Incident Tuberculosis Infection is Associated with Alcohol use in Adults in Rural Uganda.

Data on alcohol use and incident Tuberculosis (TB) infection are needed. In adults aged 15+ in rural Uganda (N=49,585), estimated risk of incident TB infection was 29.2% with alcohol use vs. 19.2% without (RR: 1.49; 95%CI: 1.40-1.60). There is potential for interventions to interrupt transmission among people who drink alcohol.

Community-Wide Universal HIV Test and Treat Intervention Reduces Tuberculosis Transmission in Rural Uganda: A Cluster-Randomized Trial.

BACKGROUND: Human immunodeficiency virus (HIV) treatment reduces tuberculosis (TB) disease and mortality; however, the population-level impact of universal HIV-test-and-treat interventions on TB infection and transmission remain unclear. METHODS: In a sub-study nested in the SEARCH trial, a community cluster-randomized trial (NCT01864603), we assessed whether a universal HIV-test-and-treat intervention reduced population-level incident TB infection in rural Uganda. Intervention communities received annual, population-level HIV testing and patient-centered linkage. Control communities received population-level HIV testing at baseline and endline. We compared estimated incident TB infection by arms, defined by tuberculin skin test conversion in a cohort of persons aged 5 and older, adjusting for participation and predictors of infection, and accounting for clustering. RESULTS: Of the 32 trial communities, 9 were included, comprising 90 801 participants (43 127 intervention and 47 674 control). One-year cumulative incidence of TB infection was 16% in the intervention and 22% in the control; SEARCH reduced the population-level risk of incident TB infection by 27% (adjusted risk ratio = 0.73; 95% confidence interval [CI]: .57-.92, P = .005). In pre-specified analyses, the effect was largest among children aged 5-11 years and males. CONCLUSIONS: A universal HIV-test-and-treat intervention reduced incident TB infection, a marker of population-level TB transmission. Investments in community-level HIV interventions have broader population-level benefits, including TB reductions.

Two-Stage TMLE to reduce bias and improve efficiency in cluster randomized trials.

Cluster randomized trials (CRTs) randomly assign an intervention to groups of individuals (e.g., clinics or communities) and measure outcomes on individuals in those groups. While offering many advantages, this experimental design introduces challenges that are only partially addressed by existing analytic approaches. First, outcomes are often missing for some individuals within clusters. Failing to appropriately adjust for differential outcome measurement can result in biased estimates and inference. Second, CRTs often randomize limited numbers of clusters, resulting in chance imbalances on baseline outcome predictors between arms. Failing to adaptively adjust for these imbalances and other predictive covariates can result in efficiency losses. To address these methodological gaps, we propose and evaluate a novel two-stage targeted minimum loss-based estimator to adjust for baseline covariates in a manner that optimizes precision, after controlling for baseline and postbaseline causes of missing outcomes. Finite sample simulations illustrate that our approach can nearly eliminate bias due to differential outcome measurement, while existing CRT estimators yield misleading results and inferences. Application to real data from the SEARCH community randomized trial demonstrates the gains in efficiency afforded through adaptive adjustment for baseline covariates, after controlling for missingness on individual-level outcomes.

Adaptive sequential surveillance with network and temporal dependence.

Strategic test allocation is important for control of both emerging and existing pandemics (eg, COVID-19, HIV). It supports effective epidemic control by (1) reducing transmission via identifying cases and (2) tracking outbreak dynamics to inform targeted interventions. However, infectious disease surveillance presents unique statistical challenges. For instance, the true outcome of interest (positive infection status) is often a latent variable. In addition, presence of both network and temporal dependence reduces data to a single observation. In this work, we study an adaptive sequential design, which allows for unspecified dependence among individuals and across time. Our causal parameter is the mean latent outcome we would have obtained, if, starting at time t given the observed past, we had carried out a stochastic intervention that maximizes the outcome under a resource constraint. The key strength of the method is that we do not have to model network and time dependence: a short-term performance Online Super Learner is used to select among dependence models and randomization schemes. The proposed strategy learns the optimal choice of testing over time while adapting to the current state of the outbreak and learning across samples, through time, or both. We demonstrate the superior performance of the proposed strategy in an agent-based simulation modeling a residential university environment during the COVID-19 pandemic.

