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ObjectivesOutcomes of community-acquired pneumonia (CAP) among HIV-infected older adults are unclear.MethodsAssociations between HIV infection and three CAP outcomes (30-day mortality, readmission within 30 days post-discharge, and hospital length of stay [LOS]) were examined in the Veterans Aging Cohort Study (VACS) of male Veterans, age ≥ 50 years, hospitalized for CAP from 10/1/2002 through 08/31/2010. Associations between the VACS Index and CAP outcomes were assessed in multivariable models.ResultsAmong 117 557 Veterans (36 922 HIV-infected and 80 635 uninfected), 1203 met our eligibility criteria. The 30-day mortality rate was 5.3%, the mean LOS was 7.3 days, and 13.2% were readmitted within 30 days of discharge. In unadjusted analyses, there were no significant differences between HIV-infected and uninfected participants regarding the three CAP outcomes (P > 0.2). A higher VACS Index was associated with increased 30-day mortality, readmission, and LOS in both HIV-infected and uninfected groups. Generic organ system components of the VACS Index were associated with adverse CAP outcomes; HIV-specific components were not. Among HIV-infected participants, those not on antiretroviral therapy (ART) had a higher 30-day mortality (HR 2.94 [95% CI 1.51, 5.72]; P = 0.002) and a longer LOS (slope 2.69 days [95% CI 0.65, 4.73]; P = 0.008), after accounting for VACS Index. Readmission was not associated with ART use (OR 1.12 [95% CI 0.62, 2.00] P = 0.714).ConclusionAmong HIV-infected and uninfected older adults hospitalized for CAP, organ system components of the VACS Index were associated with adverse CAP outcomes. Among HIV-infected individuals, ART was associated with decreased 30-day mortality and LOS.

OBJECTIVES:Community viral load (CVL) estimates vary based on analytic methods. We extended the CVL concept and used data from the Veterans Health Administration (VA) to determine trends in the health care system viral load (HSVL) and its sensitivity to varying definitions of the clinical population and assumptions regarding missing data. METHODS:We included HIV-infected patients in the Veterans Aging Cohort Study, 2000-2010, with at least one documented CD4 count, HIV-1 RNA or antiretroviral prescription (n = 37 318). We created 6-month intervals including patients with at least one visit in the past 2 years. We assessed temporal trends in clinical population size, patient clinical status and mean HSVL and explored the impact of varying definitions of the clinical population and assumptions about missing viral load. RESULTS:The clinical population size varied by definition, increasing from 16 000-19 000 patients in 2000 to 23 000-26 000 in 2010. The proportion of patients with suppressed HIV-1 RNA increased over time. Over 20% of patients had no viral load measured in a given interval or the past 2 years. Among patients with a current HIV-1 RNA, mean HSVL decreased from 97 800 HIV-1 RNA copies/mL in 2000 to 2000 copies/mL in 2010. When current HIV-1 RNA data were unavailable and the HSVL was recalculated using the last available HIV-1 RNA, HSVL decreased from 322 300 to 9900 copies/mL. HSVL was underestimated when using only current data in each interval. CONCLUSIONS:The CVL concept can be applied to a health care system, providing a measure of health care quality. Like CVL, HSVL estimates depend on definitions of the clinical population and assumptions about missing data.

OBJECTIVES:Community viral load (CVL) estimates vary based on analytic methods. We extended the CVL concept and used data from the Veterans Health Administration (VA) to determine trends in the health care system viral load (HSVL) and its sensitivity to varying definitions of the clinical population and assumptions regarding missing data. METHODS:We included HIV-infected patients in the Veterans Aging Cohort Study, 2000-2010, with at least one documented CD4 count, HIV-1 RNA or antiretroviral prescription (n = 37 318). We created 6-month intervals including patients with at least one visit in the past 2 years. We assessed temporal trends in clinical population size, patient clinical status and mean HSVL and explored the impact of varying definitions of the clinical population and assumptions about missing viral load. RESULTS:The clinical population size varied by definition, increasing from 16 000-19 000 patients in 2000 to 23 000-26 000 in 2010. The proportion of patients with suppressed HIV-1 RNA increased over time. Over 20% of patients had no viral load measured in a given interval or the past 2 years. Among patients with a current HIV-1 RNA, mean HSVL decreased from 97 800 HIV-1 RNA copies/mL in 2000 to 2000 copies/mL in 2010. When current HIV-1 RNA data were unavailable and the HSVL was recalculated using the last available HIV-1 RNA, HSVL decreased from 322 300 to 9900 copies/mL. HSVL was underestimated when using only current data in each interval. CONCLUSIONS:The CVL concept can be applied to a health care system, providing a measure of health care quality. Like CVL, HSVL estimates depend on definitions of the clinical population and assumptions about missing data.

