Mortality surveillance systems can have limitations, including reporting delays, incomplete reporting, missing data, and insufficient detail on important risk or sociodemographic factors that can impact the accuracy of estimates of current trends, disease severity, and related disparities across subpopulations. The Centers for Disease Control and Prevention used multiple data systems during the COVID-19 emergency response-line-level case‒death surveillance, aggregate death surveillance, and the National Vital Statistics System-to collectively provide more comprehensive and timely information on COVID-19‒associated mortality necessary for informed decisions. This article will review in detail the line-level, aggregate, and National Vital Statistics System surveillance systems and the purpose and use of each. This retrospective review of the hybrid surveillance systems strategy may serve as an example for adaptive informational approaches needed over the course of future public health emergencies. (Am J Public Health. Published online ahead of print July 25, 2024:e1-e10. https://doi.org/10.2105/AJPH.2024.307743).

Objective We compared suspect, probable, and confirmed case definitions, as well as diagnostic testing criteria, used in the COVID-19 pandemic’s 25 highest burden countries to aid interpretation of global and national surveillance data.Methods We identified the COVID-19 pandemic’s 25 countries with the highest disease burden based on the number of cumulative reported cases to the World Health Organization (WHO) as of 1 October 2020. We searched official websites of these countries for suspect, probable, and confirmed case definitions. Given that confirmation of COVID-19 usually requires diagnostic testing, we also searched for diagnostic testing eligibility criteria in these countries. Extracted case definitions and testing criteria were managed in a database and analyzed in Microsoft Excel.Findings We identified suspect, probable, and confirmed case definitions in 96%, 64%, and 100% of countries, respectively. Testing criteria were identified in 100% of countries. 56% of identified countries followed WHO recommendations for using a combination of clinical and epidemiological criteria as part of the suspect case definition. 75% of identified countries followed WHO recommendations on using clinical, epidemiological, and diagnostic criteria for probable cases. 72% of countries followed WHO recommendations on using PCR testing for confirming a case of COVID-19. Finally, 64% of countries used testing eligibility criteria at least as permissive as WHO.Conclusion There is marked heterogeneity in who is eligible for testing in countries and how countries define a case of COVID-19. This affects the ability to compare burden, transmission, and response impact estimates derived from case surveillance data across countries.Competing Interest StatementThe authors have declared no competing interest.Funding StatementNoneAuthor DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:Not applicableAll necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesAll relevant data are available in the manuscript body and appendices.

We compared characteristics of HIV diagnosis and recent HIV infection (i.e., likely acquired within the last year) in Cambodia. We included individuals ≥ 15 years old accessing HIV testing. From August/2020-August/2022, 53,031 people were tested for HIV, 6,868 were newly diagnosed, and 192 were recently infected. We found differences in geographical burden and risk behaviors with diagnosis and recency (e.g., men who have sex with men, transgender women, and entertainment workers had a nearly two-fold increased odds of testing recent compared to being diagnosed with HIV). Recent infection surveillance may provide unique insights into ongoing HIV acquisition to inform programs.

Early during the COVID-19 pandemic, the Centers for Disease Control and Prevention (CDC) leveraged an existing surveillance system infrastructure to monitor COVID-19 cases and deaths in the United States. Given the time needed to report individual-level (also called line-level) COVID-19 case and death data containing detailed information from individual case reports, CDC designed and implemented a new aggregate case surveillance system to inform emergency response decisions more efficiently, with timelier indicators of emerging areas of concern. We describe the processes implemented by CDC to operationalize this novel, multifaceted aggregate surveillance system for collecting COVID-19 case and death data to track the spread and impact of the SARS-CoV-2 virus at national, state, and county levels. We also review the processes established to acquire, process, and validate the aggregate number of cases and deaths due to COVID-19 in the United States at the county and jurisdiction levels during the pandemic. These processes include time-saving tools and strategies implemented to collect and validate authoritative COVID-19 case and death data from jurisdictions, such as web scraping to automate data collection and algorithms to identify and correct data anomalies. This topical review highlights the need to prepare for future emergencies, such as novel disease outbreaks, by having an event-agnostic aggregate surveillance system infrastructure in place to supplement line-level case reporting for near-real-time situational awareness and timely data.

