scholarly journals Inflammation and microbial translocation measured prior to combination antiretroviral therapy (cART) and long-term probability of clinical progression in people living with HIV

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Esther Merlini ◽  
Alessandro Cozzi-lepri ◽  
Antonella Castagna ◽  
Andrea Costantini ◽  
Sergio Lo Caputo ◽  
...  
Keyword(s):  
Cox Regression ◽  
Microbial Translocation ◽  
Study Cohort ◽  
People Living With Hiv ◽  
Clinical Progression ◽  
Cart Initiation ◽  
Increased Risk ◽  
Study Population ◽  
Hs Crp ◽  
Living With Hiv

Abstract Background Despite the effectiveness of cART, people living with HIV still experience an increased risk of serious non-AIDS events, as compared to the HIV negative population. Whether pre-cART microbial translocation (MT) and systemic inflammation might predict morbidity/mortality during suppressive cART, independently of other known risk factors, is still unclear. Thus, we aimed to investigate the role of pre-cART inflammation and MT as predictors of clinical progression in HIV+ patients enrolled in the Icona Foundation Study Cohort. Methods We included Icona patients with ≥2 vials of plasma stored within 6 months before cART initiation and at least one CD4 count after therapy available. Circulating biomarker: LPS, sCD14, EndoCab, hs-CRP. Kaplan-Meier curves and Cox regression models were used. We defined the endpoint of clinical progression as the occurrence of a new AIDS-defining condition, severe non-AIDS condition (SNAEs) or death whichever occurred first. Follow-up accrued from the data of starting cART and was censored at the time of last available clinical visit. Biomarkers were evaluated as both binary (above/below median) and continuous variables (logescale). Results We studied 486 patients with 125 clinical events: 39 (31%) AIDS, 66 (53%) SNAEs and 20 (16%) deaths. Among the analyzed MT and pro-inflammatory markers, hs-CRP seemed to be the only biomarker retaining some association with the endpoint of clinical progression (i.e. AIDS/SNAEs/death) after adjustment for confounders, both when the study population was stratified according to the median of the distribution (1.51 mg/L) and when the study population was stratified according to the 33% percentiles of the distribution (low 0.0–1.1 mg/L; intermediate 1.2–5.3 mg/L; high > 5.3 mg/L). In particular, the higher the hs-CRP values, the higher the risk of clinical progression (p = 0.056 for median-based model; p = 0.002 for 33% percentile-based model). Conclusions Our data carries evidence for an association between the risk of disease progression after cART initiation and circulating pre-cART hs-CRP levels but not with levels of MT. These results suggest that pre-therapy HIV-driven pro-inflammatory milieu might overweight MT and its downstream immune-activation.

Pre-cART Inflammation, Microbial Translocation and Long-Term Probability of Clinical Progression in People Living With HIV 

2021 ◽  
Author(s):  
Esther Merlini ◽  
Alessandro Cozzi-Lepri ◽  
Antonella Castagna ◽  
Andrea Costantini ◽  
Sergio Lo Caputo ◽  
...  
Keyword(s):  
Cox Regression ◽  
Microbial Translocation ◽  
Study Cohort ◽  
People Living With Hiv ◽  
Continuous Variables ◽  
Clinical Progression ◽  
Cart Initiation ◽  
Kaplan Meier ◽  
Hs Crp ◽  
Living With Hiv

Abstract Background. We aimed to investigate the role of pre-cART inflammation and microbial translocation (MT) as predictors of clinical progression in HIV+ patients enrolled in the Icona Foundation Study Cohort.Methods. We included Icona patients with plasma stored within 6 months before cART initiation and at least one CD4 count after therapy available. Circulating biomarker: LPS, sCD14, EndoCab, hs-CRP. Kaplan-Meier curves and Cox regression models were used. We defined the endpoint of clinical progression as the occurrence of a new AIDS-defining condition, severe non-AIDS condition (SNAEs) or death whichever occurred first. Follow-up accrued from the data of starting cART and was censored at the time of last available clinical visit. Biomarkers were evaluated as both binary (above/below median) and continuous variables (logescale).Results. We studied 486 patients with 125 clinical events:10.8 (0.77-14.8)/1000 PYFU new AIDS, 18.3 (14.2-23.3)/1000 PYFU SNAEs, and 5.56 (3.40-8.57)/1000 PYFU deaths. Among morbidity events, the incidence of infectious-related events was 19.4 (15.2-24.5)/1000 PYFU. Hs-CRP seemed to be the only biomarker retaining some association with the endpoint of clinical progression (i.e. AIDS/SNAEs/death p=.056).Conclusions. Circulating pre-cART hs-CRP but not MT seems associated with the risk of disease progression after cART initiation, suggesting that pre-therapy HIV-driven pro-inflammatory milieu might overweight MT and its downstream immune-activation. This result should help guiding the design of interventional studies.

