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We aimed to measure social protection coverage among the general population, women and men living with HIV (WLHIV, MLHV), female and male sex workers (FSW, MSW), men who have sex with men (MSM), adolescent girls young women (AGYW), and orphans vulnerable children (OVC) in Eswatini, Malawi, Tanzania, and Zambia. We used Population-Based HIV Impact Assessment data. We operationalised social protection benefits as external economic support from private and public sources to the household in the last three or 12 months. We estimated survey-weighted proportions and 95% confidence intervals (CI) for each population receiving social protection benefits. The sample size ranged from 10,233 adults ages 15-59 years in Eswatini to 29,638 in Tanzania. In the surveyed countries, social protection coverage among the general population was lower than the global average of 45%, ranging from 7.7% (95% CI 6.7%-8.8%) in Zambia to 39.6% (95% CI 36.8%-42.5%) in Eswatini. In Malawi and Zambia, social protection coverage among OVC, AGYW, SW, MSM, and people living with HIV (PLHIV) was similar to the general population. In Eswatini, more AGWY reported receiving social projection benefits than older women and more men not living with HIV reported receiving social protection benefits than MLHIV. In Tanzania, more WLHIV than women not living with HIV, MLHIV than men not living with HIV, and FSW than women who were not sex workers reported receiving social protection benefits. More data on access to social protection benefits by PLHIV or affected by HIV are needed to estimate better their social protection coverage., (© 2022. The Author(s).)

Objective: To describe the prevalence of HIV viral suppression and assess the factors associated with HIV viral suppression among persons receiving antiretroviral therapy (ART) in Malawi in 2021., Methods: Implementation study using routinely collected patient-level HIV RNA-PCR test result data extracted from the national Laboratory Management Information System (LIMS) database managed by the Department of HIV/AIDS in 2021. We calculated frequencies, proportions and odds ratios (OR) of HIV viral suppression with their associated 95% confidence intervals (95%CIs). We performed a random-effects logistic regression to determine the risk factors associated with HIV viral suppression among ART patients, controlling for the spatial autocorrelation between districts and adjusting for other variables., Results: We evaluated 515,797 adults and children receiving ART and having a viral load test in 2021. Of these, 92.8% had HIV viral suppression. ART patients living in urban areas had lower likelihood of HIV viral suppression than those living in rural areas (adjusted OR [aOR] = 0.95, 95%CI: 0.92-0.99, p = 0.01). There was an increasing trend in HIV viral suppression with increasing ART duration. Routine VL monitoring samples were 39% more likely to have suppressed VL values than confirmatory HIV VL monitoring samples (aOR = 1.39; 95%CI: 1.34-1.43, p < 0.001)., Conclusion: This is the first national analysis of Malawi HIV VL data from LIMS. Our findings show the need to particularly consider the urban residents, those below 20 years, males, those on ART for less than a year as well as those on specific ARV regimens in order to persistently suppress HIV VL and consequently achieve the goal of achieving HIV VL suppression by 2030., (© 2022 John Wiley & Sons Ltd.)

Objectives: This study aims to investigate the risk of COVID-19 transmission on aircraft., Methods: We obtained data on all international flights to Lanzhou, China, from June 1, 2020, to August 1, 2020, through the Gansu Province National Health Information Platform and the official website of the Gansu Provincial Center for Disease Control and Prevention. We then performed the statistical analysis., Results: Three international flights arrived in Lanzhou. The flights had a total of 700 passengers, of whom 405 (57.9%) were male, and 80 (11.4%) were children under the age of 14 years. Twenty-seven (3.9%) passengers were confirmed to have COVID-19. Confirmed patients were primarily male (17, 65.4%) with a median age of 27.0 years. Most confirmed cases were seated in the middle rows of economy class or near public facility areas such as restrooms and galleys. The prevalence of COVID-19 did not differ between passengers sitting in the window, aisle, or middle seats. However, compared with passengers sitting in the same row up to 2 rows behind a confirmed case, passengers seated in the 2 rows in front of a confirmed case were at a slightly higher risk of being infected., Conclusions: COVID-19 may be transmitted during a passenger flight, although there is still no direct evidence., Competing Interests: Conflict of Interest Disclosures There are no conflicts of interest to declare., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Competing Interests: Nothing to declare.

Background: There are concerns that the use of non-steroidal anti-inflammatory drugs (NSAIDs) may increase the risk of adverse outcomes among patients with coronavirus COVID-19. This study aimed to synthesize the evidence on associations between the use of NSAIDs and adverse outcomes., Methods: A systematic search of WHO COVID-19 Database, Medline, the Cochrane Library, Web of Science, Embase, China Biology Medicine disc, China National Knowledge Infrastructure, and Wanfang Database for all articles published from January 1, 2020, to November 7, 2021, as well as a supplementary search of Google Scholar. We included all comparative studies that enrolled patients who took NSAIDs during the COVID-19 pandemic. Data extraction and quality assessment of methodology of included studies were completed by two reviewers independently. We conducted a meta-analysis on the main adverse outcomes, as well as selected subgroup analyses stratified by the type of NSAID and population (both positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or not)., Findings: Forty comparative studies evaluating 4,867,795 adult cases were identified. Twenty-eight (70%) of the included studies enrolled patients positive to SARS-CoV-2 tests. The use of NSAIDs did not reduce mortality outcomes among people with COVID-19 (number of studies [N] = 29, odds ratio [OR] = 0.93, 95% confidence interval [CI]: 0.75 to 1.14, I 2  = 89%). Results suggested that the use of NSAIDs was not significantly associated with higher risk of SARS-CoV-2 infection in patients with or without COVID-19 ( N  = 10, OR = 0.96, 95% CI: 0.86 to 1.07, I 2  = 78%; N  = 8, aOR = 1.01, 95% CI: 0.94 to 1.09, I 2  = 26%), or an increased probability of intensive care unit (ICU) admission ( N  = 12, OR = 1.28, 95% CI: 0.94 to 1.75, I 2  = 82% ; N  = 4, aOR = 0.89, 95% CI: 0.65 to 1.22, I 2  = 60%), requiring mechanical ventilation ( N  = 11, OR = 1.11, 95% CI: 0.79 to 1.54, I 2  = 63%; N  = 5, aOR = 0.80, 95% CI: 0.52 to 1.24, I 2  = 66%), or administration of supplemental oxygen ( N  = 5, OR = 0.80, 95% CI: 0.52 to 1.24, I 2  = 63%; N  = 2, aOR = 1.00, 95% CI: 0.89 to 1.12, I 2  = 0%). The subgroup analysis revealed that, compared with patients not using any NSAIDs, the use of ibuprofen ( N  = 5, OR = 1.09, 95% CI: 0.50 to 2.39; N  = 4, aOR = 0.95, 95% CI: 0.78 to 1.16) and COX-2 inhibitor ( N  = 4, OR = 0.62, 95% CI: 0.35 to 1.11; N  = 2, aOR = 0.73, 95% CI: 0.45 to 1.18) were not associated with an increased risk of death., Interpretation: Data suggests that NSAIDs such as ibuprofen, aspirin and COX-2 inhibitor, can be used safely among patients positive to SARS-CoV-2. However, for some of the analyses the number of studies were limited and the quality of evidence was overall low, therefore more research is needed to corroborate these findings., Funding: There was no funding source for this study., Competing Interests: None., (© 2022 The Author(s).)