The Association Between Social Network Characteristics and Tuberculosis Infection Among Adults in 9 Rural Ugandan Communities.

BACKGROUND: Social network analysis can elucidate tuberculosis transmission dynamics outside the home and may inform novel network-based case-finding strategies. METHODS: We assessed the association between social network characteristics and prevalent tuberculosis infection among residents (aged ≥15 years) of 9 rural communities in Eastern Uganda. Social contacts named during a census were used to create community-specific nonhousehold social networks. We evaluated whether social network structure and characteristics of first-degree contacts (sex, human immunodeficiency virus [HIV] status, tuberculosis infection) were associated with revalent tuberculosis infection (positive tuberculin skin test [TST] result) after adjusting for individual-level risk factors (age, sex, HIV status, tuberculosis contact, wealth, occupation, and Bacillus Calmette-Guérin [BCG] vaccination) with targeted maximum likelihood estimation. RESULTS: Among 3 335 residents sampled for TST, 32% had a positive TST results and 4% reported a tuberculosis contact. The social network contained 15 328 first-degree contacts. Persons with the most network centrality (top 10%) (adjusted risk ratio, 1.3 [95% confidence interval, 1.1-1.1]) and the most (top 10%) male contacts (1.5 [1.3-1.9]) had a higher risk of prevalent tuberculosis, than those in the remaining 90%. People with ≥1 contact with HIV (adjusted risk ratio, 1.3 [95% confidence interval, 1.1-1.6]) and ≥2 contacts with tuberculosis infection were more likely to have tuberculosis themselves (2.6 [ 95% confidence interval: 2.2-2.9]). CONCLUSIONS: Social networks with higher centrality, more men, contacts with HIV, and tuberculosis infection were positively associated with tuberculosis infection. Tuberculosis transmission within measurable social networks may explain prevalent tuberculosis not associated with a household contact. Further study on network-informed tuberculosis case finding interventions is warranted.

Efficient and robust approaches for analysis of sequential multiple assignment randomized trials: Illustration using the ADAPT-R trial.

Personalized intervention strategies, in particular those that modify treatment based on a participant's own response, are a core component of precision medicine approaches. Sequential multiple assignment randomized trials (SMARTs) are growing in popularity and are specifically designed to facilitate the evaluation of sequential adaptive strategies, in particular those embedded within the SMART. Advances in efficient estimation approaches that are able to incorporate machine learning while retaining valid inference can allow for more precise estimates of the effectiveness of these embedded regimes. However, to the best of our knowledge, such approaches have not yet been applied as the primary analysis in SMART trials. In this paper, we present a robust and efficient approach using targeted maximum likelihood estimation (TMLE) for estimating and contrasting expected outcomes under the dynamic regimes embedded in a SMART, together with generating simultaneous confidence intervals for the resulting estimates. We contrast this method with two alternatives (G-computation and inverse probability weighting estimators). The precision gains and robust inference achievable through the use of TMLE to evaluate the effects of embedded regimes are illustrated using both outcome-blind simulations and a real-data analysis from the Adaptive Strategies for Preventing and Treating Lapses of Retention in Human Immunodeficiency Virus (HIV) Care (ADAPT-R) trial (NCT02338739), a SMART with a primary aim of identifying strategies to improve retention in HIV care among people living with HIV in sub-Saharan Africa.

Efficient targeted learning of heterogeneous treatment effects for multiple subgroups.

In biomedical science, analyzing treatment effect heterogeneity plays an essential role in assisting personalized medicine. The main goals of analyzing treatment effect heterogeneity include estimating treatment effects in clinically relevant subgroups and predicting whether a patient subpopulation might benefit from a particular treatment. Conventional approaches often evaluate the subgroup treatment effects via parametric modeling and can thus be susceptible to model mis-specifications. In this paper, we take a model-free semiparametric perspective and aim to efficiently evaluate the heterogeneous treatment effects of multiple subgroups simultaneously under the one-step targeted maximum-likelihood estimation (TMLE) framework. When the number of subgroups is large, we further expand this path of research by looking at a variation of the one-step TMLE that is robust to the presence of small estimated propensity scores in finite samples. From our simulations, our method demonstrates substantial finite sample improvements compared to conventional methods. In a case study, our method unveils the potential treatment effect heterogeneity of rs12916-T allele (a proxy for statin usage) in decreasing Alzheimer's disease risk.