scholarly journals The utility of kidney injury molecule-1 as an early biomarker of kidney injury in people living with HIV

2020 ◽  
Vol 31 (13) ◽  
pp. 1228-1237
Author(s):  
Mohammed I Danjuma ◽  
Shaikha Al Shokri ◽  
Nadia Bakhsh ◽  
Mohammed A Alamin ◽  
Mohamed GH Mohamedali ◽  
...  
Keyword(s):  
General Population ◽  
Odds Ratio ◽  
Kidney Injury ◽  
Study Cohort ◽  
People Living With Hiv ◽  
Kidney Dysfunction ◽  
Normal Volunteers ◽  
Increased Risk ◽  
Kidney Injury Molecule 1 ◽  
Living With Hiv

There are increasing reports of antiretroviral therapy (ART) drug-related kidney dysfunction. Traditional markers of kidney dysfunction such as urine protein/creatinine ratio and estimated glomerular filtration rate (eGFR) have thus far proven ineffective at detecting some sub-clinical forms of ART-related kidney injury. This is a cross-sectional examination of 114 people living with HIV (PLWH), either naïve ( N =104) or treatment experienced ( N =10). Urinary kidney injury molecule-1 (KIM-1 ng/mg) thresholds were estimated using electrochemiluminescent assays from stored urine samples and normalised for urinary creatinine excretion (KIM-1/Cr). Correlation coefficients and predictors of kidney tubular injury were compared and derived for both adjusted and unadjusted urinary KIM-1/CR (ng/mg). In PLWH (both ART-naïve and treatment experienced) had a higher baseline unadjusted and adjusted median (≥3.7 ng/mg) and upper tertile (≥6.25 ng/mg) urinary KIM-1/Cr levels compared to either non-normal volunteers (0.39 ng/mg) or those with acute kidney injury in the general population (0.57 ng/mg). When upper tertile KIM-1/Cr (≥6.25 ng/mg) was utilised as a marker of kidney injury, eGFR (ml/min/1.73 m2), white Caucasian ethnicity, and protease inhibitor exposure were significantly associated with increased risk of kidney injury in multivariate analyses (odds ratio 0.91, confidence interval [CI] 0.68–0.98, P = 0.02; odds ratio 8.9, CI 1.6–48.6, p = 0.01; and odds ratio 0.05, CI 0.03–0.9, p =0.04, respectively). We found a significant degree of sub-clinical kidney injury (high unadjusted and adjusted KIM-1/Cr) in PLWH with normal kidney function (eGFR ≥60 ml/min/1.73 m2). We also found a higher baseline KIM-1/Cr (ng/mg) in our study cohort than reported both in normal volunteers and patients with kidney injury in the general population.

scholarly journals Increased CHIP Prevalence Amongst People Living with HIV

2020 ◽  
Author(s):  
Alexander G. Bick ◽  
Konstantin Popadin ◽  
Christian W. Thorball ◽  
Md Mesbah Uddin ◽  
Markella Zanni ◽  
...  
Keyword(s):  
Hematologic Malignancy ◽  
Driver Mutations ◽  
People Living With Hiv ◽  
Hematopoietic Stem ◽  
Age Related ◽  
Increased Risk ◽  
Propensity Matching ◽  
Study Population ◽  
Artery Disease ◽  
Living With Hiv

AbstractPeople living with human immunodeficiency virus (PLWH) have significantly increased risk for cardiovascular disease in part due to inflammation and immune dysregulation. Clonal hematopoiesis of indeterminate potential (CHIP), the age-related acquisition and expansion of hematopoietic stem cells due to leukemogenic driver mutations, increases risk for both hematologic malignancy and coronary artery disease (CAD). Since increased inflammation is hypothesized to be both a cause and consequence of CHIP, we hypothesized that PLWH have a greater prevalence of CHIP. We searched for CHIP in multi-ethnic cases from the Swiss HIV Cohort Study (SHCS, n=600) and controls from the Atherosclerosis Risk in the Communities study (ARIC, n=8,111) from blood DNA-derived exome sequences. We observed that HIV is associated with increased CHIP prevalence, both in the whole study population and in a subset of 230 cases and 1002 matched controls selected by propensity matching to control for demographic imbalances (SHCS 7%, ARIC 3%, p=0.005). Additionally, unlike in ARIC, ASXL1 was the most commonly implicated mutated CHIP gene. We propose that CHIP may be one mechanism through which PLWH are at increased risk for CAD. Larger prospective studies should evaluate the hypothesis that CHIP contributes to the excess cardiovascular risk in PLWH.

