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BackgroundEstimating the medical complexity of people aging with HIV can inform clinical programs and policy to meet future healthcare needs. The objective of our study was to forecast the prevalence of comorbidities and multimorbidity among people with HIV (PWH) using antiretroviral therapy (ART) in the United States (US) through 2030.Methods and findingsUsing the PEARL model-an agent-based simulation of PWH who have initiated ART in the US-the prevalence of anxiety, depression, stage ≥3 chronic kidney disease (CKD), dyslipidemia, diabetes, hypertension, cancer, end-stage liver disease (ESLD), myocardial infarction (MI), and multimorbidity (≥2 mental or physical comorbidities, other than HIV) were forecasted through 2030. Simulations were informed by the US CDC HIV surveillance data of new HIV diagnosis and the longitudinal North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) data on risk of comorbidities from 2009 to 2017. The simulated population represented 15 subgroups of PWH including Hispanic, non-Hispanic White (White), and non-Hispanic Black/African American (Black/AA) men who have sex with men (MSM), men and women with history of injection drug use and heterosexual men and women. Simulations were replicated for 200 runs and forecasted outcomes are presented as median values (95% uncertainty ranges are presented in the Supporting information). In 2020, PEARL forecasted a median population of 670,000 individuals receiving ART in the US, of whom 9% men and 4% women with history of injection drug use, 60% MSM, 8% heterosexual men, and 19% heterosexual women. Additionally, 44% were Black/AA, 32% White, and 23% Hispanic. Along with a gradual rise in population size of PWH receiving ART-reaching 908,000 individuals by 2030-PEARL forecasted a surge in prevalence of most comorbidities to 2030. Depression and/or anxiety was high and increased from 60% in 2020 to 64% in 2030. Hypertension decreased while dyslipidemia, diabetes, CKD, and MI increased. There was little change in prevalence of cancer and ESLD. The forecasted multimorbidity among PWH receiving ART increased from 63% in 2020 to 70% in 2030. There was heterogeneity in trends across subgroups. Among Black women with history of injection drug use in 2030 (oldest demographic subgroup with median age of 66 year), dyslipidemia, CKD, hypertension, diabetes, anxiety, and depression were most prevalent, with 92% experiencing multimorbidity. Among Black MSM in 2030 (youngest demographic subgroup with median age of 42 year), depression and CKD were highly prevalent, with 57% experiencing multimorbidity. These results are limited by the assumption that trends in new HIV diagnoses, mortality, and comorbidity risk observed in 2009 to 2017 will persist through 2030; influences occurring outside this period are not accounted for in the forecasts.ConclusionsThe PEARL forecasts suggest a continued rise in comorbidity and multimorbidity prevalence to 2030, marked by heterogeneities across race/ethnicity, gender, and HIV acquisition risk subgroups. HIV clinicians must stay current on the ever-changing comorbidities-specific guidelines to provide guideline-recommended care. HIV clinical directors should ensure linkages to subspecialty care within the clinic or by referral. HIV policy decision-makers must allocate resources and support extended clinical capacity to meet the healthcare needs of people aging with HIV.

BackgroundThe efficacy of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) convalescent plasma (CCP) for preventing infection in exposed, uninfected individuals is unknown. CCP might prevent infection when administered before symptoms or laboratory evidence of infection.MethodsThis double-blinded, phase 2 randomized, controlled trial (RCT) compared the efficacy and safety of prophylactic high titer (≥1:320 by Euroimmun ELISA) CCP with standard plasma. Asymptomatic participants aged ≥18 years with close contact exposure to a person with confirmed coronavirus disease 2019 (COVID-19) in the previous 120 hours and negative SARS-CoV-2 test within 24 hours before transfusion were eligible. The primary outcome was new SARS-CoV-2 infection.ResultsIn total, 180 participants were enrolled; 87 were assigned to CCP and 93 to control plasma, and 170 transfused at 19 sites across the United States from June 2020 to March 2021. Two were excluded for screening SARS-CoV-2 reverse transcription polymerase chain reaction (RT-PCR) positivity. Of the remaining 168 participants, 12/81 (14.8%) CCP and 13/87 (14.9%) control recipients developed SARS-CoV-2 infection; 6 (7.4%) CCP and 7 (8%) control recipients developed COVID-19 (infection with symptoms). There were no COVID-19-related hospitalizations in CCP and 2 in control recipients. Efficacy by restricted mean infection free time (RMIFT) by 28 days for all SARS-CoV-2 infections (25.3 vs 25.2 days; P = .49) and COVID-19 (26.3 vs 25.9 days; P = .35) was similar for both groups.ConclusionsAdministration of high-titer CCP as post-exposure prophylaxis, although appearing safe, did not prevent SARS-CoV-2 infection.Clinical trials registrationNCT04323800.