Background: Rapid Advice Guidelines (RAG) provide decision makers with guidance to respond to public health emergencies by developing evidence-based recommendations in a short period of time with a scientific and standardized approach. However, the experience from the development process of a RAG has so far not been systematically summarized. Therefore, our working group will take the experience of the development of the RAG for children with COVID-19 as an example to systematically explore the methodology, advantages, and challenges in the development of the RAG. We shall propose suggestions and reflections for future research, in order to provide a more detailed reference for future development of RAGs., Result: The development of the RAG by a group of 67 researchers from 11 countries took 50 days from the official commencement of the work (January 28, 2020) to submission (March 17, 2020). A total of 21 meetings were held with a total duration of 48 h (average 2.3 h per meeting) and an average of 16.5 participants attending. Only two of the ten recommendations were fully supported by direct evidence for COVID-19, three recommendations were supported by indirect evidence only, and the proportion of COVID-19 studies among the body of evidence in the remaining five recommendations ranged between 10 and 83%. Six of the ten recommendations used COVID-19 preprints as evidence support, and up to 50% of the studies with direct evidence on COVID-19 were preprints., Conclusions: In order to respond to public health emergencies, the development of RAG also requires a clear and transparent formulation process, usually using a large amount of indirect and non-peer-reviewed evidence to support the formation of recommendations. Strict following of the WHO RAG handbook does not only enhance the transparency and clarity of the guideline, but also can speed up the guideline development process, thereby saving time and labor costs., (© 2022. The Author(s).)

Objective: To describe the current status of COVID-19 vaccine guidelines., Study Design and Setting: We searched databases, Google and guideline platforms to retrieve COVID-19 vaccine guidelines published between January 1, 2020 and July 8, 2021. We worked in pairs to identify the eligible guidelines and extract data of whether the methodology, funding, and conflict of interests were assessed/reported, and so on. Results were presented descriptively., Results: A total of 106 COVID-19 vaccine guidelines were included. In the first half of 2021, on average 15 guidelines were published every month. Fifty (47.2%) guidelines addressed the vaccination of people with specific medical conditions, and 18 (17.0%) guidelines focused on adverse effects after vaccination. Only 28 (26.4%) guidelines reported the methodology they used. Four (3.8%) of guidelines assessed both the quality of evidence and strength of recommendations; 42 (39.6%) and 65 (61.3%) guidelines reported their funding sources and conflict of interest, respectively. Most guidelines were published in English (n = 92, 86.8%)., Conclusion: A high number of guidelines on COVID-19 vaccines have been published in the recent months, but most of them lack clear and transparent reporting of methodology, funding, and conflicts of interest. Rigorous methodological and reporting quality evaluation of these guidelines is needed., (Copyright © 2021. Published by Elsevier Inc.)

Introduction: High yield HIV testing strategies are critical to reach epidemic control in high prevalence and low-resource settings such as East and Southern Africa. In this study, we aimed to predict the HIV status of individuals living in Angola, Burundi, Ethiopia, Lesotho, Malawi, Mozambique, Namibia, Rwanda, Zambia and Zimbabwe with the highest precision and sensitivity for different policy targets and constraints based on a minimal set of socio-behavioural characteristics., Methods: We analysed the most recent Demographic and Health Survey from these 10 countries to predict individual's HIV status using four different algorithms (a penalized logistic regression, a generalized additive model, a support vector machine, and a gradient boosting trees). The algorithms were trained and validated on 80% of the data, and tested on the remaining 20%. We compared the predictions based on the F1 score, the harmonic mean of sensitivity and positive predictive value (PPV), and we assessed the generalization of our models by testing them against an independent left-out country. The best performing algorithm was trained on a minimal subset of variables which were identified as the most predictive, and used to 1) identify 95% of people living with HIV (PLHIV) while maximising precision and 2) identify groups of individuals by adjusting the probability threshold of being HIV positive (90% in our scenario) for achieving specific testing strategies., Results: Overall 55,151 males and 69,626 females were included in the analysis. The gradient boosting trees algorithm performed best in predicting HIV status with a mean F1 score of 76.8% [95% confidence interval (CI) 76.0%-77.6%] for males (vs [CI 67.8%-70.6%] for SVM) and 78.8% [CI 78.2%-79.4%] for females (vs [CI 73.4%-75.8%] for SVM). Among the ten most predictive variables for each sex, nine were identical: longitude, latitude and, altitude of place of residence, current age, age of most recent partner, total lifetime number of sexual partners, years lived in current place of residence, condom use during last intercourse and, wealth index. Only age at first sex for male (ranked 10th) and Rohrer's index for female (ranked 6th) were not similar for both sexes. Our large-scale scenario, which consisted in identifying 95% of all PLHIV, would have required testing 49.4% of males and 48.1% of females while achieving a precision of 15.4% for males and 22.7% for females. For the second scenario, only 4.6% of males and 6.0% of females would have had to be tested to find 55.7% of all males and 50.5% of all females living with HIV., Conclusions: We trained a gradient boosting trees algorithm to find 95% of PLHIV with a precision twice higher than with general population testing by using only a limited number of socio-behavioural characteristics. We also successfully identified people at high risk of infection who may be offered pre-exposure prophylaxis or voluntary medical male circumcision. These findings can inform the implementation of new high-yield HIV tests and help develop very precise strategies based on low-resource settings constraints., Competing Interests: No.

