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Background: Roche announced that the conventional COBAS AmpliPrep/COBAS TaqMan (CAP/CTM) system will be phased out by early 2024 and replaced with new high-throughput systems, such as the Roche cobas 4800 [...]

Background: With increasingly intensive treatments and population ageing, more people face complex treatment and care decisions. We explored patterns of the decision-making processes during critical care, and sources of conflict and resolution. Methods: Ethnographic study in two Intensive Care Units (ICUs) in an inner city hospital comprising: non-participant observation of general care and decisions, followed by case studies where treatment limitation decisions, comfort care and/or end of life discussions were occurring. These involved: semi-structured interviews with consenting families, where possible, patients; direct observations of care; and review of medical records. Results: Initial non-participant observation included daytime, evenings, nights and weekends. The cases were 16 patients with varied diagnoses, aged 19-87 years; 19 family members were interviewed, aged 30-73 years. Cases were observed for <1 to 156 days (median 22), depending on length of ICU admission. Decisions were made serially over the whole trajectory, usually several days or weeks. We identified four trajectories with distinct patterns: curative care from admission; oscillating curative and comfort care; shift to comfort care; comfort care from admission. Some families considered decision-making a negative concept and preferred uncertainty. Conflict occurred most commonly in the trajectories with oscillating curative and comfort care. Conflict also occurred inside clinical teams. Families were most often involved in decision-making regarding care outcomes and seemed to find it easier when patients switched definitively from curative to comfort care. We found eight categories of decision-making; three related to the care outcomes (aim, place, response to needs) and five to the care processes (resuscitation, decision support, medications/ fluids, monitoring/interventions, other specialty involvement). Conclusions: Decision-making in critical illness involves a web of discussions regarding the potential outcomes and processes of care, across the whole disease trajectory. When measures oscillate between curative and comfort there is greatest conflict. This suggests a need to support early communication, especially around values and preferred care outcomes, from which other decisions follow, including DNAR. Offering further support, possibly with expert palliative care, communication, and discussion of ‘trial of treatment' may be beneficial at this time, rather than waiting until the ‘end of life’. [ABSTRACT FROM AUTHOR]

BACKGROUND: Recent publications suggest that increased mortality is associated with high hematocrit targets in erythropoietin-stimulating agent-treated patients with chronic kidney disease. We aim to further inform the debate about optimal hematocrit targets, advancing the hypothesis that the current hematocrit target may not optimize the survival of patients with end-stage renal disease. STUDY DESIGN: Cross-sectional observational study. SETTING & PARTICIPANTS: Medicare dialysis patients from 2002 to 2004 (n = 393,967). FACTORS: Quarterly average hematocrit and erythropoietin alfa (EPO) dose. OUTCOMES: Mortality hazard ratios from time-dependent Cox proportional hazard models, adjusting for comorbidities. RESULTS: N = 2,712,197 patient-facility quarters. During the study, 100,086 deaths were identified. Percentages of patient quarters within each hematocrit category: hematocrit less than 27% (2.0%), 27% to 28.49% (1.7%), 28.5% to 29.9% (2.9%), 30% to 31.49% (5.2%), 31.5% to 32.99% (9.0%), 33% to 34.49% (14.9%), 34.5% to 35.99% (19.2%), 36% to 37.49% (18.0%), 37.5% to 38.99% (12.0%), 39% to 40.49% (6.4%), 40.5% to 41.99% (3.0%), and 42% or greater (3.1%). Mortality hazard ratios from the fully adjusted model: hematocrit less than 27% (3.11), 27% to 28.49% (2.60), 28.5% to 29.9% (2.14), 30% to 31.49% (1.80), 31.5% to 32.99% (1.44), 33% to 34.49% (1.17), 34.5% to 35.99% (reference), 36% to 37.49% (0.98), 37.5% to 38.99% (1.01), 39% to 40.49% (1.13), 40.5% to 41.99% (1.32), and 42% or greater (1.57). LIMITATIONS: First, potential confounding by indication related to associations between underlying illness and mortality, anemia, and EPO responsiveness. Second, Medicare claims data reflect a range of conditions and degrees of severity not easily translated into the clinical context. Third, for Medicare claims, EPO reporting is not required if EPO is not billed. Greater than 95% of 'missing hematocrit' quarters are 'EPO = 0' patient quarters. Interpretation of results for the missing hematocrit and EPO = 0 use categories is complicated by data source limitations. CONCLUSIONS: We show an association between mortality and low hematocrit in dialysis patients, in part reflecting the presence of comorbidities. We also show an association between increased mortality and high hematocrit. Additional interventional trials should be undertaken to better define the optimal target for anemia management in patients with end-stage renal disease, with careful prospective identification of underlying comorbidities and clinical factors contributing to high erythropoietin-stimulating agent requirement. Copyright © 2009 American Society for Nutrition [ABSTRACT FROM AUTHOR]

