Epidemiological delays are key quantities that inform public health policy and clinical practice. They are used as inputs for mathematical and statistical models, which in turn can guide control strategies. In recent work, we found that censoring, right truncation, and dynamical bias were rarely addressed correctly when estimating delays and that these biases were large enough to have knock-on impacts across a large number of use cases. Here, we formulate a checklist of best practices for estimating and reporting epidemiological delays. We also provide a flowchart to guide practitioners based on their data. Our examples are focused on the incubation period and serial interval due to their importance in outbreak response and modeling, but our recommendations are applicable to other delays. The recommendations, which are based on the literature and our experience estimating epidemiological delay distributions during outbreak responses, can help improve the robustness and utility of reported estimates and provide guidance for the evaluation of estimates for downstream use in transmission models or other analyses.

BACKGROUND: Understanding the immune response kinetics to SARS-CoV-2 infection and COVID-19 vaccination is important in nursing home (NH) residents, a high-risk population. METHODS: An observational longitudinal evaluation of 37 consenting vaccinated NH residents with/without SARS-CoV-2 infection from October 2020 to July 2022 was conducted to characterize the immune response to spike protein due to infection and/or mRNA COVID-19 vaccine. Antibodies (IgG) to SARS-CoV-2 full-length spike, nucleocapsid, and receptor binding domain protein antigens were measured, and surrogate virus neutralization capacity was assessed using Meso Scale Discovery immunoassays. The participant's spike exposure status varied depending on the acquisition of infection or receipt of a vaccine dose. Longitudinal linear mixed effects modeling was used to describe trajectories based on the participant's last infection or vaccination; the primary series mRNA COVID-19 vaccine was considered two spike exposures. Mean antibody titer values from participants who developed an infection post receipt of mRNA COVID-19 vaccine were compared with those who did not. In a subset of participants (n = 15), memory B cell (MBC) S-specific IgG (%S IgG) responses were assessed using an ELISPOT assay. RESULTS: The median age of the 37 participants at enrollment was 70.5 years; 30 (81%) had prior SARS-CoV-2 infection, and 76% received Pfizer-BioNTech and 24% Moderna homologous vaccines. After an observed augmented effect with each spike exposure, a decline in the immune response, including %S IgG MBCs, was observed over time; the percent decline decreased with increasing spike exposures. Participants who developed an infection at least two weeks post-receipt of a vaccine were observed to have lower humoral antibody levels than those who did not develop an infection post-receipt. CONCLUSIONS: These findings suggest that understanding the durability of immune responses in this vulnerable NH population can help inform public health policy regarding the timing of booster vaccinations as new variants display immune escape.

BACKGROUND: Patients with ESKD on maintenance dialysis receive dialysis in common spaces with other patients and have a higher risk of severe SARS-CoV-2 infections. They may have persistently or intermittently positive SARS-CoV-2 RT-PCR tests after infection. We describe the clinical course of SARS-CoV-2 infection and the serologic response in a convenience sample of patients with ESKD to understand the duration of infectivity. METHODS: From August to November 2020, we enrolled patients on maintenance dialysis with SARS-CoV-2 infections from outpatient dialysis facilities in Atlanta, Georgia. We followed participants for approximately 42 days. We assessed COVID-19 symptoms and collected specimens. Oropharyngeal (OP), anterior nasal (AN), and saliva (SA) specimens were tested for the presence of SARS-CoV-2 RNA, using RT-PCR, and sent for viral culture. Serology, including neutralizing antibodies, was measured in blood specimens. RESULTS: Fifteen participants, with a median age of 58 (range, 37‒77) years, were enrolled. Median duration of RT-PCR positivity from diagnosis was 18 days (interquartile range [IQR], 8‒24 days). Ten participants had at least one, for a total of 41, positive RT-PCR specimens ≥10 days after symptoms onset. Of these 41 specimens, 21 underwent viral culture; one (5%) was positive 14 days after symptom onset. Thirteen participants developed SARS-CoV-2-specific antibodies, 11 of which included neutralizing antibodies. RT-PCRs remained positive after seroconversion in eight participants and after detection of neutralizing antibodies in four participants; however, all of these samples were culture negative. CONCLUSIONS: Patients with ESKD on maintenance dialysis remained persistently and intermittently SARS-CoV-2-RT-PCR positive. However, of the 15 participants, only one had infectious virus, on day 14 after symptom onset. Most participants mounted an antibody response, including neutralizing antibodies. Participants continued having RT-PCR-positive results in the presence of SARS-CoV-2-specific antibodies, but without replication-competent virus detected.

Currently, no Food and Drug Administration (FDA)-approved treatments for human monkeypox are available. Tecovirimat (Tpoxx), however, is an antiviral drug that has demonstrated efficacy in animal studies and is FDA-approved for treating smallpox. Use of tecovirimat for treatment of monkeypox in the United States is permitted only through an FDA-regulated Expanded Access Investigational New Drug (EA-IND) mechanism. CDC holds a nonresearch EA-IND protocol that facilitates access to and use of tecovirimat for treatment of monkeypox.() The protocol includes patient treatment and adverse event reporting forms to monitor safety and ensure intended clinical use in accordance with FDA EA-IND requirements. The current multinational monkeypox outbreak, first detected in a country where Monkeypox virus infection is not endemic in May 2022, has predominantly affected gay, bisexual, and other men who have sex with men (MSM) (1,2). To describe characteristics of persons treated with tecovirimat for Monkeypox virus infection, demographic and clinical data abstracted from available tecovirimat EA-IND treatment forms were analyzed. As of August 20, 2022, intake and outcome forms were available for 549 and 369 patients, respectively; 97.7% of patients were men, with a median age of 36.5 years. Among patients with available data, 38.8% were reported to be non-Hispanic White (White) persons, 99.8% were prescribed oral tecovirimat, and 93.1% were not hospitalized. Approximately one half of patients with Monkeypox virus infection who received tecovirimat were living with HIV infection. The median interval from initiation of tecovirimat to subjective improvement was 3 days and did not differ by HIV infection status. Adverse events were reported in 3.5% of patients; all but one adverse event were nonserious. These data support the continued access to and treatment with tecovirimat for patients with or at risk for severe disease in the ongoing monkeypox outbreak.