Objectives: We examined associations between accelerators (interventions impacting ≥2 SDG targets) and SDG-aligned well-being indicators among adolescents 16-24 years old in Zambia. Methods: We surveyed adults from 1,800 randomly sampled households receiving social cash transfers. We examined associations between accelerators (social cash transfers, life-long learning, mobile phone access) and seven well-being indicators among adolescents using multivariate logistic regressions. Results: The sample comprised 1,725 adolescents, 881 (51.1%) girls. Mobile phone access was associated with no poverty (adjusted Odds Ratio [aOR] 2.08, p < 0.001), informal cash transfers (aOR 1.82, p = 0.004), and seeking mental health support (aOR 1.61, p = 0.020). Social cash transfers were associated with no disability-related health restrictions (aOR 2.56, p = 0.004) and lesser odds of seeking mental health support (aOR 0.53, p = 0.029). Life-long learning was associated with informal cash transfers (aOR 3.49, p < 0.001) and lower school enrollment (aOR 0.70, p = 0.004). Adolescents with disabled head-of-household reported worse poverty, good health but less suicidal ideation. Conclusions: Social cash transfers, life-long learning, and mobile phone access were positively associated with well-being indicators. Adolescents living with disabled head-of-household benefited less. Governments should implement policies to correct disability-related inequalities., Competing Interests: CM and GT were employed by Palm Associates Limited. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Chipanta, Estill, Stöckl, Hertzog, Toska, Chanda, Mwanza, Kaila, Matome, Tembo, Keiser and Cluver.)

We have developed a mathematical model and stochastic numerical simulation for the transmission of COVID-19 and other similar infectious diseases that accounts for the geographic distribution of population density, detailed down to the level of location of individuals, and age-structured contact rates. Our analytical framework includes a surrogate model optimization process to rapidly fit the parameters of the model to the observed epidemic curves for cases, hospitalizations, and deaths. This toolkit (the model, the simulation code, and the optimizer) is a useful tool for policy makers and epidemic response teams, who can use it to forecast epidemic development scenarios in local settings (at the scale of cities to large countries) and design optimal response strategies. The simulation code also enables spatial visualization, where detailed views of epidemic scenarios are displayed directly on maps of population density. The model and simulation also include the vaccination process, which can be tailored to different levels of efficiency and efficacy of different vaccines. We used the developed framework to generate predictions for the spread of COVID-19 in the canton of Geneva, Switzerland, and validated them by comparing the calculated number of cases and recoveries with data from local seroprevalence studies., Competing Interests: Conflict of interestThe authors have no conflicts of interest to declare., (© The Author(s) 2022.)

Background: Despite the availability of individual-level data of infants accessing HIV DNA-PCR testing service, there has been little in-depth analysis of such data. Therefore, we describe trends in risk of HIV infection among Malawi's HIV-exposed infants (HEI) with DNA-PCR HIV test result from 2013 to 2020., Methods: This is an implementation study using routinely collected patient-level HIV DNA-PCR test result data extracted from the national Laboratory Management Information System database managed by the Department of HIV/AIDS between 1 January 2013 and 30 June 2020. We calculated frequencies, proportions and odds ratio (OR) with their associated 95% CI. We performed a random-effects logistic regression to determine the risk factors associated with HIV infection in infants, controlling for the spatial autocorrelation between districts and adjusting for other variables., Results: We evaluated 255 229 HEI across 750 facilities in 28 districts. The HIV DNA-PCR test was performed within 2 months in 57% of the children. The overall HIV prevalence among all tested HEI between 2013 and 2020 was 7.2% (95% CI 7.1% to 7.3%). We observed a decreasing trend in the proportion of HEI that tested HIV positive from 7.0% (95% CI 6.6% to 7.4%) in 2013 to 5.7% (95% CI 5.4% to 5.9%) in 2015 followed by an increase to 9.9% (95% CI 9.6% to 10.2%) in 2017 and thereafter a decreasing trend between 2017 (i.e. 9.72% (95%CI: 9.43-10.01)) and 2020 (i.e. 3.86% (95%CI: 3.34-4.37)). The HIV prevalence increased by age of the HEI. There was spatial heterogeneity of HIV prevalence between districts of Malawi. The prevalence of HIV was higher among the HEI from the Northern region of Malawi., Conclusion: The main findings of the study are that the DNA test is performed within 2 months only in 57% of the children, that the decreasing trend of HIV prevalence among HEI observed up to 2015 was followed by an increase up to 2017 and a decrease afterwards, and that the risk of HIV infection increased with age at HIV testing. We summarised spatial and temporal trends of risk of HIV infection among HEI in Malawi between 2013 and 2020. There is need to ensure that all the HEI are enrolled in HIV care by 8 weeks of age in order to further reduce the risk of HIV in this population., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: This study aimed to systematically review the methodological and reporting quality of clinical practice guidelines (CPGs) developed in China and published in medical journals between 2014 and 2018., Study Design and Setting: We conducted a comprehensive search in multiple databases: MEDLINE (via PubMed), Embase, CBM (China Biology Medicine), CNKI (China National Knowledge Infrastructure) and Wanfang Data. We included all clinical practice guidelines developed in China between 2014 and 2018. The AGREE II tool and the RIGHT checklist were used to appraise the methodological quality and reporting quality of the included guidelines, respectively., Results: We identified 17,188 records, and included finally 573 CPGs. Most (n=507, 88.5%) were published in Chinese, and 508 (88.7%) were about Western medicine. Only 62 (10.8%) of the guidelines used the GRADE approach. The mean overall score of methodological quality over all guidelines was 19.4%, and the mean scores for the AGREE II domains were 28.6% (Scope and purpose), 17.0% (Stakeholder involvement), 11.7% (Rigor of development), 32.2% (Clarity of presentation), 14.2% (Applicability) and 12.8% (Editorial independence). The mean overall score for reporting quality over all guidelines was 30.2%, with the following mean scores for each RIGHT domain: 55.6% (Basic information), 43.8% (Background), 14.5% (Evidence), 29.2% (Recommendations), 10.7% (Review and quality assurance), 12.6% (Funding and declaration of interest) and 8.4% (Other information). Subgroup analyses found that both the methodological and reporting quality were generally higher among CPGs that used evidence grading systems or reported receiving funding., Conclusion: Both the methodological quality and the reporting quality of CPGs developed in China have improved over time, but are still below the international average., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: We aimed to estimate the disease burden of Tuberculosis (TB) and return on investment of TB care in selected high-burden countries of the Western Pacific Region (WPR) until 2030., Methods: We projected the TB epidemic in Viet Nam and Lao People's Democratic Republic (PDR) 2020-2030 using a mathematical model under various scenarios: counterfactual (no TB care); baseline (TB care continues at current levels); and 12 different diagnosis and treatment interventions. We retrieved previous modeling results for China and the Philippines. We pooled the new and existing information on incidence and deaths in the four countries, covering >80% of the TB burden in WPR. We estimated the return on investment of TB care and interventions in Viet Nam and Lao PDR using a Solow model., Findings: In the baseline scenario, TB incidence in the four countries decreased from 97•0/100,000/year (2019) to 90•1/100,000/year (2030), and TB deaths from 83,300/year (2019) to 71,100/year (2030). Active case finding (ACF) strategies (screening people not seeking care for respiratory symptoms) were the most effective single interventions. Return on investment (2020-2030) for TB care in Viet Nam and Lao PDR ranged US$4-US$49/dollar spent; additional interventions brought up to US$2•7/dollar spent., Interpretation: In the modeled countries, TB incidence will only modestly decrease without additional interventions. Interventions that include ACF can reduce TB burden but achieving the End TB incidence and mortality targets will be difficult without new transformational tools (e.g. vaccine, new diagnostic tools, shorter treatment). However, TB care, even at its current level, can bring a multiple-fold return on investment., Funding: World Health Organization Western Pacific Regional Office; Swiss National Science Foundation Grant 163878., Competing Interests: This study was funded by the World Health Organization Western Pacific Regional Office and the Swiss National Science Foundation (Grant 163878). We declare no competing interests. The authors alone are responsible for the views expressed in this publication and they do not necessarily represent the decisions or policies of the WHO., (© 2021 World Health Organization; licensee Elsevier.)

