scholarly journals Altered Lipid Profiles and Vaccine Induced-Humoral Responses in Children Living With HIV on Antiretroviral Therapy in Tanzania

Author(s):  
Wilbert Mbuya ◽  
Issakwisa Mwakyula ◽  
Willyelimina Olomi ◽  
Peter Agrea ◽  
Francesco Nicoli ◽  
...  

People living with HIV, even under therapy, have a high burden of age-related co-morbidities including an increased risk of dyslipidemia (which often predisposes to cardiovascular diseases) and immune-aging. In this study, lipid profiles and antibody responses to measles and pertussis toxin vaccines were compared between ART experienced HIV+ children (n=64) aged 5-10 years, and their age- and sex-matched HIV- controls (n=47). Prevalence of high-density lipoprotein cholesterol (HDL-c) and triglyceride-driven dyslipidemia was higher among treated HIV+ children than in controls (51.6% vs 27.7% respectively, p < 0.019). In a multivariate Poisson regression model adjusted for age, sex and BMI, the association between low HDL-c, hypertriglyceridemia and HIV remained significantly high (for HDL-c: ARR: 0.89, 95% CI: 0.82 – 0.96, p = 0.003; for triglycerides: ARR: 1.54, 95% CI: 1.31 – 1.81, p < 0.001). Among HIV+ children, the use of lopinavir/ritonavir, a protease-based antiretroviral therapy was also associated elevation of triglyceride levels (p = 0.032). Also, HIV+ children had a 2.8-fold reduction of anti-measles IgG titers and 17.1-fold reduction of anti-pertussis toxin IgG levels when compared to HIV- children. Our findings suggest that dyslipidemia and inadequate vaccine-induced antibody responses observed in this population of young African HIV+ children might increase their risk for premature onset of cardiovascular illnesses and acquisition of preventable diseases.

2020 ◽  
Vol 31 (3) ◽  
pp. 308-317
Author(s):  
Lucy Graham ◽  
Mary Beth Flynn Makic

Infection with HIV is a chronic condition that requires daily medication to suppress viral replication. With appropriate treatment, people living with HIV have a life expectancy approaching that of the general population. However, they are at increased risk for comorbidities including cardiovascular disease, renal disease, type 2 diabetes, neurologic conditions, and cancers, often with worse outcomes than in patients without HIV. When they are admitted to critical care settings, care considerations, particularly regarding antiretroviral therapy, must be addressed. Antiretroviral therapy is critical for successful management of HIV infection and should be continued when possible during intensive care unit stays. However, many antiretroviral regimens result in drug-drug interactions, adverse drug-related events, and secondary complications such as insulin resistance and prolonged QT intervals. Critical care nurses have unique opportunities to provide safe, unbiased, and compassionate care that promotes health for a population of people who have a history of being stigmatized.


2019 ◽  
Vol 53 (8) ◽  
pp. 812-832 ◽  
Author(s):  
Jacqueline L. Olin ◽  
Olga Klibanov ◽  
Alexandre Chan ◽  
Linda M. Spooner

Objective: To describe data with selected malignancies in people living with HIV (PLWH) and HIV in individuals affected by both conditions and to summarize drug-drug interactions (DDIs) with clinical recommendations for point-of-care review of combination therapies. Data Sources: Literature searches were performed (2005 to December 2018) in MEDLINE and EMBASE to identify studies of malignancies in PLWH in the modern era. Study Selection and Data Extraction: Article bibliographies and drug interaction databases were reviewed. Search terms included HIV, antiretroviral therapy, antineoplastic agents, malignancies, and drug interactions. Data Synthesis: In the pre–antiretroviral therapy (ART) era, malignancies in PLWH were AIDS-defining illnesses, and life expectancy was shorter. Nowadays, PLWH are living longer and developing malignancies, including lung, anal, and prostate cancers. Concurrently, the oncology landscape has evolved, with novel oral targeted agents and immunotherapies becoming routine elements of care. The increased need for and complexity with antineoplastics in PLWH has led to recommendations for multidisciplinary care of this unique population. Evaluation of DDIs requires review of metabolic pathways, absorption mechanisms, and various drug transporters associated with antineoplastics and ART. Relevance to Patient Care and Clinical Practice: This review summarizes available data of non–AIDS-defining malignancies, principles of HIV care in the patient with malignancy, and guidance for assessing DDIs between antineoplastics and ART. Summary DDI tables provide point-of-care recommendations. Conclusions: The availability of ART has transformed AIDS into a chronic medical condition, and PLWH are experiencing age-related malignancies. Pharmacists play an important role in the management of this patient population.