ObjectiveGiven conflicting data regarding the association of HIV infection and ischemic stroke risk, we sought to determine whether HIV infection conferred an increased ischemic stroke risk among male veterans.MethodsThe Veterans Aging Cohort Study-Virtual Cohort consists of HIV-infected and uninfected veterans in care matched (1:2) for age, sex, race/ethnicity, and clinical site. We analyzed data on 76,835 male participants in the Veterans Aging Cohort Study-Virtual Cohort who were free of baseline cardiovascular disease. We assessed demographics, ischemic stroke risk factors, comorbid diseases, substance use, HIV biomarkers, and incidence of ischemic stroke from October 1, 2003, to December 31, 2009.ResultsDuring a median follow-up period of 5.9 (interquartile range 3.5-6.6) years, there were 910 stroke events (37.4% HIV-infected). Ischemic stroke rates per 1,000 person-years were higher for HIV-infected (2.79, 95% confidence interval 2.51-3.10) than for uninfected veterans (2.24 [2.06-2.43]) (incidence rate ratio 1.25 [1.09-1.43]; p < 0.01). After adjusting for demographics, ischemic stroke risk factors, comorbid diseases, and substance use, the risk of ischemic stroke was higher among male veterans with HIV infection compared with uninfected veterans (hazard ratio 1.17 [1.01-1.36]; p = 0.04).ConclusionsHIV infection is associated with an increased ischemic stroke risk among HIV-infected compared with demographically and behaviorally similar uninfected male veterans.

To study transmission patterns of Pneumocystis carinii pneumonia (PCP) in persons with AIDS, we evaluated P. carinii isolates from patients in five U.S. cities for variation at two independent genetic loci, the mitochondrial large subunit rRNA and dihydropteroate synthase. Fourteen unique multilocus genotypes were observed in 191 isolates that were examined at both loci. Mixed infections, accounting for 17.8% of cases, were associated with primary PCP. Genotype frequency distribution patterns varied by patients' place of diagnosis but not by place of birth. Genetic variation at the two loci suggests three probable characteristics of transmission: that most cases of PCP do not result from infections acquired early in life, that infections are actively acquired from a relatively common source (humans or the environment), and that humans, while not necessarily involved in direct infection of other humans, are nevertheless important in the transmission cycle of P. carinii f. sp. hominis.

Non-AIDS defining malignancies, including colorectal cancer (CRC), are emerging as significant problems in HIV-infected people. Some data suggest that HIV-positive patients have higher incidence of CRC at younger ages than those who are HIV-negative. This investigation examined CRC rates and screening types and trends between 943 HIV-infected cases and their age, race, and gender matched HIV-negative controls (n= 943) from 1 January 2005 to 31 December 2008 at the Atlanta VA Medical Center. The most common screening type among these patients was fecal occult blood testing (FOBT), but colonoscopies were more common in the controls (16.4% for cases, 27.5% for controls;p< 0.0001). Almost half of all patients included in this analysis did not have any screening for CRC during the four years of follow-up even though average age was 55 years. Fifty-one percent of cases had at least one screening test during follow-up compared to 48% of the controls; 7.6% of the cases had a screening each of the four years compared to only 2.4% of the controls (p< 0.0001). Ten HIV-positive patients were diagnosed with CRC during the study period compared to no CRC diagnoses among controls (p= 0.0015), though there was no difference in the diagnosis of colon polyps (4.6% vs. 5.1%,p= 0.5911). These data also suggest a discrepancy in CRC incidence between race and age groups: 80% of HIV-positive cases diagnosed with CRC during the study were black and two were less than 50 years of age. Future studies will need to address whether different recommendations are needed for screening based on HIV status, younger age, or race. [ABSTRACT FROM PUBLISHER]

Background: Different approaches are used to classify methicillin-resistant Staphylococcus aureus (MRSA) infections as either community-acquired (CA-MRSA) or health care-associated MRSA (HA-MRSA). Methods: We collected information on patients seen at the Atlanta Veterans Affairs Medical Center with MRSA infections from June 2007 through May 2008. We classified MRSA infections as either HA or CA using an epidemiologic definition and an antibiotic susceptibility phenotype rule. We used multivariate logistic regression to describe factors significantly associated with HA-MRSA infections compared with CA-MRSA infections. Results: Using the epidemiologic definition to classify infections, we found white race (odds ratio [OR], 3.2; 95% confidence interval [CI]: 2.0-5.2), oral antibiotics in the 3 months prior (OR, 4.0; 95% CI: 1.5-10.4), and endoscopy in the past year (OR, 3.8; 95% CI: 1.8-8.0) were significantly associated with health care-associated infections. When classifying by the resistance phenotype rule, we found hospitalization in the past year (OR: 1.8; 95% CI: 1.1-3.1) and an indwelling device in the past year (OR: 6.3; 95% CI: 2.5-15.8) were significantly associated with health care-associated infections. Conclusion: We found few differences between CA- and HA-MRSA infections, regardless of how health care-association was defined. We believe that the migration of CA-MRSA into health care settings and the recent increasing antibiotic resistance of CA-MRSA strains contribute to the lack of factors associated with HA (vs CA) MRSA. [ABSTRACT FROM AUTHOR]

Provides information on a study which examined the prevalence and survival rates for coinfection with human immunodeficiency virus and hepatitis C virus. How the study was conducted; Results; Discussion of the results.