Background: In response to the ongoing epidemic of coronavirus disease 2019 (COVID-19), China has carried out restrictive disease containment measures across the country., Methods: In this cross-sectional study, we collected demographic and epidemiological data of 376 laboratory-confirmed cases of COVID-19 among children younger than 18 years of age. Using descriptive statistics and odds ratios, we described the odds of exposure outside the family after the implementation of control measures compared to before., Results: Children diagnosed on or after February 4, 2020, had a lower odds of exposure to COVID-19 outside of the family compared to those diagnosed before February 3, 2020 (OR =0.594, 95% CI: 0.391 to 0.904). In the stratified analysis, children aged 0 to 5 years had the lowest odds of exposure outside of the family (OR =0.420, 95% CI: 0.196 to 0.904) compared to the other age groups assessed., Conclusions: Our study on the children infected with COVID-19 as well as their exposure within family provided evidence that the implementation of containment measures was effective in reducing the odds of exposure outside of the family, especially for preschool children. Continuation of these efforts, coupled with tailored prevention and health education messaging for younger aged children, may help to reduce the transmission of COVID-19 among children until other therapeutic interventions or vaccines are available., Competing Interests: Conflicts of Interests: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tp-20-214).The authors have no conflict of interest to declare., (2021 Translational Pediatrics. All rights reserved.)

Objectives: To compare and analyse the recommendations from clinical practice guidelines (CPGs) on gout worldwide, examine the consistency across CPGs, and provide suggestions to develop and update gout guidelines., Methods: We conducted systematic searches in MEDLINE, CBM, GIN, NICE, NGC, WHO, SIGN, DynaMed, UpToDate, and Best Practice databases, from their inception to August 2019 to identify and select CPGs related to gout. We used the search terms "gout", "hyperuricaemia" and "guideline". After two rounds of screening, we included the eligible CPGs of gout according to the pre-defined inclusion and exclusion criteria. Methodological quality of included guidelines was assessed with the AGREE-II instrument. The general characteristics of included guidelines and the recommendations were extracted, and the consistency of recommendations across guidelines was compared and analysed., Results: A total of 15 gout guidelines including 359 recommendations were retrieved. The main topics covered by the recommendations were diagnosis, pharmacologic treatment of gout flares, pharmacologic urate-lowering therapy (ULT) of chronic gouty arthritis, lifestyle interventions, prophylaxis, and management of asymptomatic hyperuricaemia. The results of AGREE-II appraisal showed that only two guidelines achieved high scores (≥50%) in all six domains. There was substantial discrepancy between the guidelines in recommendations covering the value of computed tomography (CT) and x-rays for diagnosis, the use of corticosteroids as a first-line treatment for flare, the use of colchicine, indications for ULT, the use of febuxostat as first-line ULT, the administration of allopurinol, and the timing of ULT initiation., Conlusions: A number of countries are devoting themselves to the development of gout guidelines, but the process of updating guidelines is slower than that suggested by the WHO. Methodological quality is not satisfactory in most guidelines, and recommendations between guidelines are not consistent.

BackgroundIn December 2019, a pneumonia caused by a novel coronavirus (SARS-CoV-2) emerged in Wuhan, China and has rapidly spread around the world since then.AimThis study aims to understand the research gaps related to COVID-19 and propose recommendations for future research.MethodsWe undertook a scoping review of COVID-19, comprehensively searching databases and other sources to identify literature on COVID-19 between 1 December 2019 and 6 February 2020. We analysed the sources, publication date, type and topic of the retrieved articles/studies.ResultsWe included 249 articles in this scoping review. More than half (59.0%) were conducted in China. Guidance/guidelines and consensuses statements (n = 56; 22.5%) were the most common. Most (n = 192; 77.1%) articles were published in peer-reviewed journals, 35 (14.1%) on preprint servers and 22 (8.8%) posted online. Ten genetic studies (4.0%) focused on the origin of SARS-CoV-2 while the topics of molecular studies varied. Nine of 22 epidemiological studies focused on estimating the basic reproduction number of COVID-19 infection (R 0 ). Of all identified guidance/guidelines (n = 35), only ten fulfilled the strict principles of evidence-based practice. The number of articles published per day increased rapidly until the end of January.ConclusionThe number of articles on COVID-19 steadily increased before 6 February 2020. However, they lack diversity and are almost non-existent in some study fields, such as clinical research. The findings suggest that evidence for the development of clinical practice guidelines and public health policies will be improved when more results from clinical research becomes available.