Defining and estimating effects in cluster randomized trials: A methods comparison.

Across research disciplines, cluster randomized trials (CRTs) are commonly implemented to evaluate interventions delivered to groups of participants, such as communities and clinics. Despite advances in the design and analysis of CRTs, several challenges remain. First, there are many possible ways to specify the causal effect of interest (eg, at the individual-level or at the cluster-level). Second, the theoretical and practical performance of common methods for CRT analysis remain poorly understood. Here, we present a general framework to formally define an array of causal effects in terms of summary measures of counterfactual outcomes. Next, we provide a comprehensive overview of CRT estimators, including the t-test, generalized estimating equations (GEE), augmented-GEE, and targeted maximum likelihood estimation (TMLE). Using finite sample simulations, we illustrate the practical performance of these estimators for different causal effects and when, as commonly occurs, there are limited numbers of clusters of different sizes. Finally, our application to data from the Preterm Birth Initiative (PTBi) study demonstrates the real-world impact of varying cluster sizes and targeting effects at the cluster-level or at the individual-level. Specifically, the relative effect of the PTBi intervention was 0.81 at the cluster-level, corresponding to a 19% reduction in outcome incidence, and was 0.66 at the individual-level, corresponding to a 34% reduction in outcome risk. Given its flexibility to estimate a variety of user-specified effects and ability to adaptively adjust for covariates for precision gains while maintaining Type-I error control, we conclude TMLE is a promising tool for CRT analysis.

Two or more significant life-events in 6-months are associated with lower rates of HIV treatment and virologic suppression among youth with HIV in Uganda and Kenya.

Youth living with HIV in sub-Saharan Africa have poor HIV care outcomes. We determined the association of recent significant life-events with HIV antiretroviral treatment (ART) initiation and HIV viral suppression in youth aged 15-24 years living with HIV in rural Kenya and Uganda. This was a cross-sectional analysis of 995 youth enrolled in the SEARCH Youth study. At baseline, providers assessed recent (within 6 months) life-events, defined as changes in schooling/employment, residence, partnerships, sickness, incarceration status, family strife or death, and birth/pregnancy, self-reported alcohol use, being a parent, and HIV-status disclosure. We examined the frequencies of events and their association with ART status and HIV viral suppression (<400 copies/ul). Recent significant life-events were prevalent (57.7%). Having >2 significant life-events (aOR = 0.61, 95% CI:0.45-0.85) and consuming alcohol (aOR = 0.61, 95% CI:0.43-0.87) were associated with a lower odds of HIV viral suppression, while disclosure of HIV-status to partner (aOR = 2.39, 95% CI:1.6-3.5) or to family (aOR = 1.86, 95% CI:1.3-2.7), being a parent (aOR = 1.8, 95% CI:1.2-2.5), and being single (aOR = 1.6, 95% CI:1.3-2.1) had a higher odds. This suggest that two or more recent life-events and alcohol use are key barriers to ART initiation and achievement of viral suppression among youth living with HIV in rural East Africa.Trial registration: ClinicalTrials.gov identifier: NCT03848728..

Comparison of SARS-CoV-2 Reverse Transcriptase Polymerase Chain Reaction and BinaxNOW Rapid Antigen Tests at a Community Site During an Omicron Surge : A Cross-Sectional Study.