The emphasis of immunization programs and schedules has traditionally been directed to infants and children, since most of the vaccine-preventable diseases are seen predominantly in these age groups. Immunization procedures in adults are less well defined but still of importance. Diseases for which immunizations are given before disease exposure include tetanus, diphtheria, influenza, rubella, and mumps; travelers to foreign countries may need immunizations against typhoid, cholera, yellow fever, typhus, poliomyelitis, plague, and viral hepatitis; other vaccines are available before disease exposure in unusual epidemiologic situations. After exposure to disease but before onset of symptoms, immunizations are available for rabies, viral hepatitis, and measles. After the onset of clinical illness, passive immunization should be given for tetanus, diphtheria, and botulism. This paper summarizes current practices for active and passive immunization against these diseases in adults. [ABSTRACT FROM AUTHOR]

BACKGROUND: Male veterans represent a large population at risk for acquiring or transmitting human immunodeficiency virus (HIV) infection. We sought to determine the prevalence of risky sexual behavior among veterans with and without HIV infection and to assess the relationship of intoxication before intercourse and other measures of drug and alcohol use to risky sexual behavior in this population. METHODS: We analyzed baseline data on 1009 HIV-positive (mean age 49 years) and 710 HIV-negative male veterans (mean age 55 years) who were participating in the Veterans Aging Cohort 5-Site Study (VACS 5). Participants completed a written questionnaire that included measures of alcohol and drug use and risky sexual behavior. RESULTS: Compared with HIV-negative veterans, HIV-positive veterans were more likely to report 5 or more sexual partners in the past year (14% vs. 4%, P < 0.01), less likely to report not using a condom at last intercourse (25% vs. 75%, P < 0.01), and similarly likely to report having 2 or more partners and inconsistent condom use (10% vs. 10%). Among sexually active HIV-positive veterans, intoxication before intercourse was significantly associated with having 5 or more sexual partners in the past year (odds ratio [OR] 1.8, 95% confidence interval [CI] 1.1-2.8), inconsistent condom use (OR 1.8, 95% CI 1.2-2.7), and the combined measure of 2 or more partners and inconsistent condom use (OR 1.8, 95% CI 1.1-3.0). Intoxication before intercourse was not significantly associated with these behaviors in HIV-negative veterans, although similar trends were noted. CONCLUSION: Risky sexual behavior was common among male veterans attending outpatient clinics and is more common among HIV-positive veterans who use alcohol and drugs in sexual situations. Asking HIV-positive men a single question about intoxication before intercourse could help to identify men at increased risk of engaging in risky sexual behavior, and specific advice to avoid intoxication in sexual situations could help to reduce risky sexual behavior. [ABSTRACT FROM AUTHOR]

Background: The Veterans Aging Cohort Study (VACS) is a study of human immunodeficiency virus (HIV) infected and uninfected patients seen in infectious disease and general medical clinics. VACS includes the earlier 3 and 5 site studies (VACS 3 and VACS 5) as well as the ongoing 8 site study.Objectives: We sought to provide background and context for analyses based upon VACS data, including study design and rationale as well as its basic protocol and the baseline characteristics of the enrolled sample.Research Design: We undertook a prospectively consented multisite observational study of veterans in care with and without HIV infection.Measures: Data were derived from patient and provider self report, telephone interviews, blood and DNA samples, focus groups, and full access to the national VA "paperless" electronic medical record system.Results: More than 7200 veterans have been enrolled in at least one of the studies. The 8 site study (VACS) has enrolled 2979 HIV-infected and 3019 HIV-uninfected age-race-site matched comparators and has achieved stratified enrollment targets for race/ethnicity and age and 99% of its total target enrollment as of October 30, 2005. Participants in VACS are similar to other veterans receiving care within the VA. VACS participants are older and more predominantly black than those reported by the Centers for Disease Control.Conclusions: VACS has assembled a rich, in-depth, and representative sample of veterans in care with and without HIV infection to conduct longitudinal analyses of questions concerning the association between alcohol use and related comorbid and AIDS-defining conditions. [ABSTRACT FROM AUTHOR]

Background: Causes of death and their trends among veterans with HIV (VWH) are different than those in the general population with HIV, but this has not been fully described. The objective was to understand the trends in, and risk factors for, all-cause and cause-specific mortality across eras of combination antiretroviral therapy (cART) among VWH., Setting: The HIV Atlanta VA Cohort Study includes all VWH who ever sought care at the Atlanta VA Medical Center., Methods: Age-adjusted all-cause and cause-specific mortality rates were calculated annually and compared between pre-cART (1982-1996), early-cART (1997-2006), and late-cART (2007-2016) eras. Trends were assessed using Kaplan-Meier curves, cumulative incidence functions, and joinpoint regression models. Risk factors were identified by Cox proportional hazards models., Results: Of the 4674 VWH in the HIV Atlanta VA Cohort Study, 1752 died; of whom, 1399 (79.9%), 301 (17.2%), and 52 (3.0%) were diagnosed with HIV in the pre-cART, early-cART, and late-cART eras, respectively. Significant increases were observed in rates of all-cause, AIDS-related, and non-AIDS-related mortality in the pre-cART era, followed by declines in the early-cART and late-cART eras. All-cause, AIDS-related, and non-AIDS-related mortality rates plummeted by 65%, 81%, and 45%, respectively, from the pre-cART to late-cART eras. However, VWH continue to die at higher rates due to AIDS-related infections, non-AIDS-related malignancies, respiratory disease, cardiovascular disease, and renal failure than those in the general population with HIV., Conclusions: In older populations with HIV, it is important that providers not only monitor for and treat diseases associated with aging but also intervene and address lifestyle risk factors., Competing Interests: V.C.M. has received investigator-initiated research grants (to the institution) and consultation fees (both unrelated to the current work) from Eli Lilly, Bayer, Gilead Sciences, and ViiV. K.J.V. received support from NICHD 1U19HD089881. V.C.M. received support from Emory CFAR P30 AI050409. The remaining authors have no funding or conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: At-risk levels of alcohol use threaten the health of patients with HIV (PWH), yet evidence-based strategies to decrease alcohol use and improve HIV-related outcomes in this population are lacking. We examined the effectiveness of integrated stepped alcohol treatment (ISAT) on alcohol use and HIV outcomes among PWH and at-risk alcohol use., Methods: In this multi-site, randomized trial conducted between January 28, 2013 through July 14, 2017, we enrolled PWH and at-risk alcohol use [defined as alcohol consumption of ≥ 14 drinks per week or ≥ 4 drinks per occasion in men ≤ 65 years old or ≥ 7 drinks per week or ≥ 3 drinks per occasion in women or men > 65 years old]. ISAT (n = 46) involved: Step 1- Brief Negotiated Interview with telephone booster, Step 2- Motivational Enhancement Therapy, and Step 3- Addiction Physician Management. Treatment as usual (TAU) (n = 47) involved receipt of a health handout plus routine care. Analyses were conducted based on intention to treat principles., Results: Despite a multi-pronged approach, we only recruited 37% of the target population (n = 93/254). Among ISAT participants, 50% advanced to Step 2, among whom 57% advanced to Step 3. Participants randomized to ISAT and TAU had no observed difference in drinks per week over the past 30 days at week 24 (primary outcome) [least square means (Ls mean) (95% CI) = 8.8 vs. 10.6; adjusted mean difference (AMD) (95% CI) =  - 0.4 (- 3.9, 3.0)]., Conclusion: An insufficient number of patients were interested in participating in the trial. Efforts to enhance motivation of PWH with at-risk alcohol use to engage in alcohol-related research and build upon ISAT are needed. Trial registration Clinicaltrials.gov: NCT01410123, First posted August 4, 2011.

