Nadir CD4 Research Articles

1932. Antibody Response to SARS-CoV-2 Vaccination in US Veterans Living with HIV

Abstract Background COVID-19 (C-19) vaccines have demonstrated effectiveness in reducing SARS-CoV-2 related morbidity/mortality. The duration of protection in the general population is showing a waning immunity over time. Variable antibody responses to C-19 vaccines have been shown in persons living with HIV. We followed the anti-SARS-CoV-2 receptor biding domain (RBD) antibody titers, after 2 and 3 (booster) C-19 vaccinations, in US Veterans living with HIV (USVLH). Methods Retrospective chart review of USVLH who had received C-19 vaccinations at Northport VAMC. Testing was done with the © Beckman Coulter enzyme immunoassay measuring total IgG antibody to the RBD, a critical target of neutralizing antibodies within the spike protein encoded in the mRNA vaccines. Titers were drawn after the 2nd and 3rd doses C-19 vaccines in variable timing. Demographic data, CD4+ T cell counts nadir and current, HIV viral load, comorbid conditions were reviewed. Results We analyzed the SARS CoV-2 RBD IgG titers in 50 vaccinated USVLH. The median age is 65 years (range 36-75). 50% were Black, Caucasian 40%, Hispanic 10%. Risk factor for HIV infection, Heterosexual 52%, IVDU 18%, MSM 26%, needle stick 2%, blood transfusion 2%. The median CD4 nadir was 200/µL (5- 600), median current CD4 656 (174-1529). All USVLH were on HAART, 92% on INSTI-based therapy. 45 had undetectable HIV viral load (< 20), 5 had viremia from 22 to 563 copies. Medical conditions: diabetes 30%, CAD 18%, HTN 60%, COPD 8%, HLD 66%, smokers 18%. Six USV had C-19 prior to vaccination, and six had C-19 after vaccination with median 102 days (90-148) from last vaccine dose. Vaccines given: Janssen in 3 USVLH: Moderna (MOD)- 2 doses: 4; MOD-3 doses:5; Pfizer (PFZ)-2: 6; PFZ-3: 32. IgG titers decrease with time after 2nd vaccine dose and increase after booster dose. IgG titers checked after 2nd dose median days 120 (11-392) {titers: median 4.63 S/CO [0.17 – 53.66]}, 91 days (5-181) after 3rd dose {titers: median 16.22 [1.15-73.92]}. Titers were higher in MOD-2 vs. PFZ-2, median 25.7 vs. 4.63, P: 0.039, MOD-3 vs. PFZ-3 33.89 vs. 15.5, P: 0.117. No death due to C-19 was seen. SARS-CoV-2 RBD IgG titers in US Veterans living with HIV after 2nd dose of COVID vaccine. COVID-19 VACCINATED IN US VETERANS LIVING WITH HIV N=50 Conclusion In a cohort of USVLH, well controlled on HAART, C-19 vaccinations produced a serologic response that decayed over time and increased after booster dose. MOD vaccine may have achieved higher titers than PFZ. Disclosures All Authors: No reported disclosures.

Characteristics and Evolution of Cerebral Aneurysms Among Adults Living With HIV: A Retrospective, Longitudinal Case Series

Objective To describe the characteristics and evolution of cerebral aneurysms in a large cohort of adults living with human immunodeficiency virus (ALWH). Background HIV-associated vasculopathy, which can predispose to cerebral aneurysm development, may result from an inflammatory process whereby HIV viral proteins lead to increased chemoattractant and adhesion particles in the vessel wall. Additionally, adventitial layer inflammation has been shown to be strongly associated with HIV infection and vascular changes that may lead to cerebral aneurysm formation. A recent population-based matched cohort study demonstrated a higher rate of subarachnoid hemorrhage in ALWH. It is important to expand the current understanding of risk factors for aneurysm development and the longitudinal course of patients with HIV-associated vasculopathy to help reduce this source of potential morbidity. Design/Methods The Clinical Data Warehouse was queried for all adult patients evaluated at Boston Medical Center between January 1, 2000, and October 22, 2021 with a history of HIV and at least one cerebral aneurysm. Charts were reviewed for variables including timing of HIV and aneurysm diagnoses, antiretroviral (ART) duration, additional aneurysm risk factors, development of new aneurysms/growth of existing aneurysms, interventions, and clinical outcomes. Results A total of 50 patients (52% female) were identified, including 82 cerebral aneurysms. Forty-six percent of patients with a nadir CD4 count less than 200 cells/mm3 (N = 13) developed new aneurysms or were found to have aneurysm growth over time compared with 29% of patients with a CD4 nadir above 200 cells/mm3 (N = 21). New aneurysms were found or existing aneurysms grew in 67% of those not on ART at time of aneurysm diagnosis (N = 6), 38% of those with inconsistent ART use (N = 8), and 21% of those with consistent ART (N = 19). Conclusions Among ALWH, lower CD4 nadir and inconsistent ART use may contribute to aneurysm formation or growth. Further studies are needed to more thoroughly characterize this trend.