Dr Amitabh Suthar and Dr Christopher Dye give their perspective on infection, immunity and surveillance of COVID-19.

During the coronavirus disease-2019 (COVID-19) pandemic, the Centers for Disease Control and Prevention (CDC) supplemented traditional COVID-19 case and death reporting with COVID-19 aggregate case and death surveillance (ACS) to track daily cumulative numbers. Later, as public health jurisdictions (PHJs) revised the historical COVID-19 case and death data due to data reconciliation and updates, CDC devised a manual process to update these records in the ACS dataset for improving the accuracy of COVID-19 case and death data. Automatic data transfer via an application programming interface (API), an intermediary that enables software applications to communicate, reduces the time and effort in transferring data from PHJs to CDC. However, APIs must meet specific content requirements for use by CDC. As of March 2022, CDC has integrated APIs from 3 jurisdictions for COVID-19 ACS. Expanded use of APIs may provide efficiencies for COVID-19 and other emergency response planning efforts as evidenced by this proof-of-concept. In this article, we share the utility of APIs in COVID-19 ACS.

BACKGROUND: We assessed the prevalence of acquired HIV drug resistance (HIVDR) and associated factors among patients receiving first-line antiretroviral therapy (ART) in Rwanda. METHODS: This cross-sectional study included 702 patients receiving first-line ART for at least 6months with last viral load (VL) results 1000 copies/mL. Blood plasma samples were subjected to VL testing; specimens with unsuppressed VL were genotyped to identify HIVDR-associated mutations. Data were analysed using STATA/SE. RESULTS: Median time on ART was 86.4 months (interquartile range [IQR], 44.8-130.2months), and median CD4 count at ART initiation was 311 cells/mm(3) (IQR, 197-484 cells/mm(3)). Of 414 (68.2%) samples with unsuppressed VL, 378 (88.3%) were genotyped. HIVDR included 347 (90.4%) non-nucleoside reverse transcriptase inhibitor- (NNRTI), 291 (75.5%) nucleoside reverse transcriptase inhibitor- (NRTI) and 13 (3.5%) protease inhibitor (PI) resistance-associated mutations. The most common HIVDR mutations were K65R (22.7%), M184V (15.4%) and D67N (9.8%) for NRTIs and K103N (34.4%) and Y181C/I/V/YC (7%) for NNRTIs. Independent predictors of acquired HIVDR included current ART regimen of zidovudine + lamivudine + nevirapine (adjusted odds ratio [aOR], 3.333 [95% confidence interval (CI): 1.022-10.870]; p = 0.046) for NRTI resistance and current ART regimen of tenofovir + emtricitabine + nevirapine (aOR, 0.148 [95% CI: 0.028-0.779]; p = 0.025), zidovudine + lamivudine + efavirenz (aOR, 0.105 [95% CI: 0.016-0.693]; p = 0.020) and zidovudine + lamivudine + nevirapine (aOR, 0.259 [95% CI: 0.084-0.793]; p = 0.019) for NNRTI resistance. History of ever switching ART regimen was associated with NRTI resistance (aOR, 2.53 [95% CI: 1.198-5.356]; p = 0.016) and NNRTI resistance (aOR, 3.23 [95% CI: 1.435-7.278], p = 0.005). CONCLUSION: The prevalence of acquired HIV drug resistance (HIVDR) was high among patient failing to re-suppress VL and was associated with current ART regimen and ever switching ART regimen. The findings of this study support the current WHO guidelines recommending that patients on an NNRTI-based regimen should be switched based on a single viral load test and suggests that national HIV VL monitoring of patients receiving ART has prevented long-term treatment failure that would result in the accumulation of TAMs and potential loss of efficacy of all NRTI used in second-line ART as the backbone in combination with either dolutegravir or boosted PIs.

