Major health impact of accelerated aging in young HIV-infected individuals on antiretroviral therapy

Rajasuriar, Reena; Chong, Meng Li; Bashah, N.S. Ahmad; Aziz, Siti Azdiah Abdul; McStea, Megan; Lee, Erica Chai Yong; Wong, Pui Li; Azwa, Iskandar; Omar, Sharifah Faridah Syed; Lai, Pauline Siew Mei; Ponampalavanar, Sasheela; Crowe, Suzanne; Lewin, Sharon R.; Kamaruzzaman, Shahrul Bahyah; Kamarulzaman, Adeeba

doi:10.1097/qad.0000000000001475

Cited by 34 publications

(32 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…One possible theory discussed in other studies is that persistent inflammatory and immune changes induced by HIV infection may underlie premature aging by accelerating the normal aging process [27][28][29]. The exact mechanisms of premature aging in PLWH have yet to be clarified in future studies that comprehensively evaluate the multifaceted aging process [30] and diverse risk factors in people with and those without HIV [29]. Nevertheless, our findings suggest that PLWH on antiretrovirals may benefit from the prevention of comorbidities and active screening for early detection of comorbidities.…”

Section: Discussionmentioning

confidence: 99%

Greater burden of chronic comorbidities and co-medications among people living with HIV versus people without HIV in Japan: A hospital claims database study

Ruzicka

Imai

Takahashi

et al. 2019

Journal of Infection and Chemotherapy

View full text Add to dashboard Cite

Objective: This study examined the prevalence of chronic comorbidities and the use of co-medications among people living with HIV (PLWH) on antiretrovirals in Japan, compared with age-matched controls without HIV. Methods: This was an observational, retrospective, cross-sectional study using a hospital claims database of Japanese hospitals with advanced medical capabilities (i.e., advanced treatment hospitals, general hospitals, acute care hospitals). We extracted data for PLWH aged !18 years with a prescription record of antiretrovirals between January 2010 and December 2015, and for age-, sex-, and hospital-matched people without HIV. For each group, chronic comorbidities (diabetes, hypertension, lipid disorders, vascular diseases, chronic kidney failure, cancers, psychiatric disorders, osteoporosis, and hepatitis B/C co-infection), and co-medications were examined by age group. Results: We analyzed data for 1445 PLWH and 14,450 people without HIV. The proportion of patients with multiple comorbidities was much greater among PLWH than controls of the same age group. Lipid disorders and diabetes were more prevalent in PLWH than controls (31.6% vs. 10.3% and 26.8% vs. 13.2%, respectively), both of which were more common in PLWH at earlier ages. Cancer was present in 8.1% of PLWH and 8.9% of controls. A greater proportion of PLWH used multiple co-medications other than antiretrovirals at earlier ages than controls. Conclusion: PLWH taking antiretrovirals in Japan had a greater burden of comorbidities and comedications with increasing age than people without HIV. In addition to appropriate management of comorbidities, medication reconciliation according to patients' co-medication profiles is important for successful management of this patient population.

show abstract

Section: Discussionmentioning

confidence: 99%

Greater burden of chronic comorbidities and co-medications among people living with HIV versus people without HIV in Japan: A hospital claims database study

Ruzicka

Imai

Takahashi

et al. 2019

Journal of Infection and Chemotherapy

View full text Add to dashboard Cite

show abstract

“…In line with the observed enhanced genomic stability, GEP revealed significant increases in DNA repair genes. Although it could be speculated that the enhanced DNA repair capabilities observed in the HIV(+) cohort stems from the age difference of the two cohorts, HIV infection is associated with accelerated aging . Indeed, HIV infected patients as young as 0–5 years of age have been shown to have significant increases in senescent and exhausted immune cells, as well as significantly shortened telomeres compared to their age matched HIV negative peers, indicating premature aging associated with HIV infection, where telomere shortening is associated with enhanced genomic instability, particularly in cells that lack the ability to induce cell cycle arrest .…”

Section: Discussionmentioning

confidence: 99%

Enhanced DNA repair and genomic stability identify a novel HIV‐related diffuse large B‐cell lymphoma signature