The influence of low-level viremia on CD4+ cell count in human immunodeficiency virus–infected patients

Following initiation of combined antiretroviral therapy, the majority of human immunodeficiency virus-infected patients experience immune reconstitution indicated by virologic suppression and an increase in peripheral CD4+ T-cell counts. Some patients may suffer from low-level viremia, which was reported to be significantly associated with acquired immunodeficiency syndrome cases, virologic failure, and death. We aimed to further investigate the influence of low-level viremia on CD4+ T-cell count. In our study, we included human immunodeficiency virus-seropositive patients on combined antiretroviral therapy, for at least 6 months, who received at least one assessment of human immunodeficiency virus plasma viral load and CD4+ cell count every 6 months, from January 2009 to January 2019. The copy-year viremia was determined by calculating the area under the curve of the plasma human immunodeficiency virus viral load. When comparing patients with a mean CD4+ cell count <200 cells/μL, there was no significant difference between patients with a mean viral load <1000 copies/mL and patients with a mean viral load ≥1000 copies/mL (p = 0.219). Among those with a mean viral load <1000 copies/mL, a higher proportion of patients had a mean CD4+ cell count ≥500 cells/µL (p < 0.001). The mean CD4+ cell count of patients with copy-years viremia (log10) <4 (577.7, interquartile range 429.2-736.7) was significantly higher than that of patients with copy-years viremia (log10) ≥4 (443.3, interquartile range 319.0-558.4) (p < 0.001). In multivariate logistic regression analysis, we observed that malignancy without history, lower copy-years viremia, and high nadir CD4+ cell count were independent predictors of mean CD4+ cell count ≥500 cells/µL. Human immunodeficiency virus-infected patients with a history of malignancy, high copy-year viremia, and lower nadir CD4+ cell counts should be monitored carefully in clinical settings.

Dynamics of Total and Intact HIV-1 DNA in Virologically Suppressed Patients Switching to DTG-Based or ATV-Based Dual Therapy

Clinical trials have demonstrated noninferior viral suppression rates of selected 2-drug regimens (2DRs) over standard 3-drug regimens (3DRs). However, the effect of simplification to 2DRs on HIV-1 reservoir remains to be fully assessed. Retrospective analyses of samples of virologically suppressed people living with HIV remaining on the same 3DRs or switching to DTG + 3TC or ATV/r + 3TC 2DRs. Whole blood samples were collected at enrollment and after 48 weeks. Total HIV-1 DNA (tDNA) and intact HIV-1 DNA (iDNA) were quantified by droplet digital polymerase chain reaction and intact proviral DNA assay, respectively. Statistical analysis was performed to identify associations among variables, and multiple linear regression was used to analyze potential predictors of tDNA and iDNA changes over time. Forty-seven individuals were switched to DTG + 3TC 2DR (N = 23) and ATV/r + 3TC 2DR (N = 24), while 18 remained on 3DRs. tDNA did not change either in the overall population or in the 3DR and 2DR groups. iDNA decreased significantly in the whole data set and in the overall 3DR and 2DR groups ( P = 0.001, P = 0.039 and P = 0.009, respectively). iDNA, but not tDNA, was inversely correlated with the time of viral suppression ( P = 0.002) and time under antiretroviral therapy ( P = 0.006). Higher nadir CD4 + T-cell counts ( P = 0.001) and lower zenith viral load ( P = 0.02) showed an association with the decrease of iDNA, but not with tDNA. Both tDNA and iDNA dynamics supported noninferior efficacy of 2DRs over 3DRs. iDNA could be more informative than tDNA in analyzing the dynamics of the HIV-1 reservoir under different treatment strategies.

Burden and correlates of significant liver fibrosis among HIV-infected and uninfected adults in urban Uganda.