BACKGROUND: SARS-CoV-2 rapid antigen tests are an important public health tool. OBJECTIVE: To evaluate field performance of the BinaxNOW rapid antigen test (Abbott) compared with reverse transcriptase polymerase chain reaction (RT-PCR) for detecting infection with the Omicron variant of SARS-CoV-2. DESIGN: Cross-sectional surveillance study. SETTING: Free, walk-up, outdoor, urban community testing and vaccine site led by Unidos en Salud, serving a predominantly Latinx community highly impacted by COVID-19. PARTICIPANTS: Persons seeking COVID-19 testing in January 2022. MEASUREMENTS: Simultaneous BinaxNOW and RT-PCR from nasal, cheek, and throat swabs, including cycle threshold (Ct) measures; a lower Ct value is a surrogate for higher amounts of virus. RESULTS: Among 731 persons tested with nasal swabs, there were 296 (40.5%) positive results on RT-PCR; 98.9% were the Omicron variant. BinaxNOW detected 95.2% (95% CI, 91% to 98%) of persons who tested positive on RT-PCR with a Ct value below 30, 82.1% (CI, 77% to 87%) of those who tested positive on RT-PCR with a Ct value below 35, and 65.2% (CI, 60% to 71%) of all who were positive on RT-PCR. Among 75 persons with simultaneous nasal and cheek swabs, BinaxNOW using a cheek swab failed to detect 91% (20 of 22) of specimens that were positive on BinaxNOW with a nasal swab. Among persons with simultaneous nasal and throat swabs who were positive on RT-PCR with a Ct value below 30, 42 of 49 (85.7%) were detected by nasal BinaxNOW, 23 of 49 (46.9%) by throat BinaxNOW, and 44 of 49 (89.8%) by either. LIMITATION: Participants were a cross-sectional sample from a community-based sentinel surveillance site, precluding study of viral or symptom dynamics. CONCLUSION: BinaxNOW detected persons with high SARS-CoV-2 levels during the Omicron surge, enabling rapid responses to positive test results. Cheek or throat swabs should not replace nasal swabs. As currently recommended, high-risk persons with an initial negative BinaxNOW result should have repeated testing. PRIMARY FUNDING SOURCE: University of California, San Francisco.

SARS-CoV-2 Variant Exposures Elicit Antibody Responses With Differential Cross-Neutralization of Established and Emerging Strains Including Delta and Omicron.

The wide spectrum of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with phenotypes impacting transmission and antibody sensitivity necessitates investigation of immune responses to different spike protein versions. Here, we compare neutralization of variants of concern, including B.1.617.2 (delta) and B.1.1.529 (omicron), in sera from individuals exposed to variant infection, vaccination, or both. We demonstrate that neutralizing antibody responses are strongest against variants sharing certain spike mutations with the immunizing exposure, and exposure to multiple spike variants increases breadth of variant cross-neutralization. These findings contribute to understanding relationships between exposures and antibody responses and may inform booster vaccination strategies.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Transmission Dynamics and Immune Responses in a Household of Vaccinated Persons.

While SARS-CoV-2 vaccines prevent severe disease effectively, postvaccination "breakthrough" COVID-19 infections and transmission among vaccinated individuals remain ongoing concerns. We present an in-depth characterization of transmission and immunity among vaccinated individuals in a household, revealing complex dynamics and unappreciated comorbidities, including autoimmunity to type 1 interferon in the presumptive index case.

Estimation of Secondary Household Attack Rates for Emergent Spike L452R Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Variants Detected by Genomic Surveillance at a Community-Based Testing Site in San Francisco.

BACKGROUND: Sequencing of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral genome from patient samples is an important epidemiological tool for monitoring and responding to the pandemic, including the emergence of new mutations in specific communities. METHODS: SARS-CoV-2 genomic sequences were generated from positive samples collected, along with epidemiological metadata, at a walk-up, rapid testing site in the Mission District of San Francisco, California during 22 November to 1 December, 2020, and 10-29 January 2021. Secondary household attack rates and mean sample viral load were estimated and compared across observed variants. RESULTS: A total of 12 124 tests were performed yielding 1099 positives. From these, 928 high-quality genomes were generated. Certain viral lineages bearing spike mutations, defined in part by L452R, S13I, and W152C, comprised 54.4% of the total sequences from January, compared to 15.7% in November. Household contacts exposed to the "California" or "West Coast" variants (B.1.427 and B.1.429) were at higher risk of infection compared to household contacts exposed to lineages lacking these variants (0.36 vs 0.29, risk ratio [RR] = 1.28; 95% confidence interval [CI]: 1.00-1.64). The reproductive number was estimated to be modestly higher than other lineages spreading in California during the second half of 2020. Viral loads were similar among persons infected with West Coast versus non-West Coast strains, as was the proportion of individuals with symptoms (60.9% vs 64.3%). CONCLUSIONS: The increase in prevalence, relative household attack rates, and reproductive number are consistent with a modest transmissibility increase of the West Coast variants. Summary: We observed a growing prevalence and modestly elevated attack rate for "West Coast" severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants in a community testing setting in San Francisco during January 2021, suggesting its modestly higher transmissibility.

