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BackgroundPost-COVID conditions (PCC) are common and have significant morbidity. Risk factors for PCC include advancing age, female sex, obesity, and diabetes mellitus. Little is known about early treatment, inflammation, and PCC.MethodsAmong 883 individuals with confirmed SARS-CoV-2 infection participating in a randomized trial of CCP vs. control plasma with available biospecimens and symptom data, the association between early COVID treatment, cytokine levels and PCC was evaluated. Cytokine and chemokine levels were assessed at baseline, day 14 and day 90 using a multiplexed sandwich immuosassay (Mesoscale Discovery). Presence of any self-reported PCC symptoms was assessed at day 90. Associations between COVID treatment, cytokine levels and PCC were examined using multivariate logistic regression models.ResultsOne-third of the 882 participants had day 90 PCC symptoms, with fatigue (14.5%) and loss of smell (14.5%) being most common. Cytokine levels decreased from baseline to day 90. In a multivariable analysis including diabetes, body mass index, race, and vaccine status, female sex (adjusted odds ratio[AOR]=2.70[1.93-3.81]), older age (AOR=1.32[1.17-1.50]), and elevated baseline levels of IL-6 (AOR=1.59[1.02-2.47]) were associated with development of PCC. There was a trend for decreased PCC in those with early CCP treatment (<5 days after symptom onset) compared to late CCP treatment.ConclusionIncreased IL-6 levels were associated with the development of PCC and there was a trend for decreased PCC with early CCP treatment in this predominately unvaccinated population. Future treatment studies should evaluate the effect of early treatment and anti-IL-6 therapies on PCC development.SummaryIncreased IL-6 levels were associated with the development of Post-COVID Conditions (PCC) and there was a trend for decreased PCC with early COVID convalescent plasma treatment in this predominately unvaccinated population.

The All of Us Research Program seeks to engage at least one million diverse participants to advance precision medicine and improve human health. We describe here the cloud-based Researcher Workbench that uses a data passport model to democratize access to analytical tools and participant information including survey, physical measurement, and electronic health record (EHR) data. We also present validation study findings for several common complex diseases to demonstrate use of this novel platform in 315,000 participants, 78% of whom are from groups historically underrepresented in biomedical research, including 49% self-reporting non-White races. Replication findings include medication usage pattern differences by race in depression and type 2 diabetes, validation of known cancer associations with smoking, and calculation of cardiovascular risk scores by reported race effects. The cloud-based Researcher Workbench represents an important advance in enabling secure access for a broad range of researchers to this large resource and analytical tools.

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

Background To 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. Methods In 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. Results Among 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. Conclusions Among 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.

PurposeTo (1) use All of Us (AoU) data to validate a previously published single-center model predicting the 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.DesignDevelopment and evaluation of machine learning models.MethodsElectronic health record data were extracted from AoU for 1,231 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 the 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.ResultsThe mean (standard deviation) age of the AoU cohort was 69.1 (10.5) years, with 57.3% women and 33.5% black, significantly exceeding representation in the single-center cohort (P=.04 and P < .001, respectively). Of 1,231 participants, 286 (23.2%) needed glaucoma surgery. When applying the single-center model to AoU data, accuracy was 0.69 and AUC was only 0.49. Using AoU data to train new models resulted in superior performance: AUCs ranged from 0.80 (logistic regression) to 0.99 (random forests).ConclusionsModels trained with national AoU data achieved superior performance compared with using single-center data. Although AoU does not currently include ophthalmic imaging, it offers several strengths over similar big-data sources such as claims data. AoU is a promising new data source for ophthalmic research.

BackgroundWith limited SARS-CoV-2 testing capacity in the US at the start of the epidemic (January - March), 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 January 2 to March 18, 2020. A participant was considered seropositive if they tested positive for SARS-CoV-2 immunoglobulin G (IgG) antibodies on the Abbott Architect SARS-CoV-2 IgG ELISA and the EUROIMMUN SARS-CoV-2 ELISA in a sequential testing algorithm. Sensitivity and specificity of the Abbott and EUROIMMUNE ELISAs and the net sensitivity and specificity of the sequential testing algorithm were estimated with 95% confidence intervals.ResultsThe estimated sensitivity of Abbott and EUROIMMUN was 100% (107/107 [96.6%, 100%]) and 90.7% (97/107 [83.5%, 95.4%]), respectively. The estimated specificity of Abbott and EUROIMMUN was 99.5% (995/1,000 [98.8%, 99.8%]) and 99.7% (997/1,000 [99.1%, 99.9%), respectively. The net sensitivity and specificity of our sequential testing algorithm was 90.7% (97/107 [83.5%, 95.4%]) and 100.0% (1,000/1,000 [99.6%, 100%]), respectively. Of the 24,079 study participants with blood specimens from January 2 to March 18, 2020, 9 were seropositive, 7 of whom were seropositive prior to the first confirmed case in the states of Illinois, Massachusetts, Wisconsin, Pennsylvania, and Mississippi.ConclusionsOur findings indicate SARS-CoV-2 infections weeks prior to the first recognized cases in 5 US states.

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.