A care cascade is a critical tool for evaluating delivery of care for chronic infections across sequential stages, starting with diagnosis and ending with viral suppression. However, there have been few data describing the hepatitis B virus (HBV) care cascade among people living with HIV infection who have HBV coinfection. We conducted a cross-sectional study among people living with HIV and HBV coinfection receiving care between January 1, 2012 and December 31, 2016 within 13 United States and Canadian clinical cohorts contributing data to the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD). We evaluated each of the steps in this cascade, including: 1) laboratory-confirmed HBV infection, 2) tenofovir-based or entecavir-based HBV therapy prescribed, 3) HBV DNA measured during treatment, and 4) viral suppression achieved via undetectable HBV DNA. Among 3,953 persons with laboratory-confirmed HBV (median age, 50 years; 6.5% female; 43.8% were Black; 7.1% were Hispanic), 3,592 (90.9%; 95% confidence interval, 90.0-91.8%) were prescribed tenofovir-based antiretroviral therapy or entecavir along with their antiretroviral therapy regimen, 2,281 (57.7%; 95% confidence interval, 56.2-59.2%) had HBV DNA measured while on therapy, and 1,624 (41.1%; 95% confidence interval, 39.5-42.6) achieved an undetectable HBV DNA during HBV treatment. Our study identified significant gaps in measurement of HBV DNA and suppression of HBV viremia among people living with HIV and HBV coinfection in the United States and Canada. Periodic evaluation of the HBV care cascade among persons with HIV/HBV will be critical to monitoring success in completion of each step.

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. IMPORTANCE What 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.

BackgroundThe 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.MethodsBecause 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

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.

BackgroundWith 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.MethodsAll 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).ResultsThe 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.ConclusionsOur findings identified SARS-CoV-2 infections weeks before the first recognized cases in 5 US states.

BackgroundPersons with HIV (PWH) with persistently low CD4 counts despite efficacious antiretroviral therapy could have higher hospitalization risk.MethodsIn six 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 pre-suppression CD4 count 500 cells/μL had an aIRR of 1.44 during early suppression (95% CI 1.01-2.06), and 1.67 (1.03-2.72) during long-term suppression. Among patients with lowest pre-suppression CD4 ≥200 (56%), patients with current CD4 351-500 versus >500 cells/μL had an aIRR of 1.22 (0.93-1.60) during early suppression and 2.09 (1.18-3.70) during long-term suppression.ConclusionsVirologically suppressed patients with lower CD4 counts experienced higher hospitalization rates, and could potentially benefit from targeted clinical management strategies.

BackgroundTo assess the possible impact of antiretroviral therapy improvements, aging, and comorbidities, we examined trends in all-cause and cause-specific hospitalization rates among persons with HIV (PWH) from 2005 to 2015.MethodsIn 6 clinical cohorts, we followed PWH in care (≥1 outpatient CD4 count or HIV load [VL] every 12 months) and categorized ICD codes of primary discharge diagnoses using modified Clinical Classifications Software. Poisson regression estimated hospitalization rate ratios for calendar time trends, adjusted for demographics, HIV risk factor, and annually updated age, CD4, and VL.ResultsAmong 28 057 patients (125 724 person-years), from 2005 to 2015, the median CD4 increased from 389 to 580 cells/µL and virologic suppression from 55% to 85% of patients. Unadjusted all-cause hospitalization rates decreased from 22.3 per 100 person-years in 2005 (95% confidence interval [CI], 20.6-24.1) to 13.0 in 2015 (95% CI, 12.2-14.0). Unadjusted rates decreased for almost all diagnostic categories. Adjusted rates decreased for all-cause, cardiovascular, and AIDS-defining conditions, increased for non-AIDS-defining infection, and were stable for most other categories.ConclusionsAmong PWH with increasing CD4 counts and viral suppression, unadjusted hospitalization rates decreased for all-cause and most cause-specific hospitalizations, despite the potential effects of aging, comorbidities, and cumulative exposure to HIV and antiretrovirals.

BackgroundIt is unknown whether gaining inpatient health care coverage had an effect on hospitalization rates among persons with HIV (PWH) after implementation of the Affordable Care Act in 2014.MethodsHospitalization data from 2015 were obtained for 1634 adults receiving longitudinal HIV care at 3 US 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 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 with PWH who remained uncovered and Ryan White HIV/AIDS Program 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.ResultsAmong PWH without inpatient health care 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.ConclusionsAcquiring 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.