Background: Cohort studies identifying the incidence, complications and co-morbidities associated with community acquired pneumonia (CAP) are largely based on administrative datasets and rely on International Classification of Diseases (ICD) codes; however, the reliability of ICD codes for hospital admissions for CAP in people with HIV (PWH) has not been systematically assessed., Methods: We used data from the Veterans Aging Cohort Study survey sample ( N  = 6824; 3410 PWH and 3414 uninfected) to validate the use of electronic health records (EHR) data to identify CAP hospitalizations when compared to chart review and to compare the performance in PWH vs. uninfected patients. We used different EHR algorithms that included a broad set of CAP ICD-9 codes, a set restricted to bacterial and viral CAP codes, and algorithms that included pharmacy data and/or other ICD-9 diagnoses frequently associated with CAP. We also compared microbiologic workup and etiologic diagnosis by HIV status among those with CAP., Results: Five hundred forty-nine patients were identified as having an ICD-9 code compatible with a CAP diagnosis (13% of PWH and 4% of the uninfected, p  < 0.01). The EHR algorithm with the best overall positive predictive value (82%) was obtained by using the restricted set of ICD-9 codes (480-487) in primary position or secondary only to selected codes as primary (HIV disease, respiratory failure, sepsis or bacteremia) with the addition of EHR pharmacy data; this algorithm yielded PPVs of 83% in PWH and 73% in uninfected ( P  = 0.1) groups. Adding aspiration pneumonia (ICD-9 code 507) to any of the ICD-9 code/pharmacy combinations increased the number of cases but decreased the overall PPV. Allowing COPD exacerbation in the primary position improved the PPV among the uninfected group only (to 76%). More PWH than uninfected patients underwent microbiologic evaluation or had respiratory samples submitted., Conclusions: ICD-9 code-based algorithms perform similarly to identify CAP in PLWH and uninfected individuals. Adding antimicrobial use data and allowing as primary diagnoses ICD-9 codes frequently used in patients with CAP improved the performance of the algorithms in both groups of patients. The algorithms consistently performed better among PWH., Competing Interests: Competing interestsThere are no competing interests for any of the co-authors., (© The Author(s) 2020.)

Background: Liver fibrosis, is independently associated with incident heart failure (HF). Investigating the association between liver fibrosis and type of HF, specifically HF with reduced ejection fraction (EF; HFrEF) or HF with preserved ejection fraction (HFpEF), may provide mechanistic insight into this association. We sought to determine the association between liver fibrosis score (FIB-4) and type of HF, and to assess whether HIV or hepatitis C status modified this association., Methods: We included patients alive on or after 4/1/2003 from the Veterans Aging Cohort Study. We followed patients without prevalent cardiovascular disease until their first HF event, death, last clinic visit, or 9/30/2015. We defined liver fibrosis as: likely advanced fibrosis (FIB-4 > 3.25), indeterminate (FIB-4 range 1.45-3.25), unlikely advanced fibrosis (FIB-4 < 1.45). Primary outcomes were HFrEF and HFpEF (defined using ICD-9 diagnoses for HF, and EF extracted from electronic medical records using natural language processing). Cox proportional hazards models were adjusted for potential confounders and used to estimate hazard ratios (HR)., Results: Among 108,708 predominantly male (96%) participants mean age was 49 years. Likely advanced fibrosis was present in 4% at baseline and was associated with an increased risk of HFpEF [HR (95% confidence interval)] [1.70 (1.3-2.3)]; and non-significantly with HFrEF [1.20 (0.9-1.7)]. These associations were not modified by HIV or hepatitis C status., Conclusion: Likely advanced fibrosis was independently associated with incident HFpEF but not HFrEF. This suggests that risk factors and/or mechanisms for liver fibrosis may have greater overlap with those for HFpEF than HFrEF., (Copyright © 2020. Published by Elsevier Inc.)

