Search

Background Coronavirus disease 2019 (COVID-19) convalescent plasma (CCP) reduces hospitalizations among outpatients treated early after symptom onset. It is unknown whether CCP reduces time to symptom resolution among outpatients. Methods We evaluated symptom resolution at day 14 by trial arm using an adjusted subdistribution hazard model, with hospitalization as a competing risk. We also assessed the prevalence of symptom clusters at day 14 between treatments. Clusters were defined based on biologic clustering, impact on ability to work, and an algorithm. Results Among 1070 outpatients followed up after transfusion, 381 of 538 (70.8%) receiving CCP and 381 of 532 (71.6%) receiving control plasma were still symptomatic (P = .78) at day 14. Associations between CCP and symptom resolution by day 14 did not differ significantly from those in controls after adjustment for baseline characteristics (adjusted subdistribution hazard ratio, 0.99; P = .62). The most common cluster consisted of cough, fatigue, shortness of breath, and headache and was found in 308 (57.2%) and 325 (61.1%) of CCP and control plasma recipients, respectively (P = .16). Conclusions In this trial of outpatients with early COVID-19, CCP was not associated with faster resolution of symptoms compared with control. Overall, there were no differences by treatment in the prevalence of each symptom or symptom clusters at day 14. Clinical Trials Registration NCT04373460.

BackgroundDuring the COVID-19 pandemic, patients experienced significant care disruptions, including lab monitoring. We investigated changes in the time between viral load (VL) checks for people with HIV associated with the pandemic.MethodsThis was an observational analysis of VLs of people with HIV in routine care at a large subspecialty clinic. At pandemic onset, the clinic temporarily closed its onsite laboratory. The exposure was time period (time-varying): pre-pandemic (January 1st 2019-March 15th, 2020); pandemic lab-closed (March 16th-July 12th, 2020); and pandemic lab-open (July 13th-December 31st, 2020). We estimated time from an index VL to a subsequent VL, stratified by whether the index VL was suppressed (≤200 copies/mL). We also calculated cumulative incidence of a non-suppressed VL following a suppressed index VL, and of re-suppression following a loss of viral suppression.ResultsCompared to pre-pandemic, hazard ratios for next VL check were: 0.34 (95% CI: 0.30, 0.37, lab-closed) and 0.73 (CI: 0.68, 0.78, lab-open) for suppressed patients; 0.56 (CI: 0.42, 0.79, lab-closed) and 0.92 (95% CI: 0.76, 1.10, lab-open) for non-suppressed patients. The 12-month cumulative incidence of loss of suppression was the same in the pandemic lab-open (4%) and pre-pandemic period (4%). The hazard of re-suppression following loss of suppression was lower during the pandemic lab-open versus the pre-pandemic period (hazard ratio: 0.68, 95% CI: 0.50, 0.92).ConclusionsEarly pandemic restrictions and lab closure significantly delayed VL monitoring. Once the lab re-opened, non-suppressed patients resumed normal monitoring. Suppressed patients still had a delay, but no significant loss of suppression.SummaryDuring the early COVID-19 pandemic, people with HIV experienced disruptions in viral load monitoring due to lab closure and pandemic restrictions. Loosening restrictions resolved delays for non-suppressed, but not suppressed patients. Delays did not significantly increase proportion of non-suppressed patients.

OBJECTIVES: Telemedicine became the primary mode of delivering care during the COVID-19 pandemic. We describe the impact of telemedicine on access to care for people with HIV (PWH) by comparing the proportion of PWH engaged in care prior to and during the COVID-19 pandemic. DESIGN AND METHODS: We conducted an observational analysis of patients enrolled in the Johns Hopkins HIV Clinical Cohort, a single-center cohort of patients at an urban HIV subspecialty clinic affiliated with an academic center. Due to the COVID-19 pandemic, the clinic transitioned from in-person to mostly telemedicine visits. We compared patients receiving care in two time periods. The pre-pandemic period included 2,010 people with ≥1 visit scheduled between September 1(st) 2019 and March 15(th) 2020. The pandemic period included 1,929 people with ≥1 visit scheduled between March 16(th) 2020 and September 30(th) 2020. We determined the proportion of patients completing ≥1 of their scheduled visits during each period. RESULTS: Visit completion increased significantly from 88% pre-pandemic to 91% during the pandemic (p=0.008). Visit completion improved significantly for patients age 20–39 (82% to 92%, p

Polyclonal convalescent plasma may be obtained from donors who have recovered from coronavirus disease 2019 (Covid-19). The efficacy of this plasma in preventing serious complications in outpatients with recent-onset Covid-19 is uncertain.In this multicenter, double-blind, randomized, controlled trial, we evaluated the efficacy and safety of Covid-19 convalescent plasma, as compared with control plasma, in symptomatic adults (≥18 years of age) who had tested positive for severe acute respiratory syndrome coronavirus 2, regardless of their risk factors for disease progression or vaccination status. Participants were enrolled within 8 days after symptom onset and received a transfusion within 1 day after randomization. The primary outcome was Covid-19-related hospitalization within 28 days after transfusion.Participants were enrolled from June 3, 2020, through October 1, 2021. A total of 1225 participants underwent randomization, and 1181 received a transfusion. In the prespecified modified intention-to-treat analysis that included only participants who received a transfusion, the primary outcome occurred in 17 of 592 participants (2.9%) who received convalescent plasma and 37 of 589 participants (6.3%) who received control plasma (absolute risk reduction, 3.4 percentage points; 95% confidence interval, 1.0 to 5.8; P = 0.005), which corresponded to a relative risk reduction of 54%. Evidence of efficacy in vaccinated participants cannot be inferred from these data because 53 of the 54 participants with Covid-19 who were hospitalized were unvaccinated and 1 participant was partially vaccinated. A total of 16 grade 3 or 4 adverse events (7 in the convalescent-plasma group and 9 in the control-plasma group) occurred in participants who were not hospitalized.In participants with Covid-19, most of whom were unvaccinated, the administration of convalescent plasma within 9 days after the onset of symptoms reduced the risk of disease progression leading to hospitalization. (Funded by the Department of Defense and others; CSSC-004 ClinicalTrials.gov number, NCT04373460.).

Background The age-distribution of men who have sex with men (MSM) continues to change in the ‘Treat-All’ era as effective test-and-treat programs target key-populations. However, the nature of these changes and potential racial heterogeneities remain uncertain. Methods The PEARL model is an agent-based simulation of MSM in HIV care in the US, calibrated to data from the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD). Results PEARL projects a gradual decrease in median age of MSM at ART initiation from 36 to 31 years during 2010–2030, accompanied by changes in mortality among Black, White, and Hispanic MSM on ART by -8.4%, 42.4% and -19.6%. The median age of all MSM on ART is projected to increase from 45 to 47 years from 2010–2030, with the proportion of ART-users age ≥60y increasing from 6.7% to 28.0%. Almost half (49.7%) of White MSM ART-users are projected to age ≥60y by 2030, compared to 19.5% of Black and 17.2% of Hispanic MSM. Conclusions The overall age of US MSM in HIV care is expected to increase over the next decade, and differentially by race/ethnicity. As this population age, HIV programs should expand care for age-related causes of morbidity and mortality.

BACKGROUND: People with HIV (PWH) have a higher hospitalization rate than the general population. The Veterans Aging Cohort Study (VACS) Index at study entry well predicts hospitalization in PWH, but it is unknown if the time-updated parameter improves hospitalization prediction. We assessed the association of parameterizations of the VACS Index 2.0 with the 5-year risk of hospitalization. SETTING: PWH ≥ 30 years old with at least 12 months of antiretroviral therapy (ART) use, and contributing hospitalization data from 2000 to 2016 in North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) were included. Three parameterizations of the VACS Index 2.0 were assessed and categorized by quartile: 1) “baseline” measurement at study entry, 2) time-updated measurements, and 3) cumulative scores calculated using the trapezoidal rule. METHODS: Discrete-time proportional hazard models estimated the crude and adjusted associations (and 95% confidence intervals [CI]) of the VACS Index parameterizations and all-cause hospitalizations. The Akaike information criterion (AIC) assessed the model fit with each of the VACS Index parameters. RESULTS: Among 7,289 patients, 1,537 were hospitalized. Time-updated VACS Index fitted hospitalization best with a more distinct dose-response relationship (score

To characterize the prevalence of anemia and risk factors between 2007 and 2017 for moderate/severe anemia among people with HIV (PWH) in North America who have initiated antiretroviral therapy (ART).Observational study of participants in the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD).We estimated the annual prevalence between 1 January 2007 and 31 December 2017 of mild (11.0-12.9 g/dl men, 11.0-11.9 g/dl women), moderate (8.0-10.9 g/dl regardless of sex) and severe (8.0 g/dl regardless of sex) anemia. Poisson regression models with robust variance and general estimating equations estimated crude and adjusted prevalence ratios (aPR) with 95% confidence intervals ([-]) comparing risk factors for moderate/severe vs. no/mild anemia between 2007 and 2017.Among 73 898 PWH we observed 366 755 hemoglobin measurements following ART initiation, 37 301 (50%) had one or more measures of anemia during follow-up (mild = 17 743 [24%]; moderate = 13 383[18%]; severe = 6175 [8%]). Moderate/severe anemia was more prevalent among women, non-Hispanic Black and Hispanic PWH (vs. non-Hispanic white), those with underweight body mass index (18.5 kg/m2) and with comorbidities and coinfections. Older age had increased prevalence of moderate/severe anemia among males and decreased prevalence among females. Prevalence of moderate/severe anemia was greater among those with lower CD4+ cell count (≤200 cells/μl) [aPR = 2.11 (2.06-2.17)] unsuppressed HIV viral load (200 copies/ml) [aPR = 1.26 (1.23-1.29)] and within the first 6 months of ART initiation (vs.1 year of ART) [aPR = 1.66 (1.61-1.72)].The prevalence of anemia among PWH is reduced after ART initiation but remains high. Risk factors differ by sex and include comorbidities and HIV disease severity. The persistent, substantial prevalence of anemia among PWH merits further investigation, targeted screening, and clinical interventions.