This project aims to evaluate the methods and reporting quality of practice guidelines of five different viruses that have caused Public Health Emergencies of International Concern (PHEIC) over 20 past years: the severe acute respiratory syndrome coronavirus (SARS-CoV), Ebola virus, Middle East respiratory syndrome coronavirus (MERS-CoV), Zika virus and the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We systematically searched databases, guideline websites and government health agency websites from their inception to February 02, 2020 to extract practice guidelines for SARS-CoV, Ebola virus, MERS-CoV, Zika virus, SARS-CoV-2 and the diseases they caused. The literature was screened independently by four researchers. Then, fifteen researchers evaluated the quality of included guidelines using the AGREE-II (Appraisal of Guidelines for Research and Evaluation II, for methodological quality) instrument and RIGHT (Reporting Items for practice Guidelines in Healthcare, for reporting quality) statement. Finally, a total of 81 guidelines were included, including 21 SARS-CoV guidelines, 11 Ebola virus (EBOV) guidelines, 9 MERS-CoV guidelines, 10 Zika Virus guidelines and 30 SARS-CoV-2 guidelines. The evaluation of the methodological quality indicated that the mean scores of each domain for guidelines of each virus were all below 60%, the scores for guidelines in the domains of "clarity of presentation" being the highest and in the "editorial independence" lowest. The mean reporting rate of each domain for guidelines of each virus was also less than 60%: the reporting rates for the domain "background" were highest, and for the domain "funding and interests" lowest. The methodological and reporting quality of the practice guidelines for SARS-CoV, Ebola virus, MERS-CoV, Zika virus and SARS-CoV-2 guidelines tend to be low. We recommend to follow evidence-based methodology and the RIGHT statement on reporting when developing guidelines., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/atm.2020.03.130). The authors have no conflicts of interest to declare., (2020 Annals of Translational Medicine. All rights reserved.)

Objective: The aim of this study was to assess the quality of global clinical practice guidelines (CPGs) on gout., Methods: We systematically searched MEDLINE, CBM (Chinese Biomedical Literature database), GIN (Guidelines International Network), NICE (National Institute for Health and Clinical Excellence), NGC (National Guideline Clearinghouse), WHO (World Health Organization), SIGN (Scottish Intercollegiate Guidelines Network), DynaMed, UpToDate, and Best Practice databases from their inception until January 2017 to identify and select CPGs related to gout. Two reviewers independently assessed the eligible gout CPGs using the AGREE II instrument., Results: We evaluated 15 CPGs published between 2007 and 2017, produced by 13 different developers. Quality of evidence and strength of recommendations were presented in 14 (93%) and 13 (87%) CPGs, respectively. The mean scores (±SD) for each AGREE II domain were as follows: (i) scope and purpose: 75% (±17%), (ii) stakeholder involvement: 39% (±19%), (iii) rigor of development: 43% (±17%), (iv) clarity and presentation: 82% (±14%), (v) applicability: 31% (±12%), and (vi) editorial independence: 23% (±29%)., Conclusions: The quality of gout CPGs was suboptimal, and various incompatible grading systems of quality of evidence and strength of recommendations were used. The use of a standardized international grading system is essential to ensure high methodological quality of gout CPGs. Tools such as AGREE II could substantially improve the development and update of future gout CPGs.

Introduction: Socio-behavioural factors may contribute to the wide variance in HIV prevalence between and within sub-Saharan African (SSA) countries. We studied the associations between socio-behavioural variables potentially related to the risk of acquiring HIV., Methods: We used Bayesian network models to study associations between socio-behavioural variables that may be related to HIV. A Bayesian network consists of nodes representing variables, and edges representing the conditional dependencies between variables. We analysed data from Demographic and Health Surveys conducted in 29 SSA countries between 2010 and 2016. We predefined and dichotomized 12 variables, including factors related to age, literacy, HIV knowledge, HIV testing, domestic violence, sexual activity and women's empowerment. We analysed data on men and women for each country separately and then summarized the results across the countries. We conducted a second analysis including also the individual HIV status in a subset of 23 countries where this information was available. We presented summary graphs showing associations that were present in at least six countries (five in the analysis with HIV status)., Results: We analysed data from 190,273 men (range across countries 2295 to 17,359) and 420,198 women (6621 to 38,948). The two variables with the highest total number of edges in the summary graphs were literacy and rural/urban location. Literacy was negatively associated with false beliefs about AIDS and, for women, early sexual initiation, in most countries. Literacy was also positively associated with ever being tested for HIV and the belief that women have the right to ask their husband to use condoms if he has a sexually transmitted infection. Rural location was positively associated with false beliefs about HIV and the belief that beating one's wife is justified, and negatively associated with having been tested for HIV. In the analysis including HIV status, being HIV positive was associated with female-headed household, older age and rural location among women, and with no variables among men., Conclusions: Literacy and urbanity were strongly associated with several factors that are important for HIV acquisition. Since literacy is one of the few variables that can be improved by interventions, this makes it a promising intervention target., (© 2019 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)

Background: Acupuncture is widely used worldwide, and systematic reviews on acupuncture are increasingly being published. Although acupuncture systematic reviews share several essential elements with other systematic reviews, some essential information for the application of acupuncture is not covered by the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement. Considering this, we aimed to develop an extension of the PRISMA statement for acupuncture systematic reviews., Methods: We used the PRISMA statement as a starting point, and conducted this study referring to the development strategy recommended by the EQUATOR network. The initial items were collected through a wide survey among evidence users and a review of relevant studies. We conducted a three-round Delphi survey and one-day face-to-face meeting to select items and formulate the checklist. After the consensus meeting, we drafted the manuscript (including the checklist) and sent it to our advisory experts for comments, following which the checklist was refined and circulated to a group of acupuncture systematic review authors for pilot test. We also selected a sample of acupuncture systematic reviews published in 2017 to test the checklist., Results: A checklist of five new sub-items (including sub items) and six modified items was formulated, involving content related to title, rationale, eligibility criteria, literature search, data extraction, and study characteristics. We clarified the rationales of the items and provided examples for each item for additional guidance., Conclusion: The PRISMA for Acupuncture checklist is developed for improving the reporting of systematic reviews of acupuncture interventions., Trial Registration: We have registered the study on the EQUATOR network ( http://www.equator-network.org/library/reporting-guidelines-under-development/#91 ).