BACKGROUND: Multisystem inflammatory syndrome in adults (MIS-A) is a severe condition temporally associated with SARS-CoV-2 infection. METHODS: In this retrospective cohort study, we applied the U.S. Centers for Disease Control and Prevention (CDC) case definition to identify diagnosed and undiagnosed MIS-A cases among adults discharged April 2020-January 2021 from four Atlanta, Georgia hospitals affiliated with a single medical center. Non-MIS-A COVID-19 hospitalizations were identified using International Classification of Diseases, Tenth Revision encounter code U07.1. We calculated the ratio of MIS-A to COVID-19 hospitalizations, compared demographic characteristics of the two cohorts, and described clinical characteristics of MIS-A patients. RESULTS: We identified 11 MIS-A cases, none of which were diagnosed by the treatment team, and 5,755 COVID-19 hospitalizations (ratio 1: 523). Compared with patients with COVID-19, patients with MIS-A were more likely to be younger than 50 years (72.7% vs. 26.1%, p < 0.01) and to be non-Hispanic Black persons (81.8% vs. 50.0%, p = 0.04). Ten patients with MIS-A (90.9%) had at least one underlying medical condition. Two MIS-A patients (18.2%) had a previous episode of laboratory-confirmed COVID-19, occurring 37 and 55 days prior to admission. All MIS-A patients developed left ventricular systolic dysfunction. None had documented mucocutaneous involvement. All required intensive care, all received systemic corticosteroids, eight (72.7%) required mechanical ventilation, two (18.2%) required mechanical cardiovascular circulatory support, and none received intravenous immunoglobulin. Two (18.2%) died or were discharged to hospice. CONCLUSIONS: MIS-A is severe but likely underrecognized complication of SARS-CoV-2 infection. Improved recognition of MIS-A is needed to quantify its burden and identify populations at highest risk.

BACKGROUND: Safe and effective long-acting injectable agents for preexposure prophylaxis (PrEP) for human immunodeficiency virus (HIV) infection are needed to increase the options for preventing HIV infection. METHODS: We conducted a randomized, double-blind, double-dummy, noninferiority trial to compare long-acting injectable cabotegravir (CAB-LA, an integrase strand-transfer inhibitor [INSTI]) at a dose of 600 mg, given intramuscularly every 8 weeks, with daily oral tenofovir disoproxil fumarate-emtricitabine (TDF-FTC) for the prevention of HIV infection in at-risk cisgender men who have sex with men (MSM) and in at-risk transgender women who have sex with men. Participants were randomly assigned (1:1) to receive one of the two regimens and were followed for 153 weeks. HIV testing and safety evaluations were performed. The primary end point was incident HIV infection. RESULTS: The intention-to-treat population included 4566 participants who underwent randomization; 570 (12.5%) identified as transgender women, and the median age was 26 years (interquartile range, 22 to 32). The trial was stopped early for efficacy on review of the results of the first preplanned interim end-point analysis. Among 1698 participants from the United States, 845 (49.8%) identified as Black. Incident HIV infection occurred in 52 participants: 13 in the cabotegravir group (incidence, 0.41 per 100 person-years) and 39 in the TDF-FTC group (incidence, 1.22 per 100 person-years) (hazard ratio, 0.34; 95% confidence interval, 0.18 to 0.62). The effect was consistent across prespecified subgroups. Injection-site reactions were reported in 81.4% of the participants in the cabotegravir group and in 31.3% of those in the TDF-FTC group. In the participants in whom HIV infection was diagnosed after exposure to CAB-LA, INSTI resistance and delays in the detection of HIV infection were noted. No safety concerns were identified. CONCLUSIONS: CAB-LA was superior to daily oral TDF-FTC in preventing HIV infection among MSM and transgender women. Strategies are needed to prevent INSTI resistance in cases of CAB-LA PrEP failure. (Funded by the National Institute of Allergy and Infectious Diseases and others; HPTN 083 ClinicalTrials.gov number, NCT02720094.).

We evaluated the association of bone fracture with mortality among persons with HIV, controlling for sociodemographic, behavioral, and clinical factors. Incident fracture was associated with 48% greater risk of all-cause mortality, underscoring the need for bone mineral density screening and fracture prevention. PURPOSE/INTRODUCTION: Low bone mineral density (BMD) and fracture are more common among persons with HIV (PWH) than those without HIV infection. We evaluated the association of bone fracture with mortality among PWH, controlling for sociodemographic, behavioral, and clinical factors. METHODS: We analyzed data from HIV Outpatient Study (HOPS) participants seen at nine US HIV clinics during January 1, 2000, through September 30, 2017. Incident fracture rates and post-fracture mortality were compared across four calendar periods. Cox proportional hazards analyses determined factors associated with all-cause mortality among all participants and those with incident fracture. RESULTS: Among 6763 HOPS participants, 504 (7.5%) had incident fracture (median age = 47 years) and 719 (10.6%) died. Of fractures, 135 (26.8%) were major osteoporotic (hip/pelvis, wrist, spine, arm/shoulder). During observation, 27 participants with major osteoporotic fractures died (crude mortality 2.97/100 person-years [PY]), and 48 with other site fractures died (crude mortality 2.51/100 PY). Post-fracture, age- and sex-adjusted all-cause mortality rates per 100 PY decreased from 8.5 during 2000-2004 to 1.9 during 2013-2017 (P<0.001 for trend). In multivariable analysis, incident fracture was significantly associated with all-cause mortality (Hazard Ratio 1.48, 95% confidence interval 1.15-1.91). Among 504 participants followed post-fracture, pulmonary, kidney, and cardiovascular disease, hepatitis C virus co-infection, and non-AIDS cancer, remained independently associated with all-cause mortality. CONCLUSIONS: Incident fracture was associated with 48% greater risk of all-cause mortality among US PWH in care, underscoring the need for BMD screening and fracture prevention. Although fracture rates among PWH increased during follow-up, post-fracture death rates decreased, likely reflecting advances in HIV care.