PURPOSE Despite effective antiretroviral therapy, rates of end-stage liver disease (ESLD) remain high. It is not clear whether contemporary antiretrovirals contribute to the risk of ESLD. METHODS We included patients from cohorts with validated ESLD data in the North American AIDS Cohort Collaboration on Research and Design. Patients had to initiate antiretroviral therapy after 1 January 2004 with a nucleos(t)ide backbone of either abacavir/lamivudine or tenofovir/emtricitabine and a contemporary third (anchor) drug. Patients were followed until a first ESLD event, death, end of a cohort's ESLD validation period, loss to follow-up or 31 December 2015. We estimated associations between cumulative exposure to each drug and ESLD using a hierarchical Bayesian survival model with weakly informative prior distributions. RESULTS Among 10 564 patients included from 12 cohorts, 62 had an ESLD event. Of the nine anchor drugs, boosted protease inhibitors atazanavir and darunavir had the strongest signals for ESLD, with increasing hazard ratios (HR) and narrowing credible intervals (CrI), from a prior HR of 1.5 (95% CrI 0.32-7.1) per 5 year's exposure to posterior HRs respectively of 1.8 (95% CrI 0.82-3.9) and 2.0 (95% CrI 0.86-4.7). Both backbones and efavirenz showed no signal. Hepatitis C coinfection was the most important covariate risk factor (HR 4.4, 95% CrI 2.6-7.0). CONCLUSIONS While contemporary antiretrovirals pose less risk for ESLD than hepatitis coinfection, atazanavir and darunavir had a toxicity signal. We show how hierarchical Bayesian modelling can be used to detect toxicity signals in cohort event monitoring data even with complex treatments and few events.

Accurate, highly specific immunoassays for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are needed to evaluate seroprevalence. This study investigated the concordance of results across four immunoassays targeting different antigens for sera collected at the beginning of the SARS-CoV-2 pandemic in the United States. Specimens from All of Us participants contributed between January and March 2020 were tested using the Abbott Architect SARS-CoV-2 IgG (immunoglobulin G) assay (Abbott) and the EuroImmun SARS-CoV-2 enzyme-linked immunosorbent assay (ELISA) (EI). Participants with discordant results, participants with concordant positive results, and a subset of concordant negative results by Abbott and EI were also tested using the Roche Elecsys anti-SARS-CoV-2 (IgG) test (Roche) and the Ortho-Clinical Diagnostics Vitros anti-SARS-CoV-2 IgG test (Ortho). The agreement and 95% confidence intervals were estimated for paired assay combinations. SARS-CoV-2 antibody concentrations were quantified for specimens with at least two positive results across four immunoassays. Among the 24,079 participants, the percent agreement for the Abbott and EI assays was 98.8% (95% confidence interval, 98.7%, 99%). Of the 490 participants who were also tested by Ortho and Roche, the probability-weighted percentage of agreement (95% confidence interval) between Ortho and Roche was 98.4% (97.9%, 98.9%), that between EI and Ortho was 98.5% (92.9%, 99.9%), that between Abbott and Roche was 98.9% (90.3%, 100.0%), that between EI and Roche was 98.9% (98.6%, 100.0%), and that between Abbott and Ortho was 98.4% (91.2%, 100.0%). Among the 32 participants who were positive by at least 2 immunoassays, 21 had quantifiable anti-SARS-CoV-2 antibody concentrations by research assays. The results across immunoassays revealed concordance during a period of low prevalence. However, the frequency of false positivity during a period of low prevalence supports the use of two sequentially performed tests for unvaccinated individuals who are seropositive by the first test.bIMPORTANCE/bWhat is the agreement of commercial SARS-CoV-2 immunoglobulin G (IgG) assays during a time of low coronavirus disease 2019 (COVID-19) prevalence and no vaccine availability? Serological tests produced concordant results in a time of low SARS-CoV-2 prevalence and no vaccine availability, driven largely by the proportion of samples that were negative by two immunoassays. The CDC recommends two sequential tests for positivity for future pandemic preparedness. In a subset analysis, quantified antinucleocapsid and antispike SARS-CoV-2 IgG antibodies do not suggest the need to specify the antigen targets of the sequential assays in the CDC's recommendation because false positivity varied as much between assays targeting the same antigen as it did between assays targeting different antigens.

PURPOSE: To (1) use All of Us (AoU) data to validate a previously published single-center model predicting need for surgery among individuals with glaucoma, (2) train new models using AoU data, and (3) share insights regarding this novel data source for ophthalmic research. DESIGN: Development and evaluation of machine learning models. METHODS: Electronic health record data were extracted from AoU for 1231 adults diagnosed with primary open-angle glaucoma. The single-center model was applied to AoU data for external validation. AoU data were then used to train new models for predicting need for glaucoma surgery using multivariable logistic regression, artificial neural networks, and random forests. Five-fold cross-validation was performed. Model performance was evaluated based on area under the receiver operating characteristic curve (AUC), accuracy, precision and recall. RESULTS: The mean (standard deviation) age of the All of Us cohort was 69.1 (10.5) years, with 57.3% women and 33.5% Black, significantly exceeding representation in the single-center cohort (p=0.04 and p

BACKGROUND: It is unknown whether gaining inpatient healthcare coverage had an effect on hospitalization rates among persons with HIV (PWH) following implementation of the Affordable Care Act (ACA) in 2014. METHODS: Hospitalization data from 2015 were obtained on 1634 adults receiving longitudinal HIV care at 3 U.S. HIV clinics within the HIV Research Network. All patients were engaged in care and previously uninsured and supported by the Ryan White HIV/AIDS Program (RWHAP) in 2013. We evaluated whether PWH who transitioned to either Medicaid or private insurance in 2014 tended to have a change in hospitalization rate compared to PWH who remained uncovered and RWHAP-supported. Analyses were performed by negative binomial regression with robust standard errors, adjusting for gender, race/ethnicity, age, HIV risk factor, CD4 count, viral load, clinic site, and 2013 hospitalization rate. RESULTS: Among PWH without inpatient healthcare coverage in 2013, transitioning to Medicaid (adjusted incidence rate ratio 1.26, [0.71,2.23] or to private insurance (0.48[0.18, 1.28]) in 2014 was not associated with 2015 hospitalization rates, after accounting for demographics, HIV characteristics, and prior hospitalization rates. The factors significantly associated with higher hospitalization rates include age 55–64, CD4 400 copies/mL, and 2013 hospitalization rate. CONCLUSIONS: Acquiring inpatient coverage was not associated with a change in hospitalization rates. These results provide some evidence to allay the concern that acquiring inpatient coverage would lead to increased inpatient utilization.

BACKGROUND: The objective of this study was to determine the healthcare resource utilization for people living with HIV (PLWH) presenting to the emergency department (ED) across the HIV Care Continuum. METHODS: This prospective study enrolled PLWH presenting to an urban ED between June 2016 and March 2017. Subjects were categorized as being linked to care, retained in care, on antiretroviral therapy (ART), and virally suppressed (

OBJECTIVE To examine recent trends and differences in all-cause and cause-specific hospitalization rates by race, ethnicity, and gender among persons with HIV (PWH) in the United States and Canada. DESIGN HIV clinical cohort consortium. METHODS We followed PWH at least 18 years old in care 2005-2015 in six clinical cohorts. We used modified Clinical Classifications Software to categorize hospital discharge diagnoses. Incidence rate ratios (IRR) were estimated using Poisson regression with robust variances to compare racial and ethnic groups, stratified by gender, adjusted for cohort, calendar year, injection drug use history, and annually updated age, CD4+, and HIV viral load. RESULTS Among 27 085 patients (122 566 person-years), 80% were cisgender men, 1% transgender, 43% White, 33% Black, 17% Hispanic of any race, and 1% Indigenous. Unadjusted all-cause hospitalization rates were higher for Black [IRR 1.46, 95% confidence interval (CI) 1.32-1.61] and Indigenous (1.99, 1.44-2.74) versus White cisgender men, and for Indigenous versus White cisgender women (2.55, 1.68-3.89). Unadjusted AIDS-related hospitalization rates were also higher for Black, Hispanic, and Indigenous versus White cisgender men (all P

Convalescent plasma, collected from donors who have recovered from a pathogen of interest, has been used to treat infectious diseases, particularly in times of outbreak, when alternative therapies were unavailable. The COVID-19 pandemic revived interest in the use of convalescent plasma. Large observational studies and clinical trials that were executed during the pandemic provided insight into how to use convalescent plasma, whereby high levels of antibodies against the pathogen of interest and administration early within the time course of the disease are critical for optimal therapeutic effect. Several studies have shown outpatient administration of COVID-19 convalescent plasma (CCP) to be both safe and effective, preventing clinical progression in patients when administered within the first week of COVID-19. The United States Food and Drug Administration expanded its emergency use authorization (EUA) to allow for the administration of CCP in an outpatient setting in December 2021, at least for immunocompromised patients or those on immunosuppressive therapy. Outpatient transfusion of CCP and infusion of monoclonal antibody therapies for a highly transmissible infectious disease introduces nuanced challenges related to infection prevention. Drawing on our experiences with the clinical and research use of CCP, we describe the logistical considerations and workflow spanning procurement of qualified products, infrastructure, staffing, transfusion, and associated management of adverse events. The purpose of this description is to facilitate the efforts of others intent on establishing outpatient transfusion programs for CCP and other antibody-based therapies.