During April 2009-June 2010, thirty-seven (0.5%) of 6,740 pandemic (H1N1) 2009 viruses submitted to a US surveillance system were oseltamivir resistant. Most patients with oseltamivir-resistant infections were severely immunocompromised (76%) and had received oseltamivir before specimen collection (89%). No evidence was found for community circulation of resistant viruses; only 4 (unlinked) patients had no oseltamivir exposure. [ABSTRACT FROM AUTHOR]

Background: WHO advocates the use of directly observed treatment with a short-course drug regimen as part of the DOTS strategy, but the potential effect of this strategy worldwide has not been investigated.Methods: We developed an age-structured mathematical model to explore the characteristics of tuberculosis control under DOTS, and to forecast the effect of improved case finding and cure on tuberculosis epidemics for each of the six WHO regions.Findings: In countries where the incidence of tuberculosis is stable and HIV-1 absent, a control programme that reaches the WHO targets of 70% case detection and 85% cure would reduce the incidence rate by 11% (range 8-12) per year and the death rate by 12% (9-13) per year. If tuberculosis has been in decline for some years, the same case detection and cure rates would have a smaller effect on incidence. DOTS saves a greater proportion of deaths than cases, and this difference is bigger in the presence of HIV-1. HIV-1 epidemics cause an increase in tuberculosis incidence, but do not substantially reduce the preventable proportion of cases and deaths. Without greater effort to control tuberculosis, the annual incidence of the disease is expected to increase by 41% (21-61) between 1998 and 2020 (from 7.4 million to 10.6 million cases per year). Achievement of WHO targets by 2010 would prevent 23% (15-30) or 48 million cases by 2020.Interpretation: The potential effect of chemotherapy (delivered as DOTS) on tuberculosis is greater in many developing countries now than it was in developed countries 50 years ago. To exploit this potential, case detection and cure rates urgently need to be improved in the main endemic areas. [ABSTRACT FROM AUTHOR]

As antiretroviral treatment (ART) coverage for people living with HIV (PLHIV) increases, HIV programmes require up-to-date information about evolving HIV risk behaviour and transmission risk, including those with low-level viremia (LLV; >50 to ≤1000 copies/mL), to guide prevention priorities. We aimed to assess differences in sexual risk behaviours, distribution of viral load (VL) and proportion of transmission across PLHIV subgroups. We analysed data from Population-based HIV Impact Assessment surveys in 14 sub-Saharan African countries during 2015-2019. We estimated adjusted prevalence ratios (aPR) of self-reported HIV high-risk behaviour (multiple partners and condomless sex) across cascade stages via generalised estimation equations. We modelled the proportions of transmission from each subgroup using relative self-reported sexual risk, a Hill function for transmission rate by VL, and proportions within cascade stages from surveys and UNAIDS country estimates for 2010-2020. Compared to PLHIV with undetectable VL (≤50 copies/mL), undiagnosed PLHIV (aPR women: 1.28 [95% CI: 1.08-1.52]; men: 1.61 [1.33-1.95]) and men diagnosed but untreated (2.06 [1.52-2.78]) were more likely to self-report high-risk sex. High-risk behaviour was not significantly associated with LLV. Mean VL was similar among undiagnosed, diagnosed but untreated, and on ART but non-suppressed sub-groups. Across surveys, undiagnosed and diagnosed but untreated contributed most to transmission (40-91% and 1-41%, respectively), with less than 1% from those with LLV. Between 2010 and 2020, the proportion of transmission from individuals on ART but non-suppressed increased. In settings with high ART coverage, effective HIV testing, ART linkage, and retention remain priorities to reduce HIV transmission. Persons with LLV are an increasing share of PLHIV but their contribution to HIV transmission was small. Improving suppression among PLHIV on ART with VL ≥1000 copies/mL will become increasingly important., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Jeffrey W. Imai-Eaton has received grants/contracts from NIH and WHO, consulting fees from BAO Systems, support for attending meetings from UNAIDS, SACEMA and the International AIDS Society and is a member of the editorial board for PLOS Global Public Health. Olanrewaju Edun has received consulting fees from University of Cape Town and WHO and support for attending meetings from UNAIDS. All other authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Background: We examined the epidemiology and transmission potential of HIV population viral load (VL) in 12 sub-Saharan African countries., Methods: We analyzed data from Population-based HIV Impact Assessments (PHIAs), large national household-based surveys conducted between 2015 and 2019 in Cameroon, Cote d'Ivoire, Eswatini, Kenya, Lesotho, Malawi, Namibia, Rwanda, Tanzania, Uganda, Zambia, and Zimbabwe. Blood-based biomarkers included HIV serology, recency of HIV infection, and VL. We estimated the number of people living with HIV (PLHIV) with suppressed viral load (<1,000 HIV-1 RNA copies/mL) and with unsuppressed viral load (viremic), the prevalence of unsuppressed HIV (population viremia), sex-specific HIV transmission ratios (number female incident HIV-1 