BackgroundWidespread viral and serological testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may present a unique opportunity to also test for human immunodeficiency virus (HIV) infection. We estimated the potential impact of adding linked, opt-out HIV testing alongside SARS-CoV-2 testing on the HIV incidence and the cost-effectiveness of this strategy in 6 US cities.MethodsUsing a previously calibrated dynamic HIV transmission model, we constructed 3 sets of scenarios for each city: (1) sustained current levels of HIV-related treatment and prevention services (status quo); (2) temporary disruptions in health services and changes in sexual and injection risk behaviors at discrete levels between 0%-50%; and (3) linked HIV and SARS-CoV-2 testing offered to 10%-90% of the adult population in addition to Scenario 2. We estimated the cumulative number of HIV infections between 2020-2025 and the incremental cost-effectiveness ratios of linked HIV testing over 20 years.ResultsIn the absence of linked, opt-out HIV testing, we estimated a total of a 16.5% decrease in HIV infections between 2020-2025 in the best-case scenario (50% reduction in risk behaviors and no service disruptions), and a 9.0% increase in the worst-case scenario (no behavioral change and 50% reduction in service access). We estimated that HIV testing (offered at 10%-90% levels) could avert a total of 576-7225 (1.6%-17.2%) new infections. The intervention would require an initial investment of $20.6M-$220.7M across cities; however, the intervention would ultimately result in savings in health-care costs in each city.ConclusionsA campaign in which HIV testing is linked with SARS-CoV-2 testing could substantially reduce the HIV incidence and reduce direct and indirect health care costs attributable to HIV.

BackgroundPersons 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.MethodsUsing 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).ResultsCombinations 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.ConclusionsEvidence-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.

BackgroundThe 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.MethodsIn 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.FindingsOptimal 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.InterpretationEvidence-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.FundingNational Institutes of Health.

BackgroundPeople 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.MethodsWe 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.ResultsCumulative 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

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.

Background. Heterogeneity in HIV microepidemics across US cities necessitates locally oriented, combination implementation strategies to prioritize resources. We calibrated and validated a dynamic, compartmental HIV transmission model to establish a status quo treatment scenario, holding constant current levels of care for 6 US cities. Methods. Built off a comprehensive evidence synthesis, we adapted and extended a previously published model to replicate the transmission, progression, and clinical care for each microepidemic. We identified a common set of 17 calibration targets between 2012 and 2015 and used the Morris method to select the most influential parameters for calibration. We then applied the Nelder-Mead algorithm to iteratively calibrate the model to generate 2000 best-fitting parameter sets. Finally, model projections were internally validated with a series of robustness checks and externally validated against published estimates of HIV incidence, while the face validity of 25-year projections was assessed by a Scientific Advisory Committee (SAC). Results. We documented our process for model development, calibration, and validation to maximize its transparency and reproducibility. The projected outcomes demonstrated a good fit to calibration targets, with a mean goodness-of-fit ranging from 0.0174 (New York City [NYC]) to 0.0861 (Atlanta). Most of the incidence predictions were within the uncertainty range for 5 of the 6 cities (ranging from 21% [Miami] to 100% [NYC]), demonstrating good external validity. The face validity of the long-term projections was confirmed by our SAC, showing that the incidence would decrease or remain stable in Atlanta, Los Angeles, NYC, and Seattle while increasing in Baltimore and Miami. Discussion. This exercise provides a basis for assessing the incremental value of further investments in HIV combination implementation strategies tailored to urban HIV microepidemics.

BackgroundThe 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.MethodsWe 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 consecutive >51 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 consecutive >500).ResultsThe 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.ConclusionLLV 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.

BackgroundAccurately 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.MethodsIn 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.FindingsThe 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.InterpretationOur 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.FundingUS National Institutes of Health, Agency for Healthcare Research and Quality, and Health Resources and Services Administration.

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).

Among 1942 persons with human immunodeficiency virus (HIV) without healthcare coverage in 2012-2015, transitioning to Medicaid (adjusted prevalence ratio, 0.95 [0.87, 1.04]) or to private health insurance (1.04 [0.95, 1.13]) was not associated with a change in consistent HIV viral suppression compared to continued reliance on the Ryan White HIV/AIDS Program.

ObjectiveThe costs of medical care for people with HIV/AIDS (PWH) vary substantially across demographic groups, stages of disease progression and regionally across the United States. We aimed to estimate medical costs for PWH and examine the heterogeneity in costs within key patient groups typically distinguished in cost-effectiveness analyses.DesignRetrospective cohort study using health administrative databases for diagnosed PWH in care at 17 HIV Research Network sites across the United States.MethodsWe estimated mean quarterly costs for key patient groups using multivariable generalized linear mixed effects models. We used quantile regression to highlight differences in the effect of covariates within each patient group (difference between covariate estimates at the mean versus the 90th percentile of quarterly costs), identifying covariates with a larger effect among the highest cost PWH, or generating greater uncertainty in mean cost estimates.ResultsOur sample included 40 022 patients with a median age of 39 years. Mean quarterly costs were highest for people who inject drugs with advanced disease progression and for PWH on antiretroviral treatment (ART). Within patient groups, we found the most heterogeneity at different levels of resource use for PWH on ART and PWH off ART with CD4 cell counts less than 200 cells/μl, people who inject drugs, as well as PWH in the South.ConclusionThe study quantifies heterogeneity in costs both across and within key PWH patient groups. Our results highlight the need for sensitivity analysis on cost estimates and may inform decisions on model structure in cost-effectiveness analyses on HIV/AIDS treatment and prevention strategies.