The ongoing evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants severely limits available effective monoclonal antibody therapies. Effective drugs are also supply limited. COVID-19 convalescent plasma (CCP) qualified for high antibody levels effectively reduces immunocompetent outpatient hospitalization. The Food and Drug Administration currently allows outpatient CCP for the immunosuppressed. Viral-specific antibody levels in CCP can range 10- to 100-fold between donors, unlike the uniform viral-specific monoclonal antibody dosing. Limited data are available on the efficacy of polyclonal CCP to neutralize variants. We examined 108 pre-δ/pre-ο donor units obtained before March 2021, 20 post-δ COVID-19/postvaccination units, and 1 pre-δ/pre-ο hyperimmunoglobulin preparation for variant-specific virus (vaccine-related isolate [WA-1], δ, and ο) neutralization correlated to Euroimmun S1 immunoglobulin G antibody levels. We observed a two- to fourfold and 20- to 40-fold drop in virus neutralization from SARS-CoV-2 WA-1 to δ or ο, respectively. CCP antibody levels in the upper 10% of the 108 donations as well as 100% of the post-δ COVID-19/postvaccination units and the hyperimmunoglobulin effectively neutralized all 3 variants. High-titer CCP neutralizes SARS-CoV-2 variants despite no previous donor exposure to the variants.

Summary Background Accurately estimating HIV disease progression and retention on antiretroviral therapy (ART) can help inform interventions to control HIV microepidemics and mathematical models used to inform health-resource allocation decisions. Our objective was to estimate the monthly probabilities of on-ART CD4 T-cell count progression, mortality, ART dropout, and ART reinitiation using a continuous-time multistate Markov model. We also aimed to validate health-state transition probability estimates to ensure they accurately reproduced the regional HIV microepidemics across the USA. Methods In our modelling study, we considered a cohort of patients from the HIV Research Network, a consortium of 17 adult and paediatric HIV-care providers located in the northeastern (n=8), southern (n=5), and western (n=4) regions of the USA. Individuals aged 15 years or older who were in HIV care (defined as one CD4 test and one HIV-care visit in a calendar year period) with at least one ART prescription between Jan 1, 2010, and Dec 31, 2015, were included in the analysis. We used continuous-time multistate Markov models to estimate transitions between CD4 strata and between on-ART and off-ART states. We examined and adjusted for differences in probability of transition by region, race or ethnicity, sex, HIV risk group, and other baseline clinical indicators. Findings The median age of the 32 242 individuals included in the analysis was 44 years (interquartile range 35–51). Over a median follow-up of 4·9 years (2·6–6·0), 8614 (26·7%) of 32 242 people interrupted ART and 1325 (4·1%) of 32 242 people died. Women, men who have sex with men, and individuals with no previous ART experience had greater increases in CD4 cell counts, whereas black people and people who inject drugs had increased probabilities of ART dropout and faster disease progression. Regardless of CD4 strata, individuals had increased hazard for ART dropout if they were from the south (adjusted hazard ratio [aHR] range from 1·91, 95% CI 1·71–2·13, to 2·45, 2·29–2·62) or the west (aHR range from 1·29, 1·10–1·51, to 1·66, 1·51–1·82) of the USA, compared with individuals from the northeast USA. Interpretation Our results show heterogeneities in disease progression during ART and probability of ART retention across race and ethnicity, HIV risk groups, and regions. These differences should be viewed as targets for intervention and should be incorporated in mathematical models of regional HIV microepidemics in the USA. Funding US National Institutes of Health, Agency for Healthcare Research and Quality, and Health Resources and Services Administration.

Background Persons who inject drugs (PWID) are at a disproportionately high risk of HIV infection. We aimed to determine the highest-valued combination implementation strategies to reduce the burden of HIV among PWID in 6 US cities. Methods Using a dynamic HIV transmission model calibrated for Atlanta, Baltimore, Los Angeles, Miami, New York City, and Seattle, we assessed the value of implementing combinations of evidence-based interventions at optimistic (drawn from best available evidence) or ideal (90% coverage) scale-up. We estimated reduction in HIV incidence among PWID, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs) for each city (10-year implementation; 20-year horizon; 2018 $ US). Results Combinations that maximized health benefits contained between 6 (Atlanta and Seattle) and 12 (Miami) interventions with ICER values ranging from $94 069/QALY in Los Angeles to $146 256/QALY in Miami. These strategies reduced HIV incidence by 8.1% (credible interval [CI], 2.8%–13.2%) in Seattle and 54.4% (CI, 37.6%–73.9%) in Miami. Incidence reduction reached 16.1%–75.5% at ideal scale. Conclusions Evidence-based interventions targeted to PWID can deliver considerable value; however, ending the HIV epidemic among PWID will require innovative implementation strategies and supporting programs to reduce social and structural barriers to care.

BACKGROUND Adolescents and young adults (AYA) with HIV experience poorer health outcomes compared with adults. To improve care for AYA with HIV, information about patterns of costly health care resource utilization is needed. METHODS Among 13-30 year olds in the US HIV Research Network, we stratified outpatient visits, emergency department (ED) visits, and inpatient days/person-year (PY) by HIV acquisition model [perinatal (PHIVY) and nonperinatal (NPHIVY)], age (13-17, 18-23, and 24-30 years), CD4 strata (

Author(s): Krebs, Emanuel; Zang, Xiao; Enns, Benjamin; Min, Jeong E; Behrends, Czarina N; Del Rio, Carlos; Dombrowski, Julia C; Feaster, Daniel J; Gebo, Kelly A; Golden, Matthew; Marshall, Brandon DL; Metsch, Lisa R; Schackman, Bruce R; Shoptaw, Steven; Strathdee, Steffanie A; Nosyk, Bohdan; Localized Economic Modeling Study Group | Abstract: ObjectiveEffective interventions to reduce the public health burden of HIV/AIDS can vary in their ability to deliver value at different levels of scale and in different epidemiological contexts. Our objective was to determine the cost-effectiveness of HIV treatment and prevention interventions implemented at previously documented scales of delivery in six US cities with diverse HIV microepidemics.DesignDynamic HIV transmission model-based cost-effectiveness analysis.MethodsWe identified and estimated previously documented scale of delivery and costs for 16 evidence-based interventions from the US CDC's Compendium of Evidence-Based Interventions and Best Practices for HIV Prevention. Using a model calibrated for Atlanta, Baltimore, Los Angeles, Miami, New York City and Seattle, we estimated averted HIV infections, quality-adjusted life years (QALY) gained and incremental cost-effectiveness ratios (healthcare perspective; 3% discount rate, 2018$US), for each intervention and city (10-year implementation) compared with the status quo over a 20-year time horizon.ResultsIncreased HIV testing was cost-saving or cost-effective across cities. Targeted preexposure prophylaxis for high-risk MSM was cost-saving in Miami and cost-effective in Atlanta ($6123/QALY), Baltimore ($18 333/QALY) and Los Angeles ($86 117/QALY). Interventions designed to improve antiretroviral therapy initiation provided greater value than other treatment engagement interventions. No single intervention was projected to reduce HIV incidence by more than 10.1% in any city.ConclusionCombination implementation strategies should be tailored to local epidemiological contexts to provide the most value. Complementary strategies addressing factors hindering access to HIV care will be necessary to meet targets for HIV elimination in the United States.

ImportanceUnderstanding the severity of postvaccination SARS-CoV-2 (ie, COVID-19) breakthrough illness among people with HIV (PWH) can inform vaccine guidelines and risk-reduction recommendations.ObjectiveTo estimate the rate and risk of severe breakthrough illness among vaccinated PWH and people without HIV (PWoH) who experience a breakthrough infection.Design, Setting, and ParticipantsIn this cohort study, the Corona-Infectious-Virus Epidemiology Team (CIVET-II) collaboration included adults (aged ≥18 years) with HIV who were receiving care and were fully vaccinated by June 30, 2021, along with PWoH matched according to date fully vaccinated, age group, race, ethnicity, and sex from 4 US integrated health systems and academic centers. Those with postvaccination COVID-19 breakthrough before December 31, 2021, were eligible.ExposuresHIV infection.Main Outcomes and MeasuresThe main outcome was severe COVID-19 breakthrough illness, defined as hospitalization within 28 days after a breakthrough SARS-CoV-2 infection with a primary or secondary COVID-19 discharge diagnosis. Discrete time proportional hazards models estimated adjusted hazard ratios (aHRs) and 95% CIs of severe breakthrough illness within 28 days of breakthrough COVID-19 by HIV status adjusting for demographic variables, COVID-19 vaccine type, and clinical factors. The proportion of patients who received mechanical ventilation or died was compared by HIV status.ResultsAmong 3649 patients with breakthrough COVID-19 (1241 PWH and 2408 PWoH), most were aged 55 years or older (2182 patients [59.8%]) and male (3244 patients [88.9%]). The cumulative incidence of severe illness in the first 28 days was low and comparable between PWoH and PWH (7.3% vs 6.7%; risk difference, −0.67%; 95% CI, −2.58% to 1.23%). The risk of severe breakthrough illness was 59% higher in PWH with CD4 cell counts less than 350 cells/μL compared with PWoH (aHR, 1.59; 95% CI, 0.99 to 2.46; P = .049). In multivariable analyses among PWH, being female, older, having a cancer diagnosis, and lower CD4 cell count were associated with increased risk of severe breakthrough illness, whereas previous COVID-19 was associated with reduced risk. Among 249 hospitalized patients, 24 (9.6%) were mechanically ventilated and 20 (8.0%) died, with no difference by HIV status.Conclusions and RelevanceIn this cohort study, the risk of severe COVID-19 breakthrough illness within 28 days of a breakthrough infection was low among vaccinated PWH and PWoH. PWH with moderate or severe immune suppression had a higher risk of severe breakthrough infection and should be included in groups prioritized for additional vaccine doses and risk-reduction strategies.