infections/number unsuppressed male PLHIV per 100 persons-years [PY] and vice versa) and examined correlations between a variety of VL metrics and incident HIV. Country sample sizes ranged from 10,016 (Eswatini) to 30,637 (Rwanda); estimates were weighted and restricted to participants 15 years and older., Results: The proportion of female PLHIV with viral suppression was higher than that among males in all countries, however, the number of unsuppressed females outnumbered that of unsuppressed males in all countries due to higher overall female HIV prevalence, with ratios ranging from 1.08 to 2.10 (median: 1.43). The spatial distribution of HIV seroprevalence, viremia prevalence, and number of unsuppressed adults often differed substantially within the same countries. The 1% and 5% of PLHIV with the highest VL on average accounted for 34% and 66%, respectively, of countries' total VL. HIV transmission ratios varied widely across countries and were higher for male-to-female (range: 2.3-28.3/100 PY) than for female-to-male transmission (range: 1.5-10.6/100 PY). In all countries mean log10 VL among unsuppressed males was higher than that among females. Correlations between VL measures and incident HIV varied, were weaker for VL metrics among females compared to males and were strongest for the number of unsuppressed PLHIV per 100 HIV-negative adults (R2 = 0.92)., Conclusions: Despite higher proportions of viral suppression, female unsuppressed PLHIV outnumbered males in all countries examined. Unsuppressed male PLHIV have consistently higher VL and a higher risk of transmitting HIV than females. Just 5% of PLHIV account for almost two-thirds of countries' total VL. Population-level VL metrics help monitor the epidemic and highlight key programmatic gaps in these African countries., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

The US President's Emergency Plan for AIDS Relief (PEPFAR) supports molecular HIV and tuberculosis diagnostic networks and information management systems in low- and middle-income countries. We describe how national programs leveraged these PEPFAR-supported laboratory resources for SARS-CoV-2 testing during the COVID-19 pandemic. We sent a spreadsheet template consisting of 46 indicators for assessing the use of PEPFAR-supported diagnostic networks for COVID-19 pandemic response activities during April 1, 2020, to March 31, 2021, to 27 PEPFAR-supported countries or regions. A total of 109 PEPFAR-supported centralized HIV viral load and early infant diagnosis laboratories and 138 decentralized HIV and TB sites reported performing SARS-CoV-2 testing in 16 countries. Together, these sites contributed to >3.4 million SARS-CoV-2 tests during the 1-year period. Our findings illustrate that PEPFAR-supported diagnostic networks provided a wide range of resources to respond to emergency COVID-19 diagnostic testing in 16 low- and middle-income countries.

Introduction: Achieving optimal HIV outcomes, as measured by global 90-90-90 targets, that is awareness of HIV-positive status, receipt of antiretroviral (ARV) therapy among aware and viral load (VL) suppression among those on ARVs, respectively, is critical. However, few data from sub-Saharan Africa (SSA) are available on older people (50+) living with HIV (OPLWH). We examined 90-90-90 progress by age, 15-49 (as a comparison) and 50+ years, with further analyses among 50+ (55-59, 60-64, 65+ vs. 50-54), in 13 countries (Cameroon, Cote d'Ivoire, Eswatini, Ethiopia, Kenya, Lesotho, Malawi, Namibia, Rwanda, Tanzania, Uganda, Zambia and Zimbabwe)., Methods: Using data from nationally representative Population-based HIV Impact Assessments, conducted between 2015and 2019, participants from randomly selected households provided demographic and clinical information and whole blood specimens for HIV serology, VL and ARV testing. Survey weighted outcomes were estimated for 90-90-90 targets. Country-specific Poisson regression models examined 90-90-90 variation among OPLWH age strata., Results: Analyses included 24,826 HIV-positive individuals (15-49 years: 20,170; 50+ years: 4656). The first, second and third 90 outcomes were achieved in 1, 10 and 5 countries, respectively, by those aged 15-49, while OPLWH achieved outcomes in 3, 13 and 12 countries, respectively. Among those aged 15-49, women were more likely to achieve 90-90-90 targets than men; however, among OPLWH, men were more likely to achieve first and third 90 targets than women, with second 90 achievement being equivalent. Country-specific 90-90-90 regression models among OPLWH demonstrated minimal variation by age stratum across 13 countries. Among OLPWH, no first 90 target differences were noted by age strata; three countries varied in the second 90 by older age strata but not in a consistent direction; one country showed higher achievement of the third 90 in an older age stratum., Conclusions: While OPLWH in these 13 countries were slightly more likely than younger people to be aware of their HIV-positive status (first 90), this target was not achieved in most countries. However, OPLWH achieved treatment (second 90) and VL suppression (third 90) targets in more countries than PLWH <50. Findings support expanded HIV testing, prevention and treatment services to meet ongoing OPLWH health needs in SSA., (© 2022 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)