scholarly journals Increased prevalence of clonal hematopoiesis of indeterminate potential amongst people living with HIV

2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Alexander G. Bick ◽  
Konstantin Popadin ◽  
Christian W. Thorball ◽  
Md Mesbah Uddin ◽  
Markella V. Zanni ◽  
...  
Keyword(s):  
Hematologic Malignancy ◽  
Driver Mutations ◽  
People Living With Hiv ◽  
Hematopoietic Stem ◽  
Clonal Hematopoiesis ◽  
Age Related ◽  
Increased Risk ◽  
Study Population ◽  
Artery Disease ◽  
Living With Hiv

AbstractPeople living with human immunodeficiency virus (PLWH) have significantly increased risk for cardiovascular disease in part due to inflammation and immune dysregulation. Clonal hematopoiesis of indeterminate potential (CHIP), the age-related acquisition and expansion of hematopoietic stem cells due to leukemogenic driver mutations, increases risk for both hematologic malignancy and coronary artery disease (CAD). Since increased inflammation is hypothesized to be both a cause and consequence of CHIP, we hypothesized that PLWH have a greater prevalence of CHIP. We searched for CHIP in multi-ethnic cases from the Swiss HIV Cohort Study (SHCS, n = 600) and controls from the Atherosclerosis Risk in the Communities study (ARIC, n = 8111) from blood DNA-derived exome sequences. We observed that HIV is associated with a twofold increase in CHIP prevalence, both in the whole study population and in a subset of 230 cases and 1002 matched controls selected by propensity matching to control for demographic imbalances (SHCS 7%, ARIC 3%, p = 0.005). We also observed that ASXL1 is the most commonly mutated CHIP-associated gene in PLWH. Our results suggest that CHIP may contribute to the excess cardiovascular risk observed in PLWH.

scholarly journals Community‐Acquired Pneumonia and Risk of Cardiovascular Events in People Living With HIV

2020 ◽  
Vol 9 (23) ◽  
Author(s):  
Jerry S. Zifodya ◽  
Meredith S. Duncan ◽  
Kaku A. So‐Armah ◽  
Engi F. Attia ◽  
Kathleen M. Akgün ◽  
...  
Keyword(s):  
Risk Factors ◽  
Hiv Infection ◽  
Cox Regression ◽  
Community Acquired Pneumonia ◽  
People Living With Hiv ◽  
Hiv Status ◽  
Cvd Risk Factors ◽  
Cvd Risk ◽  
Increased Risk ◽  
Living With Hiv

Background Hospitalization with community‐acquired pneumonia (CAP) is associated with an increased risk of cardiovascular disease (CVD) events in patients uninfected with HIV. We evaluated whether people living with HIV (PLWH) have a higher risk of CVD or mortality than individuals uninfected with HIV following hospitalization with CAP. Methods and Results We analyzed data from the Veterans Aging Cohort Study on US veterans admitted with their first episode of CAP from April 2003 through December 2014. We used Cox regression analyses to determine whether HIV status was associated with incident CVD events and mortality from date of admission through 30 days after discharge (30‐day mortality), adjusting for known CVD risk factors. We included 4384 patients (67% [n=2951] PLWH). PLWH admitted with CAP were younger, had less severe CAP, and had fewer CVD risk factors than patients with CAP who were uninfected with HIV. In multivariable‐adjusted analyses, CVD risk was similar in PLWH compared with HIV‐uninfected (hazard ratio [HR], 0.89; 95% CI, 0.70–1.12), but HIV infection was associated with higher mortality risk (HR, 1.49; 95% CI, 1.16–1.90). In models stratified by HIV status, CAP severity was significantly associated with incident CVD and 30‐day mortality in PLWH and patients uninfected with HIV. Conclusions In this study, the risk of CVD events during or after hospitalization for CAP was similar in PLWH and patients uninfected with HIV, after adjusting for known CVD risk factors and CAP severity. HIV infection, however, was associated with increased 30‐day mortality after CAP hospitalization in multivariable‐adjusted models. PLWH should be included in future studies evaluating mechanisms and prevention of CVD events after CAP.