Following chronic inflammation and other disease specific factors, the risk of liver disease is believed to be higher among HIV-infected patients than in the general population despite shared risk factors. Understanding this differentiated burden and its drivers will inform policy and priority populations for intervention. This was a cross sectional study among 516 adults attending care clinics in Kampala Uganda. Significant liver fibrosis (SLF) was defined as liver stiffness measurement ≥7.2 KPa identified by Fibroscan®. Data analyses were stratified by HIV status and we performed logistic regression performed to identify correlates. The prevalence of SLF was higher among HIV un-infected patients ((24% Vs 14%; p0.004). Overall HIV-uninfected patients were more likely to be overweight and or obese, with elevated serum cholesterol levels. Elevated measurement of fatty change in the liver (CAP scores >248 dB/m) was associated with SLF among HIV un-infected patients (OR 2.3 CI (1.0-5.2); p = 0.046). Low nadir CD4 counts (200cell/mm3) was predictive of SLF among HIV-infected patients (OR 3.3 CI (1.0-10.7); p = 0.05). The prevalence of SLF was unexpectedly higher among HIV un-infected than HIV affected patients attending care clinics in urban Uganda. This observed burden is most likely driven by non-alcoholic fatty liver disease (NAFLD) resulting from metabolic syndrome.

Host variation in type I interferon signaling genes (MX1), C-C chemokine receptor type 5 gene, and major histocompatibility complex class I alleles in treated HIV+ noncontrollers predict viral reservoir size.

Prior genomewide association studies have identified variation in major histocompatibility complex (MHC) class I alleles and C-C chemokine receptor type 5 gene (CCR5Δ32) as genetic predictors of viral control, especially in 'elite' controllers, individuals who remain virally suppressed in the absence of therapy. Cross-sectional genomewide association study. We analyzed custom whole exome sequencing and direct human leukocyte antigen (HLA) typing from 202 antiretroviral therapy (ART)-suppressed HIV+ noncontrollers in relation to four measures of the peripheral CD4+ T-cell reservoir: HIV intact DNA, total (t)DNA, unspliced (us)RNA, and RNA/DNA. Linear mixed models were adjusted for potential covariates including age, sex, nadir CD4+ T-cell count, pre-ART HIV RNA, timing of ART initiation, and duration of ART suppression. Previously reported 'protective' host genetic mutations related to viral setpoint (e.g. among elite controllers) were found to predict smaller HIV reservoir size. The HLA 'protective' B∗57:01 was associated with significantly lower HIV usRNA (q = 3.3 × 10-3), and among the largest subgroup, European ancestry individuals, the CCR5Δ32 deletion was associated with smaller HIV tDNA (P = 4.3 × 10-3) and usRNA (P = 8.7 × 10-3). In addition, genomewide analysis identified several single nucleotide polymorphisms in MX1 (an interferon stimulated gene) that were significantly associated with HIV tDNA (q = 0.02), and the direction of these associations paralleled MX1 gene eQTL expression. We observed a significant association between previously reported 'protective' MHC class I alleles and CCR5Δ32 with the HIV reservoir size in noncontrollers. We also found a novel association between MX1 and HIV total DNA (in addition to other interferon signaling relevant genes, PPP1CB, DDX3X). These findings warrant further investigation in future validation studies.

HIV and race are independently associated with endothelial dysfunction.

Evaluating the vascular function in HIV-infected compared with HIV uninfected with assessment of body composition, inflammation, and gut integrity markers. A noninvasive test that measures the endothelial function. We included participants at least 18 years old, with peripheral arterial tonometry testing (EndoPAT2000) between 2014 and 2022. Persons with HIV (PWH) had documented infection, a stable ART regimen, and a viral load less than 400 copies/ml. We measured the vessel's function with the reactive hyperemia index (RHI) (normal >1.67) and Augmentation Index. Lower Augmentation Index reflect better arterial elasticity. We assessed markers of systemic inflammation, immune activation, and gut integrity. We used linear mixed models to estimate endothelial dysfunction with a significant P value less than 0.05. Overall, 511 participants (296 HIV-infected; 215 HIV-uninfected controls) were included. Estimated RHI among PWH was 13% lower (P = 0.01) compared with persons without HIV. In nonwhite race, the estimated RHI was 9% lower (P = 0.001) than white race. For every 1% increase in BMI, we would expect RHI to increase 0.17% (P = 0.01). At the time of EndoPAT, the estimated RHI was 8% lower (P = 0.04) among protease inhibitor users compared with PWH who were not taking protease inhibitors. The estimated odds of abnormal RHI ≤1.67) is 1.56 times greater [95% confidence interval (CI) 1.05-2.31] in nonwhite race compared with white race, independent of HIV status [OR = 1.4 (95% CI 0.94-2.13)]. There was not enough evidence to suggest that inflammation, gut, or monocyte markers, current or nadir CD4+ cell count, or duration of HIV were associated with endothelial dysfunction. HIV, nonwhite race, and protease inhibitor use are independently associated with endothelial dysfunction.