Background: Little is known about HIV in South Sudan and even less about HIV among female sex workers (FSW). We characterized progress towards UNAIDS 90-90-90 targets among female sex workers (FSW) and sexually exploited female adolescents in Juba and Nimule, South Sudan., Methods: We conducted a biobehavioral survey of FSW and sexually exploited female adolescents using respondent-driven sampling (RDS) in Juba (November 2015-March 2016) and in Nimule (January-March 2017) to estimate achievements toward the UNAIDS 90-90-90 targets (90% of HIV-positive individuals know their status; of these, 90% are receiving antiretroviral therapy [ART]; and of these, 90% are virally suppressed). Eligibility criteria were girls and women who were aged ≥15 years; spoke English, Juba Arabic, or Kiswahili; received money, goods, or services in exchange for sex in the past 6 months; and resided, worked, or socialized in the survey city for ≥1 month. Data were weighted for RDS methods., Results: We sampled 838 FSW and sexually exploited female adolescents in Juba (HIV-positive, 333) and 409 in Nimule (HIV-positive, 108). Among HIV-positive FSW and sexually exploited female adolescents living in Juba, 74.8% self-reported being aware of their HIV status; of these, 73.3% self-reported being on ART; and of these, 62.2% were virally suppressed. In Nimule, 79.5% of FSW and sexually exploited female adolescents living with HIV self-reported being aware of their HIV status; of these, 62.9% self-reported being on ART; and of these, 75.7% were virally suppressed., Conclusions: Although awareness of HIV status is the lowest of the 90-90-90 indicators in many countries, treatment uptake and viral suppression were lowest among FSW and sexually exploited female adolescents in South Sudan. Differentiated service delivery facilitate linkage to and retention on treatment in support of attainment of viral suppression., (© 2022. The Author(s).)

Background: Poor adherence to scheduled dialysis treatments is common and can cause adverse clinical and economic outcomes. In 2015, the Centers for Medicare and Medicaid Innovation launched the Comprehensive ESRD Care (CEC) Model, a novel modification of the Accountable Care Organization framework. Many model participants reported efforts to increase dialysis adherence and promptly reschedule missed treatments., Methods: With Medicare databases covering 2014-2019, we used difference-in-differences models to compare treatment adherence among patients aligned to 1037 CEC facilities relative to those aligned to matched comparison facilities, while accounting for their differences at baseline. Using dates of service, we identified patients who typically received three weekly treatments and the days when treatments typically occurred. Skipped treatments were defined as days when the patient was not hospitalized but did not receive an expected treatment, and rescheduled treatments as days when a patient who had skipped their previous treatment received an additional treatment before their next expected treatment date., Results: Patients in the CEC Model had higher odds of attending as-scheduled sessions relative to the comparison group, although the effect was only marginally significant (OR, 1.02; 95% CI, 1.00 to 1.04, P =0.08). Effects were stronger among females (OR, 1.03; 95% CI, 1.00 to 1.06, P =0.06) than males (OR, 1.01; 95% CI, 0.98 to 1.04, P =0.49), and among those aged <70 years (OR, 1.02; 95% CI, 1.00 to 1.05, P =0.04) than those aged ≥70 years (OR, 1.00; 95% CI, 0.96 to 1.04, P =0.96). The CEC was associated with higher odds of rescheduled sessions (OR, 1.09; 95% CI, 1.05 to 1.14, P <0.001). Effects were significant for both sexes, but were larger among males (OR, 1.11; 95% CI, 1.05 to 1.18, P <0.001) than females (OR, 1.07; 95% CI, 1.02 to 1.13, P =0.01), and effects were significant among those <70 years (OR, 1.12; 95% CI, 1.07 to 1.17, P <0.001), but not those ≥70 years (OR, 0.99; 95% CI, 0.92 to 1.07, P =0.80)., Conclusions: The CEC Model is intended to incentivize strategies to prevent costly interventions. Because poor dialysis adherence may precipitate hospitalizations or other adverse events, many CEC Model participants encouraged adherence and promptly rescheduled missed treatments as strategic priorities. This study suggests these efforts were a success, although the absolute magnitudes of the effects were modest., Competing Interests: A. Ackerman reports having an ownership interest in UnitedHealth Group. B. Negrusa reports having an ownership interest because Lewin employees are entitled to receive UnitedHealth Groups stock. C. Dahlerus reports being a scientific advisor or member through serving as a Guest Editor with the journal Medical Care for a 2019 supplement on patient-reported outcomes scoring methodologies. D. Strubler reports having an ownership interest in GlaxoSmithKline and Sanofi. D. Ullman reports having an ownership interest in UnitedHealth Group. J. Segal reports being a scientific advisor or member of the ESRD Network 11 Medical Review/Executive Committees. J. Wiens reports having an ownership interest in UnitedHealth Group. R. Braun reports having an ownership interest in UnitedHealth Group. R. Hirth reports being a scientific advisor or member on the Board of Directors of the Association of University Programs in Health Administration, Deputy Editor of Medical Care, and the Editorial Board of the American Journal of Managed Care. All remaining authors have nothing to disclose., (Copyright © 2022 by the American Society of Nephrology.)