HIV Testing and Treatment with the Use of a Community Health Approach in Rural Africa.

BACKGROUND: Universal antiretroviral therapy (ART) with annual population testing and a multidisease, patient-centered strategy could reduce new human immunodeficiency virus (HIV) infections and improve community health. METHODS: We randomly assigned 32 rural communities in Uganda and Kenya to baseline HIV and multidisease testing and national guideline-restricted ART (control group) or to baseline testing plus annual testing, eligibility for universal ART, and patient-centered care (intervention group). The primary end point was the cumulative incidence of HIV infection at 3 years. Secondary end points included viral suppression, death, tuberculosis, hypertension control, and the change in the annual incidence of HIV infection (which was evaluated in the intervention group only). RESULTS: A total of 150,395 persons were included in the analyses. Population-level viral suppression among 15,399 HIV-infected persons was 42% at baseline and was higher in the intervention group than in the control group at 3 years (79% vs. 68%; relative prevalence, 1.15; 95% confidence interval [CI], 1.11 to 1.20). The annual incidence of HIV infection in the intervention group decreased by 32% over 3 years (from 0.43 to 0.31 cases per 100 person-years; relative rate, 0.68; 95% CI, 0.56 to 0.84). However, the 3-year cumulative incidence (704 incident HIV infections) did not differ significantly between the intervention group and the control group (0.77% and 0.81%, respectively; relative risk, 0.95; 95% CI, 0.77 to 1.17). Among HIV-infected persons, the risk of death by year 3 was 3% in the intervention group and 4% in the control group (0.99 vs. 1.29 deaths per 100 person-years; relative risk, 0.77; 95% CI, 0.64 to 0.93). The risk of HIV-associated tuberculosis or death by year 3 among HIV-infected persons was 4% in the intervention group and 5% in the control group (1.19 vs. 1.50 events per 100 person-years; relative risk, 0.79; 95% CI, 0.67 to 0.94). At 3 years, 47% of adults with hypertension in the intervention group and 37% in the control group had hypertension control (relative prevalence, 1.26; 95% CI, 1.15 to 1.39). CONCLUSIONS: Universal HIV treatment did not result in a significantly lower incidence of HIV infection than standard care, probably owing to the availability of comprehensive baseline HIV testing and the rapid expansion of ART eligibility in the control group. (Funded by the National Institutes of Health and others; SEARCH ClinicalTrials.gov number, NCT01864603.).

Performance Characteristics of a Rapid Severe Acute Respiratory Syndrome Coronavirus 2 Antigen Detection Assay at a Public Plaza Testing Site in San Francisco.

We evaluated the performance of the Abbott BinaxNOW rapid antigen test for coronavirus disease 2019 (Binax-CoV2) to detect virus among persons, regardless of symptoms, at a public plaza site of ongoing community transmission. Titration with cultured severe acute respiratory syndrome coronavirus 2 yielded a human observable threshold between 1.6 × 104-4.3 × 104 viral RNA copies (cycle threshold [Ct], 30.3-28.8). Among 878 subjects tested, 3% (26 of 878) were positive by reverse-transcription polymerase chain reaction, of whom 15 of 26 had a Ct <30, indicating high viral load; of these, 40% (6 of 15) were asymptomatic. Using this Ct threshold (<30) for Binax-CoV2 evaluation, the sensitivity of Binax-CoV2 was 93.3% (95% confidence interval, 68.1%-99.8%) (14 of 15) and the specificity was 99.9% (99.4%-99.9%) (855 of 856).