BackgroundDespite 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.SettingAdult patients enrolled at 12 sites of the HIV Research Network located in 3 regions of the United States were included.MethodsWe 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.ResultsAmong 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

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;

BackgroundThe United States National HIV/AIDS Strategy established goals to reduce disparities in retention in human immunodeficiency virus (HIV) care, antiretroviral therapy (ART) use, and viral suppression. The impact of sex, age, and sexual HIV acquisition risk (ie, heterosexual vs same-sex contact) on the magnitude of HIV-related racial/ethnic disparities is not well understood.MethodsWe estimated age-stratified racial/ethnic differences in the 5-year restricted mean percentage of person-time spent in care, on ART, and virally suppressed among 19 521 women (21.4%), men who have sex with men (MSM; 59.0%), and men who have sex with women (MSW; 19.6%) entering HIV care in the North American AIDS Cohort Collaboration on Research and Design between 2004 and 2014.ResultsAmong women aged 18-29 years, whites spent 12.0% (95% confidence interval [CI], 1.1%-20.2%), 9.2% (95% CI, .4%-20.4%), and 13.5% (95% CI, 2.7%-22.5%) less person-time in care, on ART, and virally suppressed, respectively, than Hispanics. Black MSM aged ≥50 years spent 6.3% (95% CI, 1.3%-11.7%), 11.0% (95% CI, 4.6%-18.1%), and 9.7% (95% CI, 3.6%-16.8%) less person-time in these stages, respectively, than white MSM ≥50 years of age. Among MSM aged 40-49 years, blacks spent 9.8% (95% CI, 2.4%-16.5%) and 11.9% (95% CI, 3.8%-19.3%) less person-time on ART and virally suppressed, respectively, than whites.ConclusionsRacial/ethnic differences in HIV care persist in specific populations defined by sex, age, and sexual HIV acquisition risk. Clinical and public health interventions that jointly target these demographic factors are needed.

BackgroundAdults 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.MethodsWe 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.FindingsIn 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).InterpretationThe 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.FundingNational 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.

BackgroundThere are few recent data on the rates of AIDS-defining opportunistic infections (OIs) among human immunodeficiency virus (HIV)-infected patients in care in the United States and Canada.MethodsWe studied HIV-infected participants in 16 cohorts in the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) during 2000-2010. After excluding 16 737 (21%) with any AIDS-defining clinical events documented before NA-ACCORD enrollment, we analyzed incident OIs among the remaining 63 541 persons, most of whom received antiretroviral therapy during the observation. We calculated incidence rates per 100 person-years of observation (hereafter, "person-years") with 95% confidence intervals (CIs) for the first occurrence of any OI and select individual OIs during 2000-2003, 2004-2007, and 2008-2010.ResultsA total of 63 541 persons contributed 261 573 person-years, of whom 5836 (9%) developed at least 1 OI. The incidence rate of any first OI decreased over the 3 observation periods, with 3.0 cases, 2.4 cases, and 1.5 cases per 100 person-years of observation during 2000-2003, 2004-2007, and 2008-2010, respectively (Ptrend

BackgroundAge-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.MethodsThis 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.ResultsAmong 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% (Ptrend < .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.ConclusionsMultimorbidity 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.

ObjectivesAnnual 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.MethodsWe 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.ResultsAmong 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.ConclusionsNG/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.

BackgroundCancer remains an important cause of morbidity and mortality in people with human immunodeficiency virus (PWHIV) on effective antiretroviral therapy (ART). Estimates of cancer-attributable mortality can inform public health efforts.MethodsWe evaluated 46956 PWHIV receiving ART in North American HIV cohorts (1995-2009). Using information on incident cancers and deaths, we calculated population-attributable fractions (PAFs), estimating the proportion of deaths due to cancer. Calculations were based on proportional hazards models adjusted for age, sex, race, HIV risk group, calendar year, cohort, CD4 count, and viral load.ResultsThere were 1997 incident cancers and 8956 deaths during 267145 person-years of follow-up, and 11.9% of decedents had a prior cancer. An estimated 9.8% of deaths were attributable to cancer (cancer-attributable mortality rate 327 per 100000 person-years). PAFs were 2.6% for AIDS-defining cancers (ADCs, including non-Hodgkin lymphoma, 2.0% of deaths) and 7.1% for non-AIDS-defining cancers (NADCs: lung cancer, 2.3%; liver cancer, 0.9%). PAFs for NADCs were higher in males and increased strongly with age, reaching 12.5% in PWHIV aged 55+ years. Mortality rates attributable to ADCs and NADCs were highest for PWHIV with CD4 counts