INTRODUCTION: National obesity prevention strategies may benefit from precision health approaches involving diverse participants in population health studies. We used cohort data from the National Institutes of Health All of Us Research Program (All of Us) Researcher Workbench to estimate population-level obesity prevalence. METHODS: To estimate state-level obesity prevalence we used data from physical measurements made during All of Us enrollment visits and data from participant electronic health records (EHRs) where available. Prevalence estimates were calculated and mapped by state for 2 categories of body mass index (BMI) (kg/m2): obesity (BMI >30) and severe obesity (BMI >35). We calculated and mapped prevalence by state, excluding states with fewer than 100 All of Us participants. RESULTS: Data on height and weight were available for 244,504 All of Us participants from 33 states, and corresponding EHR data were available for 88,840 of these participants. The median and IQR of BMI taken from physical measurements data was 28.4 (24.4- 33.7) and 28.5 (24.5-33.6) from EHR data, where available. Overall obesity prevalence based on physical measurements data was 41.5% (95% CI, 41.3%-41.7%); prevalence of severe obesity was 20.7% (95% CI, 20.6-20.9), with large geographic variations observed across states. Prevalence estimates from states with greater numbers of All of Us participants were more similar to national population-based estimates than states with fewer participants. CONCLUSION: All of Us participants had a high prevalence of obesity, with state-level geographic variation mirroring national trends. The diversity among All of Us participants may support future investigations on obesity prevention and treatment in diverse populations.

BACKGROUNDThe efficacy of polyclonal high titer convalescent plasma to prevent serious complications of COVID-19 in outpatients with recent onset of illness is uncertain.METHODSThis multicenter, double-blind randomized controlled trial compared the efficacy and safety of SARS-CoV-2 high titer convalescent plasma to placebo control plasma in symptomatic adults ≥18 years positive for SARS-CoV-2 regardless of risk factors for disease progression or vaccine status. Participants with symptom onset within 8 days were enrolled, then transfused within the subsequent day. The measured primary outcome was COVID-19-related hospitalization within 28 days of plasma transfusion. The enrollment period was June 3, 2020 to October 1, 2021.RESULTSA total of 1225 participants were randomized and 1181 transfused. In the pre-specified modified intention-to-treat analysis that excluded those not transfused, the primary endpoint occurred in 37 of 589 (6.3%) who received placebo control plasma and in 17 of 592 (2.9%) participants who received convalescent plasma (relative risk, 0.46; one-sided 95% upper bound confidence interval 0.733; P=0.004) corresponding to a 54% risk reduction. Examination with a model adjusting for covariates related to the outcome did not change the conclusions.CONCLUSIONEarly administration of high titer SARS-CoV-2 convalescent plasma reduced outpatient hospitalizations by more than 50%. High titer convalescent plasma is an effective early outpatient COVID-19 treatment with the advantages of low cost, wide availability, and rapid resilience to variant emergence from viral genetic drift in the face of a changing pandemic.Trial RegistrationClinicalTrials.gov number, NCT04373460.

Background The prevalence, incidence and risk factors of atrial fibrillation (AF) in a large, geographically and ethnically diverse cohort in the United States have not been fully described. Methods We analyzed data from 173,099 participants of the All of Us Research Program recruited in the period 2017–2019, with 92,318 of them having electronic health records (EHR) data available, and 35,483 having completed a medical history survey. Presence of AF at baseline was identified from self-report and EHR records. Incident AF was obtained from EHR. Demographic, anthropometric and clinical risk factors were obtained from questionnaires, baseline physical measurements and EHR. Results At enrollment, mean age was 52 years old (range 18–89). Females and males accounted for 61% and 39% respectively. Non-Hispanic Whites accounted for 67% of participants, with non-Hispanic Blacks, non-Hispanic Asians and Hispanics accounting for 26%, 4% and 3% of participants, respectively. Among 92,318 participants with available EHR data, 3,885 (4.2%) had AF at the time of study enrollment, while the corresponding figure among 35,483 with medical history data was 2,084 (5.9%). During a median follow-up of 16 months, 354 new cases of AF were identified among 88,433 eligible participants. Individuals who were older, male, non-Hispanic white, had higher body mass index, or a prior history of heart failure or coronary heart disease had higher prevalence and incidence of AF. Conclusion The epidemiology of AF in the All of Us Research Program is similar to that reported in smaller studies with careful phenotyping, highlighting the value of this new resource for the study of AF and, potentially, other cardiovascular diseases.

Benchmarks for protective immunity from infection or severe disease after SARS-CoV-2 vaccination are still being defined. Here, we characterized virus neutralizing and ELISA antibody levels, cellular immune responses, and viral variants in 4 separate groups: healthy controls (HCs) weeks (early) or months (late) following vaccination in comparison with symptomatic patients with SARS-CoV-2 after partial or full mRNA vaccination. During the period of the study, most symptomatic breakthrough infections were caused by the SARS-CoV-2 Alpha variant. Neutralizing antibody levels in the HCs were sustained over time against the vaccine parent virus but decreased against the Alpha variant, whereas IgG titers and T cell responses against the parent virus and Alpha variant declined over time. Both partially and fully vaccinated patients with symptomatic infections had lower virus neutralizing antibody levels against the parent virus than the HCs, similar IgG antibody titers, and similar virus-specific T cell responses measured by IFN-γ. Compared with HCs, neutralization activity against the Alpha variant was lower in the partially vaccinated infected patients and tended to be lower in the fully vaccinated infected patients. In this cohort of breakthrough infections, parent virus neutralization was the superior predictor of breakthrough infections with the Alpha variant of SARS-CoV-2.

Summary Background In the USA, Black and Hispanic or Latinx individuals continue to be disproportionately affected by HIV. Applying a distributional cost-effectiveness framework, we estimated the cost-effectiveness and epidemiological impact of two combination implementation approaches to identify the approach that best meets the dual objectives of improving population health and reducing racial or ethnic health disparities. Methods We adapted a dynamic, compartmental HIV transmission model to characterise HIV micro-epidemics in six US cities: Atlanta, Baltimore, Los Angeles, Miami, New York, and Seattle. We considered combinations of 16 evidence-based interventions to diagnose, treat, and prevent HIV transmission according to previously documented levels of scale-up. We then identified optimal combination strategies for each city, with the distribution of each intervention implemented according to existing service levels (proportional services approach) and the racial or ethnic distribution of new diagnoses (between Black, Hispanic or Latinx, and White or other ethnicity individuals; equity approach). We estimated total costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios of strategies implemented from 2020 to 2030 (health-care perspective; 20-year time horizon; 3% annual discount rate). We estimated three measures of health inequality (between-group variance, index of disparity, Theil index), incidence rate ratios, and rate differences for the selected strategies under each approach. Findings In all cities, optimal combination strategies under the equity approach generated more QALYs than those with proportional services, ranging from a 3·1% increase (95% credible interval [CrI] 1·4–5·3) in New York to more than double (101·9% [75·4–134·6]) in Atlanta. Compared with proportional services, the equity approach delivered lower costs over 20 years in all cities except Los Angeles; cost reductions ranged from $22·9 million (95% CrI 5·3–55·7 million) in Seattle to $579·8 million (255·4–940·5 million) in Atlanta. The equity approach also reduced incidence disparities and health inequality measures in all cities except Los Angeles. Interpretation Equity-focused HIV combination implementation strategies that reduce disparities for Black and Hispanic or Latinx individuals can significantly improve population health, reduce costs, and drive progress towards Ending the HIV Epidemic goals in the USA. Funding National Institute on Drug Abuse.

ImportancePregnant people are at increased risk of poor outcomes due to infection with SARS-CoV-2, and there are limited therapeutic options available.ObjectiveTo evaluate the clinical outcomes associated with nirmatrelvir and ritonavir used to treat SARS-CoV-2 infection in pregnant patients.Design, Setting, and ParticipantsThis case series included pregnant patients who were diagnosed with SARS-CoV-2 infection, received nirmatrelvir and ritonavir, and delivered their offspring within the Johns Hopkins Health System between December 22, 2021, and August 20, 2022.ExposuresTreatment with nirmatrelvir and ritonavir for SARS-CoV-2 infection during pregnancy.Main Outcomes and MeasuresClinical characteristics and outcomes were ascertained through manual record review.ResultsForty-seven pregnant patients (median [range] age, 34 [22-43] years) were included in the study, and the median (range) gestational age of their offspring was 28.4 (4.3-39.6) weeks. Medication was initiated at a median (range) of 1 (0-5) day after symptom onset, and only 2 patients [4.3%] did not complete the course of therapy because of adverse effects. Thirty patients (63.8%) treated with nirmatrelvir and ritonavir had a comorbidity in addition to pregnancy that could be a risk factor for developing severe COVID-19. Twenty-five patients [53.2%] delivered after treatment with nirmatrelvir and ritonavir. Twelve of these patients [48.0%] underwent cesarean delivery, 9 [75.0%] of which were scheduled. Two of 47 patients [4.3%] were hospitalized for conditions related to preexisting comorbidities.Conclusions and RelevanceIn this case series, pregnant patients who were treated with nirmatrelvir and ritonavir tolerated treatment well, although there was an unexpectedly high rate of cesarean deliveries. The lack of an increase in serious adverse effects affecting pregnant patients or offspring suggests that clinicians can use this drug combination to treat pregnant patients with SARS-CoV-2 infection.