Field Performance and Public Health Response Using the BinaxNOWTM Rapid Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Antigen Detection Assay During Community-Based Testing.

Among 3302 persons tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by BinaxNOWTM and reverse transcription polymerase chain reaction (RT-PCR) in a community setting, rapid assay sensitivity was 100%/98.5%/89% using RT-PCR cycle thresholds of 30, 35, and no threshold. The specificity was 99.9%. Performance was high across ages and those with and without symptoms. Rapid resulting permitted immediate public health action.

SEARCH Human Immunodeficiency Virus (HIV) Streamlined Treatment Intervention Reduces Mortality at a Population Level in Men With Low CD4 Counts.

BACKGROUND: We tested the hypothesis that patient-centered, streamlined human immunodeficiency virus (HIV) care would achieve lower mortality than the standard treatment model for persons with HIV and CD4 ≤ 350/uL in the setting of population-wide HIV testing. METHODS: In the SEARCH (Sustainable East Africa Research in Community Health) Study (NCT01864603), 32 communities in rural Uganda and Kenya were randomized to country-guided antiretroviral therapy (ART) versus streamlined ART care that included rapid ART start, visit spacing, flexible clinic hours, and welcoming environment. We assessed persons with HIV and CD4 ≤ 350/uL, ART eligible in both arms, and estimated the effect of streamlined care on ART initiation and mortality at 3 years. Comparisons between study arms used a cluster-level analysis with survival estimates from Kaplan-Meier; estimates of ART start among ART-naive persons treated death as a competing risk. RESULTS: Among 13 266 adults with HIV, 2973 (22.4%) had CD4 ≤ 350/uL. Of these, 33% were new diagnoses, and 10% were diagnosed but ART-naive. Men with HIV were almost twice as likely as women with HIV to have CD4 ≤ 350/uL and be untreated (15% vs 8%, respectively). Streamlined care reduced mortality by 28% versus control (risk ratio [RR] = 0.72; 95% confidence interval [CI]: .56, .93; P = .02). Despite eligibility in both arms, persons with CD4 ≤ 350/uL started ART faster under streamlined care versus control (76% vs 43% by 12 months, respectively; P < .001). Mortality was reduced substantially more among men (RR = 0.61; 95% CI: .43, .86; P = .01) than among women (RR = 0.90; 95% CI: .62, 1.32; P = .58). CONCLUSIONS: After population-based HIV testing, streamlined care reduced population-level mortality among persons with HIV and CD4 ≤ 350/uL, particularly among men. Streamlined HIV care models may play a key role in global efforts to reduce AIDS deaths.

Community Transmission of Severe Acute Respiratory Syndrome Coronavirus 2 Disproportionately Affects the Latinx Population During Shelter-in-Place in San Francisco.

BACKGROUND: There is an urgent need to understand the dynamics and risk factors driving ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission during shelter-in-place mandates. METHODS: We offered SARS-CoV-2 reverse-transcription polymerase chain reaction (PCR) and antibody (Abbott ARCHITECT IgG) testing, regardless of symptoms, to all residents (aged ≥4 years) and workers in a San Francisco census tract (population: 5174) at outdoor, community-mobilized events over 4 days. We estimated SARS-CoV-2 point prevalence (PCR positive) and cumulative incidence (antibody or PCR positive) in the census tract and evaluated risk factors for recent (PCR positive/antibody negative) vs prior infection (antibody positive/PCR negative). SARS-CoV-2 genome recovery and phylogenetics were used to measure viral strain diversity, establish viral lineages present, and estimate number of introductions. RESULTS: We tested 3953 persons (40% Latinx; 41% White; 9% Asian/Pacific Islander; and 2% Black). Overall, 2.1% (83/3871) tested PCR positive: 95% were Latinx and 52% were asymptomatic when tested; 1.7% of census tract residents and 6.0% of workers (non-census tract residents) were PCR positive. Among 2598 tract residents, estimated point prevalence of PCR positives was 2.3% (95% confidence interval [CI], 1.2%-3.8%): 3.9% (95% CI, 2.0%-6.4%) among Latinx persons vs 0.2% (95% CI, .0-.4%) among non-Latinx persons. Estimated cumulative incidence among residents was 6.1% (95% CI, 4.0%-8.6%). Prior infections were 67% Latinx, 16% White, and 17% other ethnicities. Among recent infections, 96% were Latinx. Risk factors for recent infection were Latinx ethnicity, inability to shelter in place and maintain income, frontline service work, unemployment, and household income <$50 000/year. Five SARS-CoV-2 phylogenetic lineages were detected. CONCLUSIONS: SARS-CoV-2 infections from diverse lineages continued circulating among low-income, Latinx persons unable to work from home and maintain income during San Francisco's shelter-in-place ordinance.