Background During the COVID-19 pandemic, patients at the John G. Bartlett Specialty practice experienced disruptions in viral load (VL) monitoring due to 1) conversion to telemedicine visits and 2) closure of the onsite lab from March 16-July 13, 2021. We described the impact of the pandemic on VL monitoring. Methods We measured time from all index VLs collected during 3 periods: January 1, 2019 to March 15, 2020 (pre-pandemic); March 16 to July 12, 2020 (pandemic, closed onsite lab); and July 13 to December 31, 2020 (pandemic, open onsite lab) until a subsequent VL, 1 year after the index VL, or administrative censoring on December 31, 2020, whichever came first. We classified follow-up time according to these periods (treating period as a time-varying variable). We report hazard ratios (HRs) and 95% Confidence Intervals (CI) from a Cox proportional hazards model comparing the hazard of a VL during the pandemic periods to the pre-pandemic period, stratified by whether the index VL was suppressed (≤200 copies/mL). We tested for interactions between patient characteristics (age, sex at birth, race, ethnicity, and recent substance use) and period, to investigate differential effects of the pandemic on delayed VL. Results After 7,760 suppressed VL measurements, median times to subsequent VL during the pre-pandemic, pandemic (closed lab) and pandemic (open lab) periods, were 4.6 (HR=1.0), 8.9 (HR=0.34, CI:0.30, 0.37), and 5.8 (HR=0.73, CI:0.68,0.78) months respectively. After 1,025 non-suppressed VL measurements, median times to subsequent VL were 2.0 (HR=1.0), 3.9 (HR=0.57, CI:0.42,0.79), and 2.1 (HR=0.92, CI:0.76,1.10) months respectively. Time to subsequent VL after an index suppressed VL was less affected by the pandemic for patients who are white; had private insurance; or had no recent cocaine or heroin use. The effect of the pandemic on time to subsequent VL after a non-suppressed index VL did not significantly differ across patient characteristics. Conclusion Onsite lab closure disrupted VL collection for all groups. Once the onsite lab opened, the pandemic period was still associated with a delay among suppressed patients, but not non-suppressed patients. Further studies are needed to investigate if these delays are associated with lapses in viral suppression. Disclosures All Authors: No reported disclosures

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.

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.

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.

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.

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.

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

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.

Since the human immunodeficiency virus (HIV) epidemic began, several renal complications resulting from HIV infection of renal cells, immune dysregulation, and specific medications have been noted among individuals infected with HIV [1, 2]. The most severe of these, HIV-associated nephropathy (HIVAN), caused an estimated 35% of kidney lesions among HIV-infected patients biopsied during 1995–2004 [3] and was the fourth leading cause of end-stage renal disease (ESRD) among black individuals aged 20–64 years in 1994–1998 [4]. The incidence of HIVAN has declined with increased use of potent antiretroviral therapy (ART) [5–7]; however, there are other potential causes of ESRD in HIV-infected persons. Antiretroviral medications have renal effects including nephrotoxicity and stone formation [8]. Comorbidities such as diabetes mellitus, hypertension, and hepatitis C virus (HCV) infection are risk factors for progression to ESRD and are more common among HIV-infected persons [9–11]. Illicit drug use, which is more common among HIV-infected populations, also increases the risk of ESRD [12, 13]. Studies suggest that HIV-infected persons are more likely to experience ESRD than HIV-uninfected persons, with estimated incidence rates (IRs) in the US and Europe of 3–10 per 1000 person-years [14, 15] and 0.5 per 1000 PYs [16, 17], respectively, corresponding to a 2- to 20-fold greater risk compared with the general population. A large racial discrepancy has been noted in the burden of ESRD among HIV-infected and -uninfected individuals, with disproportionately higher risk borne by black individuals [17, 18]. Data from the United States Renal Data System (USRDS) indicated that the age- and sex-adjusted incidence of ESRD was approximately 3.4 times higher among blacks in the general population compared with whites in 2010 [19]. Whether reductions in the incidence of HIVAN have impacted the magnitude of the racial disparity in rates of ESRD among HIV-infected individuals is unknown. There is sparse information on the evolving face of ESRD in the HIV-infected population despite the significant burden of morbidity and mortality that ESRD presents [20–23]. Given the many potential contributors to ESRD risk, the goal of the present study was to assess the relative contributions of clinical and demographic factors to ESRD incidence and describe recent trends in ESRD risk in a cohort of HIV-infected individuals who are representative of HIV patients in care [24]. Our data, which include ESRD cases validated through an extensive medical record review of HIV-infected patients in clinical care through 2009, allowed us to capture changes in ESRD incidence concurrent with, and likely reflective of, modern therapy improvements. We hypothesized that well-documented improvements in HIV treatment in the modern therapy era have led to declines in risk of ESRD over this period, particularly among HIV-infected black individuals in care, given the diminishing role of HIVAN.

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

BACKGROUND There 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. METHODS We 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. RESULTS A 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

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.

Author(s): Yehia, Baligh R; Stephens-Shields, Alisa J; Fleishman, John A; Berry, Stephen A; Agwu, Allison L; Metlay, Joshua P; Moore, Richard D; Christopher Mathews, W; Nijhawan, Ank; Rutstein, Richard; Gaur, Aditya H; Gebo, Kelly A; HIV Research Network | Abstract: 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.

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.

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.

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

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.