2018 ◽  
Vol 51 (4) ◽  
pp. 265-270
Author(s):  
Thiago Rodrigues Faria Vitorazzi ◽  
Taila Santos de Freitas ◽  
Loiane Sartori Oliveira ◽  
Anderson Marliere Navarro

Objective: The present study evaluated the influence of the duration of antiretroviral therapy on insulin resistance among people living with HIV with lipodystrophic syndrome. Methods: The study assessed 36 subjects of both sexes between 22 and 60 years old split into three groups: 1) HIV-positive using antiretroviral with lipodystrophy syndrome (HIV+LIPO+); 2) HIV-positive using antiretroviral therapy with no lipodystrophy syndrome (HIV+LIPO-); and 3) HIV-negative and healthy (Control). The data were collected at the Special Unit for the Treatment of Infectious Diseases (Unidade Especial de Tratamento para Doenças Infecciosas - UETDI) of the Dyslipidemia Outpatient Clinic (Ambulatório de Dislipidemia - ADIS) of the General Hospital of the Medical School of Ribeirão Preto (HC-FMRP). The biochemical assessment used laboratory kits when the results were not available in the volunteer's records. Results: Higher HOMA-IR values were observed for the group 1: HIV+LIPO+ (1,61 ± 1,17 ) compared to group 2: HIV+LIPO- (0,79 ± 0,87) and group 3: Control (0,46 ± 0,72 ) and such values were positively correlated with the time of antiretroviral medication use (r=0,41). Conclusions: The time of infection by HIV and the use of antiretrovirals impact the glucose metabolism with changes in serum insulin levels and consequent insulin resistance and increased risk for the development of diabetes and diseases related to carbohydrate metabolism.


PLoS ONE ◽  
2021 ◽  
Vol 16 (11) ◽  
pp. e0260334
Author(s):  
Vanessa Castro-Granell ◽  
Noé Garin ◽  
Ángeles Jaén ◽  
Santiago Cenoz ◽  
María José Galindo ◽  
...  

Drug use implies important challenges related to HIV management, particularly due to an increased risk of potential interactions between antiretroviral therapy (ART) and illicit drugs (pDDIs). This study analyses the prevalence and severity of pDDIs among people living with HIV (PLHIV). It also explores their awareness of pDDIs and their beliefs about the toxicity that they may cause, as well as the impact of pDDIs on selected health variables. We conducted an on-line cross-sectional survey across 33 Spanish hospitals and NGOs to collect demographics and clinical data. pDDIs were checked against the Interaction Checker developed by Liverpool University. The sample of the present study was composed of 694 PLHIV who used illicit drugs. They represented 49.5% of the 1,401 PLHIV that participated in the survey. After excluding 38 participants due to lack of information on their ART or illicit drug use, 335 (51.1%) participants consuming drugs presented with some potentially significant pDDIs between their ART and illicit drugs, with a mean of 2.1±1.7 (1–10) pDDIs per patient. The drugs most frequently involved in pDDIs were cocaine, cannabis, MDMA and nitrates ("poppers"). The prevalence of pDDIs across ART regimens was: protease inhibitors (41.7%); integrase inhibitor-boosted regimens (32.1%), and non-nucleoside reverse transcriptase inhibitors (26.3%). An awareness of pDDIs and beliefs about their potential toxicity correlated positively with intentional non-adherence (p<0.0001). Participants with pDDIs exhibited a higher prevalence of intentional non-adherence (2.19±1.04 vs. 1.93±0.94; p = 0.001). The presence of pDDIs was not associated with poorer results in the clinical variables analysed. A significant proportion of PLHIV who use drugs experience pDDIs, thereby requiring close monitoring. pDDIs should be considered in the clinical management of HIV patients. Adequate information about pDDIs and indicators about how to manage ART when PLHIV use drugs could improve ART non-adherence.


2020 ◽  
Vol 127 (11) ◽  
pp. 1365-1380
Author(s):  
Akif A. Khawaja ◽  
Kirk A. Taylor ◽  
Andrew O. Lovell ◽  
Mark Nelson ◽  
Brian Gazzard ◽  
...  

