VACS Index Research Articles

Veterans Aging Cohort Study Index 2.0 Shows Improved Discrimination of Neurocognitive Impairment and Frailty in People with HIV

Objective: This study examined whether the revised VACS2.0 index (including serum albumin, body mass index (BMI), and white blood cell (WBC) count) had stronger correlations with cognitive function, brain volume, and frailty in PWH ≥ 50 years compared to the VACS1.0. Design and Methods: Neuropsychological performance (NP) Z-scores (learning, retention, executive functioning (EF), psychomotor function/processing speed (PM/PS), language, and global cognition), and neuroimaging measures (brain volumetrics) were analyzed in PWH (n = 162). A subset of the sample (n = 159) was defined as either frail (n = 18) or non-frail (n = 141) according to the Fried phenotype criteria. Brain volumes, NP scores, and frailty subgroups were analyzed with both VACS scores, albumin, BMI, and WBC count using Pearson's significance tests and independent T-tests. Results: Higher VACS scores significantly correlated with lower brain volumes. Higher VACS2.0 scores were associated with lower NP in the EF and PM/PS domains and were primarily driven by albumin. VACS1.0 scores did not correlate with cognition Z-scores. There was no relationship between frailty status and VACS1.0. PWH who were frail had significantly greater VACS2.0 scores than non-frail PWH. Conclusions: The addition of albumin to the VACS index improved its correlations with NP and frailty in PWH. While low albumin levels may contribute to cognitive decline or frailty, the reverse causality should also be considered. These findings suggest that the VACS2.0 index (especially albumin) is a valuable measure for clinicians to improve outcomes in PWH.

DNA methylation-based telomere length is associated with HIV infection, physical frailty, cancer, and all-cause mortality.

Telomere length (TL) is an important indicator of cellular aging. Shorter TL is associated with several age-related diseases including coronary heart disease, heart failure, diabetes, osteoporosis, and cancer. Recently, a DNA methylation-based TL (DNAmTL) estimator has been developed as an alternative method for directly measuring TL. In this study, we examined the association of DNAmTL with cancer prevalence and mortality risk among people with and without HIV in the Veterans Aging Cohort Study Biomarker Cohort (VACS, N = 1917) and Women's Interagency HIV Study Cohort (WIHS, N = 481). We profiled DNAm in whole blood (VACS) or in peripheral blood mononuclear cells (WIHS) using an array-based method. Cancer prevalence was estimated from electronic medical records and cancer registry data. The VACS Index was used as a measure of physiologic frailty. Models were adjusted for self-reported race and ethnicity, batch, smoking status, alcohol consumption, and five cell types (CD4, CD8, NK, B cell, and monocyte). We found that people with HIV had shorter average DNAmTL than those without HIV infection [beta = -0.25, 95% confidence interval (-0.32, -0.18), p = 1.48E-12]. Greater value of VACS Index [beta = -0.002 (-0.003, -0.001), p = 2.82E-05] and higher cancer prevalence [beta = -0.07 (-0.10, -0.03), p = 1.37E-04 without adjusting age] were associated with shortened DNAmTL. In addition, one kilobase decrease in DNAmTL was associated with a 40% increase in mortality risk [hazard ratio: 0.60 (0.44, 0.82), p = 1.42E-03]. In summary, HIV infection, physiologic frailty, and cancer are associated with shortening DNAmTL, contributing to an increased risk of all-cause mortality.

Combining Charlson comorbidity and VACS indices improves prognostic accuracy for all-cause mortality for patients with and without HIV in the Veterans Health Administration.