Maguire

Chen

Wisner

et al. 2019

Intl Journal of Cancer

View full text Add to dashboard Cite

Diffuse large B‐cell lymphoma (DLBCL) is up to 17‐fold more likely to occur, follows a more aggressive clinical course and frequently presents at advanced stages in HIV infected (+) individuals compared to HIV negative (−) individuals. However, the molecular pathology underpinning the clinical features of DLBCL in HIV(+) patients relative to the general population is poorly understood. We performed a retrospective study examining the transcriptional, genomic and protein expression differences between HIV(+) and HIV(−) germinal center B‐cell (GCB) DLBCL cases using digital gene expression analysis, array comparative genomic hybridization (CGH) and immunohistochemistry (IHC). Genes associated with cell cycle progression (CCNA2, CCNB1, CDC25A, E2F1), DNA replication (MCM2, MCM4, MCM7) and DNA damage repair, including eight Fanconi anemia genes (FANCA, FANCD1/BRCA2, FANCE, FANCG, FANCR/RAD51, FANCS/BRCA1, FANCT/UBE2T, FANCV/MAD2L2), were significantly increased in HIV(+) GCB‐DLBCL tumors compared to HIV(−) tumors. In contrast, genes associated with cell cycle inhibition (CDKN1A, CDKN1B) as well as apoptosis regulating BCL2 family members (BCL2, BAX, BIM, BMF, PUMA) were significantly decreased in the HIV(+) cohort. BCL2 IHC confirmed this expression. Array CGH data revealed that HIV(+) GCB‐DLBCL tumors have fewer copy number variations than their HIV(−) counterparts, indicating enhanced genomic stability. Together, the results show that HIV(+) GCB‐DLBCL is a distinct molecular malignancy from HIV(−) GCB‐DLBCL; with an increased proliferative capacity, confirmed by Ki67 IHC staining, and enhanced genomic stability, the latter of which is likely related to the enhanced expression of DNA repair genes.

show abstract

“…Cardiovascular disease (CVD) is the third most frequent non-AIDS cause of death in HIV+ individuals, and in those on combination antiretroviral therapy (cART), it is the leading cause 1. CVD is predicted to increase markedly with ageing among the HIV infected, presenting obstacles to a normal life span and contributing substantially to healthcare utilisation costs in resource-rich and resource-poor settings 2–5. These disorders affect all demographics, with an equivalent impact on paediatric and adult populations 1 5.…”

Section: Introductionmentioning

confidence: 99%

“…CVD is predicted to increase markedly with ageing among the HIV infected, presenting obstacles to a normal life span and contributing substantially to healthcare utilisation costs in resource-rich and resource-poor settings 2–5. These disorders affect all demographics, with an equivalent impact on paediatric and adult populations 1 5. In terms of gender, the US Veterans Aging Cohort Study established that, after adjusting for age, race, ethnicity, lipids, tobacco use, blood pressure, diabetes, renal disease, obesity, hepatitis and substance abuse, the HR for substantial cardiovascular (CV) events was 1.48 for all HIV-infected veterans (p<0.05)6 and 2.8 among female veterans (p<0.001) 7…”

Section: Introductionmentioning

confidence: 99%

HIV-associated cardiovascular disease: importance of platelet activation and cardiac fibrosis in the setting of specific antiretroviral therapies

2018

View full text Add to dashboard Cite

HIV infection is a risk factor for cardiovascular disease (CVD). This risk is accentuated by certain combination antiretroviral therapies (cARTs), independent of their effects on lipid metabolism and insulin sensitivity. We sought to define potential mechanisms for this association through systematic review of clinical and preclinical studies of CVD in the setting of HIV/cART from the English language literature from 1989 to March 2018. We used PubMed, Web of Knowledge and Google Scholar, and conference abstracts for the years 2015–March 2018. We uncovered three themes: (1) a critical role for the HIV protease inhibitor (PI) ritonavir and certain other PI-based regimens. (2) The importance of platelet activation. Virtually all PIs, and one nucleoside reverse transcriptase inhibitor, abacavir, activate platelets, but a role for this phenomenon in clinical CVD risk may require additional postactivation processes, including: release of platelet transforming growth factor-β1; induction of oxidative stress with production of reactive oxygen species from vascular cells; suppression of extracellular matrix autophagy; and/or sustained proinflammatory signalling, leading to cardiac fibrosis and dysfunction. Cardiac fibrosis may underlie an apparent shift in the character of HIV-linked CVD over the past decade from primarily left ventricular systolic to diastolic dysfunction, possibly driven by cART. (3) Recognition of the need for novel interventions. Switching from cART regimens based on PIs to contemporary antiretroviral agents such as the integrase strand transfer inhibitors, which have not been linked to clinical CVD, may not mitigate CVD risk assumed under prior cART. In conclusion, attention to the effects of specific antiretroviral drugs on platelet activation and related profibrotic signalling pathways should help: guide selection of appropriate anti-HIV therapy; assist in evaluation of CVD risk related to novel antiretrovirals; and direct appropriate interventions.

show abstract

Major health impact of accelerated aging in young HIV-infected individuals on antiretroviral therapy

Abstract: A high burden of geriatric conditions with significant impact on health outcomes, including mortality risk scores are observed among HIV-infected individuals on ART in a resource-limited setting.

Cited by 34 publications

References 56 publications

Greater burden of chronic comorbidities and co-medications among people living with HIV versus people without HIV in Japan: A hospital claims database study

Greater burden of chronic comorbidities and co-medications among people living with HIV versus people without HIV in Japan: A hospital claims database study

Enhanced DNA repair and genomic stability identify a novel HIV‐related diffuse large B‐cell lymphoma signature

HIV-associated cardiovascular disease: importance of platelet activation and cardiac fibrosis in the setting of specific antiretroviral therapies

Contact Info

Product

Resources

About