Objective: Despite the success of antiretroviral therapy (ART), excess mortality continues for those with HIV infection. A comprehensive approach to risk assessment, addressing multiorgan system injury on ART, is needed. We sought to develop and validate a practical and generalizable mortality risk index for HIV-infected individuals on ART. Design and methods: The Veterans Aging Cohort Study (VACS) was used to develop the VACS Index, based on age, CD4 cell count, HIV-1 RNA, hemoglobin, aspartate and alanine transaminase, platelets, creatinine and hepatitis C status, and a Restricted Index based on age, CD4 cell count and HIV-1 RNA with an outcome of death up to 6 years after ART initiation. Validation was in six independent cohorts participating in the ART Cohort Collaboration (ART-CC). Results: In both the development (4932 patients, 656 deaths) and validation cohorts (3146 patients, 86 deaths) the VACS Index had better discrimination than the Restricted Index (c-statistics 0.78 and 0.72 in VACS, 0.82 and 0.78 in ART-CC). The VACS Index also demonstrated better discrimination than the Restricted Index for HIV deaths and non-HIV deaths, in men and women, those younger and older than 50 years, with and without detectable HIV-1 RNA, and with or without HCV coinfection. Conclusions: Among HIV-infected patients treated with ART, the VACS Index more accurately discriminates mortality risk than traditional HIV markers and age alone. By accounting for multiorgan system injury, the VACS Index may prove a useful tool in clinical care and research.

Background. Weight gain after antiretroviral therapy (ART) initiation is common, but its implication for mortality is unknown. We evaluated weight change in the first year after ART initiation and its association with subsequent mortality. Methods. Human immunodeficiency virus-infected patients from the Veterans Aging Cohort Study (VACS) who initiated ART between 2000 and 2008, with weight recorded at baseline and 1 year later, were followed another 5 years for mortality. Baseline body mass index (BMI) was classified as underweight (<18.5 kg/m²), normal (18.5–24.9 kg/m²), overweight (25–29.9 kg/m²), and obese (≥30 kg/m²). We used multivariable Cox models to assess mortality risk with adjustment for disease severity using the VACS Index. Results. The sample consisted of 4184 men and 127 women with a mean age of 47.9 ± 10.0 years. After 1 year of ART, median weight change was 5.9 pounds (2.7 kg) (interquartile range, −2.9 to 17.0 pounds, −1.3 to 7.7 kg). Weight gain after ART initiation was associated with lower mortality among underweight and normal-weight patients. A minimum threshold of 10- to 19.9-pound (4.5 to 9.0 kg) weight gain was beneficial for normal-weight patients (hazard ratio, 0.56; 95% confidence interval, .41–.78), but there was no clear benefit to weight gain for overweight/obese patients. Baseline weight, CD4 cell count status, and hemoglobin level were strongly associated with weight gain. Risk for weight gain was higher among those with greater disease severity, regardless of weight at initiation. Conclusions. The survival benefits of weight gain after ART initiation are dependent on starting BMI. Weight gain after ART is associated with lower mortality for those who are not initially overweight.

Importance: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes coronavirus disease 2019 (Covid-19), an evolving pandemic. Limited data are available characterizing SARS-Cov-2 infection in the United States. Objective: To determine associations between demographic and clinical factors and testing positive for coronavirus 2019 (Covid-19+), and among Covid-19+ subsequent hospitalization and intensive care. Design, Setting, and Participants: Retrospective cohort study including all patients tested for Covid-19 between February 8 and March 30, 2020, inclusive. We extracted electronic health record data from the national Veterans Affairs Healthcare System, the largest integrated healthcare system in the United States, on 2,026,227 patients born between 1945 and 1965 and active in care. Exposures: Demographic data, comorbidities, medication history, substance use, vital signs, and laboratory measures. Laboratory tests were analyzed first individually and then grouped into a validated summary measure of physiologic injury (VACS Index). Main Outcomes and Measures: We evaluated which factors were associated with Covid-19+ among all who tested. Among Covid-19+ we identified factors associated with hospitalization or intensive care. We identified independent associations using multivariable and conditional multivariable logistic regression with multiple imputation of missing values. Results: Among Veterans aged 54-75 years, 585/3,789 (15.4%) tested Covid-19+. In adjusted analysis (C-statistic=0.806) black race was associated with Covid-19+ (OR 4.68, 95% CI 3.79-5.78) and the association remained in analyses conditional on site (OR 2.56, 95% CI 1.89-3.46). In adjusted models, laboratory abnormalities (especially fibrosis-4 score [FIB-4] >3.25 OR 8.73, 95% CI 4.11-18.56), and VACS Index (per 5-point increase OR 1.62, 95% CI 1.43-1.84) were strongly associated with hospitalization. Associations were similar for intensive care. Although significant in unadjusted analyses, associations with comorbid conditions and medications were substantially reduced and, in most cases, no longer significant after adjustment. Conclusions and Relevance: Black race was strongly associated with Covid-19+, but not with hospitalization or intensive care. Among Covid-19+, risk of hospitalization and intensive care may be better characterized by laboratory measures and vital signs than by comorbid conditions or prior medication exposure. Key Points: Question: What are the demographic and clinical characteristics associated with testing positive for coronavirus 2019 (Covid-19+), and among Covid-19+ subsequent hospitalization and intensive care among Veterans in the United States? Findings: In this retrospective cohort study of 2,026,227 Veterans aged 54-75 years and active in care, 585/3,789 (15.4%) tested Covid-19+. Black race was strongly associated with Covid-19+, but not with hospitalization or intensive care. Among Covid-19+, laboratory abnormalities and a summary measure of physiologic injury were strongly associated with hospitalization and intensive care. Meaning: Racial differences in testing positive for Covid-19 may be an underestimate of the general population as racial health disparities in the Veterans Affairs Healthcare System tend to be smaller than in the private sector. Risk of hospitalization and intensive care may be better characterized by laboratory measures and vital signs than by comorbid conditions or prior medication exposure.