Rationale: People living with HIV on effective antiretroviral therapy are at increased risk of cardiovascular complications, possibly due to off-target drug effects. Some studies have associated antiretroviral therapy with increased risk of myocardial infarction and endothelial dysfunction, but a link between endothelial function and antiretrovirals has not been established. Objective: To determine the effects of antiretrovirals in common clinical use upon in vitro endothelial function to better understand cardiovascular risk in people living with HIV. Methods and Results: Human umbilical cord vein endothelial cells or human coronary artery endothelial cells were pretreated with the antiretrovirals abacavir sulphate (ABC), tenofovir disoproxil fumarate, or tenofovir alafenamide. Expression of adhesion molecules, ectonucleotidases (CD39 and CD73), tissue factor (TF), endothelial-derived microparticle (EMP) numbers and phenotype, and platelet activation were evaluated by flow cytometry. TF and ectonucleotidase activities were measured using colourimetric plate-based assays. ABC-treated endothelial cells had higher levels of ICAM (intercellular adhesion molecule)-1 and TF expression following TNF (tumor necrosis factor)-α stimulation. In contrast, tenofovir disoproxil fumarate and tenofovir alafenamide treatment gave rise to greater populations of CD39 + CD73 + cells. These cell surface differences were also observed within EMP repertoires. ABC-treated cells and EMP had greater TF activity, while tenofovir disoproxil fumarate- and tenofovir alafenamide-treated cells and EMP displayed higher ectonucleotidase activity. Finally, EMP isolated from ABC-treated cells enhanced collagen-evoked platelet integrin activation and α-granule release. Conclusions: We report differential effects of antiretrovirals used in the treatment of HIV upon endothelial function. ABC treatment led to an inflammatory, prothrombotic endothelial phenotype that promoted platelet activation. In contrast, tenofovir disoproxil fumarate and tenofovir alafenamide conferred potentially cardioprotective properties associated with ectonucleotidase activity. These observations establish a link between antiretrovirals and specific functional effects that provide insight into cardiovascular disease in people living with HIV.


2020 ◽  
Author(s):  
Alexander G. Bick ◽  
Konstantin Popadin ◽  
Christian W. Thorball ◽  
Md Mesbah Uddin ◽  
Markella Zanni ◽  
...  

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.


2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Alexander G. Bick ◽  
Konstantin Popadin ◽  
Christian W. Thorball ◽  
Md Mesbah Uddin ◽  
Markella V. Zanni ◽  
...  

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.


2021 ◽  
Author(s):  
Shabir Madhi ◽  
Anthonet Koen ◽  
Lee Fairlie ◽  
Clare Cutland ◽  
Vicky Baillie ◽  
...  

Abstract Coronavirus disease 2019 (COVID-19) is a public health emergency of international concern1. People living with HIV (PLWH) are at increased risk for adverse COVID-19 outcomes compared with HIV-negative individuals2-5, and are a high-risk group for COVID-19 prevention4. The ChAdOx1 nCoV-19 (AZD1222) vaccine has demonstrated safety and efficacy against COVID-19 in clinical trials6-8. To date, there are no reports on the safety and immunogenicity of this, or any COVID-19 vaccine, in PLWH, and reports on the immunogenicity of COVID-19 vaccines in Africa are limited9. Here, we show comparable safety and immunogenicity of two doses of ChAdOx1 nCoV-19 between PLWH and HIV-negative individuals in South Africa. Furthermore, in PLWH previously exposed to SARS-CoV-2, antibody responses increased substantially from baseline following a priming dose, with modest increases after a booster dose. Full-length spike and receptor-binding domain IgG geometric mean concentrations after a single dose of ChAdOx1 nCoV-19 in PLWH previously exposed to SARS-CoV-2 were 6.49–6.84-fold higher than after two doses in those who were SARS-CoV-2 naïve at enrollment. Neutralizing antibody responses were consistent with the antibody-binding responses. This is the first report of a COVID-19 vaccine specific to PLWH, and specific to Africa, and demonstrates favorable safety and immunogenicity of ChAdOx1 nCoV-19 in PLWH.


2020 ◽  
Vol 10 (1) ◽  
pp. 5-7
Author(s):  
Muhammad Naveed Noor

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.


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