INTRODUCTION: Studies among HIV-uninfected persons (mostly in their sixth decade of life) show that detectable coronary artery calcium (CAC) is independently associated with low bone mineral density (BMD), suggesting a possible common pathogenic mechanism. AIM: We assessed the relationship between CAC and BMD, which has not been well described among younger to middle-aged HIV-infected persons. METHODS: We studied participants with baseline CAC and BMD measures from a prospective cohort of HIV-infected persons enrolled in the Study to Understand the Natural History of HIV/AIDS in the Era of Effective Therapy (SUN) during 2004-2006. We used logistic regression to assess the association between detectable CAC (>0 Agatston score) and BMD (g/cm2, T-score), and adjusted for known traditional and HIV-related risk factors. RESULTS: Among 472 participants (76% male, 30% non-Hispanic black, median age 41 years, 71% with HIV RNA <400 copies/mL), the majority had no detectable CAC (82%), but had baseline osteopenia (53%) or osteoporosis (10%). In univariate analysis, participants with detectable CAC had lower femoral neck/total hip T-scores, lower femoral neck/total hip/lumbar spine BMD, and higher rates of osteopenia/osteoporosis. After adjustment for age, all associations were no longer significant; adjustment for traditional risk factors excluding age and HIV-related variables failed to attenuate these associations. CONCLUSIONS: We found aging attenuates the association between detectable CAC and BMD in this cohort. Aging remains an important contributor to non-AIDS-defining illnesses. These data reinforce the importance of developing screening and prevention strategies for ageing HIV-infected persons given their excess risk across a wide spectrum of end-organ complications.

OBJECTIVES: Sepsis-3 defines organ dysfunction as an increase in the Sequential Organ Failure Assessment score by greater than or equal to 2 points. However, some Sequential Organ Failure Assessment score components are not routinely recorded in all hospitals' electronic health record systems, limiting its utility for wide-scale sepsis surveillance. The Centers for Disease Control and Prevention recently released the Adult Sepsis Event surveillance definition that includes simplified organ dysfunction criteria optimized for electronic health records (eSOFA). We compared eSOFA versus Sequential Organ Failure Assessment with regard to sepsis prevalence, overlap, and outcomes. DESIGN: Retrospective cohort study. SETTING: One hundred eleven U.S. hospitals in the Cerner HealthFacts dataset. PATIENTS: Adults hospitalized in 2013-2015. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We identified clinical indicators of presumed infection (blood cultures and antibiotics) concurrent with either: 1) an increase in Sequential Organ Failure Assessment score by 2 or more points (Sepsis-3) or 2) 1 or more eSOFA criteria: vasopressor initiation, mechanical ventilation initiation, lactate greater than or equal to 2.0 mmol/L, doubling in creatinine, doubling in bilirubin to greater than or equal to 2.0 mg/dL, or greater than or equal to 50% decrease in platelet count to less than 100 cells/muL (Centers for Disease Control and Prevention Adult Sepsis Event). We compared area under the receiver operating characteristic curves for discriminating in-hospital mortality, adjusting for baseline characteristics. Of 942,360 patients in the cohort, 57,242 (6.1%) had sepsis by Sequential Organ Failure Assessment versus 41,618 (4.4%) by eSOFA. Agreement between sepsis by Sequential Organ Failure Assessment and eSOFA was good (Cronbach's alpha 0.81). Baseline characteristics and infectious diagnoses were similar, but mortality was higher with eSOFA (17.1%) versus Sequential Organ Failure Assessment (14.4%; p < 0.001) as was discrimination for mortality (area under the receiver operating characteristic curve, 0.774 vs 0.759; p < 0.001). Comparisons were consistent across subgroups of age, infectious diagnoses, and comorbidities. CONCLUSIONS: The Adult Sepsis Event's eSOFA organ dysfunction criteria identify a smaller, more severely ill sepsis cohort compared with the Sequential Organ Failure Assessment score, but with good overlap and similar clinical characteristics. Adult Sepsis Events may facilitate wide-scale automated sepsis surveillance that tracks closely with the more complex Sepsis-3 criteria.