Abstract 13277: Hiv and Race Are Independently Associated With Endothelial Dysfunction

Objective: Assessing the vascular function in HIV + compared to HIV - with assessment of body composition, inflammation, and gut integrity markers. Introduction: HIV and ART are associated with an increased risk of CVD. Thus, the need for a non-invasive test to detect increased risk or early signs of CVD. Hypothesis: HIV and non-white race are independently associated with vascular dysfunction. High viral load, BMI, and inflammation damage endothelial function. Methods: We included participants ≥18 years, with peripheral arterial tonometry testing (EndoPAT2000) between 2014-2022. HIV + had a stable ART regimen, and a VL ≤400 c/mL. We measured the vessel’s adaptability with Reactive Hyperemia Index (RHI) (normal&gt;1.67) and elasticity with Augmentation Index (AI) (normal&lt;-10). We assessed markers of systemic inflammation, immune activation, and gut integrity. We used linear mixed models to estimate endothelial dysfunction with a significant p-value&lt;0.05. Results: Overall, 511 participants (296 HIV+ and 215 HIV-) were included. The estimated RHI among HIV+ was 13% lower (p=0.01) compared to HIV-. In Non-White, the estimated RHI was 9% lower (p=0.001) than in White. Every 1% increase in BMI we would expect RHI to increase 0.17% (p=0.01). At the time of EndoPAT, the estimated RHI was 8% lower (p=0.04) among PI antiretroviral therapy use compared to HIV+ who were taking NRTI or NNRTIs. The estimated odds of having endothelial dysfunction (RHI ≤ 1.67) is 1.56 times greater (95% CI: 1.05, 2.31) in Non-White compared to White, independent of HIV status [OR=1.4 (95% CI: 0.94, 2.13)]. There was not enough evidence to suggest that inflammation, gut, or monocyte markers, current or nadir CD4, duration of HIV, or current treatment with NRTI or NNRTIs at the time of EndoPat was associated with endothelial dysfunction. Conclusions: HIV and non-white race are independently associated with endothelial dysfunction. PI use was associated with vascular dysfunction in all racial groups.

Neuroimaging and immunological features of neurocognitive function related to substance use in people with HIV.

This study sought to identify neuroimaging and immunological factors associated with substance use and that contribute to neurocognitive impairment (NCI) in people with HIV (PWH). We performed cross-sectional immunological phenotyping, neuroimaging, and neurocognitive testing on virally suppressed PWH in four substance groups: cocaine only users (COC), marijuana only users (MJ), dual users (Dual), and Non-users. Participants completed substance use assessments, multimodal MRI brain scan, neuropsychological testing, and blood and CSF sampling. We employed a two-stage analysis of 305 possible biomarkers of cognitive function associated with substance use. Feature reduction (Kruskal Wallis p-value < 0.05) identified 53 biomarkers associated with substance use (22 MRI and 31 immunological) for model inclusion along with clinical and demographic variables. We employed eXtreme Gradient Boosting (XGBoost) with these markers to predict cognitive function (global T-score). SHapley Additive exPlanations (SHAP) values were calculated to rank features for impact on model output and NCI. Participants were 110 PWH with sustained HIV viral suppression (33MJ, 12 COC, 22 Dual, and 43 Non-users). The ten highest ranking biomarkers for predicting global T-score were 4 neuroimaging biomarkers including functional connectivity, gray matter volume, and white matter integrity; 5 soluble biomarkers (plasma glycine, alanine, lyso-phosphatidylcholine (lysoPC) aC17.0, hydroxy-sphingomyelin (SM.OH) C14.1, and phosphatidylcholinediacyl (PC aa) C28.1); and 1 clinical variable (nadir CD4 count). The results of our machine learning model suggest that substance use may indirectly contribute to NCI in PWH through both metabolomic and neuropathological mechanisms.