As people age with HIV (PWH), many comorbid diseases are more common than among age matched comparators without HIV (PWoH). While the Veterans Aging Cohort (VACS) Index 2.0 accurately predicts mortality in PWH using age and clinical biomarkers, the only included comorbidity is hepatitis C. We asked whether adding comorbid disease groupings from the Charlson Comorbidity Index (CCI) improves the accuracy of VACS Index. To maximize our ability to model mortality among older age groups, we began with PWoH in Veterans Health Administration (VA) from 2007-2017, divided into development and validation samples. Baseline predictors included age, and components of CCI and VACS Index (excluding CD4 count and HIV RNA). Patients were followed until December 31, 2021. We used Cox models to develop the VACS-CCI score and estimated mortality using a parametric (gamma) survival model. We compared accuracy using C-statistics and calibration curves in validation overall and within subgroups (gender, age </≥65 years, race/ethnicity, and CCI score). We then applied VACS-CCI in PWH and compared its accuracy to age, VACS Index 2.0, CCI and VACS-CCI with CD4 and HIV RNA added. The analytic sample consisted of 6,588,688 PWoH and 30,539 PWH. Among PWoH/PWH, median age was 65/55 years; 6%/3% were women; 15%/48% were Black and 5%/7% Hispanic. VACS-CCI provided the best discrimination (C-statistic = 0.81) with excellent calibration (predicted and observed mortality largely overlapped) overall and within subgroups. When VACS-CCI was applied to PWH it demonstrated similar discrimination as VACS Index 2.0 (C-statistic = 0.77 for both) but superior calibration among those with CD4 < 200. Discrimination was improved when CD4 and HIV RNA were added VACS-CCI (C-statistic = 0.79). Liver and kidney disease, congestive heart failure, malignancy, and dementia were negatively associated with CD4 (p-trends all <0.0001). Among PWH and PWoH in VA care, age alone weakly discriminates risk of mortality. VACS Index 2.0, CCI, and VACS-CCI all provide better discrimination, but VACS-CCI is more consistently calibrated. The association of comorbid diseases with lower CD4 underscores the likely role of HIV in non-AIDS conditions. Future work will include adding CD4 and HIV RNA to VACS-CCI and validating it in independent data.

Cognitive concerns are a risk factor for mortality in people with human immunodeficiency virus and COVID-19.

Data supporting dementia as a risk factor for COVID-19 mortality relied on ICD-10 codes, yet nearly 40% of individuals with probable dementia lack a formal diagnosis. Dementia coding is not well-established for people with HIV (PWH), and its reliance may affect risk assessment. This retrospective cohort analysis of PWH with SARS-CoV-2 polymerase chain reaction positivity includes comparisons to people without HIV (PWoH), matched by age, sex, race, and zipcode. Primary exposures were dementia diagnosis, by ICD-10 codes, and cognitive concerns, defined as possible cognitive impairment up to 12 months before COVID-19 diagnosis after clinical review of notes from the electronic health record. Logistic regression models assessed the effect of dementia and cognitive concerns on odds of death (OR [95% confidence interval]); models adjusted for VACS Index 2.0. Sixty-four PWH were identified out of 14,129 patients with SARS-CoV-2 infection and matched to 463 PWoH. Compared to PWoH, PWH had a higher prevalence of dementia (15.6% vs. 6%, p = 0.01) and cognitive concerns (21.9% vs. 15.8%, p = 0.04). Death was more frequent in PWH (p < 0.01). Adjusted for VACS Index 2.0, dementia (2.4 [1.0-5.8], p = 0.05) and cognitive concerns (2.4 [1.1-5.3], p = 0.03) were associated with increased odds of death. In PWH, the association between cognitive concern and death trended towards statistical significance (3.92 [0.81-20.19], p = 0.09); there was no association with dementia. Cognitive status assessments are important for care in COVID-19, especially among PWH. Larger studies should validate findings and determine long-term COVID-19 consequences in PWH with pre-existing cognitive deficits.

Assessing the contributions of modifiable risk factors to serious falls and fragility fractures among older persons living with HIV.