BACKGROUND: Prevalence rates of low bone mineral density (BMD) and bone fractures are higher among HIV-infected adults compared with the general United States (US) population, but the relationship between BMD and incident fractures in HIV-infected persons has not been well described. METHODS: Dual energy X-ray absorptiometry (DXA) results of the femoral neck of the hip and clinical data were obtained prospectively during 2004-2012 from participants in two HIV cohort studies. Low BMD was defined by a T-score in the interval >-2.5 to <-1.0 (osteopenia) or ≤-2.5 (osteoporosis). We analysed the association of low BMD with risk of subsequent incident fractures, adjusted for sociodemographics, other risk factors and covariables, using multivariable proportional hazards regression. RESULTS: Among 1,006 participants analysed (median age 43 years [IQR 36-49], 83% male, 67% non-Hispanic white, median CD4(+) T-cell count 461 cells/mm(3) [IQR 311-658]), 36% (n=358) had osteopenia and 4% (n=37) osteoporosis; 67 had a prior fracture documented. During 4,068 person-years of observation after DXA scanning, 85 incident fractures occurred, predominantly rib/sternum (n=18), hand (n=14), foot (n=13) and wrist (n=11). In multivariable analyses, osteoporosis (adjusted hazard ratio [aHR] 4.02, 95% CI 2.02, 8.01) and current/prior tobacco use (aHR 1.59, 95% CI 1.02, 2.50) were associated with incident fracture. CONCLUSIONS: In this large sample of HIV-infected adults in the US, low baseline BMD was significantly associated with elevated risk of incident fracture. There is potential value of DXA screening in this population.

The duration of influenza virus shedding in HIV-infected adults is unknown and could affect quarantine and treatment recommendations. Participants were monitored for influenza-like illness (ILI), defined as fever and cough or sore throat, using weekly telephone audio computer-assisted self-interviews. Those with ILI were further evaluated at three HIV-specialty clinics. For those with influenza, we collected nasopharyngeal washes every three days after the date of confirmed influenza infection for 21-28 days; specimens underwent RT-PCR and viral culture. Duration of influenza virus shedding was the interval from the date of onset (day 0) of ILI to the date of last culture-positive specimen. Characteristics were compared between patients with and without influenza using Fisher's exact test. We used the Wilcoxon rank-sum test to examine factors that may have affected influenza virus shedding. From 10/2010 to 4/2011, we enrolled 961 participants in syndromic surveillance and diagnosed 20 patients with influenza whose characteristics were: median age 48 years (interquartile range [IQR]: 43-53), 60% male, 50% non-Hispanic black, 95% had been prescribed cART, 85% were virologically suppressed (HIV RNA <400 copies/mL), median CD4 cell count 317 cells/mm3 (IQR: 190-544), and median follow-up time 21 days (IQR: 19-22). Compared with persons without influenza, persons with influenza were more likely to be older, use injection drugs, have a lower median CD4 cell count, and were less likely to have had an influenza vaccination in the past 12 months. Median durations of shedding, PCR detection, and ILI symptoms were 3 (IQR: 0-5), 10 (IQR: 6-15), and 14 days (IQR: 12-26), respectively. Median days of shedding were similar among patients with and without any prior influenza vaccination (0 vs. 4, p=0.448), HIV viral suppression (2 vs. 6, p=0.053), and oseltamivir use (5 vs. 0, p=0.083). HIV-infected persons on cART in our study shed influenza virus for a similar duration as that reported for HIV-uninfected persons.

HIV-infected persons are living longer on combination antiretroviral therapy (cART) but experiencing more comorbidities including low bone mineral density (BMD). Using data from the Study to Understand the Natural History of HIV and AIDS in the Era of Effective Therapy (SUN Study), we determined the prevalence of low BMD (T-score below one standard deviation of the reference mean) and compared it with matched controls from the National Health and Nutrition Examination Survey (NHANES). We also assessed 4-year longitudinal BMD changes among participants virologically suppressed on cART. Of 653 participants included in this analysis (77% male, 29% black, median age 41 years, median CD4+ cell count 464 cells/mm3, 89% with HIV RNA <400 copies/ml), 51% and 10% had baseline osteopenia and osteoporosis, respectively. Low BMD at the femoral neck was significantly more prevalent than for the NHANES controls (47% versus 29%, p<0.001). Lower body mass index, nonwhite race, longer tenofovir exposure, older age, being unemployed or retired, and lower apolipoprotein E were independently associated with baseline osteoporosis. Among 170 participants virologically suppressed on cART and with longitudinal BMD data, 31% experienced substantial bone loss (≥5% BMD decline from baseline) over 4 years. Female sex, current smoking, and longer stavudine use were more common among participants who had substantial bone loss, although these variables failed to reach statistical significance. Low BMD was highly prevalent among HIV-infected persons. One-third of participants experienced substantial bone loss despite cART, suggesting the need for monitoring and potential clinical interventions.

BACKGROUND: Anal cancer rates are higher for HIV-infected than uninfected adults. Limited published data exist characterizing precursor abnormal anal cytology incidence. METHODS: The Study to Understand the Natural History of HIV/AIDS in the Era of Effective Therapy was a prospective cohort of 700 HIV-infected participants in four U.S. cities. At baseline and annually thereafter, each completed a behavioral questionnaire, and providers collected anorectal swabs for cytologic examination and human papillomavirus (HPV) detection and genotyping. RESULTS: Among 243 participants with negative baseline anal cytology, 37% developed abnormal cytology (incidence rate 13.9/100 person-years [p-y], 95% confidence interval [CI] 11.3 - 16.9) over a median 2.1 years of follow-up. Rates among men having sex with men, women, and men having sex with women, were 17.9 p-y (CI: 13.9 - 22.7), 9.4 p-y (CI: 5.6 - 14.9), 8.9 p-y (CI: 4.8 - 15.6), respectively. In multivariable analysis, number of persistent high-risk HPV (HR) types (adjusted hazards ratio [adjHR] 1.17, CI: 1.01 - 1.36), persistent HR-HPV types except 16 or 18 ([adjHR] 2.46, CI 1.31 - 4.60), and persistent types 16 or 18 (adjHR 3.90, CI: 1.78 - 8.54) remained associated with incident abnormalities. CONCLUSIONS: Abnormal anal cytology incidence was high and more likely to develop among persons with persistent HR-HPV.