Objectives: We systematically analysed recommendations from gout guidelines as an example, to provide a basis for developing a reporting standard of recommendations in clinical practice guidelines (CPGs)., Design: Systematic review without meta-analysis., Methods: We systematically searched MEDLINE and all relevant guideline websites (National Institute for Health and Care Excellence, National Guideline Clearinghouse, Scottish Intercollegiate Guidelines Network, WHO, Guidelines International Network, DynaMed, UpTodate, Best Practice) from their inception to January 2017 to identify and select gout CPGs. We used search terms such as 'gout', 'hyperuricemia' and 'guideline'. We included the eligible CPGs of gout according to the predefined inclusion and exclusion criteria after screening titles, abstracts and full texts. The characteristics of recommendations reported in the included guidelines were extracted and analysed., Results: A total of 15 gout guidelines with a range of 5-80 recommendations were retrieved. Several indicators were used in the gout guidelines to facilitate identification of recommendations, including grouping all recommendations in a summary section, formatting recommendations in a particular or special way, using locating words for recommendations and indicating the strength of recommendation and quality of evidence. We found some components commonly used in the recommendations. The wording of recommendations varied across guidelines. Recommendations were detailed and explained in the section of rationale and explanation of recommendations. In some guidelines, recommendations were accompanied with other material to assist their reporting., Conclusions: Variability and inconsistency were found on the reporting and presentation of recommendations in gout guidelines. Several points for reporting recommendation can be summarised. First, we suggested summarising and highlighting the core recommendations in a guideline. Second, guideline developers should try to structure and write recommendations reasonably. Third, it was necessary to detail and explain the recommendations and their rationale. Finally, describing and providing other potential useful contents was also a helpful way for clear reporting., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To compare birth weight and weight gain in HIV-exposed, uninfected (HEU) infants up to 24 months old, who enrolled in the Malawian national HIV care clinic (HCC) programme either before or after Option B+ (OB+) was implemented., Design, Setting and Participants: HIV-exposed infants enrol in the HCC programme as soon as possible after birth and are followed up to at least 24 months old. This analysis includes HEU infants with recorded birth weight, date of birth, gender and at least one follow-up weight measurement from 21 health facilities in central and southern Malawi (January 2010-December 2014). Weight-for-age z scores (WAZ) were derived and compared by birth period using linear regression at birth and mixed effects models for postnatal weight gain up to 24 months old., Results: Of 6845 HEU infants included in this study, 88.5% were born after OB+. The proportion of infants exposed in utero to combination antiretroviral therapy (ART) significantly increased after OB+ was implemented, and infants were exposed to ART for a longer time. There was no significant difference in WAZ at birth (P = 0.654) among HEU infants by birth period, but postnatal weight gain was faster among HEU infants born in the Option B+ period than infants born pre-Option B+., Conclusion: Birth weight was not affected by longer exposure to ART during pregnancy after OB+ was introduced, when weight gain in HEU infants was faster, possibly because their mothers were in better health.

Objectives: We aimed to examine the declaration of interests (DOIs), management of conflict of interest (COI), and the funders for World Health Organization (WHO) guidelines., Study Design and Setting: We examined all Guidelines Review Committee (GRC)-approved WHO guidelines published in English from January 2007 (inception of the GRC) to November 2016. We obtained a list of all such guidelines from the GRC Secretariat. Characteristics of guidelines including funders and individual contributors' DOI were independently extracted by two researchers. Binary logistic regression was used to assess the association between declarations and the number of organizations involved in development., Results: A total of 176 guidelines fulfilled inclusion criteria, encompassing 14 clinical or public health fields. Funders were reported in 128 (73%) of the guidelines: the most common were governments. DOI for external contributors were reported in 157 (89%) of the guidelines: 75 (48%) indicated no contributors with COI, 57 (36%) reported contributors with COI, and 25 (16%) reported collecting DOI but not whether COI existed. Financial COI were reported more frequently than nonfinancial COI. Of 57 guidelines that reported COI, 45 (79%) indicated how the COI were managed., Conclusion: The majority of WHO guidelines reported their funding sources and the DOI and COI of external contributors in their guideline documents. However, there is a need for improvement, in particular for reporting of funders and their role, declaration processes, and management of COI., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: To move towards ending AIDS by 2030, HIV resources should be allocated cost-effectively. We used the Optima HIV model to estimate how global HIV resources could be retargeted for greatest epidemiological effect and how many additional new infections could be averted by 2030., Methods: We collated standard data used in country modelling exercises (including demographic, epidemiological, behavioural, programmatic, and expenditure data) from Jan 1, 2000, to Dec 31, 2015 for 44 countries, capturing 80% of people living with HIV worldwide. These data were used to parameterise separate subnational and national models within the Optima HIV framework. To estimate optimal resource allocation at subnational, national, regional, and global levels, we used an adaptive stochastic descent optimisation algorithm in combination with the epidemic models and cost functions for each programme in each country. Optimal allocation analyses were done with international HIV funds remaining the same to each country and by redistributing these funds between countries., Findings: Without additional funding, if countries were to optimally allocate their HIV resources from 2016 to 2030, we estimate that an additional 7·4 million (uncertainty range 3·9 million-14·0 million) new infections could be averted, representing a 26% (uncertainty range 13-50%) incidence reduction. Redistribution of international funds between countries could avert a further 1·9 million infections, which represents a 33% (uncertainty range 20-58%) incidence reduction overall. To reduce HIV incidence by 90% relative to 2010, we estimate that more than a three-fold increase of current annual funds will be necessary until 2030. The most common priorities for optimal resource reallocation are to scale up treatment and prevention programmes targeting key populations at greatest risk in each setting. Prioritisation of other HIV programmes depends on the epidemiology and cost-effectiveness of service delivery in each setting as well as resource availability., Interpretation: Further reductions in global HIV incidence are possible through improved targeting of international and national HIV resources., Funding: World Bank and Australian NHMRC., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: The incidence of anal cancer is high in HIV-positive MSM. We modeled the impact of screening strategies and combination antiretroviral therapy (cART) coverage on anal cancer incidence in Switzerland., Methods: Individual-based, dynamic simulation model parameterized with Swiss HIV Cohort Study and literature data. We assumed all men to be human papillomavirus infected. CD4 cell count trajectories were the main predictors of anal cancer. From 2016 we modeled cART coverage either as below 100% (corresponding to 2010-2015) or as 100%, and the following four screening strategies: no screening, yearly anal cytology (Papanicolaou smears), yearly anoscopy and targeted anoscopy 5 years after CD4 count dropped below 200 cells/μl., Results: Median nadir CD4 cell count of 6411 MSM increased from 229 cells/μl during 1980-1989 to 394 cells/μl during 2010-2015; cART coverage increased from 0 to 83.4%. Modeled anal cancer incidence peaked at 81.7/100 000 in 2009, plateaued 2010-2015 and will decrease to 58.7 by 2030 with stable cART coverage, and to 52.0 with 100% cART coverage. With yearly cytology, incidence declined to 38.2/100 000 by 2030, with yearly anoscopy to 32.8 and with CD4 cell count guided anoscopy to 51.3. The numbers needed to screen over 15 years to prevent one anal cancer case were 384 for yearly cytology, 313 for yearly anoscopy and 242 for CD4 cell count-dependent screening., Conclusion: Yearly screening of HIV-positive MSM may reduce anal cancer incidence substantially, with a number needed to screen that is comparable with other screening interventions to prevent cancer.