Background: Norovirus is an important cause of epidemic acute gastroenteritis (AGE), yet the burden of endemic disease in adults has not been well documented. We estimated the prevalence and incidence of outpatient and community-acquired inpatient norovirus AGE at 4 Veterans Affairs Medical Centers (VAMC) (Atlanta, Georgia; Bronx, New York; Houston, Texas; and Los Angeles, California) and examined trends over 4 surveillance years., Methods: From November 2011 to September 2015, stool specimens collected within 7 days of AGE symptom onset for clinician-requested diagnostic testing were tested for norovirus, and positive samples were genotyped. Incidence was calculated by multiplying norovirus prevalence among tested specimens by AGE-coded outpatient encounters and inpatient discharges, and dividing by the number of unique patients served., Results: Of 1603 stool specimens, 6% tested were positive for norovirus; GII.4 viruses (GII.4 New Orleans [17%] and GII.4 Sydney [47%]) were the most common genotypes. Overall prevalence and outpatient and inpatient community-acquired incidence followed a seasonal pattern, with higher median rates during November-April (9.2%, 376/100 000, and 45/100 000, respectively) compared to May-October (3.0%, 131/100 000, and 13/100 000, respectively). An alternate-year pattern was also detected, with highest peak prevalence and outpatient and inpatient community-acquired norovirus incidence rates in the first and third years of surveillance (14%-25%, 349-613/100 000, and 43-46/100 000, respectively)., Conclusions: This multiyear analysis of laboratory-confirmed AGE surveillance from 4 VAMCs demonstrates dynamic intra- and interannual variability in prevalence and incidence of outpatient and inpatient community-acquired norovirus in US Veterans, highlighting the burden of norovirus disease in this adult population., (Published by Oxford University Press for the Infectious Diseases Society of America 2019.)

Background: There is no known safe level of alcohol use among patients with HIV and liver disease. We examined the effectiveness of integrated stepped alcohol treatment (ISAT) on alcohol use, HIV, and liver outcomes among patients with HIV and liver disease., Methods: In this multi-site, randomized trial conducted between January 28, 2013 through July 15, 2016, we enrolled 95 patients with HIV and liver disease [defined as having active hepatitis C infection or FIB-4 score > 1.45]. ISAT (n = 49) involved: Step 1- Brief Negotiated Interview with telephone booster, Step 2- Motivational Enhancement Therapy, and Step 3- Addiction Physician Management. Treatment as usual (TAU) (n = 46) involved receipt of a health handout plus routine care. Analyses were conducted based on intention to treat., Results: Among ISAT participants, 55% advanced to Step 2, among whom 70% advanced to Step 3. Participants randomized to ISAT and TAU increased abstinence (primary outcome) over time. Abstinence rates were non-significantly higher by self-report (38% vs. 23%, adjusted odds ratio [AOR] [95% CI] = 2.6 [0.8, 9.0]) and phosphatidylethanol (43% vs. 32%, AOR [95% CI] = 1.8 [0.5, 6.3] among those randomized to ISAT vs. TAU at week 24. VACS Index scores (AMD [95% CI] = 1.1 [-3.2, 5.5]) and the proportion with an undetectable HIV viral load (AOR [95% CI] = 0.3 [0.1, 1.3]) did not differ by group at week 24 (p values >0.05). ISAT had non-significantly lower FIB-4 scores (adjusted mean difference [AMD] [95% CI] = -0.2 [-0.9, 0.5]), ALT (AMD [95% CI] = -7 [-20, 7]) and AST (AMD [95% CI] = -4 [-15, 7]) at week 24 compared to TAU., Conclusion: ISAT is feasible and potentially effective at enhancing delivery of evidence-based alcohol treatment to promote alcohol abstinence and improve liver biomarkers among patients with HIV and liver disease., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: We examined the effectiveness of integrated stepped alcohol treatment (ISAT) on alcohol use and HIV outcomes among patients living with HIV and alcohol use disorder., Methods: In this multisite, randomised controlled trial, conducted in five Veterans Affairs-based HIV clinics in the USA (Atlanta, GA; Brooklyn-Manhattan, NY; Dallas and Houston, TX; and Washington, DC), we recruited people living with HIV and an alcohol use disorder who were not otherwise receiving formal alcohol treatment. Patients were eligible if they were aged 18 years or older, HIV positive, English speaking, and met criteria for alcohol use disorder by the Diagnostic and Statistical Manual for Mental Disorders-IV criteria for alcohol abuse or dependence. Key exclusion criteria included if the patient was acutely suicidal or had a psychiatric condition that affected their ability to participate in counselling interventions, or if they had any medical conditions that would preclude completing the study or cause harm during the course of the study. Using a web-based clinical trial management system, we randomly assigned participants (1:1) to receive ISAT or treatment as usual; patients, investigators, and clinicians were unmasked to allocation. ISAT involved three steps: step 1, addiction physician management, comprising eight sessions; step 2, addiction physician management plus motivational enhancement therapy, comprising four sessions; and step 3, specialty referral. Participants were stepped up at weeks 4 and 12 if they exceeded a priori drinking criteria. Treatment as usual involved referral to substance use treatment services. The primary outcome was number of drinks per week over the past 30 days at week 24 by use of the timeline followback method, assessed in the intention-to-treat population. Adverse events were tracked throughout the study period in all randomly assigned participants. This trial is registered at ClinicalTrials.gov, number NCT01410123., Findings: Between Jan 28, 2013, and July 14, 2017, 128 of 351 patients assessed for eligibility were eligible and randomly assigned to receive ISAT (n=63) or treatment as usual (n=65). Mean age was 54 years (range 23-70), 125 (98%) of 128 participants were men, and 101 (79%) were black. 25 (20%) were lost to follow-up. In the ISAT group, of 57 participants who did not die or withdraw, 30 (52%) advanced to step 2, and 17 (57%) of 30 advanced to step 3. 32 (51%) of 63 participants assigned to ISAT versus 17 (26%) of 65 assigned to treatment as usual received at least one alcohol treatment medication (p=0·004). Participants in both groups decreased their alcohol consumption, but at week 24 we did not detect a difference in number of drinks per week between the groups (least squares mean 10·4 drinks per week [SD 16·5] in the ISAT group vs 15·6 drinks per week [SD 17·6] in the treatment as usual group; adjusted mean difference -4·2, 95% CI -9·4 to 0·9; p=0·11). One adverse event occurred that was possibly related to treatment occurred in the ISAT group (headache)., Interpretation: ISAT increases the receipt of alcohol treatment medications and counselling without changes in drinking at week 24. Strategies to implement and enhance ISAT are needed. Future efforts should focus on promoting ISAT with attention to enhancing patient engagement and retention in alcohol-related care., Funding: US National Institute on Alcohol Abuse and Alcoholism., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