Obesity has been on the rise in the United States over the past three decades, and is high. In addition to population-wide trends, it is clear that obesity affects some groups more than others and can be associated with age, income, education, gender, race and ethnicity, and geographic region. To reverse the obesity epidemic, the Centers for Disease Control and Prevention) promotes evidence-based and practice-informed strategies to address nutrition and physical activity environments and behaviors. These public health strategies require translation into actionable approaches that can be implemented by state and local entities to address disparities. The Centers for Disease Control and Prevention used findings from an expert panel meeting to guide the development and dissemination of the Health Equity Resource Toolkit for State Practitioners Addressing Obesity Disparities (available at http://www.cdc.gov/obesity/health_equity/toolkit.html). The Toolkit helps public health practitioners take a systematic approach to program planning using a health equity lens. The Toolkit provides a six-step process for planning, implementing, and evaluating strategies to address obesity disparities. Each section contains (a) a basic description of the steps of the process and suggested evidence-informed actions to help address obesity disparities, (b) practical tools for carrying out activities to help reduce obesity disparities, and (c) a "real-world" case study of a successful state-level effort to address obesity with a focus on health equity that is particularly relevant to the content in that section. Hyperlinks to additional resources are included throughout.

BACKGROUND: Certain sociodemographic subgroups of HIV-infected patients may experience more chronic disease than others due to behavioral risk factors, advanced HIV disease, or complications from extended use of combination antiretroviral therapy (cART), but recent comparative data are limited. METHODS: We studied HIV-infected adult patients in care during 2006-2010 who had been prescribed ≥ 6 months of cART. We analyzed the prevalence of selected key chronic conditions, and polymorbidity (having 2 or more out of 10 key conditions) by gender and race/ethnicity. RESULTS: Of the 3,166 HIV-infected patients (median age, 47 years; CD4+ cell count, 496 cells/mm(3); duration of cART use, 6.8 years), 21% were female, 57% were non-Hispanic white, and over half were current or former tobacco smokers. The five most frequent conditions among women (median age, 45 years) were dyslipidemia (67.3%), hypertension (57.4%), obesity (31.7%), viral hepatitis B or C coinfection (29.0%), and low HDLc (27.3%). The five most frequent conditions in men (median age, 47 years) were dyslipidemia (81.2%), hypertension (54.4%), low HDLc (41.1%), elevated triglycerides (32.3%), and elevated non-HDLc (26.8%). In multivariable analyses, Hispanic patients had higher prevalence of obesity and diabetes than white patients; black patients had higher prevalence of obesity and hypertension but lower rates of lipid abnormalities. Of all patients, 73.7% of women and 66.8% of men had polymorbidity, with no evidence of disparities by race/ethnicity. CONCLUSIONS: Among contemporary cART-treated HIV-infected adults, chronic conditions and polymorbidity were common, underscoring the importance of chronic disease prevention and management among aging HIV-infected patients.

BACKGROUND: We evaluated whether routine biannual sexually transmitted disease (STD) testing coupled with brief risk-reduction counseling reduces STD incidence and high-risk behaviors. METHODS: The SUN study is a prospective observational HIV cohort study conducted in 4 US cities. At enrollment and every 6 months thereafter, participants completed a behavioral survey and were screened for STDs, and if diagnosed, were treated. Medical providers conducted brief risk-reduction counseling with all patients. Among men who have sex with men (MSM), we examined trends in STD incidence and rates of self-reported risk behaviors before and after exposure to the risk-reduction intervention. The "preintervention" visit was the study visit that was at least 6 months after enrollment STD screening and treatment and at which the participant was first exposed to the intervention. The "postintervention" visit was 12 months later. RESULTS: Among 216 MSM with complete STD and behavioral data, median age was 44.5 years; 77% were non-Hispanic white; 83% were on highly active antiretroviral treatment; 84% had an HIV RNA level <400 copies/mL and the median CD4 (cluster of differentiation 4) count was 511 cells/mm. Twelve months after first exposure to the risk-reduction intervention, STD incidence declined from 8.8% to 4.2% (P = 0.041). Rates of unprotected receptive or insertive anal intercourse with HIV-positive partners increased (19% to 25%, P = 0.024), but did not change with HIV-negative partners or partners of unknown HIV status (24% to 22%, P = 0.590). CONCLUSIONS: STD incidence declined significantly among HIV-infected MSM after implementing frequent, routine STD testing coupled with risk-reduction counseling. These findings support adoption of routine STD screening and risk-reduction counseling for HIV-infected MSM.

In the combination antiretroviral therapy (cART) era, renal dysfunction remains common. The Study to Understand the Natural History of HIV/AIDS in the Era of Effective Therapy (SUN) (ClinicalTrials.gov number, NCT00146419) is a prospective observational cohort study of HIV-infected adults. At baseline, comprehensive data were collected, including cystatin C and measures of renal function. Univariate and multivariate regression analyses were performed to identify factors associated with baseline renal dysfunction [estimated glomerular filtration rate (eGFR) < 90 ml/min/1.73 m(2) calculated using the simplified Modification of Diet in Renal Disease equation] and elevated cystatin C (>1.0 mg/liter) in a cross-sectional analysis. Among 670 subjects with complete data (mean age 41 years, mean CD4 cell count 530 cells/mm(3), 79% prescribed cART), the mean eGFR was 96.8 ml/min/1.73 m(2). Forty percent of subjects had renal dysfunction; 3.3% had chronic kidney disease (eGFR < 60 ml/min/1.73 m(2)). Elevated cystatin C was present in 18% of subjects. In multivariate analysis, renal dysfunction was associated with older age, non-Hispanic white race/ethnicity, higher body mass index (BMI), hypertension, higher cystatin C levels, and current prescription of ritonavir. Factors associated with elevated cystatin C included hepatitis C coinfection, hypertension, current smoking, older age, current tenofovir use, detectable plasma HIV RNA, and elevated microalbuminuria. The prevalence of chronic kidney disease (CKD) was low in this contemporary HIV cohort. However, mild to moderate renal dysfunction was common despite the widespread use of cART.