Background The updated Veterans Aging Cohort Study (VACS) Index 2.0 combines general and human immunodeficiency virus (HIV)–specific biomarkers to generate a continuous score that accurately discriminates risk of mortality in diverse cohorts of persons with HIV (PWH), but a score alone is difficult to interpret. Using data from the North American AIDS Cohort Collaboration (NA-ACCORD), we translate VACS Index 2.0 scores into validated probability estimates of mortality. Methods Because complete mortality ascertainment is essential for accurate calibration, we restricted analyses to cohorts with mortality from the National Death Index or equivalent sources. VACS Index 2.0 components were ascertained from October 1999 to April 2018. Mortality was observed up to March 2019. Calibration curves compared predicted (estimated by fitting a gamma model to the score) to observed mortality overall and within subgroups: cohort (VACS/NA-ACCORD subset), sex, age 500 copies/mL, CD4 count Results Among 37230 PWH in VACS and 8061 PWH in the NA-ACCORD subset, median age was 53 and 44 years; 3% and 19% were women; and 48% and 39% were black. Discrimination in NA-ACCORD (C-statistic = 0.842 [95% confidence interval {CI}, .830–.854]) was better than in VACS (C-statistic = 0.813 [95% CI, .809–.817]). Predicted and observed mortality largely overlapped in VACS and the NA-ACCORD subset, overall and within subgroups. Conclusions Based on this validation, VACS Index 2.0 can reliably estimate probability of all-cause mortality, at various follow-up times, among PWH in North America.

BACKGROUND: Despite the high prevalence of hepatitis C virus (HCV) among persons living with HIV (PWH), the prevalence of HCV screening, treatment, and sustained virologic response (SVR) is unknown. This study aims to characterize the continuum of HCV screening and treatment among PWH in HIV care. SETTING: Adult patients enrolled at 12 sites of the HIV Research Network located in 3 regions of the United States were included. METHODS: We examined the prevalence of HCV screening, HCV coinfection, direct-acting antiretroviral (DAA) treatment, and SVR-12 between 2014 and 2015. Multivariate logistic regression was performed to identify characteristics associated with outcomes, adjusted for site. RESULTS: Among 29,071 PWH (age 18–87, 74.8% male, 44.4% black), 77.9% were screened for HCV antibodies; 94.6% of those screened had a confirmatory HCV RNA viral load test. Among those tested, 61.1% were determined to have chronic HCV. We estimate that only 23.4% of those eligible for DAA were prescribed DAA, and only 17.8% of those eligible evidenced initiating DAA treatment. Those who initiated treatment achieved SVR-12 at a rate of 95.2%. Blacks and people who inject drugs (PWID) were more likely to be screened for HCV than whites or those with heterosexual risk. Persons older than 40 years, whites, Hispanics, and PWID [adjusted odds ratio (AOR) 8.70 (7.74 to 9.78)] were more likely to be coinfected than their counterparts. When examining treatment with DAA, persons older than 50 years, on antiretroviral therapy [AOR 2.27 (1.11 to 4.64)], with HIV-1 RNA

ObjectivesCurrent guidelines recommend screening sexually active persons with HIV (PWH) for Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT) at least annually. Yet, screening rates in many HIV clinics remain low. In this study, we estimated the number needed to screen (NNS) to detect a NG and/or CT infection at each anatomic site among different subpopulations of PWH. NNS provides a concrete, practical measure to aid in assessing the practical impact of screening.Methods We included adults in care at three HIV Research Network sites in 2011–2014. Restricting to first tests within each year, annual NNS was defined as number of persons tested divided by number positive. We computed urogenital and extragenital NNS by age and risk group (women, men who have sex with women (MSW) and men who have sex with men (MSM)).Results A total of 16 864 NG/CT tests were included. Among patients aged ≤25 years, urogenital NNS was similar among women (15 (95% CI 6 to 71)), MSW (21 (95% CI 6 to 167)) and MSM (20 (95% CI 12 to 36)). Over 25, urogenital NNS increased to a greater extent for women (363 (95% CI 167 to 1000)) and MSW (160 (95% CI 100 to 333)) than MSM (46 (95% CI 38 to 56)). The increase for women versus MSM >25 remained significant (p25 years and pharyngeal NNS values were 8 (95% CI 5 to 13) and 20 (95% CI 16 to 24).ConclusionsThese findings suggest the importance of regular, at least annual NG/CT screening, particularly extragenital, of HIV positive MSM of all ages. They provide some support for age-based cutoffs for women and MSW (eg, universal screening for those aged ≤25 and targeted screening for those aged >25 years).

Recommendations for additional doses of COVID-19 vaccines for people with HIV (PWH) are restricted to those with advanced disease or unsuppressed HIV viral load. Understanding SARS-CoV-2 infection risk after vaccination among PWH is essential for informing vaccination guidelines.To estimate the rate and risk of breakthrough infections among fully vaccinated PWH and people without HIV (PWoH) in the United States.This cohort study used the Corona-Infectious-Virus Epidemiology Team (CIVET)-II (of the North American AIDS Cohort Collaboration on Research and Design [NA-ACCORD], which is part of the International Epidemiology Databases to Evaluate AIDS [IeDEA]), collaboration of 4 prospective, electronic health record-based cohorts from integrated health systems and academic health centers. Adult PWH who were fully vaccinated prior to June 30, 2021, were matched with PWoH on date of full vaccination, age, race and ethnicity, and sex and followed up through December 31, 2021.HIV infection.COVID-19 breakthrough infections, defined as laboratory evidence of SARS-CoV-2 infection or COVID-19 diagnosis after a patient was fully vaccinated.Among 113 994 patients (33 029 PWH and 80 965 PWoH), most were 55 years or older (80 017 [70%]) and male (104 967 [92%]); 47 098 (41%) were non-Hispanic Black, and 43 218 (38%) were non-Hispanic White. The rate of breakthrough infections was higher in PWH vs PWoH (55 [95% CI, 52-58] cases per 1000 person-years vs 43 [95% CI, 42-45] cases per 1000 person-years). Cumulative incidence of breakthroughs 9 months after full vaccination was low (3.8% [95% CI, 3.7%-3.9%]), albeit higher in PWH vs PWoH (4.4% vs 3.5%; log-rank P .001; risk difference, 0.9% [95% CI, 0.6%-1.2%]) and within each vaccine type. Breakthrough infection risk was 28% higher in PWH vs PWoH (adjusted hazard ratio, 1.28 [95% CI, 1.19-1.37]). Among PWH, younger age (45 y vs 45-54 y), history of COVID-19, and not receiving an additional dose (aHR, 0.71 [95% CI, 0.58-0.88]) were associated with increased risk of breakthrough infections. There was no association of breakthrough with HIV viral load suppression, but high CD4 count (ie, ≥500 cells/mm3) was associated with fewer breakthroughs among PWH.In this study, COVID-19 vaccination, especially with an additional dose, was effective against infection with SARS-CoV-2 strains circulating through December 31, 2021. PWH had an increased risk of breakthrough infections compared with PWoH. Expansion of recommendations for additional vaccine doses to all PWH should be considered.

Background With limited severe acute respiratory syndrome coronavirus (SARS-CoV-2) testing capacity in the United States at the start of the epidemic (January–March 2020), testing was focused on symptomatic patients with a travel history throughout February, obscuring the picture of SARS-CoV-2 seeding and community transmission. We sought to identify individuals with SARS-CoV-2 antibodies in the early weeks of the US epidemic. Methods All of Us study participants in all 50 US states provided blood specimens during study visits from 2 January to 18 March 2020. Participants were considered seropositive if they tested positive for SARS-CoV-2 immunoglobulin G (IgG) antibodies with the Abbott Architect SARS-CoV-2 IgG enzyme-linked immunosorbent assay (ELISA) and the EUROIMMUN SARS-CoV-2 ELISA in a sequential testing algorithm. The sensitivity and specificity of these ELISAs and the net sensitivity and specificity of the sequential testing algorithm were estimated, along with 95% confidence intervals (CIs). Results The estimated sensitivities of the Abbott and EUROIMMUN assays were 100% (107 of 107 [95% CI: 96.6%–100%]) and 90.7% (97 of 107 [83.5%–95.4%]), respectively, and the estimated specificities were 99.5% (995 of 1000 [98.8%–99.8%]) and 99.7% (997 of 1000 [99.1%–99.9%]), respectively. The net sensitivity and specificity of our sequential testing algorithm were 90.7% (97 of 107 [95% CI: 83.5%–95.4%]) and 100.0% (1000 of 1000 [99.6%–100%]), respectively. Of the 24 079 study participants with blood specimens from 2 January to 18 March 2020, 9 were seropositive, 7 before the first confirmed case in the states of Illinois, Massachusetts, Wisconsin, Pennsylvania, and Mississippi. Conclusions Our findings identified SARS-CoV-2 infections weeks before the first recognized cases in 5 US states., Seven individuals had detectable severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunoglobulin G before the first confirmed cases in Illinois, Massachusetts, Wisconsin, Pennsylvania, and Mississippi, suggesting that SARS-CoV-2 infections occurred weeks before recognized cases in at least 5 US states.