Objective: We present findings from the nationally representative Zimbabwe Population-based HIV Impact Assessment that characterize Zimbabwe's progress toward the Joint United Nations Programme on HIV/AIDS 90-90-90 targets., Design: We conducted a cross-sectional household survey., Methods: Consenting adults and children in the household were eligible to participate in Zimbabwe Population-based HIV Impact Assessment (October 2015-August 2016). Participants completed face-to-face interviews and provided blood for HIV, CD4, viral load, and syphilis testing. Viral load suppression (VLS) was defined as HIV RNA <1000 copies/mL. HIV-positive specimens were tested for the presence of selected antiretroviral drugs. Data were weighted. Analysis was restricted to HIV-positive adults aged 15-64 years., Results: We enrolled 11,098 men and 14,033 women aged 15-64 years. HIV prevalence was 14.1%. Of those living with HIV, 76.8% (95% confidence interval [CI]: 74.9 to 78.7) were aware of their HIV status or had detectable antiretroviral levels. Of these, 88.4% (95% CI: 87.1 to 89.7) were receiving antiretroviral therapy (ART), and of these people, 85.3% (95% CI: 83.4 to 87.1) had VLS. Male sex age 15-34 years and having 1 or more sexual partners were associated with being unaware of one's HIV-positive status. Age <50 years and not taking cotrimoxazole were associated with being less likely to be being both aware and taking ART. Male sex, age <50 years, and taking cotrimoxazole were associated with being on ART but not having VLS., Conclusions: Zimbabwe has made great strides toward epidemic control. Focusing resources on case finding, particularly among men, people aged <35 years, and sexually active individuals can help Zimbabwe attain 90-90-90 targets., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Importance: There is a need for studies to evaluate the risk factors for COVID-19 and mortality among the entire Medicare long-term dialysis population using Medicare claims data., Objective: To identify risk factors associated with COVID-19 and mortality in Medicare patients undergoing long-term dialysis., Design, Setting, and Participants: This retrospective, claims-based cohort study compared mortality trends of patients receiving long-term dialysis in 2020 with previous years (2013-2019) and fit Cox regression models to identify risk factors for contracting COVID-19 and postdiagnosis mortality. The cohort included the national population of Medicare patients receiving long-term dialysis in 2020, derived from clinical and administrative databases. COVID-19 was identified through Medicare claims sources. Data were analyzed on May 17, 2021., Main Outcomes and Measures: The 2 main outcomes were COVID-19 and all-cause mortality. Associations of claims-based risk factors with COVID-19 and mortality were investigated prediagnosis and postdiagnosis., Results: Among a total of 498 169 Medicare patients undergoing dialysis (median [IQR] age, 66 [56-74] years; 215 935 [43.1%] women and 283 227 [56.9%] men), 60 090 (12.1%) had COVID-19, among whom 15 612 patients (26.0%) died. COVID-19 rates were significantly higher among Black (21 787 of 165 830 patients [13.1%]) and Hispanic (13 530 of 86 871 patients [15.6%]) patients compared with non-Black patients (38 303 of 332 339 [11.5%]), as well as patients with short (ie, 1-89 days; 7738 of 55 184 patients [14.0%]) and extended (ie, ≥90 days; 10 737 of 30 196 patients [35.6%]) nursing home stays in the prior year. Adjusting for all other risk factors, residing in a nursing home 1 to 89 days in the prior year was associated with a higher hazard for COVID-19 (hazard ratio [HR] vs 0 days, 1.60; 95% CI 1.56-1.65) and for postdiagnosis mortality (HR, 1.31; 95% CI, 1.25-1.37), as was residing in a nursing home for an extended stay (COVID-19: HR, 4.48; 95% CI, 4.37-4.59; mortality: HR, 1.12; 95% CI, 1.07-1.16). Black race (HR vs non-Black: HR, 1.25; 95% CI, 1.23-1.28) and Hispanic ethnicity (HR vs non-Hispanic: HR, 1.68; 95% CI, 1.64-1.72) were associated with significantly higher hazards of COVID-19. Although home dialysis was associated with lower COVID-19 rates (HR, 0.77; 95% CI, 0.75-0.80), it was associated with higher mortality (HR, 1.18; 95% CI, 1.11-1.25)., Conclusions and Relevance: These results shed light on COVID-19 risk factors and outcomes among Medicare patients receiving long-term chronic dialysis and could inform policy decisions to mitigate the significant extra burden of COVID-19 and death in this population.