Although 50 years represents middle age among uninfected individuals, studies have shown that persons living with HIV (PWH) begin to demonstrate elevated risk for serious falls and fragility fractures in the sixth decade; the proportions of these outcomes attributable to modifiable factors are unknown. We analyzed 21,041 older PWH on antiretroviral therapy (ART) from the Veterans Aging Cohort Study from 01/01/2010 through 09/30/2015. Serious falls were identified by Ecodes and a machine-learning algorithm applied to radiology reports. Fragility fractures (hip, vertebral, and upper arm) were identified using ICD9 codes. Predictors for both models included a serious fall within the past 12 months, body mass index, physiologic frailty (VACS Index 2.0), illicit substance and alcohol use disorders, and measures of multimorbidity and polypharmacy. We separately fit multivariable logistic models to each outcome using generalized estimating equations. From these models, the longitudinal extensions of average attributable fraction (LE-AAF) for modifiable risk factors were estimated. Key risk factors for both outcomes included physiologic frailty (VACS Index 2.0) (serious falls [15%; 95% CI 14%-15%]; fractures [13%; 95% CI 12%-14%]), a serious fall in the past year (serious falls [7%; 95% CI 7%-7%]; fractures [5%; 95% CI 4%-5%]), polypharmacy (serious falls [5%; 95% CI 4%-5%]; fractures [5%; 95% CI 4%-5%]), an opioid prescription in the past month (serious falls [7%; 95% CI 6%-7%]; fractures [9%; 95% CI 8%-9%]), and diagnosis of alcohol use disorder (serious falls [4%; 95% CI 4%-5%]; fractures [8%; 95% CI 7%-8%]). This study confirms the contributions of risk factors important in the general population to both serious falls and fragility fractures among older PWH. Successful prevention programs for these outcomes should build on existing prevention efforts while including risk factors specific to PWH.

Effects of frailty, geriatric syndromes, and comorbidity on mortality and quality of life in older adults with HIV

BackgroundTo understand the effects of frailty, geriatric syndromes, and comorbidity on quality of life and mortality in older adults with HIV (OAWH).MethodsCross-sectional study of the FUNCFRAIL multicenter cohort. The setting was outpatient HIV-Clinic. OAWH, 50 year or over were included. We recorded sociodemographic data, HIV infection-related data, comorbidity, frailty, geriatric syndromes (depression, cognitive impairment, falls and malnutrition), quality of life (QOL) and the estimated risk of all-cause 5-year mortality by VACS Index. Association of frailty with geriatric syndromes and comorbidity was evaluated using the Cochran-Mantel-Haenszel test.ResultsSeven hundred ninety six patients were included. 24.7% were women, mean age was 58.2 (6.3). 14.7% were 65 or over. 517 (65%) patients had ≥3 comorbidities, ≥ 1 geriatric syndrome and/or frailty. There were significant differences in the estimated risk of mortality [(frailty 10.8%) vs. (≥ 3 comorbidities 8.2%) vs. (≥ 1 geriatric syndrome 8.2%) vs. (nothing 6.2%); p = 0.01] and in the prevalence of fair or poor QOL [(frailty 71.7%) vs. (≥ 3 comorbidities 52%) vs. (≥ 1 geriatric syndrome 58.4%) vs. (nothing 51%); p = 0.01]. Cognitive impairment was significantly associated to mortality (8.7% vs. 6.2%; p = 0.02) and depression to poor QOL [76.5% vs. 50%; p = 0.01].ConclusionsFrailty, geriatric syndromes, and comorbidity had negative effects on mortality and QOL, but frailty had the greatest negative effect out of the three factors. Our results should be a wake-up call to standardize the screening for frailty and geriatric syndromes in OAWH in the clinical practice.Trial registrationNCT03558438.

Association of Phenotypic Aging Marker with comorbidities, frailty and inflammatory markers in people living with HIV

BackgroundAging characteristics in people living with HIV (PLWH) are heterogeneous, and the identification of risk factors associated with aging-related comorbidities such as neurocognitive impairment (NCI) and frailty is important. We evaluated predictors of novel aging markers, phenotypic age (PhenoAge) and phenotypic age acceleration (PAA) and their association with comorbidities, frailty, and NCI.MethodsIn a cohort of PLWH and age- and sex-matched HIV-negative controls, we calculated PhenoAge using chronological age and 9 biomarkers from complete blood counts, inflammatory, metabolic-, liver- and kidney-related parameters. PAA was calculated as the difference between chronological age and PhenoAge. Multivariate logistic regression models were used to identify the factors associated with higher (>median) PAA. Area under the receiver operating characteristics curve (AUROC) was used to assess model discrimination for frailty.ResultsAmong 333 PLWH and 102 HIV-negative controls (38% female), the median phenotypic age (49.4 vs. 48.5 years, p = 0.54) and PAA (− 6.7 vs. -7.5, p = 0.24) was slightly higher and PAA slightly less in PLWH although this did not reach statistical significance. In multivariate analysis, male sex (adjusted odds ratio = 1.68 [95%CI = 1.03–2.73]), current smoking (2.74 [1.30–5.79]), diabetes mellitus (2.97 [1.48–5.99]), hypertension (1.67 [1.02–2.72]), frailty (3.82 [1.33–10.93]), and higher IL-6 levels (1.09 [1.04–1.15]), but not HIV status and NCI, were independently associated with higher PAA. PhenoAge marker discriminated frailty better than chronological age alone (AUROC: 0.75 [0.66–0.85] vs. 0.65 [0.55–0.77], p = 0.04). In the analysis restricted to PLWH, PhenoAge alone predicted frailty better than chronological age alone (AUROC: 0.7412 vs. 0.6499, P = 0.09) and VACS index (AUROC: 0.7412 vs. 0.6811, P = 0.34) despite not statistically significant.ConclusionsWhile PLWH did not appear to have accelerated aging in our cohort, the phenotypic aging marker was significantly associated with systemic inflammation, frailty, and cardiovascular disease risk factors. This simple aging marker could be useful to identify high-risk PLWH within a similar chronological age group.