SARS-CoV-2 vaccine boosters: The time to act is now.

We have a new and unprecedented opportunity to mitigate the suffering, death and inequities of COVID-19 in the United States with vaccine boosters-if we deploy them effectively, rapidly, and widely with simplified messaging to all eligible adults.

Effect of a patient-centered hypertension delivery strategy on all-cause mortality: Secondary analysis of SEARCH, a community-randomized trial in rural Kenya and Uganda.

BACKGROUND: Hypertension treatment reduces morbidity and mortality yet has not been broadly implemented in many low-resource settings, including sub-Saharan Africa (SSA). We hypothesized that a patient-centered integrated chronic disease model that included hypertension treatment and leveraged the HIV care system would reduce mortality among adults with uncontrolled hypertension in rural Kenya and Uganda. METHODS AND FINDINGS: This is a secondary analysis of the SEARCH trial (NCT:01864603), in which 32 communities underwent baseline population-based multidisease testing, including hypertension screening, and were randomized to standard country-guided treatment or to a patient-centered integrated chronic care model including treatment for hypertension, diabetes, and HIV. Patient-centered care included on-site introduction to clinic staff at screening, nursing triage to expedite visits, reduced visit frequency, flexible clinic hours, and a welcoming clinic environment. The analytic population included nonpregnant adults (≥18 years) with baseline uncontrolled hypertension (blood pressure ≥140/90 mm Hg). The primary outcome was 3-year all-cause mortality with comprehensive population-level assessment. Secondary outcomes included hypertension control assessed at a population level at year 3 (defined per country guidelines as at least 1 blood pressure measure <140/90 mm Hg on 3 repeated measures). Between-arm comparisons used cluster-level targeted maximum likelihood estimation. Among 86,078 adults screened at study baseline (June 2013 to July 2014), 10,928 (13%) had uncontrolled hypertension. Median age was 53 years (25th to 75th percentile 40 to 66); 6,058 (55%) were female; 677 (6%) were HIV infected; and 477 (4%) had diabetes mellitus. Overall, 174 participants (3.2%) in the intervention group and 225 participants (4.1%) in the control group died during 3 years of follow-up (adjusted relative risk (aRR) 0.79, 95% confidence interval (CI) 0.64 to 0.97, p = 0.028). Among those with baseline grade 3 hypertension (≥180/110 mm Hg), 22 (4.9%) in the intervention group and 42 (7.9%) in the control group died during 3 years of follow-up (aRR 0.62, 95% CI 0.39 to 0.97, p = 0.038). Estimated population-level hypertension control at year 3 was 53% in intervention and 44% in control communities (aRR 1.22, 95% CI 1.12 to 1.33, p < 0.001). Study limitations include inability to identify specific causes of death and control conditions that exceeded current standard hypertension care. CONCLUSIONS: In this cluster randomized comparison where both arms received population-level hypertension screening, implementation of a patient-centered hypertension care model was associated with a 21% reduction in all-cause mortality and a 22% improvement in hypertension control compared to standard care among adults with baseline uncontrolled hypertension. Patient-centered chronic care programs for HIV can be leveraged to reduce the overall burden of cardiovascular mortality in SSA. TRIAL REGISTRATION: ClinicalTrials.gov NCT01864603.