Background: Control of the pediatric HIV epidemic is hampered by gaps in diagnosis and linkage to effective treatment. The 2015-2016 Malawi Population-based HIV impact assessment data were analyzed to identify gaps in pediatric HIV diagnosis, treatment, and viral load suppression., Methods: In half of the surveyed households, children ages ≥18 months to <15 years were tested using the national HIV rapid test algorithm. Children ≤18 months reactive by the initial rapid test underwent HIV total nucleic acid polymerase chain reaction confirmatory testing. Blood from HIV-positive children was tested for viral load (VL) and presence of antiretroviral drugs. HIV diagnosis and antiretroviral treatment (ART) use were defined using guardian-reporting or antiretroviral detection., Results: Of the 6166 children tested, 99 were HIV-positive for a prevalence of 1.5% (95% confidence intervals [CI]: 1.1-1.9) and 8.0% (95% CI: 5.6-10.5) among HIV-exposed children. The prevalence of 1.5% was extrapolated to a national estimate of 119,501 (95% CI: 89,028-149,974) children living with HIV (CLHIV), of whom, 30.7% (95% CI: 20.3-41.1) were previously undiagnosed. Of the 69.3% diagnosed CLHIV, 86.1% (95% CI: 76.8-95.6) were on ART and 57.9% (95% CI: 41.4-74.4) of those on ART had suppressed VL (<1000 HIV RNA copies/mL). Among all CLHIV, irrespective of HIV diagnosis or ART use, 57.7% (95% CI: 45.0-70.5) had unsuppressed VL., Conclusions: Critical gaps in HIV diagnosis in children persist in Malawi. The large proportion of CLHIV with unsuppressed VL reflects gaps in diagnosis and need for more effective first- and second-line ART regimens and adherence interventions., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Children living with human immunodeficiency virus (HIV) (CLHIV) receiving antiretroviral therapy (ART) in resource-limited settings are susceptible to high rates of acquired HIV drug resistance (HIVDR), but few studies include children initiating age-appropriate World Health Organization (WHO)-recommended first-line regimens. We report data from a cohort of ART-naive South African children who initiated first-line ART., Methods: ART-eligible CLHIV aged 0-12 years were enrolled from 2012 to 2014 at 5 public South African facilities and were followed for up to 24 months. Enrolled CLHIV received standard-of-care WHO-recommended first-line ART. At the final study visit, a dried blood spot sample was obtained for viral load and genotypic resistance testing., Results: Among 72 successfully genotyped CLHIV, 49 (68.1%) received ABC/3TC/LPV/r, and 23 (31.9%) received ABC/3TC/EFV. All but 2 children on ABC/3TC/LPV/r were <3 years, and all CLHIV on ABC/3TC/EFV were ≥3 years. Overall, 80.6% (58/72) had at least one drug resistance mutation (DRM). DRMs to nonnucleoside reverse transcriptase inhibitors (NNRTIs) and nucleoside reverse transcriptase inhibitors (NRTIs) were found among 65% and 51% of all CLHIV, respectively, with no statistical difference by ART regimen. More CLHIV on ABC/3TC/EFV, 47.8% (11/23), were found to have 0 or only 1 effective antiretroviral drug remaining in their current regimen compared to 8.2% (4/49) on ABC/3TC/LPV/r., Conclusions: High levels of NNRTI and NRTI DRMs among CLHIV receiving ABC/3TC/LPV/r suggests a lasting impact of failed mother-to-child transmission interventions on DRMs. However, drug susceptibility analysis reveals that CLHIV with detectable viremia on ABC/3TC/LPV/r are more likely to have maintained at least 2 effective agents on their current HIV regimen than those on ABC/3TC/EFV., (Published by Oxford University Press for the Infectious Diseases Society of America 2020.)