REDUCED LEVELS OF NAD IN SKELETAL MUSCLE IN PEOPLE AGING WITH HIV INFECTION ON TREATMENT

Abstract People living with HIV (PLWH) are disproportionately burdened with multimorbidity and decline in physiologic function compared to their uninfected counterparts, but biological mechanisms that differentially contribute to the decline in muscle function in PLWH compared to uninfected people remains understudied. The study site was Brigham and Women’s Hospital, Harvard Medical School, Boston MA. We evaluated skeletal muscle tissue for levels of total NAD, NAD+ and NADH in middle-aged asymptomatic PLWH, coinfected with hepatitis C virus (HCV) and/or cytomegalovirus (CMV) and compared them to uninfected control participants. Of the 54 persons with muscle biopsy data, the mean age 57 years with 33% women. Total NAD levels declined in skeletal muscle in association with HIV infection, and was exacerbated by HCV and CMV coinfection, with lowest levels of total NAD, NAD+ and NADH among persons that were coinfected with all three viruses (P=0.015, P=0.014, P=0.076; respectively). Levels of total NAD, NAD+ and NADH in skeletal muscle were inversely associated with inflammation (P=0.014, P=0.013, P=0.055; respectively). Coinfections were also associated with measures of inflammation (CD4/CD8 ratio: P&amp;lt; 0.001 and sCD163: P&amp;lt; 0.001), immune activation (CD38 and HLA-DR expression on CD8 T cells: P&amp;lt; 0.001). Additionally, coinfection was associated with increased physiologic frailty, based on the VACS Index 1.0 assessment (P=0.001). Further research is warranted to determine the clinical relevance of preclinical deficits in NAD metabolites in skeletal muscle in association with viral coinfection and inflammation, as well as the observed association between viral coinfection and physiologic frailty.

Crack cocaine use frequency is associated with HIV disease severity independent of antiretroviral therapy exposure: a prospective cohort study.

We sought to evaluate the effect of crack cocaine use frequency on HIV disease severity among HIV-positive people who use unregulated drugs (PWUD). We analyzed data from the ACCESS study, an open prospective cohort of HIV-positive PWUD including comprehensive HIV clinical monitoring in a setting with no-cost healthcare. Multivariable generalized linear mixed-effects models were used to estimate the independent effect of time-updated crack cocaine use frequency on HIV disease severity, adjusting for ART exposure and relevant confounders. In multivariable adjusted models, daily or greater frequency of crack cocaine use was significantly associated with higher VACS Index scores (β = 0.8, 95% confidence interval: 0.1, 1.5) as compared to none. Our finding suggests that daily or greater frequency of crack cocaine use exacerbates HIV disease severity independent of ART exposure. The observed effect may reflect an underlying biological mechanism or other factors linked with crack cocaine use; further investigation is warranted.

Long-Term Outcomes of Patients With Cocaine Use Disorder: A 18-years Addiction Cohort Study.