Background: There is growing concern that racial and ethnic minority communities around the world are experiencing a disproportionate burden of morbidity and mortality from symptomatic SARS-Cov-2 infection or coronavirus disease 2019 (Covid-19). Most studies investigating racial and ethnic disparities to date have focused on hospitalized patients or have not characterized who received testing or those who tested positive for Covid-19. Objective: To compare patterns of testing and test results for coronavirus 2019 (Covid-19) and subsequent mortality by race and ethnicity in the largest integrated healthcare system in the United States. Design: Retrospective cohort study. Setting: United States Department of Veterans Affairs (VA). Participants: 5,834,543 individuals in care, among whom 62,098 were tested and 5,630 tested positive for Covid-19 between February 8 and May 4, 2020. Exposures: Self-reported race/ethnicity. Main outcome measures: We evaluated associations between race/ethnicity and receipt of Covid-19 testing, a positive test result, and 30-day mortality, accounting for a wide range of demographic and clinical risk factors including comorbid conditions, site of care, and urban versus rural residence. Results: Among all individuals in care, 74% were non-Hispanic white (white), 19% non-Hispanic black (black), and 7% Hispanic. Compared with white individuals, black and Hispanic individuals were more likely to be tested for Covid-19 (tests per 1000: white=9.0, [95% CI 8.9 to 9.1]; black=16.4, [16.2 to 16.7]; and Hispanic=12.2, [11.9 to 12.5]). While individuals from minority backgrounds were more likely to test positive (black vs white: OR 1.96, 95% CI 1.81 to 2.12; Hispanic vs white: OR 1.73, 95% CI 1.53 to 1.96), 30-day mortality did not differ by race/ethnicity (black vs white: OR 0.93, 95% CI 0.64 to 1.33; Hispanic vs white: OR 1.07, 95% CI 0.61 to 1.87). Conclusions: Black and Hispanic individuals are experiencing an excess burden of Covid-19 not entirely explained by underlying medical conditions or where they live or receive care. While there was no observed difference in mortality by race or ethnicity, our findings may underestimate risk in the broader US population as health disparities tend to be reduced in VA.

Background. Human immunodeficiency virus (HIV) coinfection accelerates the rate of liver disease outcomes in individuals chronically infected with hepatitis C virus (HCV). It remains unclear to what degree combination antiretroviral therapy (ART) protects against HCV-associated liver failure. Methods. We evaluated 10 090 HIV/HCV-coinfected males from the Veterans Aging Cohort Study Virtual Cohort, who had not initiated ART at entry, for incident hepatic decompensation between 1996 and 2010. We defined ART initiation as the first pharmacy fill date of a qualifying ART regimen of ≥3 drugs from ≥2 classes. Hepatic decompensation was defined as the first occurrence of 1 hospital discharge diagnosis or 2 outpatient diagnoses for ascites, spontaneous bacterial peritonitis, or esophageal variceal hemorrhage. To account for potential confounding by indication, marginal structural models were used to estimate hazard ratios (HRs) of hepatic decompensation, comparing initiation of ART to noninitiation. Results. We observed 645 hepatic decompensation events in 46 444 person-years of follow-up (incidence rate, 1.4/100 person-years). Coinfected patients who initiated ART had a significantly reduced rate of hepatic decompensation relative to noninitiators (HR = 0.72; 95% confidence interval [CI], .54–.94). When we removed individuals with HIV RNA ≤400 copies/mL at baseline from the analysis (assuming that they may have received undocumented ART at entry), the hazard ratio became more pronounced (HR = 0.59; 95% CI, .43–.82). Conclusions. Initiation of ART significantly reduced the rate of hepatic decompensation by 28%–41% on average. These results suggest that ART should be administered to HIV/HCV-coinfected patients to lower the risk of end-stage liver disease.