Background Persons with human immunodeficiency virus (PWH) with persistently low CD4 counts despite efficacious antiretroviral therapy could have higher hospitalization risk. Methods In 6 US and Canadian clinical cohorts, PWH with virologic suppression for ≥1 year in 2005–2015 were followed until virologic failure, loss to follow-up, death, or study end. Stratified by early (years 2–5) and long-term (years 6–11) suppression and lowest presuppression CD4 count Results The 6997 included patients (19 980 person-years) were 81% cisgender men and 40% white. Among patients with lowest presuppression CD4 count 500 cells/μL had aIRRs of 1.44 during early suppression (95% confidence interval [CI], 1.01–2.06), and 1.67 (95% CI, 1.03–2.72) during long-term suppression. Among patients with lowest presuppression CD4 count ≥200 (56%), patients with current CD4 351–500 vs >500 cells/μL had an aIRR of 1.22 (95% CI, .93–1.60) during early suppression and 2.09 (95% CI, 1.18–3.70) during long-term suppression. Conclusions Virologically suppressed patients with lower CD4 counts experienced higher hospitalization rates and could potentially benefit from targeted clinical management strategies.

Background The Scholarly Concentrations program was established at Johns Hopkins University School of Medicine in 2009 with the aim of instilling passion for scholarship. Objective Our study aimed to determine whether the Scholarly Concentrations program achieves positive changes in medical student self-efficacy in conducting research and, if so, whether this results in future career aspirations toward scholarship. Design We used the Clinical Research Appraisal Inventory-Short Form (CRAI-SF) to assess changes in self-efficacy among students completing the Scholarly Concentrations program between 2014 and 2017. We calculated composite mean scores of six domains. We included outcomes on whether students published a manuscript, overall program perceptions, and likelihood of future research careers. We analyzed relationships between CRAI-SF scores and outcomes using paired t-tests and multivariable-adjusted logistic regression. Results A total of 419 students completed the Scholarly Concentrations program. All 6 CRAI domain scores showed significant improvements in self-efficacy between the pre-Scholarly Concentrations and post-Scholarly Concentrations ratings (range of changes 0.76–1.39, p

Background People living with human immunodeficiency virus (HIV; PLWH) have a markedly elevated anal cancer risk, largely due to loss of immunoregulatory control of oncogenic human papillomavirus infection. To better understand anal cancer development and prevention, we determined whether recent, past, cumulative, or nadir/peak CD4+ T-cell count (CD4) and/or HIV-1 RNA level (HIV RNA) best predict anal cancer risk. Methods We studied 102 777 PLWH during 1996–2014 from 21 cohorts participating in the North American AIDS Cohort Collaboration on Research and Design. Using demographics-adjusted, cohort-stratified Cox models, we assessed associations between anal cancer risk and various time-updated CD4 and HIV RNA measures, including cumulative and nadir/peak measures during prespecified moving time windows. We compared models using the Akaike information criterion. Results Cumulative and nadir/peak CD4 or HIV RNA measures from approximately 8.5 to 4.5 years in the past were generally better predictors for anal cancer risk than their corresponding more recent measures. However, the best model included CD4 nadir (ie, the lowest CD4) from approximately 8.5 years to 6 months in the past (hazard ratio [HR] for Conclusions Our results are consistent with anal cancer promotion by severe, prolonged HIV-induced immunosuppression. Nadir and cumulative CD4 may represent useful markers for identifying PLWH at higher anal cancer risk.

Persons with HIV (PWH) are aging. The impact of aging on healthcare utilization is unknown. The objective of this study was to evaluate hospitalization rates and reasons stratified by age among PWH in longitudinal HIV care. Hospitalization data from 2014-2015 was obtained on all adults receiving HIV care at 14 diverse sites within the HIV Research Network in the United States. Modified clinical classification software from the Agency for Healthcare Research and Quality assigned primary ICD-9 codes into diagnostic categories. Analysis performed with multivariate negative binomial regression. Among 20,608 subjects during 2014-2015, all cause hospitalization rate was 201/1000PY. Non-AIDS defining infection (non-ADI) was the leading cause for admission (44.2/1000PY), followed by cardiovascular disease (CVD) (21.2/1000PY). In multivariate analysis of all-cause admissions, the incidence rate ratio (aIRR) increased with older age (age 18-29 reference): age 30-39 aIRR 1.09 (0.90,1.32), age 40-49 1.38 (1.16,1.63), age 50-59 1.58 (1.33,1.87), and age ≥ 60 2.14 (1.77,2.59). Hospitalization rates increased significantly with age for CVD, endocrine, renal, pulmonary, and oncology. All cause hospitalization rates increased with older age, especially among non-communicable diseases (NCDs), while non-ADIs remained the leading cause for hospitalization. HIV providers should be comfortable screening for and treating NCDs.

Background Prescription opioid use is greater among people living with HIV (PLWH), yet little is known about the prevalence of specific types of high-risk use among these individuals. Setting We analyzed clinical and demographic data from the HIV Research Network and prescribing data from Medicaid for noncancer patients seeking HIV treatment at 4 urban clinics between 2006 and 2010. Methods HIV Research Network patients were included in the analytic sample if they received at least one incident opioid prescription. We examined 4 measures of high-risk opioid use: (1) high daily dosage; (2) early refills; (3) overlapping prescriptions; and (4) multiple prescribers. Results Of 4605 eligible PLWH, 1814 (39.4%) received at least one incident opioid prescription during follow-up. The sample was 61% men and 62% African American with a median age of 44.5 years. High-risk opioid use occurred among 30% of incident opioid users (high daily dosage: 7.9%; early refills: 15.9%; overlapping prescriptions: 16.4%; and multiple prescribers: 19.7%). About half of the cumulative incidence of high-risk use occurred within 1 year of receiving an opioid prescription. After adjusting for study site, high-risk opioid use was greater among patients with injection drug use as an HIV risk factor [adjusted hazard ratio (aHR) = 1.39, 95% confidence interval: 1.11 to 1.74], non-Hispanic whites [aHR = 1.61, (1.21 to 2.14)], patients age 35-45 [aHR = 1.94, (1.33 to 2.80)] and 45-55 [aHR = 1.84, (1.27 to 2.67)], and patients with a diagnosis of chronic pain [aHR = 1.32, (1.03 to 1.70)]. Conclusions A large proportion of PLWH received opioid prescriptions, and among these opioid recipients, high-risk opioid use was common. High-risk use patterns often occurred within the first year, suggesting this is a critical time for intervention.

BACKGROUND: Age-associated conditions are increasingly common among persons living with human immunodeficiency virus (HIV) (PLWH). A longitudinal investigation of their accrual is needed given their implications on clinical care complexity. We examined trends in the co-occurrence of age-associated conditions among PLWH receiving clinical care, and differences in their prevalence by demographic subgroup. METHODS: This cohort study was nested within the North American AIDS Cohort Collaboration on Research and Design. Participants from HIV outpatient clinics were antiretroviral therapy–exposed PLWH receiving clinical care (ie, ≥1 CD4 count) in the United States during 2000–2009. Multimorbidity was irreversible, defined as having ≥2: hypertension, diabetes mellitus, chronic kidney disease, hypercholesterolemia, end-stage liver disease, or non–AIDS-related cancer. Adjusted prevalence ratios (aPR) and 95% confidence intervals (CIs) comparing demographic subgroups were obtained by Poisson regression with robust error variance, using generalized estimating equations for repeated measures. RESULTS: Among 22969 adults, 79% were male, 36% were black, and the median baseline age was 40 years (interquartile range, 34–46 years). Between 2000 and 2009, multimorbidity prevalence increased from 8.2% to 22.4% (P(trend) < .001). Adjusting for age, this trend was still significant (P < .001). There was no difference by sex, but blacks were less likely than whites to have multimorbidity (aPR, 0.87; 95% CI, .77–.99). Multimorbidity was the highest among heterosexuals, relative to men who have sex with men (aPR, 1.16; 95% CI, 1.01–1.34). Hypertension and hypercholesterolemia most commonly co-occurred. CONCLUSIONS: Multimorbidity prevalence has increased among PLWH. Comorbidity prevention and multisubspecialty management of increasingly complex healthcare needs will be vital to ensuring that they receive needed care.

BACKGROUND Some individuals who appear poorly retained by clinic visit-based retention measures are using antiretroviral therapy (ART) and maintaining viral suppression. We examined whether individuals with a gap in HIV primary care (≥180 days between HIV outpatient clinic visits) obtained ART during that gap after 180 days. SETTING HIV Research Network data from 5 sites and Medicaid Analytic Extract eligibility and pharmacy data were combined. METHODS Factors associated with having both an HIV primary care gap and a new (ie, nonrefill) ART prescription during a gap were evaluated with multinomial logistic regression. RESULTS Of 6892 HIV Research Network patients, 6196 (90%) were linked to Medicaid data, and 4275 had any Medicaid ART prescription. Over half (54%) had occasional gaps in HIV primary care. Women, older people, and those with suppressed viral load were less likely to have a gap. Among those with occasional gaps (n = 2282), 51% received a new ART prescription in a gap. Viral load suppression before gap was associated with receiving a new ART prescription in a gap (odds ratio = 1.91, 95% confidence interval: 1.57 to 2.32), as was number of days in a gap (odds ratio = 1.04, 95% confidence interval: 1.02 to 1.05), and the proportion of months in the gap enrolled in Medicaid. CONCLUSIONS Medicaid-insured individuals commonly receive ART during gaps in HIV primary care, but almost half do not. Retention measures based on visit frequency data that do not incorporate receipt of ART and/or viral suppression may misclassify individuals who remain suppressed on ART as not retained.