Concurrent Cervical and Anal High-Risk Human Papillomavirus Infection in Women Living With HIV: An Observational Case-Control Study.

To evaluate the prevalence and correlates of concurrent uterine cervical and anal HR-HPV infections in women living with HIV (WLHIV). A cross-sectional study was undertaken at a tertiary care hospital and linked ART center. One hundred and forty-one WLHIV and 161 HIV-negative women were enrolled for cervical and anal cytology as well as HR-HPV testing using the HC2 method. Screen-positive women were followed-up with colposcopy/anoscopy and/or repeat cytology. Appropriate statistical tests were applied to assess the association of concurrent HR-HPV with various parameters. Concurrent cervical and anal HR-HPV infection was detected in 22 WLHIV (16.3%) and 5 HIV-negative women (3.1%), the difference being statistically significant ( P &lt; 0.001 ). Among WLHIV, concurrent HR-HPV was associated with tobacco use ( P &lt; 0.001 ), receptive anal intercourse ( P = 0.02 ), low CD4 counts ( P = 0.001 ), and negatively with ART intake ( P = 0.004 ) on bivariate analysis. Multivariate logistic regression analysis showed a positive association of concurrent HR-HPV positivity with tobacco use ( P = 0.02 ) and low nadir CD4 counts ( P = 0.03 ). WLHIV, especially those with CD4 counts less than 200/µL, should be offered HR-HPV screening and follow-up to detect cervical and anal lesions.

Abnormal Magnetic Resonance Image Signature in Virologically Stable HIV Individuals.

With implementation of combination antiretroviral therapy (cART), changes to brain integrity in people with HIV (PWH) are subtle compared to those observed in the pre-cART era. T1-weighted/T2-weighted (T1w/T2w) ratio has been proposed as a measure of cortical myelin. This study examines T1w/T2w values between virologically controlled PWH and persons without HIV (PWoH). Virologically well-controlled PWH (n = 164) and PWoH (n = 120) were compared on global and regional T1w/T2w values. T1w/T2w values were associated with HIV disease variables (nadir and current CD4 T-cell count, and CNS penetration effectiveness of cART regimen) in PWH, and as a function of age for both PWoH and PWH. PWH had reduced global and regional T1w/T2w values compared to PWoH in the posterior cingulate cortex, caudal anterior cingulate cortex, and insula. T1w/T2w values did not correlate with HIV variables except for a negative relationship with CNS penetration effectiveness. Greater cardiovascular disease risk and older age were associated with lower T1w/T2w values only for PWH. T1w/T2w values obtained from commonly acquired MRI protocols differentiates virologically well-controlled PWH from PWoH. Changes in T1w/T2w ratio do not correlate with typical HIV measures. Future studies are needed to determine the biological mechanisms underlying this measure.

Variation in Heart Failure Risk by HIV Severity and Sex in People With HIV Infection.

HIV is an independent risk factor for heart failure (HF). However, the association of HIV severity with incident HF and the potential interaction with sex are incompletely understood. Integrated health care system. We conducted a cohort study of people with HIV (PWH) and matched people without HIV (PWoH), all aged ≥ 21 years and with no previous HF. Poisson regression was used to compare incident HF by HIV status, with PWH stratified by severity of HIV infection [defined by recent (<6 months) CD4 count, nadir CD4 count, or recent HIV RNA level]. Models were adjusted for sociodemographic characteristics, substance use, and HF risk factors. Analyses were conducted for men and women combined, then by sex. The study included 38,868 PWH and 386,569 PWoH (mean baseline age = 41.0 ± 10.8 years; 88% men). Compared with PWoH, incident HF risk was higher among PWH with lower recent CD4 [200-499 cells/µL, adjusted rate ratio (aRR) = 1.82, 95% confidence interval (CI) = 1.50 to 2.21 and <200 cells/µL, aRR = 3.26 (2.47 to 4.30)] and a low nadir CD4 [<200 cells/µL, aRR = 1.56 (1.37 to 1.79)] but not among PWH with normal CD4 [≥500 cells/µL, aRR = 1.14 (0.90 to 1.44)]. Higher incident HF risk was observed among PWH at all HIV RNA levels, with greater HF risk at higher HIV RNA levels. The excess HF risk associated with low CD4 (recent or nadir) and high HIV RNA was stronger among women than men (P interactions=0.05, 0.08, and 0.01, respectively). Given the association of HIV severity with HF, optimizing HIV treatment and management may be important for HF prevention among PWH.