BACKGROUND: This study examined the effect of abacavir on acute changes in biomarkers associated with cardiovascular dysfunction. METHODS: Among the Study to Understand the Natural History of HIV/AIDS in the Era of Effective therapy (SUN) participants, we identified 25 individuals (cases) who were HLA-B5701-negative and who had ≥2 weeks without abacavir exposure at one visit and ≥2 weeks with abacavir exposure at the consecutive visit while maintaining viral suppression. We identified 43 individuals (controls) similarly unexposed and exposed to tenofovir. We assessed concentrations of prothrombin fragment F(1+2), D-dimer, high-sensitivity C-reactive protein, interleukin-8, intercellular adhesion molecule-1, vascular adhesion molecule-1, E-selectin, P-selectin, serum amyloid A and serum amyloid P. We examined the median percentage change of these biomarkers from the unexposed to exposed state among cases and controls compared with the expected assay variability using a sign test, and compared changes among cases with controls using the Wilcoxon rank-sum test. RESULTS: Baseline characteristics were similar between cases and controls: median age 45 versus 46 years, 80% versus 81% male, 64% versus 63% non-Hispanic White and median CD4(+) T-cell count 538 versus 601 cells/mm(3), respectively. Mean exposure times were 65 and 15 weeks for abacavir and tenofovir, respectively. We observed no significant changes in biomarkers from the unexposed to exposed state among cases or controls compared with the expected assay variability. We found that no biomarkers were significantly increased among cases compared with controls; however, prothrombin fragment F(1+2) was significantly lower among controls (P=0.035). CONCLUSIONS: In virologically suppressed contemporary HIV-infected patients, abacavir exposure was not associated with increases in biomarkers associated with increased cardiovascular risk.

BACKGROUND: We compared the herpes simplex virus type 2 (HSV-2) seroprevalence in a contemporary HIV cohort with the general US population and determined risk factors for HSV-2 infection among HIV-infected persons. METHODS: The Study to Understand the Natural History of HIV and AIDS in the Era of Effective Therapy (SUN) Study is a prospective observational cohort of 700 HIV-infected adults enrolled in 4 US cities between 2004 and 2006. At baseline, participants completed a behavioral risk questionnaire and provided specimens for HSV-2 serology. We calculated HSV-2 seroprevalence, standardized by age, gender, and race among HIV-infected persons compared with the general US adult population, using data from the National Health and Nutrition Examination Survey from 2003 to 2006. We examined risk factors associated with HSV-2 infection among HIV-infected persons using multivariate logistic regression. RESULTS: Among 660 (94%) SUN participants with adequate specimens for HSV-2 serologic testing, 548 (83%) were 20 to 49 years old (median age, 39 years; 77% male; 59% non-Hispanic white; median CD4 count, 470 cells/mm; 74% with HIV RNA viral loads <400 copies/mL). HSV-2 seroprevalence was significantly higher among HIV-infected adults (59.7%, 95% confidence interval: 55.8-63.6) compared with the general US population (19.2%, 95% confidence interval: 17.5-21.1). In multivariate analysis, we found that older age, female gender, black non-Hispanic race/ethnicity, being currently unemployed, high-risk anal HPV infection, and longer duration since HIV diagnosis were associated with significantly higher odds of HSV-2 infection. CONCLUSION: HSV-2 seroprevalence is 3 times as high among HIV-infected adults as in the general US population. Clinicians should be aware that increased risk for HSV-2 infection was distributed broadly among HIV-infected persons and not limited to those with high-risk sexual behaviors.

BACKGROUND: To better understand the factors associated with HIV- and sexually transmitted disease (STD)-transmitting behavior among HIV-infected persons, we estimated STD prevalence and incidence and associated risk factors among a diverse sample of HIV-infected patients in primary care. METHODS: We analyzed data from 557 participants in the SUN Study, a prospective observational cohort of HIV-infected adults in primary care in 4 US cities. At enrollment and 6 months thereafter, participants completed an audio computer-assisted self-interview about their sexual behavior, and were screened for genitourinary, rectal, and pharyngeal Neisseria gonorrhoeae and Chlamydia trachomatis infections by nucleic acid amplification testing, and for serologic evidence of syphilis. Women provided cervicovaginal samples and men provided urine to screen for Trichomonas vaginalis by polymerase chain reaction. RESULTS: Thirteen percent of participants had a prevalent STD at enrollment and 7% an incident STD 6 months later. The most commonly diagnosed infections were rectal chlamydia, oropharyngeal gonorrhea, and chlamydial urethritis among the men and trichomoniasis among the women. Other than trichomoniasis, 94% of incident STDs were identified in men who have sex with men. Polysubstance abuse other than marijuana, and having ≥4 sex partners in the 6 months before testing were associated with diagnosis of an incident STD. CONCLUSIONS: STDs were commonly diagnosed among contemporary HIV-infected patients receiving routine outpatient care, particularly among sexually active men who have sex with men who used recreational drugs. These findings underscore the need for frequent STD screening, prevention counseling, and substance abuse treatment for HIV-infected persons in care.