Background: Microbiome dysbiosis predisposes to colorectal cancer (CRC), but a population-based study of antibiotic exposure and risk patterns is lacking. In this study, oral antibiotic use on CRC incidence was assessed. Methods: A matched case-control study (incident CRC cases and up to 5 matched controls) was performed using the Clinical Practice Research Datalink (CPRD; January 1, 1989 to December 31, 2012). Conditional logistic regression was used to assess CRC association with oral antibiotic use, adjusting for potential confounders. Antibiotic exposure in categorical and continuous terms (spline) was investigated for pattern of risk, stratified by specific tumour location. Findings: 28,980 CRC cases and 137,077 controls were identified. Oral antibiotic use was associated with CRC risk, but effects differed by anatomic location. Antibiotic use was found to be associated with excess risk of colon cancer in a dose-dependent fashion (Ptrend 60 days (Adjusted Odds Ratio [AOR], 0·85, 95% CI 0·79-0·93) as compared with no antibiotic exposure. Penicillins were associated with increased risk of colon cancer (AOR,1·09, [1·05-1·13]) whereas tetracyclines were associated with risk reduction for rectal cancer (AOR, 0·90, [0·84- 0·97]). Significant interactions were detected between antibiotic use and tumour location (colon vs rectum, Pinteraction ten years before diagnosis (AOR, 1·17, [1·06-1·31]). Interpretation: Oral antibiotic use is associated with an increased risk of colon cancer risk but a reduced risk for rectal cancer. This effect heterogeneity may suggest differences in gut microbiota and carcinogenesis mechanisms along the lower intestine tract. Funding Statement: This project was funded by Johns Hopkins Fisher Center Discovery Program and Bloomberg~Kimmel Institute for Cancer Immunotherapy. Declaration of Interests: All authors have no directly relevant conflicts of interest to disclose. DP reports grant and patent royalties through institution from Bristol Myers Squibb, grant from Compugen, stock from Trieza Therapeutics and Dracen Pharmaceuticals, and founder 22 equity from Potenza; being consultant for Aduro Biotech, Amgen, Astra Zeneca (Medimmune/Amplimmune), Bayer, DNAtrix, Dynavax Technologies Corporation, Ervaxx, FLX Bio, Rock Springs Capital, Janssen, Merck, Tizona, and ImmunomicTherapeutics; being scientific advisory board of Five Prime Therapeutics, Camden Nexus II, WindMil; being board of director for Dracen Pharmaceuticals outside the submitted work. SC reports being consultant for Novartis and Theravance outside the submitted work. CS reports grants from Bristol Myers Squibb for microbiome research outside the submitted work. All other authors have nothing to declare. Ethics Approval Statement: This study was approved by the Institutional Review Board of the Johns Hopkins University

Summary Background The HIV epidemic in the USA is a collection of diverse local microepidemics. We aimed to identify optimal combination implementation strategies of evidence-based interventions to reach 90% reduction of incidence in 10 years, in six US cities that comprise 24·1% of people living with HIV in the USA. Methods In this economic modelling study, we used a dynamic HIV transmission model calibrated with the best available evidence on epidemiological and structural conditions for six US cities: Atlanta (GA), Baltimore (MD), Los Angeles (CA), Miami (FL), New York City (NY), and Seattle (WA). We assessed 23 040 combinations of 16 evidence-based interventions (ie, HIV prevention, testing, treatment, engagement, and re-engagement) to identify combination strategies providing the greatest health benefit while remaining cost-effective. Main outcomes included averted HIV infections, quality-adjusted life-years (QALYs), total cost (in 2018 US$), and incremental cost-effectiveness ratio (ICER; from the health-care sector perspective, 3% annual discount rate). Interventions were implemented at previously documented and ideal (90% coverage or adoption) scale-up, and sustained from 2020 to 2030, with outcomes evaluated until 2040. Findings Optimal combination strategies providing health benefit and cost-effectiveness contained between nine (Seattle) and 13 (Miami) individual interventions. If implemented at previously documented scale-up, these strategies could reduce incidence by between 30·7% (95% credible interval 19·1–43·7; Seattle) and 50·1% (41·5–58·0; New York City) by 2030, at ICERs ranging from cost-saving in Atlanta, Baltimore, and Miami, to $95 416 per QALY in Seattle. Incidence reductions reached between 39·5% (26·3–53·8) in Seattle and 83·6% (70·8–87·0) in Baltimore at ideal implementation. Total costs of implementing strategies across the cities at previously documented scale-up reached $559 million per year in 2024; however, costs were offset by long-term reductions in new infections and delayed disease progression, with Atlanta, Baltimore, and Miami projecting cost savings over the 20 year study period. Interpretation Evidence-based interventions can deliver substantial public health and economic value; however, complementary strategies to overcome social and structural barriers to HIV care will be required to reach national targets of the ending the HIV epidemic initiative by 2030. Funding National Institutes of Health.

The clinical management of low-level viremia (LLV) remains unclear. The objective of this study was to investigate the association of blips and LLV with virologic failure.We enlisted patients who newly enrolled into the HIV Research Network between 2005 and 2015, had HIV-1 RNA more than 200 copies/ml, and were either antiretroviral therapy (ART)-naive or ART-experienced and not on ART. Patients were included who achieved virologic suppression (≤50 on two consecutive viral loads) and had at least two viral loads following suppression. Blips and LLV (≥2 consecutive51 copies/ml) were categorized separately into three categories: no blips/LLV, 51-200, 201-500. Cox proportional hazards regression was used to assess association between rates of blips/LLV and virologic failure (two consecutive500).The 2795 patients were mostly male (75.4%), black (50.3%), and MSM (52.9%). Median age was 38 years old (interquartile range 29-48). Most patients (88.8%) were ART-naive at study entry. Overall, 283 (10.1%) patients experienced virologic failure. A total of 152 (5.4%) patients experienced LLV to 51-200 and 110 (3.9%) patients experienced LLV to 201-500. Both LLV 51-200 [adjusted hazard ratio (aHR) 1.83 (1.10,3.04)] and LLV 201-500 [aHR 4.26 (2.65,6.86)] were associated with virologic failure. In sensitivity analysis excluding ART-experienced patients, the association between LLV 51 and 200 and virologic failure was not statistically significant.LLV between 201 and 500 was associated with virologic failure, as was LLV between 51 and 200, particularly among ART-experienced patients. Patients with LLV below the current Department of Health and Human Services threshold for virologic failure (persistent viremia ≥200) may require more intensive monitoring because of increased risk for virologic failure.

BackgroundResearch is needed to better understand relations between immunosuppression and HIV viraemia and risk for non-Hodgkin lymphoma, a common cancer in people living with HIV. We aimed to identify key CD4 count and HIV RNA (viral load) predictors of risk for non-Hodgkin lymphoma, overall and by subtype.MethodsWe studied people living with HIV during 1996-2014 from 21 Canadian and US cohorts participating in the North American AIDS Cohort Collaboration on Research and Design. To determine key independent predictors of risk for non-Hodgkin lymphoma, we assessed associations with time-updated recent, past, cumulative, and nadir or peak measures of CD4 count and viral load, using demographics-adjusted, cohort-stratified Cox models, and we compared models using Akaike's information criterion.FindingsOf 102 131 people living with HIV during the study period, 712 people developed non-Hodgkin lymphoma. The key independent predictors of risk for overall non-Hodgkin lymphoma were recent CD4 count (ie, lagged by 6 months

Background: Adults with HIV have an increased burden of non-AIDS-defining cancers, myocardial infarction, end-stage liver disease, and end-stage renal disease. The objective of this study was to estimate the population attributable fractions (PAFs) of preventable or modifiable HIV-related and traditional risk factors for non-AIDS-defining cancers, myocardial infarction, end-stage liver disease, and end-stage renal disease outcomes. Methods: We included participants receiving care in academic and community-based outpatient HIV clinical cohorts in the USA and Canada from Jan 1, 2000, to Dec 31, 2014, who contributed to the North American AIDS Cohort Collaboration on Research and Design and who had validated non-AIDS-defining cancers, myocardial infarction, end-stage liver disease, or end-stage renal disease outcomes. Traditional risk factors were tobacco smoking, hypertension, elevated total cholesterol, type 2 diabetes, renal impairment (stage 4 chronic kidney disease), and hepatitis C virus and hepatitis B virus infections. HIV-related risk factors were low CD4 count (400 copies per mL), and history of a clinical AIDS diagnosis. PAFs and 95% CIs were estimated to quantify the proportion of outcomes that could be avoided if the risk factor was prevented. Findings: In each of the study populations for the four outcomes (1405 of 61 500 had non-AIDS-defining cancer, 347 of 29 515 had myocardial infarctions, 387 of 35 044 had end-stage liver disease events, and 255 of 35 620 had end-stage renal disease events), about 17% were older than 50 years at study entry, about 50% were non-white, and about 80% were men. Preventing smoking would avoid 24% (95% CI 13–35) of these cancers and 37% (7–66) of the myocardial infarctions. Preventing elevated total cholesterol and hypertension would avoid the greatest proportion of myocardial infarctions: 44% (30–58) for cholesterol and 42% (28–56) for hypertension. For liver disease, the PAF was greatest for hepatitis C infection (33%; 95% CI 17–48). For renal disease, the PAF was greatest for hypertension (39%; 26–51) followed by elevated total cholesterol (22%; 13–31), detectable HIV RNA (19; 9–31), and low CD4 cell count (13%; 4–21). Interpretation: The substantial proportion of non-AIDS-defining cancers, myocardial infarction, end-stage liver disease, and end-stage renal disease outcomes that could be prevented with interventions on traditional risk factors elevates the importance of screening for these risk factors, improving the effectiveness of prevention (or modification) of these risk factors, and creating sustainable care models to implement such interventions during the decades of life of adults living with HIV who are receiving care. Funding: National Institutes of Health, US Centers for Disease Control and Prevention, the US Agency for Healthcare Research and Quality, the US Health Resources and Services Administration, the Canadian Institutes of Health Research, the Ontario Ministry of Health and Long Term Care, and the Government of Alberta.

