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 (HAVACS) 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- (1982–1996), early- (1997–2006), and late-cART (2007–2016) eras. Trends were assessed using Kaplan-Meier curves, cumulative incidence functions, and join-point regression models. Risk factors were identified by Cox proportional hazards models. Results: Of the 4,674 VWH in HAVACS, 1,752 died; of whom, 1,399 (79.9%), 301 (17.2%), and 52 (3.0%) were diagnosed with HIV in the pre-, early-, 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- and late-cART eras. All-cause, AIDS-related, and non-AIDS-related mortality rates plummeted by 65%, 81%, and 45%, respectively, from the pre- 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.

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.

Objective: Liver disease markers have been associated with mortality in HIV-infected individuals in the modern era of effective antiretroviral therapy. Our objective was to determine which markers are most predictive of mortality in HIV-monoinfected and HIV/hepatitis C virus (HCV)-coinfected persons. Research design and methods: We measured serum albumin, total protein, calculated globulin, aspartate transaminase (AST), and alanine transaminase in 193 HIV/HCV-coinfected and 720 HIV-monoinfected persons in the study of Fat Redistribution and Metabolic Change in HIV Infection. We evaluated associations of each marker with 5-year, all-cause mortality, adjusting for cardiovascular, HIV-related factors, inflammation, renal disease, muscle, and adiposity. Results: After 5 years of follow-up, overall mortality was 21% in HIV/HCV-coinfected and 12% in HIV-monoinfected participants. After multivariable adjustment, lower albumin and higher AST were independently associated with increased mortality. Lower albumin was associated with 49% increased odds of mortality overall [per 0.5 g/dl decrease, 95% confidence interval (CI): 1.2–1.9]; the association was stronger in HIV/HCV-coinfected [odds ratio (OR) = 2.1, 95% CI: 1.4–3.2] vs. HIV-monoinfected (OR = 1.3, 95% CI: 1.0–1.7; HCV-by-albumin interaction: P = 0.038). Higher AST was associated with 41% increased odds of mortality (per AST doubling; 95% CI: 1.1–1.8); associations were much stronger among HIV/HCV-coinfected (OR = 2.5, 95% CI: 1.5–4.1) than HIV-monoinfected (OR = 1.1, 95% CI: 0.8–1.5; HCV-by-AST interaction: P = 0.0042). Conclusion: Lower serum albumin and higher AST appear to be important mortality risk factors in HIV/HCV-coinfection, but much less so in HIV-monoinfected individuals. The association of low albumin with mortality may reflect its role as a negative acute phase response protein. AST levels do not appear to be useful in predicting mortality in HIV-monoinfection and should be considered primarily in the context of HCV-coinfection.

Unhealthy alcohol use is common among HIV-positive patients, yet effective evidence-based treatments are rarely provided in clinical settings providing HIV care. Further, given patient variability in response to initial treatments, stepped care approaches may be beneficial. We describe the rationale, aims and study design for the current Starting Treatment for Ethanol in Primary care Trials (STEP Trials); three parallel randomized controlled effectiveness trials being conducted in five Infectious Disease Clinics. Participants meeting criteria for: 1) at-risk drinking, 2) moderate alcohol use with liver disease (MALD), or 3) alcohol use disorder (AUD) are randomized to integrated stepped care versus treatment as usual. For those with at-risk drinking or MALD, integrated stepped care starts with a one session brief intervention and follow-up 2-week telephone booster. Based on pre-specified nonresponse criteria, participants may be “stepped up” at week 4 to receive four sessions of motivational enhancement therapy (MET) and “stepped up” again at week 12 for addiction physician management (APM) and consideration of alcohol pharmacotherapy. For those with AUD, integrated stepped care begins with APM. Non-responders may be “stepped up” at week 4 to receive MET and again at week 12 for a higher level of care (e.g. intensive outpatient program). The primary outcome is alcohol consumption assessed at 24 weeks, and secondary outcome is the VACS Index, a validated measure of HIV morbidity and mortality risk. Results from the STEP Trials should inform future research and the implementation of interventions to address unhealthy alcohol use among HIV-positive individuals.

Concordant with the emergence of methicillin-resistant Staphylococcus aureus (MRSA) in the community setting, colonization and infections with this pathogen have become a prevalent problem among the human immunodeficiency virus (HIV)-positive population. A variety of different host- and, possibly, pathogen-related factors may play a role in explaining the increased prevalence and incidence observed. In this article, we review pathophysiology, epidemiology, clinical manifestations, and treatment of MRSA in the HIV-infected population.

Objective: To determine the association between HIV infection and other risk factors for acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Design: Longitudinal, national Veterans Aging Cohort Study including 43 618 HIV-infected and 86 492 uninfected veterans. Methods: AECOPD was defined as an inpatient or outpatient COPD ICD-9 diagnosis accompanied by steroid and/or antibiotic prescription within 5 days. We calculated incidence rate ratios (IRR) and 95% confidence intervals (CI) for first AECOPD over 2 years and used Poisson regression models to adjust for risk factors. Results: Over 234 099 person-years of follow-up, 1428 HIV-infected and 2104 uninfected patients had at least one AECOPD. HIV-infected patients had an increased rate of AECOPD compared with uninfected (18.8 vs. 13.3 per 1000 person-years, P < 0.001). In adjusted models, AECOPD risk was greater in HIV-infected individuals overall (IRR 1.54; 95% CI 1.44-1.65), particularly in those with more severe immune suppression when stratified by CD4 cell count (cells/ml) compared with uninfected (HIV-infected CD4+ < 200: IRR 2.30, 95% CI 2.10-2.53, HIV-infected CD4+ ≥ 200-349: IRR 1.32, 95% CI 1.15-1.51, HIV-infected CD4+≥350: IRR 0.99, 95% CI 0.88-1.10). HIV infection also modified the association between current smoking and alcohol-related diagnoses with risk for AECOPD such that interaction terms for HIV and current smoking or HIV and alcohol-related diagnoses were each significantly associated with AECOPD. Conclusion: HIV infection, especially with lower CD4+ cell count, is an independent risk factor for AECOPD. Enhanced susceptibility to harm from current smoking or unhealthy alcohol use in HIV-infected patients may also contribute to the greater rate of AECOPD.