BackgroundIt is unclear whether immunosuppression leads to younger ages at cancer diagnosis among people living with human immunodeficiency virus (PLWH). A previous study found that most cancers are not diagnosed at a younger age in people with AIDS, with the exception of anal and lung cancers. This study extends prior work to include all PLWH and examines associations between AIDS, CD4 count, and age at cancer diagnosis.MethodsWe compared the median age at cancer diagnosis between PLWH in the North American AIDS Cohort Collaboration on Research and Design and the general population using data from the Surveillance, Epidemiology and End Results Program. We used statistical weights to adjust for population differences. We also compared median age at cancer diagnosis by AIDS status and CD4 count.ResultsAfter adjusting for population differences, younger ages at diagnosis (P < .05) were observed for PLWH compared with the general population for lung (difference in medians = 4 years), anal (difference = 4), oral cavity/pharynx (difference = 2), and kidney cancers (difference = 2) and myeloma (difference = 4). Among PLWH, having an AIDS-defining event was associated with a younger age at myeloma diagnosis (difference = 4; P = .01), and CD4 count

BackgroundHuman immunodeficiency virus (HIV)-infected patients coinfected with hepatitis B (HBV) and C (HCV) viruses are at increased risk of end-stage liver disease (ESLD). Whether modern antiretroviral therapy has reduced ESLD risk is unknown.MethodsTwelve clinical cohorts in the United States and Canada participating in the North American AIDS Cohort Collaboration on Research and Design validated ESLD events from 1996 to 2010. ESLD incidence rates and rate ratios according to hepatitis status adjusted for age, sex, race, cohort, time-updated CD4 cell count and HIV RNA were estimated in calendar periods corresponding to major changes in antiretroviral therapy: early (1996-2000), middle (2001-2005), and modern (2006-2010) eras.ResultsAmong 34 119 HIV-infected adults followed for 129 818 person-years, 380 incident ESLD outcomes occurred. ESLD incidence (per 1000 person-years) was highest in triply infected (11.57) followed by HBV- (8.72) and HCV- (6.10) coinfected vs 1.27 in HIV-monoinfected patients. Adjusted incidence rate ratios (95% confidence intervals) comparing the modern to the early antiretroviral era were 0.95 (.61-1.47) for HCV, 0.95 (.40-2.26) for HBV, and 1.52 (.46-5.02) for triply infected patients. Use of antiretrovirals dually activity against HBV increased over time. However, in the modern era, 35% of HBV-coinfected patients were not receiving tenofovir. There was little use of HCV therapy.ConclusionsDespite increasing use of antiretrovirals, no clear reduction in ESLD risk was observed over 15 years. Treatment with direct-acting antivirals for HCV and wider use of tenofovir-based regimens for HBV should be prioritized for coinfected patients.

We estimated US Department of Health and Human Services (DHHS)-approved human immunodeficiency virus (HIV) indicators. Among patients, 71% were retained in care, 82% were prescribed treatment, and 78% had HIV RNA ≤200 copies/mL; younger adults, women, blacks, and injection drug users had poorer outcomes. Interventions are needed to reduce retention- and treatment-related disparities.

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.

BackgroundHuman immunodeficiency virus (HIV)-infected adults, particularly those of black race, are at high-risk for end-stage renal disease (ESRD), but contributing factors are evolving. We hypothesized that improvements in HIV treatment have led to declines in risk of ESRD, particularly among HIV-infected blacks.MethodsUsing data from the North American AIDS Cohort Collaboration for Research and Design from January 2000 to December 2009, we validated 286 incident ESRD cases using abstracted medical evidence of dialysis (lasting >6 months) or renal transplant. A total of 38 354 HIV-infected adults aged 18-80 years contributed 159 825 person-years (PYs). Age- and sex-standardized incidence ratios (SIRs) were estimated by race. Poisson regression was used to identify predictors of ESRD.ResultsHIV-infected ESRD cases were more likely to be of black race, have diabetes mellitus or hypertension, inject drugs, and/or have a prior AIDS-defining illness. The overall SIR was 3.2 (95% confidence interval [CI], 2.8-3.6) but was significantly higher among black patients (4.5 [95% CI, 3.9-5.2]). ESRD incidence declined from 532 to 303 per 100 000 PYs and 138 to 34 per 100 000 PYs over the time period for blacks and nonblacks, respectively, coincident with notable increases in both the prevalence of viral suppression and the prevalence of ESRD risk factors including diabetes mellitus, hypertension, and hepatitis C virus coinfection.ConclusionsThe risk of ESRD remains high among HIV-infected individuals in care but is declining with improvements in virologic suppression. HIV-infected black persons continue to comprise the majority of cases, as a result of higher viral loads, comorbidities, and genetic susceptibility.