OBJECTIVE: To evaluate the impact of vaccine scale-up on population level covid-19 mortality and incidence in the United States. DESIGN: Observational study. SETTING: US county level case surveillance and vaccine administration data reported from 14 December 2020 to 18 December 2021. PARTICIPANTS: Residents of 2558 counties from 48 US states. MAIN OUTCOME MEASURES: The primary outcome was county covid-19 mortality rates (deaths/100 000 population/county week). The secondary outcome was incidence of covid-19 (cases/100 000 population/county week). Incidence rate ratios were used to compare rates across vaccination coverage levels. The impact of a 10% improvement in county vaccination coverage (defined as at least one dose of a covid-19 vaccine among adults ≥18 years of age) was estimated During the eras of alpha and delta variant predominance, the impact of very low (0-9%), low (10-39%), medium (40-69%), and high (≥70%) vaccination coverage levels was compared. RESULTS: In total, 30 643 878 cases of covid-19 and 439 682 deaths associated with covid-19 occurred over 132 791 county weeks. A 10% improvement in vaccination coverage was associated with an 8% (95% confidence interval 8% to 9%) reduction in mortality rates and a 7% (6% to 8%) reduction in incidence. Higher vaccination coverage levels were associated with reduced mortality and incidence rates during the eras of alpha and delta variant predominance. CONCLUSIONS: Higher vaccination coverage was associated with lower rates of population level covid-19 mortality and incidence in the US.

We compared case definitions for suspected, probable, and confirmed coronavirus disease (COVID-19), as well as diagnostic testing criteria, used in the 25 countries with the highest reported case counts as of October 1, 2020. Of the identified countries, 56% followed World Health Organization (WHO) recommendations for using a combination of clinical and epidemiologic criteria as part of the suspected case definition. A total of 75% of identified countries followed WHO recommendations on using clinical, epidemiologic, and diagnostic criteria for probable cases; 72% followed WHO recommendations to use PCR testing to confirm COVID-19. Finally, 64% of countries used testing eligibility criteria at least as permissive as WHO. We observed marked heterogeneity in testing eligibility requirements and in how countries define a COVID-19 case. This heterogeneity affects the ability to compare case counts, transmission, and vaccine effectiveness, as well as estimates derived from case surveillance data across countries.

COVID-19 vaccine breakthrough infection surveillance helps monitor trends in disease incidence and severe outcomes in fully vaccinated persons, including the impact of the highly transmissible B.1.617.2 (Delta) variant of SARS-CoV-2, the virus that causes COVID-19. Reported COVID-19 cases, hospitalizations, and deaths occurring among persons aged ≥18 years during April 4-July 17, 2021, were analyzed by vaccination status across 13 U.S. jurisdictions that routinely linked case surveillance and immunization registry data. Averaged weekly, age-standardized incidence rate ratios (IRRs) for cases among persons who were not fully vaccinated compared with those among fully vaccinated persons decreased from 11.1 (95% confidence interval [CI] = 7.8-15.8) to 4.6 (95% CI = 2.5-8.5) between two periods when prevalence of the Delta variant was lower (<50% of sequenced isolates; April 4-June 19) and higher (≥50%; June 20-July 17), and IRRs for hospitalizations and deaths decreased between the same two periods, from 13.3 (95% CI = 11.3-15.6) to 10.4 (95% CI = 8.1-13.3) and from 16.6 (95% CI = 13.5-20.4) to 11.3 (95% CI = 9.1-13.9). Findings were consistent with a potential decline in vaccine protection against confirmed SARS-CoV-2 infection and continued strong protection against COVID-19-associated hospitalization and death. Getting vaccinated protects against severe illness from COVID-19, including the Delta variant, and monitoring COVID-19 incidence by vaccination status might provide early signals of changes in vaccine-related protection that can be confirmed through well-controlled vaccine effectiveness (VE) studies.