Background. After adjustment for cardiovascular risk factors and despite higher mortality, those with human immunodeficiency virus (HIV+) have a greater risk of acute myocardial infarction (AMI) than uninfected individuals. Methods. We included HIV+ individuals who started combination antiretroviral therapy (cART) in the Veterans Aging Cohort Study (VACS) from 1996 to 2012. We fit multivariable proportional hazards models for baseline, time-updated and cumulative measures of HIV-1 RNA, CD4 counts, and the VACS Index. We used the trapezoidal rule to build the following cumulative measures: viremia copy-years, CD4-years, and VACS Index score-years, captured 180 days after cART initiation until AMI, death, last clinic visit, or 30 September 2012. The primary outcomes were incident AMI (Medicaid, Medicare, and Veterans Affairs International Classification of Diseases-9 codes) and death. Results. A total of 8168 HIV+ individuals (53 861 person-years) were analyzed with 196 incident AMIs and 1710 deaths. Controlling for known cardiovascular risk factors, 6 of the 9 metrics predicted AMI and all metrics predicted mortality. Time-updated VACS Index had the lowest Akaike information criterion among all models for both outcomes. A time-updated VACS Index score of 55+ was associated with a hazard ratio (HR) of 3.31 (95% confidence interval [CI], 2.11-5.20) for AMI and a HR of 31.77 (95% CI, 26.17-38.57) for mortality. Conclusions. Time-updated VACS Index provided better AMI and mortality prediction than CD4 count and HIV-1 RNA, suggesting that current health determines risk more accurately than prior history and that risk assessment can be improved by biomarkers of organ injury.

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: Pulmonary infections remain more common in HIV-infected (HIV+) compared to uninfected individuals. The increase in chronic lung diseases among aging HIV+ individuals may contribute to this persistent risk. We sought to determine whether chronic obstructive pulmonary disease (COPD) is an independent risk factor for different pulmonary infections requiring hospitalization among HIV+ patients. Methods: We analyzed data from 41,993 HIV+ Veterans in the nationwide Veterans Aging Cohort Study Virtual Cohort (VACS-VC) from 1996–2009. Using ICD-9 codes, we identified baseline comorbid conditions, including COPD, and incident community-acquired pneumonia (CAP), pulmonary tuberculosis (TB) and Pneumocystis jirovecii pneumonia (PCP) requiring hospitalization within two years after baseline. We used multivariable Poisson regression to determine incidence rate ratios (IRR) associated with COPD for each type of pulmonary infection, adjusting for comorbidities, CD4+ cell count, HIV viral load, smoking status, substance use, vaccinations and calendar year at baseline. Results: Unadjusted incidence rates of CAP, TB and PCP requiring hospitalization were significantly higher among persons with COPD compared to those without COPD (CAP: 53.9 vs. 19.4 per 1,000 person-years; TB: 8.7 vs. 2.8; PCP: 15.5 vs. 9.2; p ≤0.001). In multivariable Poisson regression models, COPD was independently associated with increased risk of CAP, TB and PCP (IRR 1.94, 95% CI 1.64–2.30; IRR 2.60, 95% CI 1.70–3.97; and IRR 1.48, 95% CI 1.10–2.01, respectively). Conclusions: COPD is an independent risk factor for CAP, TB and PCP requiring hospitalization among HIV+ individuals. As the HIV+ population ages, the growing burden of COPD may confer substantial risk for pulmonary infections.

Background: Given the growing interest in the cancer burden in persons living with HIV/AIDS, we examined the validity of data sources for cancer diagnoses (cancer registry versus International Classification of Diseases, Ninth Revision [ICD-9 codes]) and compared the association between HIV status and cancer risk using each data source in the Veterans Aging Cohort Study (VACS), a prospective cohort of HIV-infected and uninfected veterans from 1996 to 2008. Methods: We reviewed charts to confirm potential incident cancers at four VACS sites. In the entire cohort, we calculated cancer-type-specific age-, sex-, race/ethnicity-, and calendar-period-standardized incidence rates and incidence rate ratios (IRR) (HIV-infected versus uninfected). We calculated standardized incidence ratios (SIR) to compare VACS and Surveillance, Epidemiology, and End Results rates. Results: Compared to chart review, both Veterans Affairs Central Cancer Registry (VACCR) and ICD-9 diagnoses had approximately 90% sensitivity; however, VACCR had higher positive predictive value (96% versus 63%). There were 6,010 VACCR and 13,386 ICD-9 incident cancers among 116,072 veterans. Although ICD-9 rates tended to be double VACCR rates, most IRRs were in the same direction and of similar magnitude, regardless of data source. Using either source, all cancers combined, most viral-infection-related cancers, lung cancer, melanoma, and leukemia had significantly elevated IRRs. Using ICD-9, eight additional IRRs were significantly elevated, most likely due to false positive diagnoses. Most ICD-9 SIRs were significantly elevated and all were higher than the corresponding VACCR SIR. Conclusions: ICD-9 may be used with caution for estimating IRRs, but should be avoided when estimating incidence or SIRs. Elevated cancer risk based on VACCR diagnoses among HIV-infected veterans was consistent with other studies.