Objective: Cocaine Use Disorder (CUD) has been associated with multiple complications and premature death. The purpose of the present study was to analyze the relationship between baseline medical comorbidity and long-term medical outcomes (i.e., hospitalization, death) in a cohort of patients primarily admitted for detoxification. In addition, we aimed to analyze cause-specific mortality. Methods: longitudinal study in CUD patients admitted for detoxification between 2001 and 2018. Substance use characteristics, laboratory parameters and medical comorbidity by VACS Index were assessed at admission. Follow-up and health-related outcomes were ascertained through visits and e-health records. Kaplan-Meier and Cox regression models were used to analyze survival and predictors of hospitalization and death. Results: 175 patients (77.7% men) were included. Age at admission was 35 years [IQR: 30–41 years], 59.4% of the patients being intranasal users, 33.5% injectors, and 7.1% smokers. Almost 23% of patients had concomitant alcohol use disorder, 39% were cannabis users and 9% opiate users. The median VACS Index score on admission was 10 points [IQR: 0–22]. After 12 years [IQR: 8.6–15 years] of follow-up there were 1,292 (80.7%) ED admissions and 308 (19.3%) hospitalizations. The incidence rate of ED admission and hospitalization was 18.6 × 100 p-y (95% CI: 15.8–21.8 × 100 p-y). Mortality rate was 1.4 × 100 p-y (95% CI: 0.9–2.0 × 100 p-y) and, baseline comorbidity predicted hospitalization and mortality: those with VACS Index >40 were 3.5 times (HR:3.52, 95% CI: 1.19–10.4) more likely to dye with respect to patients with VACS < 20. Conclusion: addiction care warrants optimal stratification of medical comorbidity to improve health outcomes and survival of CUD patients seeking treatment of the disorder.

96-week results of a dual therapy with darunavir/ritonavir plus rilpivirine once a day vs triple therapy in patients with suppressed viraemia: virological success and non-HIV related morbidity evaluation

Antiretroviral therapies have been tested with the goal of maintaining virological suppression with a particular attention in limiting drug-related toxicity. With this aim we designed the DUAL study: a randomized, open-label, multicenter, 96 weeks-long pilot exploratory study in virologically suppressed HIV-1+ patients with the aim of evaluating the immunovirological success and the impact on non-HIV related morbidity of switching to a dual therapy with darunavir-ritonavir (DRV/r) and rilpivirine (RPV). We recruited patients who received a PI/r-containing HAART for ≥6 months, HIV-RNA < 50 cp/mL for ≥3 months, eGFR > 60 mL/min/1,73m2, without DRV or RPV RAMs. We randomized patients in arm A: RPV + DRV/r QD or arm B: ongoing triple therapy. The primary endpoint has been defined as the percentage of patients with HIV-RNA < 50 cp/mL at week 48 (ITT). VACS index, Framingham CVD risk (FRS) and urinary RBP (uRBP) were calculated. We used Chi-square or Fisher statistics for categorical variables and Mann-Whitney U for continuous ones. Forty-one patients were enrolled (22 in arm A, 14 in arm B, plus 5 screening failures): 30 patients reached 96 weeks: 100% had HIV-RNA < 50 cp/mL in arm A versus 91.7% in arm B. Similar changes were observed in median CD4/mL between baseline and week 96 (+59 versus − 31, p: n.s.). Thirty-one in arm A and 23 in arm B adverse events took place, whereas only 1 was serious (arm A: turbinate hypertrophy, unrelated to HAART). Among the 6 discontinuations (3 in A, 3 in B), only 1 was related to adverse event (arm A: G3 depression, insomnia, weakness). VACS index, median FRS and median uRBP values did not vary from baseline to week 96. At 96-weeks all patients switched to a QD 2-drug regimen based on DRV/r + RPV maintained HIV-RNA suppression, but a single patient who showed a virological failure at week 4. CD4 counts increased overtime without significant differences between the two arms. The novel dual regimen was well tolerated with the same amount of discontinuation as the control arm. VACS index, FRS and uRBP did not differ between arms at week 96.

Strengths and Limitations of the Veterans Aging Cohort Study Index as a Measure of Physiologic Frailty.