Objective: To estimate the cost-effectiveness of prevention of mother-to-child transmission (MTCT) of HIV with lifelong antiretroviral therapy (ART) for pregnant and breastfeeding women ('Option B+') compared with ART during pregnancy or breastfeeding only unless clinically indicated ('Option B')., Design: Mathematical modelling study of first and second pregnancy, informed by data from the Malawi Option B+ programme., Methods: Individual-based simulation model. We simulated cohorts of 10 000 women and their infants during two subsequent pregnancies, including the breastfeeding period, with either Option B+ or B. We parameterized the model with data from the literature and by analysing programmatic data. We compared total costs of antenatal and postnatal care, and lifetime costs and disability-adjusted life-years of the infected infants between Option B+ and Option B., Results: During the first pregnancy, 15% of the infants born to HIV-infected mothers acquired the infection. With Option B+, 39% of the women were on ART at the beginning of the second pregnancy, compared with 18% with Option B. For second pregnancies, the rates MTCT were 11.3% with Option B+ and 12.3% with Option B. The incremental cost-effectiveness ratio comparing the two options ranged between about US$ 500 and US$ 1300 per DALY averted., Conclusion: Option B+ prevents more vertical transmissions of HIV than Option B, mainly because more women are already on ART at the beginning of the next pregnancy. Option B+ is a cost-effective strategy for PMTCT if the total future costs and lost lifetime of the infected infants are taken into account.

Background: The number of patients in need of second-line antiretroviral drugs is increasing in sub-Saharan Africa. We aimed to project the need of second-line antiretroviral therapy in adults in sub-Saharan Africa up to 2030., Methods: We developed a simulation model for HIV and applied it to each sub-Saharan African country. We used the WHO country intelligence database to estimate the number of adult patients receiving antiretroviral therapy from 2005 to 2014. We fitted the number of adult patients receiving antiretroviral therapy to observed estimates, and predicted first-line and second-line needs between 2015 and 2030. We present results for sub-Saharan Africa, and eight selected countries. We present 18 scenarios, combining the availability of viral load monitoring, speed of antiretroviral scale-up, and rates of retention and switching to second-line. HIV transmission was not included., Findings: Depending on the scenario, 8·7-25·6 million people are expected to receive antiretroviral therapy in 2020, of whom 0·5-3·0 million will be receiving second-line antiretroviral therapy. The proportion of patients on treatment receiving second-line therapy was highest (15·6%) in the scenario with perfect retention and immediate switching, no further scale-up, and universal routine viral load monitoring. In 2030, the estimated range of patients receiving antiretroviral therapy will remain constant, but the number of patients receiving second-line antiretroviral therapy will increase to 0·8-4·6 million (6·6-19·6%). The need for second-line antiretroviral therapy was two to three times higher if routine viral load monitoring was implemented throughout the region, compared with a scenario of no further viral load monitoring scale-up. For each monitoring strategy, the future proportion of patients receiving second-line antiretroviral therapy differed only minimally between countries., Interpretation: Donors and countries in sub-Saharan Africa should prepare for a substantial increase in the need for second-line drugs during the next few years as access to viral load monitoring improves. An urgent need exists to decrease the costs of second-line drugs., Funding: World Health Organization, Swiss National Science Foundation, National Institutes of Health., (Copyright © 2016 World Health Organization. Published by Elsevier Ltd/Inc/BV. All rights reserved. Published by Elsevier Ltd.. All rights reserved.)

Malawi adopted the Option B+ strategy in 2011. Its success in reducing mother-to-child transmission depends on coverage and timing of HIV testing. We assessed HIV status ascertainment and its predictors during pregnancy. HIV status ascertainment was 82.3% (95% confidence interval: 80.2 to 85.9) in the pre-Option B+ period and 85.7% (95% confidence interval: 83.4 to 88.0) in the Option B+ period. Higher HIV ascertainment was independently associated with higher age, attending antenatal care more than once, and registration in 2010. The observed high variability of HIV ascertainment between sites (50.6%-97.7%) and over time suggests that HIV test kit shortages and insufficient numbers of staff posed major barriers to reducing mother-to-child transmission.

Mathematical models of disease progression predict disease outcomes and are useful epidemiological tools for planners and evaluators of health interventions. The 𝖱 package gems is a tool that simulates disease progression in patients and predicts the effect of different interventions on patient outcome. Disease progression is represented by a series of events (e.g., diagnosis, treatment and death), displayed in a directed acyclic graph. The vertices correspond to disease states and the directed edges represent events. The package gems allows simulations based on a generalized multistate model that can be described by a directed acyclic graph with continuous transition-specific hazard functions. The user can specify an arbitrary hazard function and its parameters. The model includes parameter uncertainty, does not need to be a Markov model, and may take the history of previous events into account. Applications are not limited to the medical field and extend to other areas where multistate simulation is of interest. We provide a technical explanation of the multistate models used by gems , explain the functions of gems and their arguments, and show a sample application.