HIV +Elite and Viremic controllers (EC/VCs) are able to control virus infection, perhaps because of host genetic determinants. We identified 16% (21 of 131) EC/VCs with CD4 +T cells with resistance specific to R5-tropic HIV, reversed after introduction of ccr5 . R5 resistance was not observed in macrophages and depended upon the method of T cell activation. CD4 +T cells of these EC/VCs had lower ccr2 and ccr5 RNA levels, reduced CCR2 and CCR5 cell-surface expression, and decreased levels of secreted chemokines. T cells had no changes in chemokine receptor mRNA half-life but instead had lower levels of active transcription of ccr2 and ccr5 , despite having more accessible chromatin by ATAC-seq. Other nearby genes were also down-regulated, over a region of ~500 kb on chromosome 3p21. This same R5 resistance phenotype was observed in family members of an index VC, also associated with ccr2 / ccr5 down-regulation, suggesting that the phenotype is heritable., Competing Interests: EG, PR, UI, RL, SM, AC, JP, TL, VM, DR, BW, SD, RS No competing interests declared

Background: HIV, hepatitis C virus (HCV), and alcohol-related diagnoses (ARD) independently contribute increased risk of all-cause hospitalization. We sought to determine annual medical intensive care unit (MICU) admission rates and relative risk of MICU admission between 1997 and 2014 among people with and without HIV, HCV, and ARD, using data from the largest HIV and HCV care provider in the United States., Setting: Veterans Health Administration., Methods: Annual MICU admission rates were calculated among 155,550 patients in the Veterans Aging Cohort Study by HIV, HCV, and ARD status. Adjusted rate ratios and 95% confidence intervals (CIs) were estimated with Poisson regression. Significance of trends in age-adjusted admission rates were tested with generalized linear regression. Models were stratified by calendar period to identify shifts in MICU admission risk over time., Results: Compared to HIV-/HCV-/ARD- patients, relative risk of MICU admission decreased among HIV-mono-infected patients from 61% (95% CI: 1.56 to 1.65) in 1997-2009% to 21% (95% CI: 1.16 to 1.27) in 2010-2014, increased among HCV-mono-infected patients from 22% (95% CI: 1.16 to 1.29) in 1997-2009% to 54% (95% CI: 1.43 to 1.67) in 2010-2014, and remained consistent among patients with ARD only at 46% (95% CI: 1.42 to 1.50). MICU admission rates decreased by 48% among HCV-uninfected patients (P-trend <0.0001) but did not change among HCV+ patients (P-trend = 0.34)., Conclusion: HCV infection and ARD remain key contributors to MICU admission risk. The impact of each of these conditions could be mitigated with combination of treatment of HIV, HCV, and interventions targeting unhealthy alcohol use.

Background: Despite historically high rates of herpes zoster among people living with HIV (PLWH), comparative studies of herpes zoster by HIV serostatus are lacking since the advent of combination antiretroviral therapy and availability of zoster vaccine., Methods: Annual rates (2002-2015) of first-episode herpes zoster and zoster vaccination were calculated for PLWH and uninfected adults in the Veterans Aging Cohort Study and stratified by HIV serostatus and age. Herpes zoster was captured using ICD9 codes and vaccine receipt with procedural codes and pharmacy data., Results: Of 45,177 PLWH and 103,040 uninfected veterans, rates of herpes zoster decreased among PLWH (17.6-8.1/1000) over the study period but remained higher than uninfected adults (4.1/1000) at the end of study period. Rates were higher in PLWH with lower CD4 (<200 vs >500 cells/µL: 18.0 vs 6.8/1000) and unsuppressed vs suppressed HIV-1 RNA (21.8 vs 7.1/1000). Restricted to virologically suppressed participants with CD4 >350 cells per microliter, herpes zoster rates were similar among PLWH aged younger than 60 years and aged 60 years and older in 2015 (6.6 vs 6.7/1000) but higher than all uninfected age groups. At study end, cumulative receipt of zoster vaccine for PLWH aged 60 years and older was less than half that of uninfected veterans: 98.7 vs 215.2/1000., Conclusions: Herpes zoster rates among PLWH have markedly decreased, but, even in cART-treated individuals, remain 50% higher than uninfected adults. Lower rates of zoster vaccine receipt combined with high rates of herpes zoster support the need for a safe and effective vaccine against herpes zoster for PLWH, formal zoster vaccine guidelines for PLWH, and consideration for expanded use at younger ages.

