cause of hospitalization overall; the proportion of adult hospitalizations because of TB exceeded 10% in all regions except the European region. Of all paediatric hospitalizations, 10.8% (95% CI 7.6 to 13.9%) were because of TB. There was insufficient data among children for analysis by region. In-hospital mortality attributable to TB was 24.9% (95% CI 19.0 to 30.8%) among adults and 30.1% (95% CI 11.2 to 48.9%) among children. DISCUSSION: TB remains a leading cause of hospitalization and in-hospital death among adults and children living with HIV worldwide.