BackgroundThe HIV care continuum (diagnosis, linkage to care, retention in care, receipt of antiretroviral therapy (ART), viral suppression) has been used to identify opportunities for improving the delivery of HIV care. Continuum steps are typically calculated in a conditional manner, with the number of persons completing the prior step serving as the base population for the next step. This approach may underestimate the prevalence of viral suppression by excluding patients who are suppressed but do not meet standard definitions of retention in care. Understanding how retention in care and viral suppression interact and change over time may improve our ability to intervene on these steps in the continuum.MethodsWe followed 17,140 patients at 11 U.S. HIV clinics between 2010-2012. For each calendar year, patients were classified into one of five categories: (1) retained/suppressed, (2) retained/not-suppressed, (3) not-retained/suppressed, (4) not-retained/not-suppressed, and (5) lost to follow-up (for calendar years 2011 and 2012 only). Retained individuals were those completing ≥ 2 HIV medical visits separated by ≥ 90 days in the year. Persons not retained completed ≥ 1 HIV medical visit during the year, but did not meet the retention definition. Persons lost to follow-up had no HIV medical visits in the year. HIV viral suppression was defined as HIV-1 RNA ≤ 200 copies/mL at the last measure in the year. Multinomial logistic regression was used to determine the probability of patients' transitioning between retention/suppression categories from 2010 to 2011 and 2010 to 2012, adjusting for age, sex, race/ethnicity, HIV risk factor, insurance status, CD4 count, and use of ART.ResultsOverall, 65.8% of patients were retained/suppressed, 17.4% retained/not-suppressed, 10.0% not-retained/suppressed, and 6.8% not-retained/not-suppressed in 2010. 59.5% of patients maintained the same status in 2011 (kappa=0.458) and 53.3% maintained the same status in 2012 (kappa=0.437).ConclusionsNot counting patients not-retained/suppressed as virally suppressed, as is commonly done in the HIV care continuum, underestimated the proportion suppressed by 13%. Applying the care continuum in a longitudinal manner will enhance its utility.

Background The role of active hepatitis C virus (HCV) replication in chronic kidney disease (CKD) risk has not been clarified.Methods We compared CKD incidence in a large cohort of HIV-infected subjects who were HCV seronegative, HCV viremic (detectable HCV RNA), or HCV aviremic (HCV seropositive, undetectable HCV RNA). Stages 3 and 5 CKD were defined according to standard criteria. Progressive CKD was defined as a sustained 25% glomerular filtration rate (GFR) decrease from baseline to a GFR < 60 mL/min/1.73 m2. We used Cox models to calculate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs).Results A total of 52 602 HCV seronegative, 9508 HCV viremic, and 913 HCV aviremic subjects were included. Compared with HCV seronegative subjects, HCV viremic subjects were at increased risk for stage 3 CKD (adjusted HR 1.36 [95% CI, 1.26, 1.46]), stage 5 CKD (1.95 [1.64, 2.31]), and progressive CKD (1.31 [1.19, 1.44]), while HCV aviremic subjects were also at increased risk for stage 3 CKD (1.19 [0.98, 1.45]), stage 5 CKD (1.69 [1.07, 2.65]), and progressive CKD (1.31 [1.02, 1.68]).Conclusions Compared with HIV-infected subjects who were HCV seronegative, both HCV viremic and HCV aviremic individuals were at increased risk for moderate and advanced CKD.

BackgroundSince the mid-1990s, effective antiretroviral therapy (ART) regimens have improved in potency, tolerability, ease of use, and class diversity. We sought to examine trends in treatment initiation and resulting human immunodeficiency virus (HIV) virologic suppression in North America between 2001 and 2009, and demographic and geographic disparities in these outcomes.MethodsWe analyzed data on HIV-infected individuals newly clinically eligible for ART (ie, first reported CD4+ count

ObjectiveHIV infection and low CD4+ T-cell count are associated with an increased risk of persistent oncogenic human papillomavirus infection-the major risk factor for cervical cancer. Few reported prospective cohort studies have characterized the incidence of invasive cervical cancer (ICC) in HIV-infected women.MethodsData were obtained from HIV-infected and -uninfected female participants in the North American AIDS Cohort Collaboration on Research and Design with no history of ICC at enrollment. Participants were followed from study entry or January 1996 through ICC, loss to follow-up, or December 2010. The relationship of HIV infection and CD4+ T-cell count with risk of ICC was assessed using age-adjusted Poisson regression models and standardized incidence ratios. All cases were confirmed by cancer registry records and/or pathology reports. Cervical cytology screening history was assessed through medical record abstraction.ResultsA total of 13,690 HIV-infected and 12,021 HIV-uninfected women contributed 66,249 and 70,815 person-years of observation, respectively. Incident ICC was diagnosed in 17 HIV-infected and 4 HIV-uninfected women (incidence rate of 26 and 6 per 100,000 person-years, respectively). HIV-infected women with baseline CD4+ T-cells of ≥350, 200-349, and