Background: Viral suppression is a primary marker of HIV treatment success. Persons with HIV are at increased risk for AIDS-defining cancer (ADC) and several types of non-AIDS-defining cancer (NADC), some of which are caused by oncogenic viruses., Objective: To determine whether viral suppression is associated with decreased cancer risk., Design: Prospective cohort., Setting: Department of Veterans Affairs., Participants: HIV-positive veterans (n = 42 441) and demographically matched uninfected veterans (n = 104 712) from 1999 to 2015., Measurements: Standardized cancer incidence rates and Poisson regression rate ratios (RRs; HIV-positive vs. uninfected persons) by viral suppression status (unsuppressed: person-time with HIV RNA levels ≥500 copies/mL; early suppression: initial 2 years with HIV RNA levels <500 copies/mL; long-term suppression: person-time after early suppression with HIV RNA levels <500 copies/mL)., Results: Cancer incidence for HIV-positive versus uninfected persons was highest for unsuppressed persons (RR, 2.35 [95% CI, 2.19 to 2.51]), lower among persons with early suppression (RR, 1.99 [CI, 1.87 to 2.12]), and lowest among persons with long-term suppression (RR, 1.52 [CI, 1.44 to 1.61]). This trend was strongest for ADC (unsuppressed: RR, 22.73 [CI, 19.01 to 27.19]; early suppression: RR, 9.48 [CI, 7.78 to 11.55]; long-term suppression: RR, 2.22 [CI, 1.69 to 2.93]), much weaker for NADC caused by viruses (unsuppressed: RR, 3.82 [CI, 3.24 to 4.49]; early suppression: RR, 3.42 [CI, 2.95 to 3.97]; long-term suppression: RR, 3.17 [CI, 2.78 to 3.62]), and absent for NADC not caused by viruses., Limitation: Lower viral suppression thresholds, duration of long-term suppression, and effects of CD4+ and CD8+ T-cell counts were not thoroughly evaluated., Conclusion: Antiretroviral therapy resulting in long-term viral suppression may contribute to cancer prevention, to a greater degree for ADC than for NADC. Patients with long-term viral suppression still had excess cancer risk., Primary Funding Source: National Cancer Institute and National Institute on Alcohol Abuse and Alcoholism of the National Institutes of Health.

In the original publication of the article, the given and family name of the fourth author was not correct. The name has been corrected with this erratum.

Background: D-dimer blood levels in persons with HIV infection are associated with risk of serious non-AIDS conditions and death. Black race has been correlated with higher D-dimer levels in several studies. We examined the effects of race and HIV on D-dimer over time and the impact of viral load suppression by longitudinally comparing changes in levels among healthy young adult male African Americans and whites before HIV seroconversion and before and after initiation of antiretroviral therapy (ART)., Methods: We analyzed D-dimer levels and clinical and laboratory data of 192 participants enrolled in the US Military HIV Natural History Study, a 30-year cohort of military personnel infected with HIV. D-dimer levels were measured on stored sera from each participant at 3 time points: (1) before HIV seroconversion (Pre-SC), (2) ≥6 months after HIV seroconversion but before ART initiation (Post-SC), and (3) ≥6 months after ART with documented viral suppression (Post-ART). Levels were compared at each time point using nonparametric and logistic regression analysis., Results: Compared with whites (n = 106), African Americans (n = 86) had higher D-dimer levels post-SC (P = 0.007), but in the same individuals, pre-SC baseline and post-ART levels were similar (P = 0.40 and P = 0.99, respectively). There were no racial differences in CD4 cell counts, HIV RNA viral load, time from estimated seroconversion to ART initiation, and duration on ART., Conclusions: Observed longitudinally, racial differences in D-dimer levels were seen only during HIV viremia. Higher levels of D-dimer commonly observed in African Americans are likely due to factors in addition to race.

Background: HIV-positive individuals (HIV+) on antiretrovirals commonly take enough other medications to cross a threshold for polypharmacy but little is known about associated outcomes. We asked whether non-antiretroviral polypharmacy is associated with hospitalization and mortality and whether associations differ by HIV status., Methods: Data on HIV+ and uninfected individuals in the US Veterans Affairs Healthcare System were analyzed. Eligible HIV+ were on antiretrovirals with suppressed HIV-1 RNA and uninfected individuals received at least one medication. We calculated average non-antiretroviral medication count for fiscal year 2009. As there is no established threshold for non-antiretroviral polypharmacy, we considered more than two and at least five medications. We followed for hospitalization and mortality (fiscal year 2010-2015), adjusting for age, sex, race/ethnicity and VACS Index., Results: Among 9473 HIV+ and 39 812 uninfected individuals respectively, non-antiretroviral polypharmacy was common (>2: 67, 71%; ≥5: 34, 39%). VACS Index discriminated risk of hospitalization (c-statistic: 0.62, 0.60) and mortality (c-statistic: 0.72, 0.70) similarly in both groups. After adjustment, more than two (hazard ratio 1.51, 95% CI 1.46-1.55) and at least five non-antiretrovirals (hazard ratio 1.52, 95% CI 1.49-1.56) were associated with hospitalization with no interaction by HIV status. Risk of mortality associated with more than two non-antiretrovirals interacted with HIV status (P = 0.002), but not for at least five (adjusted hazard ratio 1.43, 95% CI 1.36-1.50). For both groups and both outcomes, average medication count demonstrated an independent, dose response, association., Conclusion: Neither severity of illness nor demographics explain a dose response, association of non-antiretroviral polypharmacy with adverse health outcomes among HIV+ and uninfected individuals.