Although COVID-19 generally results in milder disease in children and adolescents than in adults, severe illness from COVID-19 can occur in children and adolescents and might require hospitalization and intensive care unit (ICU) support (1-3). It is not known whether the B.1.617.2 (Delta) variant,* which has been the predominant variant of SARS-CoV-2 (the virus that causes COVID-19) in the United States since late June 2021,(†) causes different clinical outcomes in children and adolescents compared with variants that circulated earlier. To assess trends among children and adolescents, CDC analyzed new COVID-19 cases, emergency department (ED) visits with a COVID-19 diagnosis code, and hospital admissions of patients with confirmed COVID-19 among persons aged 0-17 years during August 1, 2020-August 27, 2021. Since July 2021, after Delta had become the predominant circulating variant, the rate of new COVID-19 cases and COVID-19-related ED visits increased for persons aged 0-4, 5-11, and 12-17 years, and hospital admissions of patients with confirmed COVID-19 increased for persons aged 0-17 years. Among persons aged 0-17 years during the most recent 2-week period (August 14-27, 2021), COVID-19-related ED visits and hospital admissions in the states with the lowest vaccination coverage were 3.4 and 3.7 times that in the states with the highest vaccination coverage, respectively. At selected hospitals, the proportion of COVID-19 patients aged 0-17 years who were admitted to an ICU ranged from 10% to 25% during August 2020-June 2021 and was 20% and 18% during July and August 2021, respectively. Broad, community-wide vaccination of all eligible persons is a critical component of mitigation strategies to protect pediatric populations from SARS-CoV-2 infection and severe COVID-19 illness.

BACKGROUND: Civil registration and vital statistics (CRVS) systems play a key role in upholding human rights and generating data for health and good governance. They also can help monitor progress in achieving the United Nations Sustainable Development Goals. Although many countries have made substantial progress in strengthening their CRVS systems, most low- and middle-income countries still have underdeveloped systems. The objective of this systematic review is to identify national policies that can help countries strengthen their systems. METHODS AND FINDINGS: The ABI/INFORM, Embase, JSTOR, PubMed, and WHO Index Medicus databases were systematically searched for policies to improve birth and/or death registration on 24 January 2017. Global stakeholders were also contacted for relevant grey literature. For the purposes of this review, policies were categorised as supply, demand, incentive, penalty, or combination (i.e., at least two of the preceding policy approaches). Quantitative results on changes in vital event registration rates were presented for individual comparative articles. Qualitative systematic review methodology, including meta-ethnography, was used for qualitative syntheses on operational considerations encompassing acceptability to recipients and staff, human resource requirements, information technology or infrastructure requirements, costs to the health system, unintended effects, facilitators, and barriers. This study is registered with PROSPERO, number CRD42018085768. Thirty-five articles documenting experience in implementing policies to improve birth and/or death registration were identified. Although 25 countries representing all global regions (Africa, the Americas, Southeast Asia, the Western Pacific, Europe, and the Eastern Mediterranean) were reflected, there were limited countries from the Eastern Mediterranean and Europe regions. Twenty-four articles reported policy effects on birth and/or death registration. Twenty-one of the 24 articles found that the change in registration rate after the policy was positive, with two supply and one penalty articles being the exceptions. The qualitative syntheses identified 15 operational considerations across all policy categories. Human and financial resource requirements were not quantified. The primary limitation of this systematic review was the threat of publication bias wherein many countries may not have documented their experience; this threat is most concerning for policies that had neutral or negative effects. CONCLUSIONS: Our systematic review suggests that combination policy approaches, consisting of at least a supply and demand component, were consistently associated with improved registration rates in different geographical contexts. Operational considerations should be interpreted based on health system, governance, and sociocultural context. More evaluations and research are needed from the Eastern Mediterranean and Europe regions. Further research and evaluation are also needed to estimate the human and financial resource requirements required for different policies.