The Veterans Aging Cohort Study Index (VACS Index) is an index comprised of routine clinical laboratory tests that accurately and generalizably predicts all-cause mortality among those living with and without HIV infection. Increasing evidence supports its use as a measure of physiologic frailty among those aging with HIV because of its associations with frailty related outcomes including mortality, hospitalization, fragility fractures, serious falls, pneumonia, cognitive decline, delirium, and functional decline. In this review, we explore the evidence supporting the validity (construct, correlative, and predictive), responsiveness, and feasibility of the VACS Index as an early indicator of physiologic frailty. We also consider its limitations.

Machine learning models reveal neurocognitive impairment type and prevalence are associated with distinct variables in HIV/AIDS.

Neurocognitive impairment (NCI) among HIV-infected patients is heterogeneous in its reported presentations and frequencies. To determine the prevalence of NCI and its associated subtypes as well as predictive variables, we investigated patients with HIV/AIDS receiving universal health care. Recruited adult HIV-infected subjects underwent a neuropsychological (NP) test battery with established normative (sex-, age-, and education-matched) values together with assessment of their demographic and clinical variables. Three patient groups were identified including neurocognitively normal (NN, n = 246), HIV-associated neurocognitive disorders (HAND, n = 78), and neurocognitively impaired-other disorders (NCI-OD, n = 46). Univariate, multiple logistic regression and machine learning analyses were applied. Univariate analyses showed variables differed significantly between groups including birth continent, quality of life, substance use, and PHQ-9. Multiple logistic regression models revealed groups again differed significantly for substance use, PHQ-9 score, VACS index, and head injury. Random forest (RF) models disclosed that classification algorithms distinguished HAND from NN and NCI-OD from NN with area under the curve (AUC) values of 0.87 and 0.77, respectively. Relative importance plots derived from the RF model exhibited distinct variable rankings that were predictive of NCI status for both NN versus HAND and NN versus NCI-OD comparisons. Thus, NCI was frequently detected (33.5%) although HAND prevalence (21%) was lower than in several earlier reports underscoring the potential contribution of other factors to NCI. Machine learning models uncovered variables related to individual NCI types that were not identified by univariate or multiple logistic regression analyses, highlighting the value of other approaches to understanding NCI in HIV/AIDS.

Opioid use trajectory groups and changes in a physical health biomarker among HIV-positive and uninfected patients receiving opioid agonist treatment

BackgroundObjective outcomes for measuring the physical health effects of substance use disorder treatment are needed. We compared the responsiveness of CD4, HIV-1 RNA and a biomarker index (VACS Index 2.0) to changes in opioid use among people with HIV (PWH) and uninfected individuals receiving opioid agonist treatment (OAT). MethodsElectronic health record data were used to identify patients who received ≥90 days of OAT and had ≥1 urine toxicology test in the Veterans Aging Cohort Study. Trajectory models identified patterns of opioid urine toxicology results. We used linear regression adjusted for age and race/ethnicity to determine associations between opioid toxicology groups and biomarker changes from up to one-year pre OAT to 3–15 months after OAT initiation. ResultsAmong 266 with detectable HIV-1 RNA, 366 with suppressed HIV-1 RNA, and 1183 uninfected patients, we identified five opioid toxicology groups ranging from consistently negative (54%) to consistently positive (9%). Among PWH with detectable HIV-1 RNA, all three biomarkers improved more for those consistently negative compared to those consistently positive (all p < .05). Among PWH with suppressed HIV-1 RNA, CD4 improved for those consistently negative; and worsened for those in the slow decrease toward negative group (p = .04). Among those uninfected, VACS Index 2.0 did not differ by opioid toxicology groups. ConclusionsAmong patients on OAT, changes in biomarkers are associated with opioid toxicology groups among PWH, but vary by HIV-1 RNA. These findings may be useful for measuring the health effects of OAT.

Integrated stepped alcohol treatment for patients with HIV and liver disease: A randomized trial

BackgroundThere 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. MethodsIn 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. ResultsAmong 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. ConclusionISAT 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.