Ghrelin level as a biomarker for knee osteoarthritis severity and appearance in HIV + patients

BackgroundKnee Osteoarthritis (KOA) is a multifactorial disease with several mechanisms to promote articular cartilage damage. New molecules, such as ghrelin, have been recently reported to participate in the pathogenesis and progression of KOA. In HIV + patients, arthralgias are the most frequent musculoskeletal manifestations, mainly affecting joints such as the knee. Also, it has been reported that HIV + patients have a reduction of ghrelin even with treatment compared to HIV- patients. However, there is no report in the literature evaluating ghrelin and KOA in the HIV + population. We aimed to evaluate whether serum ghrelin levels can function as a biomarker for OA in HIV + patients. MethodsWe recruited 40 patients, 20 HIV+, and 20 HIV- controls, and grouped as follows: HIV+/KOA+; HIV+/KOA-; HIV-/KOA+; HIV-/KOA-. Clinical features were obtained during clinical visits. Peripheral blood samples were acquired to measure serum ghrelin levels. ResultsThe HIV+/KOA + group significantly reduced serum ghrelin levels when compared with the other groups. Comparing the ghrelin levels with the patients’ nadir of CD4+ T-cells count, we identified a statistically significant negative correlation in the KOA- group (r = −0.80, P < 0.007). An ROC curve analysis, for the accuracy of ghrelin levels to identified HIV+/KOA + from HIV+/KOA- patients, found an area under the curve of 0.83 (95 % CI 0.65–0.10; P = 0.017), with a cut-off < 4026 pg/mL serum ghrelin levels, with a sensitivity of 0.62 (95 % CI 0.32–0.86), and a specificity of 0.10 (95 % CI 0.59–0.10). ConclusionThis study shows the potential use of ghrelin levels as a biomarker for KOA in the high-risk HIV population that should be further analyzed.

Previous Syphilis Not Associated With Neurocognitive Outcomes in People Living With Human Immunodeficiency Virus in Ontario, Canada.

Background About 40% to 60% of people living with human immunodeficiency virus (HIV) experience neurocognitive impairments, irrespective of antiretroviral status. We hypothesized that a history of syphilis or neurosyphilis would be associated with worse neurocognitive outcomes in this population. Methods Among health care–engaged people living with HIV in Ontario older than 16 years enrolled in the OHTN Cohort Study, neurocognitive outcomes were as follows: (1) self-reported Medical Outcome Study–HIV Health Survey 4-item cognitive scale; (2) average T score summary scores based on objective neuropsychological testing of complex attention, speed of processing, and learning/memory; and (3) global deficit score dichotomized into impaired/unimpaired neurocognitive status. Syphilis history was determined by laboratory data or chart review. Univariable and multivariable generalized linear mixed models assessed the association between each of: syphilis, number of episodes of syphilis, and years since syphilis diagnosis with these neurocognitive outcomes controlling for age, sex, race, education, income, years of HIV, nadir and most recent CD4 count, most recent HIV viral load, substance use, depression, and number of prior neurocognitive tests. Results Of 1288 eligible participants, 218 (16.9%) had a history of syphilis at baseline and an additional 53 were diagnosed during follow up for a total of 271 (21.0%) at the most recent visit. Of those with past infection at baseline, 179 (82.1%) had 1 and 39 (17.9%) had 2 or more episodes of syphilis. In longitudinal multivariable models, we observed no relationship between syphilis diagnosis or years since syphilis diagnosis and any of the neurocognitive outcomes. Conclusions In this sample, prior syphilis was not associated with worse neurocognitive outcomes over time according to self-reported scales or objective neuropsychological testing.

Predicting Risk of Multidrug-Resistant Enterobacterales Infections Among People With HIV.