OBJECTIVES: Achieving the Sustainable Development Goals will require data-driven public health action. There are limited publications on national health information systems that continuously generate health data. Given the need to develop these systems, we summarised their current status in low-income and middle-income countries. SETTING: The survey team jointly developed a questionnaire covering policy, planning, legislation and organisation of case reporting, patient monitoring and civil registration and vital statistics (CRVS) systems. From January until May 2017, we administered the questionnaire to key informants in 51 Centers for Disease Control country offices. Countries were aggregated for descriptive analyses in Microsoft Excel. RESULTS: Key informants in 15 countries responded to the questionnaire. Several key informants did not answer all questions, leading to different denominators across questions. The Ministry of Health coordinated case reporting, patient monitoring and CRVS systems in 93% (14/15), 93% (13/14) and 53% (8/15) of responding countries, respectively. Domestic financing supported case reporting, patient monitoring and CRVS systems in 86% (12/14), 75% (9/12) and 92% (11/12) of responding countries, respectively. The most common uses for system-generated data were to guide programme response in 100% (15/15) of countries for case reporting, to calculate service coverage in 92% (12/13) of countries for patient monitoring and to estimate the national burden of disease in 83% (10/12) of countries for CRVS. Systems with an electronic component were being used for case reporting, patient monitoring, birth registration and death registration in 87% (13/15), 92% (11/12), 77% (10/13) and 64% (7/11) of responding countries, respectively. CONCLUSIONS: Most responding countries have a solid foundation for policy, planning, legislation and organisation of health information systems. Further evaluation is needed to assess the quality of data generated from systems. Periodic evaluations may be useful in monitoring progress in strengthening and harmonising these systems over time.

Wallis et al recently reviewed key determinants of human immunodeficiency virus (HIV) drug resistance in low- and middle-income countries (LMICs) [1]. In addition to the determinants that were reviewed, we believe the quality of antiretrovirals (ARVs) available in antiretroviral therapy regimens also merits attention. | | The World Health Organization (WHO) recently released a report on the burden of substandard and falsified antimicrobials. Based on their global analysis, 11% of antimicrobials contained subtherapeutic concentrations of active pharmaceutical ingredients [2]. The proportion for ARVs was 4.2% [2]. People with HIV exposed to subtherapeutic ARVs are at increased risk of developing HIV drug resistance [3, 4]. Continued vigilance to ensure use of quality ARVs is critical for three reasons. First, in many countries procurement is transitioning to domestic mechanisms that may not have the same stringent requirements for quality as the President’s Emergency Plan for AIDS Relief (PEPFAR) and Global Fund (GF). Second, there may not be enough supply from qualified manufacturers to supply all countries with newly recommended ARVs, such as dolutegravir-containing regimens, increasing the risk of a possible influx of nonquality-assured ARVs in some countries. Finally, in countries moving toward national and privatized health insurance schemes as part of universal health coverage, different pharmacies may procure ARVs through different manufacturers (some of which may not adhere to stringent quality standards).

New WHO guidelines recommend monitoring individual-level HIV data using case reporting, patient monitoring and vital statistics systems. | Electronic software, deduplication and case verification may help improve the quality of case reporting data. | Incorporating HIV treatment into social health insurance as part of universal health coverage changed data routinely generated in patient monitoring systems. | Strengthening collection of vital statistics at the lowest level of the health system can help improve the sensitivity of the vital statistics system; although systematic and robust ascertainment of cause-of-death is needed. | Leveraging national unique identification may help improve linkages between information systems in the future.

In a Perspective on the research article from Jacobson and colleagues, Amitabh Suthar and colleagues from the Centers for Disease Control and Prevention discuss the importance of and considerations for developing real-time and large-scale reporting systems for tracking and controlling antimicrobial resistance.

In a Perspective, Amitabh Suthar and Till Barnighausen discuss progress made so far in reducing HIV-related mortality in South Africa and keys towards further population mortality reductions going forward.