A-03 Ethnic/Racial Differences in Longitudinal Neurocognitive Change among People Living with HIV

Abstract HIV disproportionately affects Black and Latino people in the United States, but data on longitudinal neurocognitive patterns for these groups are scarce. This study evaluated the incidence and predictors of neurocognitive decline by ethnicity/race in a cohort of Black, Latino, and White people living with HIV (PLWH). Participants included 499 PLWH (43.5% White, 42.7% Black, 13.8% Latino; mean age at baseline = 43.5) from the six-site CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER) study. Participants completed comprehensive neurocognitive and neuromedical evaluations over 3-7 study visits for an average of 2.8 years (SD = 1.1). Interpertation of neurocognitive change was based on published methods using regression-based norms that correct for baseline performance and practice effects. Survival analyses investigated the relationship between ethnicity/race and neurocognitive change, and predictors of neurocognitive decline. In follow-up, 108 participants (21.6%) declined, 311 (62.3%) remained stable, and 80 (16.0%) improved. In Cox proportional hazard models, hazard ratios for neurocognitive decline were increased for Latinos compared to Whites (HR = 2.19, 95%CI = 1.32-3.63, p = .002) and Blacks (HR = 1.87, 95%CI = 1.14-3.04, p = .01). Including significant covariates (baseline nadir CD4, hepatitis C Virus, and VACS Index: a composite marker of physical health among PLWH)did not significantly decrease the elevated risk for decline among Latinos. We found that Latino PLWH appear to have higher risk of neurocognitive decline compared to White and Black PLWH. Traditional markers of HIV disease and physical health at baseline did not explain this elevated risk of neurocognitive decline. Future research examining economic, socio-environmental, and culturally-relevant biomedical factors may help to explain this observed ethnic/racial disparity in longitudinal neurocognitive function in HIV.

HIV-1 coreceptor tropism: A syllogistic connection with The Veterans Aging Cohort Study Index and the CD4/CD8 ratio.

BackgroundThe association between X4 virus and an increased risk of non-AIDS-events has been reported. Morbidity/mortality due to non-AIDS events, which are properly predicted by the CD4/CD8 ratio and VACS index, have become particularly remarkable in HIV-infected patients receiving effective combined antiretroviral therapy (cART).MethodsWe verified the validity of the syllogism: as HIV-tropism (CRT) contributes to the onset of non-AIDS events which are successfully predicted by the CD4/CD8 ratio and VACS index, then CRT correlates with these two variables. The CD4/CD8 ratio and VACS index at baseline and overtime were analyzed according to CRT tested before the first successful cART regimen in newly-diagnosed patients.ResultsPatients with R5 variants had a significantly lower baseline VACS percentage risk [mean (95%CI):18.2%(16.1–20.3) vs 24.3%(18.2–22.5), p = 0.002] and higher baseline CD4/CD8 ratio [mean (95%CI):0.43 (0.38–0.47) vs 0.28 (0.19–0.36), p = 0.002] than non-R5 patients. After an initial drop, VACS increased again in R5 and non-R5 patients and the two trend curves almost overlapped. The CD4/CD8 ratio had an increasing trend in both R5 and non-R5 patients; however, even though non-R5 patients had a greater gain of CD4+, they maintained a lower CD4/CD8 ratio at any time point.ConclusionOur study confirms an association between pre-therapy CRT, CD4/CD8 ratio and VACS. A successful cART regimen positively affects the CD4/CD8 ratio; however, the disadvantage conferred by a non-R5 CRT is maintained overtime. The restoration of VACS in all patients could be directly due to variables included in the VACS calculation and to factors that adversely influence these variables.

1470. Neurocognitively-Acting Potentially Inappropriate Medications, Alcohol, and Community-Acquired Pneumonia Among Patients with and Without HIV