Objectives: To clarify real-world linguistic nuances around dying in hospital as well as inaccuracy in individual-level prognostication to support advance care planning and personalised discussions on limitation of life sustaining treatment (LST)., Design: Retrospective cross-sectional study of real-world clinical data., Setting: Secondary care, urban and suburban teaching hospitals., Participants: All inpatients in 12-month period from 1 October 2018 to 30 September 2019., Methods: Using unsupervised natural language processing, word embedding in latent space was used to generate phrase clusters with most similar semantic embeddings to 'Ceiling of Treatment' and their prognostication value., Results: Word embeddings with most similarity to 'Ceiling of Treatment' clustered around phrases describing end-of-life care, ceiling of care and LST discussions. The phrases have differing prognostic profile with the highest 7-day mortality in the phrases most explicitly referring to end of life-'Withdrawal of care' (56.7%), 'terminal care/end of life care' (57.5%) and 'un-survivable' (57.6%)., Conclusion: Vocabulary used at end-of-life discussions are diverse and has a range of associations to 7-day mortality. This highlights the importance of correct application of terminology during LST and end-of-life discussions., Competing Interests: Competing interests: The authors have received research funding support from the Cicely Saunders Institute on Palliative Care, NIHR Applied Research Centre South London and the NIHR Maudsley Biomedical Research Centre., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Background: Conducting HIV surveys in resource-limited settings is challenging because of logistics, limited availability of trained personnel, and complexity of testing. We described the procedures and systems deemed critical to ensure high-quality laboratory data in the population-based HIV impact assessments and large-scale household surveys., Methods: Laboratory professionals were engaged in every stage of the surveys, including protocol development, site assessments, procurement, training, quality assurance, monitoring, analysis, and reporting writing. A tiered network of household, satellite laboratories, and central laboratories, accompanied with trainings, optimized process for blood specimen collection, storage, transport, and real-time monitoring of specimen quality, and test results at each level proved critical in maintaining specimen integrity and high-quality testing. A plausibility review of aggregate merged data was conducted to confirm associations between key variables as a final quality check for quality of laboratory results., Results: Overall, we conducted a hands-on training for 3355 survey staff across 13 surveys, with 160-387 personnel trained per survey on biomarker processes. Extensive training and monitoring demonstrated that overall, 99% of specimens had adequate volume and 99.8% had no hemolysis, indicating high quality. We implemented quality control and proficiency testing for testing, resolved discrepancies, verified >300 Pima CD4 instruments, and monitored user errors. Aggregate data review for plausibility further confirmed the high quality of testing., Conclusions: Ongoing engagement of laboratory personnel to oversee processes at all levels of the surveys is critical for successful national surveys. High-quality population-based HIV impact assessments laboratory data ensured reliable results and demonstrated the impact of HIV programs in 13 countries., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: In the population-based HIV impact assessment surveys, early infant diagnosis (EID) was provided to infants <18 months without a prior diagnosis. For the Namibia population-based HIV impact assessment (NAMPHIA), the GeneXpert platform was assessed for the feasibility of near POC EID testing compared with the standard Roche COBAS AmpliPrep/COBAS TaqMan (CAP/CTM) platform. Quality assurance measures and turnaround time were compared to improve EID results reporting., Methods: NAMPHIA participants were screened for HIV exposure using Determine HIV-1/2 rapid test; samples reactive on Determine received EID testing on the GeneXpert instrument and Xpert HIV-1 Qual assay using whole blood. Results were confirmed at the Namibia Institute of Pathology using dried blood spots on the Roche CAP/CTM platform per national guidelines., Results: Of the 762 screened infants, 61 (8.0%) were Determine-reactive and considered HIV-exposed. Of the 61 exposed infants, 2 were found to be HIV-infected whereas 59 were negative on both GeneXpert and Roche platforms, achieving 100% concordance. Average turnaround time was 3.4 days for the Xpert HIV-1 Qual assay, and average time from collection to testing was 1.0 days for GeneXpert compared with 10.7 days for Roche. No samples failed using GeneXpert whereas 1 sample failed using Roche and was repeated., Conclusion: Quality POC EID testing is feasible in a national survey through extensive training and external quality assurance measures. The use of decentralized POC EID for national testing would provide rapid diagnosis and improve TATs which may prevent loss to follow-up, ensure linkage to care, and improve clinical outcomes for infants., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Specialist palliative care services play an important role in conducting advance care planning during COVID-19. Little is known about the challenges to advance care planning in this context, or the changes services made to adapt., Aim: Describe the challenges that UK specialist palliative care services experienced regarding advance care planning during COVID-19 and changes made to support timely conversations., Design: Online survey of UK palliative/hospice services' response to COVID-19. Closed-ended responses are reported descriptively. Open-ended responses were analysed using a thematic Framework approach using the Social Ecological Model to understand challenges., Respondents: Two hundred and seventy-seven services., Results: More direct advance care planning was provided by 38% of services, and 59% provided more support to others. Some challenges to advance care planning pre-dated the pandemic, whilst others were specific to/exacerbated by COVID-19. Challenges are demonstrated through six themes: complex decision making in the face of a new infectious disease; maintaining a personalised approach; COVID-19-specific communication difficulties; workload and pressure; sharing information; and national context of fear and uncertainty. Two themes demonstrate changes made to support: adapting local processes and adapting local structures., Conclusions: Professionals and healthcare providers need to ensure advance care planning is individualised by tailoring it to the values, priorities, and ethnic/cultural/religious context of each person. Policymakers need to consider how high-quality advance care planning can be resourced as a part of standard healthcare ahead of future pandemic waves. In facilitating this, we provide questions to consider at each level of the Social Ecological Model.