INTRODUCTION: Co-trimoxazole prophylaxis is used to reduce morbidity and mortality in people with HIV. We systematically reviewed three topics related to co-trimoxazole prophylaxis to update WHO guidelines: initiation, discontinuation, and dose. METHODS: We searched PubMed, Embase, WHO Global Index Medicus, and clinical trial registries in November, 2013, for randomised controlled trials and observational studies including co-trimoxazole prophylaxis and a comparator group. Studies were eligible if they reported death, WHO clinical stage 3 or 4 events, admittance to hospital, severe bacterial infections, tuberculosis, pneumonia, diarrhoea, malaria, or treatment-limiting adverse events. Infant mortality, low birthweight, and placental malaria were additional outcomes for the comparison of co-trimoxazole prophylaxis and intermittent preventive treatment for malaria in pregnant women (IPTp). We compared a dose of 480 mg co-trimoxazole once a day with one of 960 mg co-trimoxazole once a day. We used a 10% margin for non-inferiority and equivalence analyses. We used random-effects models for all meta-analyses. This study is registered with PROSPERO, number CRD42014007163. FINDINGS: 19 articles, published from 1995 to 2014 and including 35 328 participants, met the inclusion criteria. Co-trimoxazole prophylaxis reduced rates of death (hazard ratio [HR] 0.40, 95% CI 0.26-0.64) when started at CD4 counts of 350 cells per muL or lower with antiretroviral therapy (ART) worldwide. Co-trimoxazole prophylaxis started at higher than 350 cells per muL without ART reduced rates of death (0.50, 0.30-0.83) and malaria (0.25, 0.10-0.57) in Africa. Co-trimoxazole prophylaxis was non-inferior to IPTp with respect to infant mortality (risk difference [RD] -0.05, 95% CI -0.12 to 0.02), low birthweight (0.00, -0.07 to 0.07), and placental malaria (0.00, -0.10 to 0.10). Co-trimoxazole prophylaxis continuation after ART-induced recovery with CD4 counts higher than 350 cells per muL reduced admittances to hospital (HR 0.42, 95% CI 0.22-0.80), pneumonia (0.73, 0.61-0.88), malaria (0.03, 0.01-0.10), and diarrhoea (0.61, 0.48-0.78) in Africa. A dose of 480 mg co-trimoxazole prophylaxis once a day did not reduce treatment-limiting adverse events compared with 960 mg once a day (RD -0.07, 95% CI -0.52 to 0.39). INTERPRETATION: Co-trimoxazole prophylaxis should be given with ART in people with CD4 counts of 350 cells per muL or lower in low-income and middle-income countries. Co-trimoxazole prophylaxis should be provided irrespective of CD4 count in settings with a high burden of infectious diseases. Pregnant women with HIV in Africa should use co-trimoxazole rather than IPTp to prevent malaria complications in infants. Further research is needed to inform dose optimisation and co-trimoxazole use in the context of expanded ART in different epidemiological settings. FUNDING: None.

Vietnam has a concentrated HIV epidemic, with the highest HIV prevalence being observed among people who inject drugs (PWID). Based on its experience scaling-up robust HIV interventions, Vietnam aims to further strengthen its response by harnessing the preventive benefits of antiretroviral therapy (ART). Mathematical modelling suggests that prioritizing key populations for earlier access to ART, combined with other prevention interventions, may have significant impact on the epidemic, cost-effectively reducing new HIV infections and deaths. Pilot studies are being conducted to assess feasibility and acceptability of expansion of HIV testing and counselling (HTC) and early ART among key populations and to demonstrate innovative service delivery models to address challenges in uptake of services across the care cascade. Earlier access of key populations to combination prevention interventions, combined with sustained political commitment and supportive environment for key populations, are essential for maximum impact of ART on the HIV epidemic in Vietnam.