Complementary and alternative medicine (CAM), often pursued independent of prescribing clinicians, may interact with traditional treatments, yet CAM use has not been well characterized among people living with HIV (PLWH) in the combined antiretroviral therapy (ART) era. We analyzed data from the Veterans Aging Cohort Study (October 2012-April 2015) to characterize CAM use in PLWH on ART. CAM users were more likely to have lived longer with HIV, report more bothersome symptoms, be prescribed more benzodiazepines and opioids, and consume less nicotine and alcohol. Given its high prevalence, clinicians should routinely assess for CAM use and its impact among PLWH.

Background: Patients with human immunodeficiency virus (HIV) and/or chronic hepatitis C virus (HCV) infection may be prescribed statins as treatment for metabolic/cardiovascular disease, but it remains unclear if the risk of acute liver injury (ALI) is increased for statin initiators compared to nonusers in groups classified by HIV/HCV status., Methods: We conducted a cohort study to compare rates of ALI in statin initiators vs nonusers among 7686 HIV/HCV-coinfected, 8155 HCV-monoinfected, 17739 HIV-monoinfected, and 36604 uninfected persons in the Veterans Aging Cohort Study (2000-2012). We determined development of (1) liver aminotransferases >200 U/L, (2) severe ALI (coagulopathy with hyperbilirubinemia), and (3) death, all within 18 months. Cox regression was used to determine propensity score-adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) of outcomes in statin initiators compared to nonusers across the groups., Results: Among HIV/HCV-coinfected patients, statin initiators had lower risks of aminotransferase levels >200 U/L (HR, 0.66 [95% CI, .53-.83]), severe ALI (HR, 0.23 [95% CI, .12-.46]), and death (HR, 0.36 [95% CI, .28-.46]) compared with statin nonusers. In the setting of chronic HCV alone, statin initiators had reduced risks of aminotransferase elevations (HR, 0.57 [95% CI, .45-.72]), severe ALI (HR, 0.15 [95% CI, .06-.37]), and death (HR, 0.42 [95% CI, .32-.54]) than nonusers. Among HIV-monoinfected patients, statin initiators had lower risks of aminotransferase increases (HR, 0.52 [95% CI, .40-.66]), severe ALI (HR, 0.26 [95% CI, .13-.55]), and death (HR, 0.19 [95% CI, .16-.23]) compared with nonusers. Results were similar among uninfected persons., Conclusions: Regardless of HIV and/or chronic HCV status, statin initiators had a lower risk of ALI and death within 18 months compared with statin nonusers., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Institutional barriers in HIV primary care settings can contribute substantially to disparities in retention in HIV treatment and HIV-related outcomes. This qualitative study compared the perceptions of clinic experiences of persons living with HIV (PLWH) in a Veterans Affairs HIV primary care clinic setting who were retained in care with the experiences of those who were not retained in care. Qualitative data from 25 in-depth interviews were analyzed to identify facilitators and barriers to retention in HIV care. Results showed that participants not retained in care experienced barriers to retention involving dissatisfaction with clinic wait times, low confidence in clinicians, and customer service concerns. For participants retained in care, patience with procedural issues, confidence in clinicians, and interpersonal connections were factors that enhanced retention despite the fact that these participants recognized the same barriers as those who were not retained in care. These findings can inform interventions aimed at improving retention in HIV care.

Liver fibrosis is common, particularly in individuals who are infected with human immunodeficiency virus (HIV). HIV-infected individuals have excess congestive heart failure (CHF) risk compared with uninfected people. It remains unknown whether liver fibrosis stage influences the CHF risk or if HIV or hepatitis C virus (HCV) infection modifies this association. Our objectives were to assess whether 1) stage of liver fibrosis is independently associated with incident CHF and 2) the association between stage of liver fibrosis and incident CHF is modified by HIV/HCV status. Participants alive on or after April 1, 2003, in the Veterans Aging Cohort Study were included. Those without prevalent cardiovascular disease were followed until their first CHF event, death, last follow-up date, or December 31, 2011. Liver fibrosis was measured using the fibrosis 4 index (FIB-4), which is calculated using age, aminotransferases, and platelets. Cox proportional hazards regression models were adjusted for cardiovascular disease risk factors. Among 96,373 participants over 6.9 years, 3844 incident CHF events occurred. FIB-4 between 1.45 and 3.25 (moderate fibrosis) and FIB-4 > 3.25 (advanced fibrosis/cirrhosis) were associated with CHF (hazard ratio [95% confidence interval], 1.17 [1.07-1.27] and 1.65 [1.43-1.92], respectively). The association of advanced fibrosis/cirrhosis and incident CHF persisted regardless of HIV/HCV status., Conclusion: Moderate and advanced liver fibrosis/cirrhosis are associated with an increased risk of CHF. The association for advanced fibrosis/cirrhosis persists even among participants without hepatitis C and/or HIV infection. Assessing liver health may be important for reducing the risk of future CHF events, particularly among HIV and hepatitis C infected people among whom cardiovascular disease risk is elevated and liver disease is common. (Hepatology 2017;66:1286-1295)., (© 2017 by the American Association for the Study of Liver Diseases.)