BackgroundMedically vulnerable individuals are at increased risk of acquiring multidrug-resistant Enterobacterales (MDR-E) infections. People with HIV (PWH) experience a greater burden of comorbidities and may be more susceptible to MDR-E due to HIV-specific factors.MethodsWe performed an observational study of PWH participating in an HIV clinical cohort and engaged in care at a tertiary care center in the Southeastern United States from 2000 to 2018. We evaluated demographic and clinical predictors of MDR-E by estimating prevalence ratios (PRs) and employing machine learning classification algorithms. In addition, we created a predictive model to estimate risk of MDR-E among PWH using a machine learning approach.ResultsAmong 4734 study participants, MDR-E was isolated from 1.6% (95% CI, 1.2%–2.1%). In unadjusted analyses, MDR-E was strongly associated with nadir CD4 cell count ≤200 cells/mm3 (PR, 4.0; 95% CI, 2.3–7.4), history of an AIDS-defining clinical condition (PR, 3.7; 95% CI, 2.3–6.2), and hospital admission in the prior 12 months (PR, 5.0; 95% CI, 3.2–7.9). With all variables included in machine learning algorithms, the most important clinical predictors of MDR-E were hospitalization, history of renal disease, history of an AIDS-defining clinical condition, CD4 cell count nadir ≤200 cells/mm3, and current CD4 cell count 201–500 cells/mm3. Female gender was the most important demographic predictor.ConclusionsPWH are at risk for MDR-E infection due to HIV-specific factors, in addition to established risk factors. Early HIV diagnosis, linkage to care, and antiretroviral therapy to prevent immunosuppression, comorbidities, and coinfections protect against antimicrobial-resistant bacterial infections.

Can simplified antiretroviral drug combination therapies resist resistance?

Can simplified antiretroviral drug combination therapies resist resistance?

Ageing with HIV: a longitudinal study of markers of resilience in young adults with perinatal exposure to HIV, with or without perinatally acquired HIV.

IntroductionMedical challenges, including perinatally acquired HIV (PHIV), can be considered adversity with the potential to compromise individuals’ ability to meet societal expectations across the lifespan. Studies suggest that resilience, defined as positive adaptation in the context of adversity, helps individuals overcome challenges and improve their quality of life. Few longitudinal studies have examined resilience in young adults with perinatally acquired HIV (YAPHIV) or perinatal HIV exposure, uninfected (YAPHEU). We examined three young adult milestones, which can affect the life‐long quality of life, as markers of resilience: high school graduation, postsecondary education and current employment.MethodsAnalyses included YAPHIV and YAPHEU, ages 19–27 years, followed in longitudinal cohort studies: Pediatric HIV/AIDS Cohort Study Adolescent Master Protocol (AMP) (7–17 years) and AMP Up (≥18 years). Factors known to influence the attainment of milestones (outcomes) were examined: executive function, cognitive efficiency (working memory and processing speed), behavioural/social‐emotional functioning, parent/caregiver mental/physical health and cumulative risk. HIV disease markers for YAPHIV were examined. The most recent AMP assessment was used for each factor; outcomes were measured at AMP Up 1‐year follow‐up. Separate robust Poisson regression models were used to assess associations of each factor with each outcome; PHIV status was explored as an effect modifier of each association.ResultsParticipants (N = 315; YAPHIV = 228): 58% female, 67% Black and 27% Hispanic. Compared to YAPHEU, YAPHIV were older and from families with higher median income and fewer symptoms of parent/caregiver mental health/substance use disorders. Proportions of YAPHIV and YAPHEU, respectively, who achieved each milestone were comparable: 82% versus 78% for high school graduation (p = 0.49), 45% versus 51% for postsecondary education (p = 0.35) and 48% versus 54% for current employment (p = 0.32). Higher cognitive efficiency was positively associated with postsecondary education and current employment. Higher executive function, age‐appropriate behavioural/social‐emotional functioning and lower cumulative risk were associated with academic milestones. Among YAPHIV, positive associations were: higher current CD4 with postsecondary education and lower nadir CD4 with current employment. PHIV status did not modify any association.ConclusionsYAPHIV and YAPHEU demonstrated resilience, attaining at least one young adult milestone. Cognitive, behavioural and social resources to support resilience in childhood and adolescence may provide the foundation for continued achievement throughout adulthood.

Immunogenicity to COVID-19 mRNA vaccine third dose in people living with HIV

In order to investigate safety and immunogenicity of SARS-CoV-2 vaccine third dose in people living with HIV (PLWH), we analyze anti-RBD, microneutralization assay and IFN-γ production in 216 PLWH on ART with advanced disease (CD4 count <200 cell/mm3 and/or previous AIDS) receiving the third dose of a mRNA vaccine (BNT162b2 or mRNA-1273) after a median of 142 days from the second dose. Median age is 54 years, median CD4 nadir 45 cell/mm3 (20–122), 93% HIV-RNA < 50 c/mL. In 68% of PLWH at least one side-effect, generally mild, is recorded. Humoral response after the third dose was strong and higher than that achieved with the second dose (>2 log2 difference), especially when a heterologous combination with mRNA-1273 as third shot is used. In contrast, cell-mediated immunity remain stable. Our data support usefulness of third dose in PLWH currently receiving suppressive ART who presented with severe immune dysregulation.