OBJECTIVE: To evaluate the cost-effectiveness of the Three I's for HIV/TB (human immunodeficiency virus/tuberculosis): antiretroviral therapy (ART), intensified TB case finding (ICF), isoniazid preventive treatment (IPT), and TB infection control (IC). METHODS: Using a 3-year decision-analytic model, we estimated the cost-effectiveness of a base scenario (55% ART coverage at CD4 count 350 cells/mm(3)) and 19 strategies that included one or more of the following: 1) 90% ART coverage, 2) IC and 3) ICF using four-symptom screening and 6- or 36-month IPT. The TB diagnostic algorithm included 1) sputum smear microscopy with chest X-ray, and 2) Xpert((R)) MTB/RIF. RESULTS: In resource-constrained settings with a high burden of HIV and TB, the most cost-effective strategies under both diagnostic algorithms included 1) 55% ART coverage and IC, 2) 55% ART coverage, IC and 36-month IPT, and 3) expanded ART at 90% coverage with IC and 36-month IPT. The latter averted more TB cases than other scenarios with increased ART coverage, IC, 6-month IPT and/or IPT for tuberculin skin test positive individuals. The cost-effectiveness results did not change significantly under the sensitivity analyses. CONCLUSION: Expanded ART to 90% coverage, IC and a 36-month IPT strategy averted most TB cases and is among the cost-effective strategies.

BACKGROUND: Effective national and global HIV responses require a significant expansion of HIV testing and counselling (HTC) to expand access to prevention and care. Facility-based HTC, while essential, is unlikely to meet national and global targets on its own. This article systematically reviews the evidence for community-based HTC. METHODS AND FINDINGS: PubMed was searched on 4 March 2013, clinical trial registries were searched on 3 September 2012, and Embase and the World Health Organization Global Index Medicus were searched on 10 April 2012 for studies including community-based HTC (i.e., HTC outside of health facilities). Randomised controlled trials, and observational studies were eligible if they included a community-based testing approach and reported one or more of the following outcomes: uptake, proportion receiving their first HIV test, CD4 value at diagnosis, linkage to care, HIV positivity rate, HTC coverage, HIV incidence, or cost per person tested (outcomes are defined fully in the text). The following community-based HTC approaches were reviewed: (1) door-to-door testing (systematically offering HTC to homes in a catchment area), (2) mobile testing for the general population (offering HTC via a mobile HTC service), (3) index testing (offering HTC to household members of people with HIV and persons who may have been exposed to HIV), (4) mobile testing for men who have sex with men, (5) mobile testing for people who inject drugs, (6) mobile testing for female sex workers, (7) mobile testing for adolescents, (8) self-testing, (9) workplace HTC, (10) church-based HTC, and (11) school-based HTC. The Newcastle-Ottawa Quality Assessment Scale and the Cochrane Collaboration's "risk of bias" tool were used to assess the risk of bias in studies with a comparator arm included in pooled estimates. 117 studies, including 864,651 participants completing HTC, met the inclusion criteria. The percentage of people offered community-based HTC who accepted HTC was as follows: index testing, 88% of 12,052 participants; self-testing, 87% of 1,839 participants; mobile testing, 87% of 79,475 participants; door-to-door testing, 80% of 555,267 participants; workplace testing, 67% of 62,406 participants; and school-based testing, 62% of 2,593 participants. Mobile HTC uptake among key populations (men who have sex with men, people who inject drugs, female sex workers, and adolescents) ranged from 9% to 100% (among 41,110 participants across studies), with heterogeneity related to how testing was offered. Community-based approaches increased HTC uptake (relative risk [RR] 10.65, 95% confidence interval [CI] 6.27-18.08), the proportion of first-time testers (RR 1.23, 95% CI 1.06-1.42), and the proportion of participants with CD4 counts above 350 cells/µl (RR 1.42, 95% CI 1.16-1.74), and obtained a lower positivity rate (RR 0.59, 95% CI 0.37-0.96), relative to facility-based approaches. 80% (95% CI 75%-85%) of 5,832 community-based HTC participants obtained a CD4 measurement following HIV diagnosis, and 73% (95% CI 61%-85%) of 527 community-based HTC participants initiated antiretroviral therapy following a CD4 measurement indicating eligibility. The data on linking participants without HIV to prevention services were limited. In low- and middle-income countries, the cost per person tested ranged from US$2-US$126. At the population level, community-based HTC increased HTC coverage (RR 7.07, 95% CI 3.52-14.22) and reduced HIV incidence (RR 0.86, 95% CI 0.73-1.02), although the incidence reduction lacked statistical significance. No studies reported any harm arising as a result of having been tested. CONCLUSIONS: Community-based HTC achieved high rates of HTC uptake, reached people with high CD4 counts, and linked people to care. It also obtained a lower HIV positivity rate relative to facility-based approaches. Further research is needed to further improve acceptability of community-based HTC for key populations. HIV programmes should offer community-based HTC linked to prevention and care, in addition to facility-based HTC, to support increased access to HIV prevention, care, and treatment. REVIEW REGISTRATION: International Prospective Register of Systematic Reviews CRD42012002554 Please see later in the article for the Editors' Summary.