Background: Rheumatic heart disease accounts for up to 250 000 premature deaths every year worldwide and can be regarded as a physical manifestation of poverty and social inequality. We aimed to estimate the prevalence of rheumatic heart disease in endemic countries as assessed by different screening modalities and as a function of age., Methods: We searched Medline, Embase, the Latin American and Caribbean System on Health Sciences Information, African Journals Online, and the Cochrane Database of Systematic Reviews for population-based studies published between Jan 1, 1993, and June 30, 2014, that reported on prevalence of rheumatic heart disease among children and adolescents (≥ 5 years to <18 years). We assessed prevalence of clinically silent and clinically manifest rheumatic heart disease in random effects meta-analyses according to screening modality and geographical region. We assessed the association between social inequality and rheumatic heart disease with the Gini coefficient. We used Poisson regression to analyse the effect of age on prevalence of rheumatic heart disease and estimated the incidence of rheumatic heart disease from prevalence data., Findings: We included 37 populations in the systematic review and meta-analysis. The pooled prevalence of rheumatic heart disease detected by cardiac auscultation was 2·9 per 1000 people (95% CI 1·7-5·0) and by echocardiography it was 12·9 per 1000 people (8·9-18·6), with substantial heterogeneity between individual reports for both screening modalities (I² = 99·0% and 94·9%, respectively). We noted an association between social inequality expressed by the Gini coefficient and prevalence of rheumatic heart disease (p = 0·0002). The prevalence of clinically silent rheumatic heart disease (21·1 per 1000 people, 95% CI 14·1-31·4) was about seven to eight times higher than that of clinically manifest disease (2·7 per 1000 people, 1·6-4·4). Prevalence progressively increased with advancing age, from 4·7 per 1000 people (95% CI 0·0-11·2) at age 5 years to 21·0 per 1000 people (6·8-35·1) at 16 years. The estimated incidence was 1·6 per 1000 people (0·8-2·3) and remained constant across age categories (range 2·5, 95% CI 1·3-3·7 in 5-year-old children to 1·7, 0·0-5·1 in 15-year-old adolescents). We noted no sex-related differences in prevalence (p = 0·829)., (Copyright © 2014 Rothenbühler et al. Open Access article distributed under the terms of CC BY. Published by .. All rights reserved.)

Objective: Treatment as prevention depends on retaining HIV-infected patients in care. We investigated the effect on HIV transmission of bringing patients lost to follow-up (LTFU) back into care., Design: Mathematical model., Methods: Stochastic mathematical model of cohorts of 1000 HIV-infected patients on antiretroviral therapy, based on the data from 2 clinics in Lilongwe, Malawi. We calculated cohort viral load (sum of individual mean viral loads each year) and used a mathematical relationship between viral load and transmission probability to estimate the number of new HIV infections. We simulated 4 scenarios: "no LTFU" (all patients stay in care), "no tracing" (patients LTFU are not traced), "immediate tracing" (after missed clinic appointment), and "delayed tracing" (after 6 months)., Results: About 440 of 1000 patients were LTFU over 5 years. Cohort viral loads (million copies/mL per 1000 patients) were 3.7 [95% prediction interval (PrI), 2.9-4.9] for no LTFU, 8.6 (95% PrI, 7.3-10.0) for no tracing, 7.7 (95% PrI, 6.2-9.1) for immediate, and 8.0 (95% PrI, 6.7-9.5) for delayed tracing. Comparing no LTFU with no tracing, the number of new infections increased from 33 (95% PrI, 29-38) to 54 (95% PrI, 47-60) per 1000 patients. Immediate tracing prevented 3.6 (95% PrI, -3.3 to 12.8) and delayed tracing 2.5 (95% PrI, -5.8 to 11.1) new infections per 1000. Immediate tracing was more efficient than delayed tracing: to 116 and 142 tracing efforts, respectively, were needed prevent 1 new infection., Conclusions: Tracing of patients LTFU enhances the preventive effect of antiretroviral therapy, but the number of transmissions prevented is small.

Background: WHO's 2013 revisions to its Consolidated Guidelines on antiretroviral drugs recommend routine viral load monitoring, rather than clinical or immunological monitoring, as the preferred monitoring approach on the basis of clinical evidence. However, HIV programmes in resource-limited settings require guidance on the most cost-effective use of resources in view of other competing priorities such as expansion of antiretroviral therapy coverage. We assessed the cost-effectiveness of alternative patient monitoring strategies., Methods: We evaluated a range of monitoring strategies, including clinical, CD4 cell count, and viral load monitoring, alone and together, at different frequencies and with different criteria for switching to second-line therapies. We used three independently constructed and validated models simultaneously. We estimated costs on the basis of resource use projected in the models and associated unit costs; we quantified impact as disability-adjusted life years (DALYs) averted. We compared alternatives using incremental cost-effectiveness analysis., Findings: All models show that clinical monitoring delivers significant benefit compared with a hypothetical baseline scenario with no monitoring or switching. Regular CD4 cell count monitoring confers a benefit over clinical monitoring alone, at an incremental cost that makes it affordable in more settings than viral load monitoring, which is currently more expensive. Viral load monitoring without CD4 cell count every 6-12 months provides the greatest reductions in morbidity and mortality, but incurs a high cost per DALY averted, resulting in lost opportunities to generate health gains if implemented instead of increasing antiretroviral therapy coverage or expanding antiretroviral therapy eligibility., Interpretation: The priority for HIV programmes should be to expand antiretroviral therapy coverage, firstly at CD4 cell count lower than 350 cells per μL, and then at a CD4 cell count lower than 500 cells per μL, using lower-cost clinical or CD4 monitoring. At current costs, viral load monitoring should be considered only after high antiretroviral therapy coverage has been achieved. Point-of-care technologies and other factors reducing costs might make viral load monitoring more affordable in future., Funding: Bill & Melinda Gates Foundation, WHO., (Copyright © 2014 Keebler et al. Open Access article distributed under the terms CC BY-NC-ND. Published by .. All rights reserved.)