One component of the Joint United Nations Programme on HIV/AIDS (UNAIDS) goal to end the HIV/AIDS epidemic by 2030, is that 95% of all persons receiving antiretroviral therapy (ART) achieve viral suppression. † Thus, testing all HIV-positive persons for viral load (number of copies of viral RNA per mL) is a global health priority (1). CDC and other U.S. government agencies, as part of the U.S. President's Emergency Plan for AIDS Relief (PEPFAR), together with other stakeholders, have provided technical assistance and supported the cost for multiple countries in sub-Saharan Africa to expand viral load testing as the preferred monitoring strategy for clinical response to ART. The individual and population-level benefits of ART are well understood (2). Persons receiving ART who achieve and sustain an undetectable viral load do not transmit HIV to their sex partners, thereby disrupting onward transmission (2,3). Viral load testing is a cost-effective and sustainable programmatic approach for monitoring treatment success, allowing reduced frequency of health care visits for patients who are virally suppressed (4). Viral load monitoring enables early and accurate detection of treatment failure before immunologic decline. This report describes progress on the scale-up of viral load testing in eight sub-Saharan African countries from 2013 to 2018 and examines the trajectory of improvement with viral load testing scale-up that has paralleled government commitments, sustained technical assistance, and financial resources from international donors. Viral load testing in low- and middle-income countries enables monitoring of viral load suppression at the individual and population level, which is necessary to achieve global epidemic control. Although there has been substantial achievement in improving viral load coverage for all patients receiving ART, continued engagement is needed to reach global targets., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

Background: Early antiretroviral therapy (ART) is necessary for HIV epidemic control and depends on early diagnosis and successful linkage to care. Since 2014, annual household-based HIV testing and counseling and linkage services have been provided through the Chókwè Health and Demographic Surveillance System for residents testing HIV positive in this high HIV-burden district., Methods: District-wide Test and Start [T&S, ART for all people living with HIV (PLHIV)] began in August 2016, supported by systematic interventions to improve linkage to care and treatment. Annual rounds (R) of random household surveys were conducted to assess trends in population prevalence of ART use and viral load suppression (<1000 viral RNA copies/mL)., Results: Between R1 (April 2014-April 2015) and R5 (April 2018-Mar 2019), 46,090 (67.2%) of 68,620 residents aged 15-59 years were tested for HIV at home at least once, and 3711 were newly diagnosed with HIV and provided linkage services. Population prevalence of current ART use among PLHIV increased from 65.0% to 87.5% between R1 and R5. ART population prevalence was lowest among men aged 25-34 years (67.8%) and women aged 15-24 (78.0%), and highest among women aged 35-44 years (93.6%) and 45-59 years (93.7%) in R5. Viral load suppression prevalence increased among all PLHIV aged 15-59 years from 52.0% in R1 to 78.3% in R5., Discussion: Between 2014 and 2019, Chókwè Health and Demographic Surveillance System residents surpassed the UNAIDS targets of ≥81% of PLHIV on ART and ≥73% virally suppressed. This achievement supports the combination of efforts from household-based HIV testing and counseling, support for linkage to care and treatment, and continued investments in T&S implementation., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: The global target for 2020 is that ≥90% of people living with HIV (PLHIV) receiving antiretroviral therapy (ART) will achieve viral load suppression (VLS). We examined VLS and its determinants among adults receiving ART for at least four months., Methods: We analysed data from the population-based HIV impact assessment (PHIA) surveys in Eswatini, Lesotho, Malawi, Zambia and Zimbabwe (2015 to 2017). PHIA surveys are nationally representative, cross-sectional household surveys. Data collection included structured interviews, home-based HIV testing and laboratory testing. Blood samples from PLHIV were analysed for HIV RNA, CD4 counts and recent exposure to antiretroviral drugs (ARVs). We calculated representative estimates for the prevalence of VLS (viral load <1000 copies/mL), nonsuppressed viral load (NVL; viral load ≥1000 copies/mL), virologic failure (VF; ARVs present and viral load ≥1000 copies/mL), interrupted ART (ARVs absent and viral load ≥1000 copies/mL) and rates of switching to second-line ART (protease inhibitors present) among PLHIV aged 15 to 59 years who participated in the PHIA surveys in Eswatini, Lesotho, Malawi, Zambia and Zimbabwe, initiated ART at least four months before the survey and were receiving ART at the time of the survey (according to self-report or ARV testing). We calculated odds ratios and incidence rate ratios for factors associated with NVL, VF, interrupted ART, and switching to second-line ART., Results: We included 9200 adults receiving ART of whom 88.8% had VLS and 11.2% had NVL including 8.2% who experienced VF and 3.0% who interrupted ART. Younger age, male sex, less education, suboptimal adherence, receiving nevirapine, HIV non-disclosure, never having married and residing in Zimbabwe, Lesotho or Zambia were associated with higher odds of NVL. Among people with NVL, marriage, female sex, shorter ART duration, higher CD4 count and alcohol use were associated with lower odds for VF and higher odds for interrupted ART. Many people with VF (44.8%) had CD4 counts <200 cells/µL, but few (0.31% per year) switched to second-line ART., Conclusions: Countries are approaching global VLS targets for adults. Treatment support, in particular for younger adults, and people with higher CD4 counts, and switching of people to protease inhibitor- or integrase inhibitor-based regimens may further reduce NVL prevalence., (© 2020 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)