BackgroundAlcohol interactions with neurocognitively-acting potentially inappropriate medications (NC-PIMs) may be more common, more harmful, and associated with lower levels of alcohol use among people living with HIV.MethodsWe conducted a nested case–control study using data from the Veterans Aging Cohort Study (2007–2015). Cases with community-acquired pneumonia (CAP) requiring hospitalization (n = 6,716) were 1:5 matched to controls without CAP (n = 33,253) at the time of event by age, sex, race, HIV status, baseline year, and duration of observation time. Index date was defined as CAP date for cases and match date for controls. Based on pharmacy data in the year prior to index date, NC-PIMs included receipt of at least one prescription of any duration for anticonvulsants, sedatives (including benzodiazepines), prescription opioids, antidepressants, antipsychotics, and muscle relaxants. Among HIV+, NC-PIMs exposure also included ritonavir (RTV), cobicistat (COBI), and efavirenz (EFV). Conditional logistic regression models were used to obtain adjusted odds ratios (OR) and 95% confidence intervals (CI) for NC-PIMs (any and count overall, and by class), alcohol use disorder (AUD) diagnoses in the year prior to index date, and their interaction adjusted for smoking status, VACS Index, steroids, vaccination status (influenza and pneumonia), hepatitis C, previous CAP, and various comorbidities.ResultsAmong 39,989 patients, 17,161 (43%) were HIV+, 98% were male, and median age was 58 years. An increase in number of classes of NC-PIMs was associated with a 17% increase in the odds of CAP among HIV+ and uninfected, and this effect was augmented by contemporaneous AUD. Among HIV+, all classes of NC-PIMs apart from EFV were positively associated with CAP, most notably antipsychotics (OR 1.66, 95% CI 1.43–1.93). Among uninfected, the highest risk of CAP was associated with antipsychotics (OR 1.81, 95% CI 1.61–2.03) and anticonvulsants (OR 1.64, 95% CI 1.49–1.80). AUD positively interacted with sedatives, opioids, antidepressants, and muscle relaxants in both groups, and with RTV/COBI in HIV+ patients.ConclusionNC-PIMs, especially with concurrent AUD, are associated with increased CAP risk among those living with and without HIV. Disclosures All authors: No reported disclosures.

Elevated risk of viral rebound on ART in migrants living in France: role of socioeconomic factors.

In Western countries, viral rebound on antiretroviral therapy (ART) appears to occur more frequently in migrants. We aimed to assess the respective roles of socioeconomic factors and migration on viral rebound in people living with HIV (PLHIV) in France. We included PLHIV in France, enrolled from 2004 to 2008 in the French ANRS-COPANA cohort, who started a first ART and achieved undetectability (<50 copies/ml) within 1 year. Determinants of viral rebound were assessed using Cox models including geographical origin, HIV transmission group, and clinicobiological and sociodemographic data. Of 499 included individuals, 288 were born in France, 158 in sub-Saharan Africa (SSA) and 53 in another country. Kaplan-Meier probabilities of viral rebound-free survival were similar for men having sex with men (MSM) and heterosexuals born in France, and lower in migrants from SSA or other countries (P<0.001). The crude hazard ratio (HR) of viral rebound was 2.49 (95% CI, 1.59, 3.90) in migrants from SSA and 1.78 (0.94, 3.88) in migrants from other countries compared with MSM born in France. Educational level, financial difficulties and HIV status disclosure had the biggest impact on the difference between the crude and adjusted HRs for viral rebound in migrants. In multivariable analysis, viral rebound was no longer associated with geographical origin, but with protease inhibitor-containing ART, a VACS index ≥35 as a potential indicator of frailty, poor financial status (difficulties or debts) and non-disclosure to friend(s). Socioeconomic factors affect outcomes on ART, even in the context of free access to HIV care and treatment. Patient-centred strategies should be encouraged with the intervention of social workers to address basic needs and promote social support for more socially vulnerable individuals.

Efficacy of Extended-Release Naltrexone on HIV-Related and Drinking Outcomes Among HIV-Positive Patients: A Randomized-Controlled Trial.

We sought to test the efficacy of extended-release naltrexone (XR-NTX) on HIV-related and drinking outcomes. From April 2011-February 2015, we conducted a 4-site randomized double-blind placebo controlled clinical trial involving 51 HIV-positive patients with heavy drinking and < 95% antiretroviral (ART) adherence. All participants received counseling. The primary outcome was proportion with ≥ 95% ART adherence. Secondary outcomes included HIV biomarkers, VACS Index score, and past 30-day heavy drinking days. Based on receipt of ≥ 5 injections, 23 participants were retained at 24weeks. We did not detect an effect of XR-NTX on ART adherence (p = 0.38); undetectable HIV viral load (p = 0.26); CD4 cell count (p = 0.75) or VACS Index score (p = 0.70). XR-NTX was associated with fewer heavy drinking days (p = 0.03). While XR-NTX decreases heavy drinking days, we did not detect improvements in ART adherence or HIV outcomes. Strategies to improve retention in alcohol treatment and HIV-related outcomes among heavy drinking HIV-positive patients are needed.