BackgroundRetention in care is key to improving HIV outcomes. The goal of this study was to describe 'churn' in patterns of entry, exit, and retention in HIV care in the United States and Canada.MethodsAdults contributing ≥1 CD4 count or HIV-1 RNA (HIV-lab) from 2000 to 2008 in North American AIDS Cohort Collaboration on Research and Design clinical cohorts were included. Incomplete retention was defined as lack of 2 HIV-laboratories (≥90 days apart) within 12 months, summarized by calendar year. Beta-binomial regression models were used to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI) of factors associated with incomplete retention.ResultsAmong 61,438 participants, 15,360 (25%) with incomplete retention significantly differed in univariate analyses (P < 0.001) from 46,078 (75%) consistently retained by age, race/ethnicity, HIV risk, CD4, antiretroviral therapy use, and country of care (United States vs. Canada). From 2000 to 2004, females (OR = 0.82, CI: 0.70 to 0.95), older individuals (OR = 0.78, CI: 0.74 to 0.83 per 10 years), and antiretroviral therapy users (OR = 0.61, CI: 0.54 to 0.68 vs. all others) were less likely to have incomplete retention, whereas black individuals (OR = 1.31, CI: 1.16 to 1.49, vs. white), those with injection drug use HIV risk (OR = 1.68, CI: 1.49 to 1.89, vs. noninjection drug use), and those in care longer (OR = 1.09, CI: 1.07 to 1.11 per year) were more likely to have incomplete retention. Results from 2005 to 2008 were similar.DiscussionFrom 2000 to 2008, 75% of the North American AIDS Cohort Collaboration on Research and Design population was consistently retained in care with 25% experiencing some changes in status or churn. In addition to the programmatic and policy implications, the findings of this study identify patient groups who may benefit from focused retention efforts.

BackgroundBy supplementing an index composed of HIV biomarkers and age (restricted index) with measures of organ injury, the Veterans Aging Cohort Study (VACS) index more completely reflects risk of mortality. We compare the accuracy of the VACS and restricted indices (1) among subjects outside the Veterans Affairs Healthcare System, (2) more than 1-5 years of prior exposure to antiretroviral therapy (ART), and (3) within important patient subgroups.MethodsWe used data from 13 cohorts in the North American AIDS Cohort Collaboration (n = 10, 835) limiting analyses to HIV-infected subjects with at least 12 months exposure to ART. Variables included demographic, laboratory (CD4 count, HIV-1 RNA, hemoglobin, platelets, aspartate and alanine transaminase, creatinine, and hepatitis C status), and survival. We used C-statistics and net reclassification improvement (NRI) to test discrimination varying prior ART exposure from 1 to 5 years. We then combined Veterans Affairs Healthcare System (n = 5066) and North American AIDS Cohort Collaboration data, fit a parametric survival model, and compared predicted to observed mortality by cohort, gender, age, race, and HIV-1 RNA level.ResultsMean follow-up was 3.3 years (655 deaths). Compared with the restricted index, the VACS index showed greater discrimination (C-statistics: 0.77 vs. 0.74; NRI: 12%; P < 0.0001). NRI was highest among those with HIV-1 RNA

BackgroundCombination antiretroviral therapy (ART) has significantly increased survival among HIV-positive adults in the United States (U.S.) and Canada, but gains in life expectancy for this region have not been well characterized. We aim to estimate temporal changes in life expectancy among HIV-positive adults on ART from 2000-2007 in the U.S. and Canada.MethodsParticipants were from the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD), aged ≥20 years and on ART. Mortality rates were calculated using participants' person-time from January 1, 2000 or ART initiation until death, loss to follow-up, or administrative censoring December 31, 2007. Life expectancy at age 20, defined as the average number of additional years that a person of a specific age will live, provided the current age-specific mortality rates remain constant, was estimated using abridged life tables.ResultsThe crude mortality rate was 19.8/1,000 person-years, among 22,937 individuals contributing 82,022 person-years and 1,622 deaths. Life expectancy increased from 36.1 [standard error (SE) 0.5] to 51.4 [SE 0.5] years from 2000-2002 to 2006-2007. Men and women had comparable life expectancies in all periods except the last (2006-2007). Life expectancy was lower for individuals with a history of injection drug use, non-whites, and in patients with baseline CD4 counts