Living with HIV in the Time of COVID-19

2020 ◽  
Vol 10 (1) ◽  
pp. 5-7
Author(s):  
Muhammad Naveed Noor
Keyword(s):  
Medical Care ◽  
Developing Country ◽  
People Living With Hiv ◽  
Evidence Based ◽  
Comorbid Conditions ◽  
Increased Risk ◽  
Associated Conditions ◽  
Living With Hiv

This commentary foregrounds the need to examine how the coronavirus disease 2019 (COVID-19) pandemic and associated conditions may be affecting the lives of people living with HIV (PLWH) in a developing country context like Pakistan. It raises some important questions on medical care and updated information regarding PLWH in the time of COVID-19. Since PLWH are at an increased risk of developing comorbid conditions – something that makes them more vulnerable to COVID-19 – it is critical that timely research and evidence-based actions are undertaken to protect their health.

Prevalence of Asymptomatic Cryptococcal Antigenemia and Association with Follow-up risk of Cryptococcal Meningitis and Mortality among HIV Infected Patients in North West India – A Prospective Cohort Study

2020 ◽  
Vol 18 ◽  
Author(s):  
Rajendra Bhati ◽  
Pramendra Sirohi ◽  
Bharat Sejoo ◽  
Deepak Kumar ◽  
Gopal K Bohra ◽  
...  
Keyword(s):  
Cryptococcal Meningitis ◽  
Morbidity And Mortality ◽  
People Living With Hiv ◽  
Cryptococcal Antigen ◽  
North West ◽  
Cryptococcal Disease ◽  
Increased Risk ◽  
Living With Hiv ◽  
Inflammatory Syndrome

Objective: Cryptococcal meningitis is an important cause of morbidity and mortality in HIV infected individuals. In the era of universal antiretroviral therapy incidence of immune reconstitution inflammatory syndrome (IRIS) related cryptococcal meningitis has increased. Detection of serum cryptococcal antigen in asymptomatic PLHIV (People Living With HIV) and pre-emptive treatment with fluconazole can decrease the burden of cryptococcal disease. We conducted this study to find the prevalence of asymptomatic cryptococcal antigenemia in India and its correlation with mortality in PLHIV. Method and material: This was a prospective observational study. HIV infected ART naïve patients with age of ≥ 18 years who had CD4 counts ≤ 100 /µL were included and serum cryptococcal antigen test was done. These patients were followed for six months to look for the development of Cryptococcal meningitis and mortality. Results: A total of 116 patients were analysed. Asymptomatic cryptococcal antigenemia was detected in 5.17% patients and it correlated with increased risk of cryptococcal meningitis and mortality on follow-up in PLHIV. Conclusion: Serum cryptococcal positivity is correlated with increased risk of Cryptococcal meningitis and mortality in PLHIV. We recommend the screening of asymptomatic PLHIV with CD4 ≤ 100/µL for serum cryptococcal antigen, so that pre-emptive treatment can be initiated to reduce morbidity and mortality.

scholarly journals A Step Closer to the “Fourth 90”: A Practical Narrative Review of Diagnosis and Management of Nutritional Issues of People Living with HIV

Diagnostics ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 2047
Author(s):  
Davide Fiore Bavaro ◽  
Paola Laghetti ◽  
Mariacristina Poliseno ◽  
Nicolò De Gennaro ◽  
Francesco Di Gennaro ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Cardiovascular Risk ◽  
Kidney Disease ◽  
Current Knowledge ◽  
Disease Stage ◽  
Oral Glucose ◽  
People Living With Hiv ◽  
Diagnosis And Management ◽  
Increased Risk ◽  
Living With Hiv