Improved induced innate immune response after cART initiation in people with HIV.

IntroductionImpairment of the innate immune function may contribute to the increased risk of bacterial and viral infections in people with HIV (PWH). In this study we aimed to investigate the induced innate immune responses in PWH prior to and after initiation of combinational antiretroviral therapy (cART). Furthermore, we aimed to investigate if the induced innate immune responses before initiation of cART were associated with CD4+ T-cell recovery one year after initiating cART.Material and methodThe induced innate immune response was assessed by the TruCulture® whole blood technique in 32 PWH before cART initiation and after 1, 6 and 12 months. To mimic bacterial and viral infections we used a panel of three stimuli (lipopolysaccharide (LPS), resiquimod (R848), and polyinosinic:polycytidylic acid (Poly I:C)) to stimulate the extracellular Toll-like receptor (TLR) 4 and the intracellular TLR7/8 and TLR3, respectively. The following cytokine responses were analyzed by Luminex 200: Tumor Necrosis Factor (TNF)-α, Interleukin (IL)-1b, IL-6, IL-8, IL-10, IL-12p40, IL17A, Interferon (IFN)-α, and IFN-γ.ResultsAt baseline PWH with nadir CD4+ T-cell count <350 cell/µL had lower levels of LPS-, R848-, and Poly I:C-induced IL-6 and IFN-γ, LPS- and R848-induced TNF-α and IL-12, LPS induced IL-1b, and R848-induced IL-10 than PWH with nadir CD4+ T-cell count >350 cells/µL. The majority (>50%) had induced cytokine concentrations below the reference intervals at baseline which was most pronounced for the LPS- and Poly I:C-induced responses. The induced responses in the whole population improved after 12 months of cART, and more PWH had induced cytokine concentrations within the reference intervals after 12 months. However, the majority of PWH still had LPS-induced INF-α, INF-γ and Poly I:C-induced TNF-α and IL-6 below the reference interval. The induced innate immune responses before cART initiation were not associated with the CD4+ T-cell recovery after 12 months of cART.ConclusionThe innate immune response was impaired in PWH, with a more pronounced impairment in PWH with low nadir CD4+ T-cell count. Initiation of cART improved the innate immune response, but compared to the reference intervals, some impairment remained in PWH without viral replication.

Cytomegalovirus Immunoglobulin G (IgG) Titer and Coronary Artery Disease in People With Human Immunodeficiency Virus (HIV).

Cytomegalovirus (CMV) infection is thought to result in increased immune activation in people with human immunodeficiency virus (HIV, PWH). Although some data have linked asymptomatic CMV infection to cardiovascular disease among PWH, it remains unknown whether CMV is associated with increased or high-risk coronary plaque. The Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE) enrolled PWH aged 40-75 years on stable antiretroviral therapy (ART) with low-to-moderate atherosclerotic cardiovascular disease (ASCVD) risk. Among a subset of US REPRIEVE participants, coronary plaque was assessed by coronary computed tomography angiography. Here, we assessed the relationship between CMV immunoglobulin G (IgG) titer and (1) levels of immune activation, (2) inflammatory biomarkers, and (3) coronary plaque phenotypes at study entry. Of 672 participants, mean age was 51 years, 83% were men, median ASCVD risk score was 4.5%, and 66% had current CD4+ T-cell count ≥500 cells/mm3. Higher CMV IgG quartile group was associated with older age and lower current and nadir CD4+ T-cell counts. CMV IgG titer was associated with specific inflammatory biomarkers (sCD163, MCP-1, interleukin [IL]-6, hsCRP) in univariate analysis, but not after controlling for HIV-specific factors. In contrast, CMV IgG titer was not associated with coronary artery disease indexes, including presence of plaque, coronary artery calcium (CAC) score >0, vulnerable plaque presence, or Leaman score >5. No meaningful association was seen between CMV IgG titer and coronary artery disease indexes among ART-treated PWH at study enrollment. Longitudinal assessments in REPRIEVE will determine the relationship of CMV IgG titer to plaque progression and cardiovascular events. NCT02344290.