BackgroundThe U.S. National HIV/AIDS Strategy targets for 2015 include "increasing access to care and improving health outcomes for persons living with HIV in the United States" (PLWH-US).ObjectiveTo demonstrate the utility of the NA-ACCORD (North American AIDS Cohort Collaboration on Research and Design) for monitoring trends in the HIV epidemic in the United States and to present trends in HIV treatment and related health outcomes.DesignTrends from annual cross-sectional analyses comparing patients from pooled, multicenter, prospective, clinical HIV cohort studies with PLWH-US, as reported to national surveillance systems in 40 states.SettingU.S. HIV outpatient clinics.PatientsHIV-infected adults with 1 or more HIV RNA plasma viral load (HIV VL) or CD4 T-lymphocyte (CD4) cell count measured in any calendar year from 1 January 2000 to 31 December 2008.MeasurementsAnnual rates of antiretroviral therapy use, HIV VL, and CD4 cell count at death.Results45 529 HIV-infected persons received care in an NA-ACCORD-participating U.S. clinical cohort from 2000 to 2008. In 2008, the 26 030 NA-ACCORD participants in care and the 655 966 PLWH-US had qualitatively similar demographic characteristics. From 2000 to 2008, the proportion of participants prescribed highly active antiretroviral therapy increased by 9 percentage points to 83% (P < 0.001), whereas the proportion with suppressed HIV VL (≤2.7 log10 copies/mL) increased by 26 percentage points to 72% (P < 0.001). Median CD4 cell count at death more than tripled to 0.209 × 109 cells/L (P < 0.001).LimitationThe usual limitations of observational data apply.ConclusionThe NA-ACCORD is the largest cohort of HIV-infected adults in clinical care in the United States that is demographically similar to PLWH-US in 2008. From 2000 to 2008, increases were observed in the percentage of prescribed HAART, the percentage who achieved a suppressed HIV VL, and the median CD4 cell count at death.Primary funding sourceNational Institutes of Health; Centers for Disease Control and Prevention; Canadian Institutes of Health Research; Canadian HIV Trials Network; and the government of British Columbia, Canada.

HIV risk behaviors, susceptibility to HIV acquisition, progression of disease after infection, and response to antiretroviral therapy all vary by age. In those living with HIV, current effective treatment has increased the median life expectancy to >70 years of age. Biologic, medical, individual, social, and societal issues change as one ages with HIV infection, but there has been only a small amount of research in this field. Therefore, the Office of AIDS Research of the National Institutes of Health commissioned a working group to develop an outline of the current state of knowledge and areas of critical need for research in HIV and Aging; the working groups' findings and recommendations are summarized in this report. Key overarching themes identified by the group included the following: multimorbidity, polypharmacy, and the need to emphasize maintenance of function; the complexity of assessing HIV versus treatment effects versus aging versus concurrent disease; the inter-related mechanisms of immune senescence, inflammation, and hypercoagulability; the utility of multivariable indices for predicting outcomes; a need to emphasize human studies to account for complexity; and a required focus on issues of community support, caregivers, and systems infrastructure. Critical resources are needed to enact this research agenda and include expanded review panel expertise in aging, functional measures, and multimorbidity, and facilitated use and continued funding to allow long-term follow-up of cohorts aging with HIV.

BACKGROUND. Initiatives to improve early detection and access to human immunodeficiency virus (HIV) services have increased over time. We assessed the immune status of patients at initial presentation for HIV care from 1997 to 2007 in 13 US and Canadian clinical cohorts. METHODS. We analyzed data from 44,491 HIV-infected patients enrolled in the North American-AIDS Cohort Collaboration on Research and Design. We identified first presentation for HIV care as the time of first CD4(+) T lymphocyte (CD4) count and excluded patients who prior to this date had HIV RNA measurements, evidence of antiretroviral exposure, or a history of AIDS-defining illness. Trends in mean CD4 count (measured as cells/mm(3)) and 95% confidence intervals were determined using linear regression adjusted for age, sex, race/ethnicity, HIV transmission risk, and cohort. RESULTS. Median age at first presentation for HIV care increased over time (range, 40-43 years; P < .01), whereas the percentage of patients with injection drug use HIV transmission risk decreased (from 26% to 14%; P < .01) and heterosexual transmission risk increased (from 16% to 23%; P < .01). Median CD4 count at presentation increased from 256 cells/mm(3) (interquartile range, 96-455 cells/mm(3)) to 317 cells/mm(3) (interquartile range, 135-517 cells/mm(3)) from 1997 to 2007 (P < .01). The percentage of patients with a CD4 count > or = 350 cells/mm(3) at first presentation also increased from 1997 to 2007 (from 38% to 46%; P < .01). The estimated adjusted mean CD4 count increased at a rate of 6 cells/mm(3) per year (95% confidence interval, 5-7 cells/mm(3) per year). CONCLUSION. CD4 count at first presentation for HIV care has increased annually over the past 11 years but has remained