The quality of life of people living with HIV (PLWH) has remarkably increased thanks to the introduction of combined antiretroviral therapy. Still, PLWH are exposed to an increased risk of cardiovascular diseases, diabetes, chronic kidney disease, and liver disease. Hence, the purpose of this review is to summarize the current knowledge about diagnosis and nutritional management with specific indication of macro and micronutrients intake for the main comorbidities of PLWH. In fact, a prompt diagnosis and management of lifestyle behaviors are fundamental steps to reach the “fourth 90”. To achieve an early diagnosis of these comorbidities, clinicians have at their disposal algorithms such as the Framingham Score to assess cardiovascular risk; transient elastography and liver biopsy to detect NAFLD and NASH; and markers such as the oral glucose tolerance test and GFR to identify glucose impairment and renal failure, respectively. Furthermore, maintenance of ideal body weight is the goal for reducing cardiovascular risk and to improve diabetes, steatosis and fibrosis; while Mediterranean and low-carbohydrate diets are the dietetic approaches proposed for cardioprotective effects and for glycemic control, respectively. Conversely, diet management of chronic kidney disease requires different nutritional assessment, especially regarding protein intake, according to disease stage and eventually concomitant diabetes.

scholarly journals 834. Characterization of Heavily Treatment Experienced HIV-1 Infected Clinical Trial Participants Infected with SARS-CoV-2 COVID 19: Fostemsavir BRIGHTE Phase 3 Clinical Trial

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S509-S509
Author(s):  
Shiven Chabria ◽  
Stephane De Wit ◽  
Amy Pierce ◽  
Bronagh M Shepherd ◽  
Michael Warwick-Sanders ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Supplemental Oxygen ◽  
Multidrug Resistant ◽  
Cd4 Count ◽  
People Living With Hiv ◽  
Research Support ◽  
Increased Risk ◽  
Living With Hiv ◽  
Hiv 1

Abstract Background BRIGHTE is an ongoing global study evaluating the gp120 attachment inhibitor fostemsavir (FTR) in heavily treatment-experienced (HTE) adults with multidrug resistant (MDR) HIV-1 unable to form a viable antiretroviral (ARV) regimen. An estimated 2 million people living with HIV-1 have been infected with SARS-CoV-2. Those with HIV viremia and/or low CD4+ counts are at increased risk of serious adverse outcome. We describe the reported COVID cases in a clinical trial population of people living with MDR HIV and immune suppression. Methods At the start of the COVID pandemic, all ongoing BRIGHTE subjects had achieved ≥ 192 weeks on FTR and optimized background ARVs; results through Week 96 were presented previously. Investigators used WHO guidelines for COVID diagnosis and reported exposure, testing results and symptom presence. Figure 1. BRIGHTE Study Design Results 371 subjects [272 Randomized Cohort (RC), 99 Non-Randomized Cohort (NC)] were enrolled; 44% were ≥ 50 years of age and 86% had an AIDS history. Median CD4+ count at study start of was 80 cells/mm3 (IQR 11–202); 30% with ≤ 20 cells/mm3. 250 subjects remained in BRIGHTE at pandemic start. By April 2021, 17 subjects (14 RC, 3 NC) had confirmed COVID infection (positive PCR test). Severity was Grade 1-3, all cases resolved with no deaths. Six subjects were hospitalized (Table 1); most recent CD4+ count prior to COVID were 293-1641 cells/mm3 and 5/6 subjects were virologically suppressed. Treatments often included prophylactic anticoagulants and supplemental oxygen; no cART changes were made. The remaining 11/17 confirmed cases were managed outpatient. Five more subjects had suspect COVID not confirmed by PCR and 2 subjects had negative PCR tests. Table 1. Characterization of Participants with Serious AEs of Confirmed COVID-19 Infections – All Hospitalizations Conclusion A total of 22/250 COVID-19 cases (17 confirmed, 5 unconfirmed) have been reported in BRIGHTE. Outcomes were reassuring with no deaths or known persistent sequelae, despite having advanced HIV and comorbid diseases at baseline associated with poorer COVID outcomes. Outcomes may have benefitted from immunologic improvement during the trial. Disclosures Shiven Chabria, MD, Viiv Healthcare (Employee) Stephane De Wit, MD, Gilead (Grant/Research Support)Janssen (Grant/Research Support)Merck Sharpe & Dohme (Grant/Research Support)ViiV Healthcare (Grant/Research Support) Amy Pierce, BS, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) Bronagh M. Shepherd, PhD, GlaxoSmithKline (Employee, Shareholder) Michael Warwick-Sanders, BM BSc DPM MFPM, GSK (Employee) Marcia Wang, PhD, GlaxoSmithKline (Employee, Shareholder) Andrew Clark, MD, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) Peter Ackerman, MD, GSK/ViiV Healthcare (Employee, Shareholder)

Sign in / Sign up

Export Citation Format

Share Document