BACKGROUND Before implementation of the Patient Protection and Affordable Care Act (ACA) in 2014, 100 000 persons living with human immunodeficiency virus (HIV) (PLWH) lacked healthcare coverage and relied on a safety net of Ryan White HIV/AIDS Program support, local charities, or uncompensated care (RWHAP/Uncomp) to cover visits to HIV providers. We compared HIV provider coverage before (2011-2013) versus after (first half of 2014) ACA implementation among a total of 28 374 PLWH followed up in 4 sites in Medicaid expansion states (California, Oregon, and Maryland), 4 in a state (New York) that expanded Medicaid in 2001, and 2 in nonexpansion states (Texas and Florida). METHODS Multivariate multinomial logistic models were used to assess changes in RWHAP/Uncomp, Medicaid, and private insurance coverage, using Medicare as a referent. RESULTS In expansion state sites, RWHAP/Uncomp coverage decreased (unadjusted, 28% before and 13% after ACA; adjusted relative risk ratio [ARRR], 0.44; 95% confidence interval [CI], .40-.48). Medicaid coverage increased (23% and 38%; ARRR, 1.82; 95% CI, 1.70-1.94), and private coverage was unchanged (21% and 19%; 0.96; .89-1.03). In New York sites, both RWHAP/Uncomp (20% and 19%) and Medicaid (50% and 50%) coverage were unchanged, while private coverage decreased (13% and 12%; ARRR, 0.86; 95% CI, .80-.92). In nonexpansion state sites, RWHAP/Uncomp (57% and 52%) and Medicaid (18% and 18%) coverage were unchanged, while private coverage increased (4% and 7%; ARRR, 1.79; 95% CI, 1.62-1.99). CONCLUSIONS In expansion state sites, half of PLWH relying on RWHAP/Uncomp coverage shifted to Medicaid, while in New York and nonexpansion state sites, reliance on RWHAP/Uncomp remained constant. In the first half of 2014, the ACA did not eliminate the need for RWHAP safety net provider visit coverage.

Several single-tablet regimens (STRs) are now available and are recommended for first-line antiretroviral therapy (ART); however, STR use for youth with HIV (YHIV) has not been systematically studied. We examined the characteristics associated with initiation of STRs versus multi-tablet regimens (MTRs) and the virological outcomes for youth with nonperinatally acquired HIV (nPHIV).A retrospective cohort study of nPHIV youth aged 13-24 years initiating ART between 2006 and 2014 at 18 US HIV clinical sites in the HIV Research Network was performed. The outcomes measured were initiation of STRs versus MTRs, virological suppression (VS) at 12 months, and time to VS. Demographic and clinical factors associated with initiation of STR versus MTR ART and VS ( 400 HIV-1 RNA copies/mL) at 12 months after initiation were assessed using multivariable logistic regression. Cox proportional hazards regression was used to assess VS within the first year.Of 987 youth, 67% initiated STRs. Of the 589 who had viral load data at 1 year, 84% of those on STRs versus 67% of those on MTRs achieved VS (P 0.01). VS was associated with STR use [adjusted odds ratio (AOR) 1.61; 95% confidence interval (CI) 1.01-2.58], white (AOR 2.41; 95% CI 1.13-5.13) or Hispanic (AOR 2.38; 95% CI 1.32-4.27) race/ethnicity, and baseline CD4 count 351-500 cells/μL (AOR 1.94; 95% CI 1.18-3.19) and 500 cells/μL (AOR 1.76; 95% CI 1.0-3.10). STR use was not associated with a shorter time to VS compared with MTR use [hazard ratio (HR) 1.07; 95% CI 0.90-1.28].Use of STR was associated with a greater likelihood of sustained VS 12 months after ART initiation in YHIV.

INTRODUCTION: Gaps in Medicaid enrollment may affect HIV outcomes. We evaluated factors associated with Medicaid enrollment gaps and their effect on viral suppression (VS) within the HIV Research Network. METHODS: We used a combined data set with Medicaid enrollment files from 2006 to 2010 and HIV Research Network demographic and clinical data. A gap was defined as ≥1 month without Medicaid and gap length was determined. We used multivariable logistic regression to determine factors associated with a gap and multivariable logistic regression with generalized estimated equations to evaluate factors associated with VS after gap. RESULTS: Of 5836 participants, the majority were male, of black race, and aged 25–50 years. More than half had a gap in Medicaid. Factors associated with a gap included male sex [adjusted odds ratio (aOR) 1.79, (1.53, 2.08)] and younger age (aORs ranging from 1.50 to 4.13 comparing younger age groups to age >50, P < 0.05 for all). About a quarter of gaps had VS information before and after gap. Of those, 53.7% had VS both before and after gap and 25.8% were unsuppressed both before and after gap. The strongest association with VS after gap was VS before gap [aOR 15.76 (10.48, 23.69)]. Transition into Ryan White HIV/AIDS Program coverage during Medicaid gaps was common (28% of all transitions). CONCLUSIONS: Gaps in Medicaid enrollment were common and many individuals with pre-gap VS maintained VS after gap, possibly due to accessing other sources of antiretroviral therapy coverage. Implementing initiatives to maintain Medicaid enrollment and to expedite Medicaid reenrollment and having alternate resources available in gaps are important to ensure continuous antiretroviral therapy to optimize HIV outcomes.

Because of limitations in the availability of data on primary care encounters, patient retention in human immunodeficiency virus (HIV) care is often estimated using laboratory measurement dates as proxies for clinical encounters, leading to possible outcome misclassification. This study included 83,041 HIV-infected adults from 14 clinical cohorts in the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) who had ≥1 HIV primary care encounters during 2000–2010, contributing 468,816 person-years of follow-up. Encounter-based retention (REB) was defined as ≥2 encounters in a calendar year, ≥90 days apart. Laboratory-based retention (RLB) was defined similarly, using the dates of CD4-positive cell counts or HIV-1 RNA measurements. Percentage of agreement and the κ statistic were used to characterize agreement between RLB and REB. Logistic regression with generalized estimating equations and stabilized inverse-probability-of-selection weights was used to elucidate temporal trends and the discriminatory power of RLB as a predictor of REB, accounting for age, sex, race/ethnicity, primary HIV risk factor, and cohort site as potential confounders. Both REB and RLB increased from 2000 to 2010 (from 67% to 78% and from 65% to 77%, respectively), though REB was higher than RLB throughout (P < 0.01). RLB agreed well with REB (80%–86% agreement; κ = 0.55–0.62, P < 0.01) and had a strong, imperfect ability to discriminate between persons retained and not retained in care by REB (C statistic: C = 0.81, P < 0.05). As a proxy for REB, RLB had a sensitivity and specificity of 84% and 77%, respectively, with misclassification error of 18%.

Screening persons living with HIV for gonorrhea and chlamydia has been recommended since 2003. We compared annual gonorrhea/chlamydia testing to syphilis and lipid testing among 19,368 adults (41% men who have sex with men, 30% heterosexual men, and 29% women) engaged in HIV care. In 2004, 22%, 62%, and 70% of all patients were tested for gonorrhea/chlamydia, syphilis, and lipid levels, respectively. Despite increasing steadily [odds ratio per year (95% confidence interval): 1.14 (1.13 to 1.15)], gonorrhea/chlamydia testing in 2010 remained lower than syphilis and lipid testing (39%, 77%, 76%, respectively). Interventions to improve gonorrhea/chlamydia screening are needed. A more targeted screening approach may be warranted.

Annual screening for gonorrhea [Neisseria gonorrhoeae (NG)] and chlamydia [Chlamydia trachomatis (CT)] is recommended for all sexually active persons living with HIV but is poorly implemented. Studies demonstrating no increases in NG and/or CT (NG/CT) case detection in clinics that successfully expanded NG/CT screening raise questions about this broad screening approach. We evaluated NG/CT case detection in the HIV Research Network during 2004-2014, a period of expanding testing.We analyzed linear time trends in annual testing (patients tested divided by all patients in care), test positivity (patients positive divided by all tested), and case detection (the number of patients with a positive result divided by all patients in care) using multivariate repeated measures logistic regression. We determined trends overall and stratified by men who have sex with men (MSM), men who have sex exclusively with women, and women.Among 15,614 patients (50% MSM, 26% men who have sex exclusively with women, and 24% women), annual NG/CT testing increased from 22% in 2004 to 60% in 2014 [adjusted odds ratio (AOR) per year 1.22 (1.21-1.22)]. Despite the increase in testing, test positivity also increased [AOR per year 1.10 (1.07-1.12)], and overall case detection increased from 0.8% in 2004 to 3.9% in 2014 [AOR per year 1.20 (1.17-1.22)]. Case detection was highest among MSM but increased over time among all 3 groups.NG/CT case detection increased as testing expanded in the population. This supports a broad approach to NG/CT screening among persons living with HIV to decrease transmission and complications of NG/CT and of HIV.