HIV-associated neurocognitive disorders remain prevalent but challenging to diagnose particularly among non-demented individuals. To determine whether a brief computerized battery correlates with formal neurocognitive testing, we identified 46 HIV-infected persons who had undergone both formal neurocognitive testing and a brief computerized battery. Simple detection tests correlated best with formal neuropsychological testing. By multivariable regression model, 53% of the variance in the composite Global Deficit Score was accounted for by elements from the brief computerized tool (P < 0.01). These data confirm previous correlation data with the computerized battery. Using the five significant parameters from the regression model in a Receiver Operating Characteristic curve, 90% of persons were accurately classified as being cognitively impaired or not. The test battery requires additional evaluation, specifically for identifying persons with mild impairment, a state upon which interventions may be effective.

BACKGROUND: Persons with human immunodeficiency virus (HIV) infection are at risk for premature cardiovascular disease (CVD). Predictors of atherosclerotic disease progression in contemporary patients have not been well described. METHODS: Using data from a prospective observational cohort of adults infected with HIV (Study to Understand the Natural History of HIV/AIDS in the Era of Effective Therapy), we assessed common carotid artery intima-media thickness (CIMT) at baseline and year 2 by ultrasound. We examined HIV-associated predictors of CIMT progression after adjusting for age, sex, race/ethnicity, body mass index, smoking, hypertension, diabetes, low-density lipoprotein cholesterol level, and baseline CIMT using linear regression. RESULTS: Among 389 participants (median age at baseline, 42 years; male sex, 77%; median CD4+ cell count at baseline, 485 cells/mm(3); 78% receiving antiretroviral therapy), the median 2-year CIMT change was 0.016 mm (interquartile range, -0.003 to 0.033 mm; P < .001). Lesser CIMT progression was associated with a suppressed viral load at baseline (-0.009 mm change; P = .015) and remaining virologically suppressed throughout follow-up (-0.011 mm change; P < .001). After adjusting for additional risk factors and a suppressed viral load during follow-up, nonnucleoside reverse transcriptase inhibitor versus protease inhibitor exposure was associated with lesser CIMT progression (-0.011 mm change; P = .02). CONCLUSIONS: Suppressing HIV replication below clinical thresholds was associated with less progression of atherosclerosis. The proatherogenic mechanisms of HIV replication and the net CVD benefit of different antiretroviral drugs should be a focus of future research.

BACKGROUND: In the era of highly active antiretroviral therapy (HAART), human immunodeficiency virus (HIV)-infected persons have higher cardiovascular disease risk. Little is known about asymptomatic abnormalities in cardiac structure and function in this population. METHODS: The Study to Understand the Natural History of HIV/AIDS in the Era of Effective Therapy (SUN Study) is a prospective, observational, multi-site cohort of 656 HIV-infected participants who underwent baseline echocardiography during 2004-2006. We examined prevalence of and factors associated with left ventricular systolic dysfunction (LVSD), diastolic dysfunction (DD), pulmonary hypertension (PHTN), left ventricular hypertrophy (LVH), and left atrial enlargement (LAE). RESULTS: Participant characteristics were as follows: median age, 41 years; 24% women; 29% non-Hispanic black; 73% receiving HAART; and median CD4+ cell count, 462 cells/muL. Among evaluable participants, 18% had LVSD, 26% had DD, 57% had PHTN (right ventricular pressure >30 mm Hg), 6.5% had LVH, and 40% had LAE. In multivariate analyses, significant factors (P < .05) associated with LVSD were history of MI, elevated highly sensitive C-reactive protein (hsCRP) level, and current tobacco smoking; for DD, elevated hsCRP level and hypertension; for PHTN, current use of ritonavir; for LVH, hypertension, diabetes, non-white race, female sex with elevated body mass index, calculated as the weight in kilograms divided by the square of height in meters, of ≥ 25, elevated hsCRP level, and current use of abacavir; for LAE, hypertension and recent marijuana use. CONCLUSIONS: In this large contemporary HIV cohort, the prevalence of subclinical functional and structural cardiac abnormalities was greater than expected for age. Abnormalities were mostly associated with expected and often modifiable risks. Lifestyle modification should become a greater priority in the management of chronic HIV disease.

BACKGROUND: Adherence of 95% or greater to highly active combination antiretroviral therapy is generally considered necessary to achieve optimal virologic suppression in HIV-infected patients. Understanding factors associated with poor adherence is essential to improve patient compliance, maximize virologic suppression, and reduce morbidity and mortality. METHODS: We evaluated baseline data from 528 patients taking antiretrovirals, enrolled from March 2004 to June 2006, in a multicenter, longitudinal, prospective cohort study (the SUN study). Using multiple logistic regression, we examined independent risk factors for non-adherence, defined as reporting having missed one or more antiretroviral doses in the past three days on the baseline questionnaire. RESULTS: Of 528 participants (22% female, 28% black, median age 41 years, and median CD4 cell count 486 cells/mm(3)), 85 (16%) were non-adherent. In the final parsimonious multivariate model, factors independently associated with non-adherence included black race (adjusted odds ratio (aOR): 2.08, 95% confidence interval (CI): 1.20-3.60 vs. white race), being unemployed and looking for work (aOR: 2.03, 95% CI: 1.14-3.61 vs. all other employment categories), having been diagnosed with HIV ≥5 years ago (aOR: 1.95, 95% CI: 1.18-3.24 vs. being HIV-diagnosed <5 years ago), drinking three or more drinks per day (aOR: 1.73, 95% CI: 1.02-2.91 vs. drinking <3 drinks per day), and having not engaged in any aerobic exercise in the last 30 days (aOR: 2.13, 95% CI: 1.25-3.57). CONCLUSION: Although the above factors may not be causally related to non-adherence, they might serve as proxies for identifying HIV-infected patients at greatest risk for non-adherence who may benefit from additional adherence support.