OBJECTIVE: This article reviews the antiretroviral therapy (ART) initiation criteria from national treatment guidelines for 70 countries and determines the extent of consistency with the current World Health Organization (WHO) recommendations. METHODS: Published ART guidelines were collected from the Internet, databases, and WHO staff. ART eligibility criteria for asymptomatic people, pregnant women, people with HIV-associated tuberculosis, serodiscordant couples, injecting drug users, men who have sex with men, and sex workers were abstracted from them. Multiple regression analysis was used to determine the relation between ART eligibility criteria, ART coverage, and various population characteristics and policy interventions. RESULTS: Of the 70 countries, 42 (60%) follow WHO's ART guidelines for asymptomatic people and 31 (44%) for pregnant women, recommending ART at CD4 count of #350 cells/mm(3). Twenty-three (33%) countries recommend ART for people with HIV-associated tuberculosis irrespective of CD4 count. Nineteen countries are also recommending or considering earlier ART above CD4 count ≤ 350 cell/mm(3) for asymptomatic people, pregnant women, and/or serodiscordant couples. Multiple linear regression analysis shows that HIV prevalence, year of publication of guidelines, and HIV expenditure are significantly associated with published ART eligibility criteria. On average, the ART coverage is similar irrespective of published guidelines being consistent with the WHO recommendation (P < 0.53). CONCLUSIONS: Published guidelines from a significant number of countries are not following WHO recommendations. Although published guidelines may not reflect practice, it is important to adapt recommendations and services quickly to reflect the emerging science on the health and prevention benefits of earlier access to ART. (Copyright 2012 by Lippincott Williams and Wilkins.)

OBJECTIVE: To determine whether cotrimoxazole reduces mortality in adults receiving antiretroviral therapy (ART) for human immunodeficiency virus (HIV) infection in low-and middle-income countries through a systematic review and meta-analysis. METHODS: PubMed and Embase were searched for randomized controlled trials and prospective and retrospective cohort studies that compared mortality or morbidity in HIV-infected individuals aged ≥13 years on cotrimoxazole and ART and on ART alone. The Newcastle-Ottawa Quality Assessment Scale was used to assess selection, confounding and measurement bias. Publication bias was assessed using Egger's and Begg's tests. Sensitivity analysis was performed because the I-squared statistic indicated substantial heterogeneity in study results. A random-effects model was used for meta-analysis. FINDINGS: Nine studies were included. Begg and Egger P-values for the seven that reported the effect of cotrimoxazole on mortality were 0.29 and 0.49, respectively, suggesting no publication bias. The I-squared statistic was 93.2%, indicating high heterogeneity in study results. The sensitivity analysis showed that neither the follow-up duration nor the percentage of individuals with World Health Organization stage 3 or 4 HIV disease at baseline explained the heterogeneity. The summary estimate of the effect of cotrimoxazole on the incidence rate of death was 0.42 (95% confidence interval: 0.29-0.61). Since most studies followed participants for less than 1 year, it was not possible to determine whether cotrimoxazole can be stopped safely after ART-induced immune reconstitution. CONCLUSION: Cotrimoxazole significantly increased survival in HIV-infected adults on ART. Further research is needed to determine the optimum duration of cotrimoxazole treatment in these patients.