BACKGROUND: We explored serum 25-hydroxyvitamin D (25[OH]D) levels and associated factors for insufficiency or deficiency in an adult human immunodeficiency virus (HIV) cohort and compared 25(OH)D levels with those in the general US population. METHODS: Using baseline data from the Study to Understand the Natural History of HIV and AIDS in the Era of Effective Therapy (SUN), a prospective, observational cohort study of HIV-infected adults enrolled at 7 HIV specialty clinics in 4 US cities from March 2004 to June 2006, we estimated the prevalence of vitamin D insufficiency or deficiency (defined as 25(OH)D levels <30 ng/mL), standardized by age, race, and sex. Using multiple logistic regression, we examined risk factors for vitamin D insufficiency or deficiency. RESULTS: Among 672 SUN participants with baseline serum 25(OH)D determinations who were not receiving vitamin D supplements, 70.3% (95% confidence interval [CI], 68.1%-74.9%) were vitamin D insufficient or deficient, compared with 79.1% (95% CI, 76.7-81.3) of US adults. Factors associated with vitamin D insufficiency or deficiency included black race (adjusted odds ratio [aOR], 4.51; 95% CI, 2.59-7.85), Hispanic ethnicity (aOR, 2.78; 95% CI, 1.31-5.90), higher body mass index (aOR, 1.04; 95% CI, 1.00-1.09), hypertension (aOR, 1.88; 95% CI, 1.10-3.22), lack of exercise (aOR, 3.14; 95% CI, 1.80-5.47), exposure to efavirenz (aOR, 1.98; 95% CI, 1.18-3.34), higher exposure to ultraviolet light (aOR, .78; 95% CI, .71-.86), renal insufficiency (aOR, .55; 95% CI, .36-.83), and exposure to ritonavir (aOR, .56; 95% CI, .35-0.89). CONCLUSIONS: Similar to findings in US adults generally, vitamin D insufficiency or deficiency is highly prevalent among HIV-infected adults and is associated with known risk factors. Observed associations of vitamin D levels with renal insufficiency and with use of ritonavir- and efavirenz-containing regimens are consistent with both HIV-related and therapy-mediated alterations in vitamin D metabolism. Clinicians should consider screening all patients for vitamin D insufficiency or deficiency.

BACKGROUND: Human papillomavirus (HPV) infection of the cervix and related abnormal cervical cytology in HIV-infected women has been well described. Little is known about anal HPV infection in HIV-infected women. METHODS: The SUN Study is a prospective cohort study of 700 HIV-infected patients including 167 women. At baseline, patients completed a behavioral questionnaire and provided, among other samples, cervical and anal swabs for HPV detection and genotyping and for cytologic examination. Here, we present the available baseline data on the 167 women in the SUN study. RESULTS: Baseline results were available for 120 women (median age: 38 years, 57% non-Hispanic black, median CD4 cell count 444.5 cells/mm), of whom, 77% were taking antiretroviral therapy. The prevalences in the anus and cervix of any HPV were 90% and 83%, respectively (P = 0.039), and of high-risk (HR) types 85% and 70%, respectively, (P = 0.001). There was no significant difference in the prevalences of abnormal cytology between the anus and cervix: 38% and 33%, respectively (P = 0.217). Although the presence of abnormal cervical cytology was associated with the presence of abnormal anal cytology (relative risk: 1.7, P = 0.024), its sensitivity (52.5%) and positive predictive value positive (45.6%) for identifying women with abnormal anal cytology were poor. A history of anal sex was not associated with anal HPV infection or abnormal anal cytology. CONCLUSIONS: In this cohort of HIV-infected women, anal HPV infection was more prevalent and diverse than cervical HPV infection. Anal cytologic abnormalities were as prevalent as cervical cytologic abnormalities, and although abnormal cervical cytology was predictive of abnormal anal cytology, results were not highly concordant. These data support the need for studies of anal cytologic screening of HIV-infected women.

BACKGROUND: The prevalence of and risk factors for abnormal anal cytology among men and women with human immunodeficiency virus (HIV) infection have not been extensively investigated. METHODS: The Study to Understand the Natural History of HIV and AIDS in the Era of Effective Therapy (SUN study) is a prospective cohort study of HIV-infected patients in 4 US cities. Baseline questionnaires were administered and anal samples for cytology and human papillomavirus (HPV) detection and genotyping were collected. RESULTS: Among 471 men and 150 women (median age, 41 years), 78% of participants were receiving combination antiretroviral therapy, 41% had a CD4+ cell count of ≥500 cells/muL, and 71% had an HIV RNA viral load of <400 copies/mL. The anal cytology results were as follows: 336 participants (54%) had negative results, 96 participants (15%) had atypical squamous cells, 149 participants (24%) had low-grade squamous intraepithelial lesions, and 40 participants (6%) had high-grade squamous intraepithelial lesions. In a multivariate analysis, abnormal anal cytology was associated with number of high-risk and low-risk HPV types (adjusted odds ratio [AOR] for both, 1.28; P < .001), nadir CD4+ cell count of <50 cells/muL (AOR, 2.38; P=.001), baseline CD4+ cell count of <500 cells/muL (AOR, 1.75; P=.004), and ever having receptive anal intercourse (AOR, 2.51; P < .001). CONCLUSION: HIV-infected persons with multiple anal HPV types or a nadir CD4+ cell count of <50 cells/muL have an increased risk for abnormal anal cytology.