Immunosenescence and hurdles in the clinical management of older HIV-patients

Figures & data

Figure 1. Cellular pathways leading to cellular senescence. ROS: reactive oxygen species. SASP: senescence-associated secretory phenotype. © The American Society for Clinical Investigation. Adapted by permission of James L. Kirkland. Permission to reuse must be obtained from the rightsholder.⁹

Table 1. Guidelines for older HIV-infected patients.

Guidelines	DHHS 2016^64	WHO 2016^65-66	EACS 2016^67	BHIVA 2015(2016 INTERIM UPDATE)^68
Recommendations	ART is recommended for all patients regardless of CD4 T lymphocyte cell count (AI). ART is especially important for older patients because they have a greater risk of serious non-AIDS complications and potentially a blunted immunologic response to ART.	ART should be initiated in all adults living with HIV, regardless of WHO clinical stage and at any CD4 cell count (strong recommendation, moderate-quality evidence).	ART should always be recommended irrespective of the CD4 count with the possible exception of elite controllers with high and stable CD4 count.	We recommend standard criteria are used to determine when to commence antiretroviral therapy in older PLWH (1C). We recommend standard antiretroviral regimens are commenced in older PLWH (1C)
Notes	Special attention to: adverse drugs events from ART and comedications; drug-drug interactions comorbidites	No specific recommendations for older HIV-infected patients.	No specific recommendations for older HIV-infected patients	Special attention to: non-infectious comorbidities concomitant medications clinical pharmacology

Note. ART: antiretroviral therapy; PLWH: people living with HIV.

Table 2. Interactions between first-line antiretrovirals and commonly prescribed drugs in aging population, extracted from⁶⁸ and http://www.hiv-druginteractions.org/.

	DRV/r	RPV	DTG	EVG/COBI	RAL	ABC	FTC or 3TC	TDF or TAF
Cardiovascular medications
Atorvastatin	↑	=	=	↑	=	=	=	=
Rosuvastatin	↑	=	=	↑	=	=	=	=
Pravastatin	↑	=	=	↑	=	=	=	=
Simvastatin	↑	=	=	↑	=	=	=	=
Fluvastatin	=	=	=	↑	=	=	=	=
Calcium channel blockers – Dihydropiridine	↑	=	=	↑	=	=	=	=
Calcium channel blockers – Non-dihydropiridine	↑	E	=	↑	=	=	=	=
Metoprolol	↑	=	=	↑	=	=	=	=
Atenolol	=	=	=	=	=	=	=	=
Bisoprolol	↑	=	=	↑	=	=	=	=
Carvedilol	↑/↓	=	=	↑	=	=	=	=
Propranolol	↑	=	=	↑	=	=	=	=
Warfarin	↑	=	=	↑/↓	=	=	=	=
Rivaroxaban	↑	=	=	↑	=	=	=	=
ACE-inhibitors	=	=	=	=	=	=	=	=
Irbesartan	↓	=	=	↓	=	=	=	=
Losartan	↓	=	=	↓	=	=	=	=
Other Angiotens-receptor blockers	=	=	=	=	=	=	=	=
Amiloride	=	=	=	=	=	=	=	=
Furosemide	=	=	=	=	=	=	=	E
Torasemide	=	=	=	↑	=	=	=	=
Spironolactone	=	=	=	=	=	=	=	=
Doxazosin	↑	=	=	↑	=	=	=	=
Acetylsalicilate	=	=	=	=	=	=	=	=
Amiodarone	↑	=	=	↑	=	=	=	E
Ivabradine	↑	=	=	↑	=	=	=	=
Digoxin	↑	↑	=	↑	=	=	=	=
Gastrointestinal medications
Metformin		↑	↑	↑
Antacids	=	D	D	D	D	=	=	=
PPIs	=	D	=	=	E	=	=	=
H2 blockers	=	D	=	=	E	=	=	=
Domperidone	↑	=	=	↑	=	=	=	=
Neurologic and psychiatric medications
Ergot derivatives	↑	↑/E	=	↑	=	=	=	=
Quetiapine	↑	=	=	↑	=	=	=	=
Citalopram	↑	=	=	↑	=	=	=	=
Paroxetine	↓	=	=	↑/↓	=	=	=	=
Sertraline	↓	=	=	↑	=	=	=	=
Fluvoxamine	↑	=	=	↑	=	=	=	=
Fluoxetine	↑	=	=	↑	=	=	=	=
Duloxetine	↑/↓	=	=	↑	=	=	=	=
Venlafaxine	↑	=	=	↑	=	=	=	=
Amitriptyline	↑	=	=	↑	=	=	=	=
Mirtazapine	↑	=	=	↑	=	=	=	=
Carbamazepine	↑	=	=	D	=	=	=	=
Lamotrigine	↓	=	=	=	=	=	=	=
Phenytoin	↓D	D	D	D	D	D	=	=
Diazepam	↑	=	=	↑	=	=	=	=
Triazolam	↑	=	=	↑	=	=	=	=
Miscellaneous medications
Alfuzosine	↑	=	=	↑	=	=	=	=
Sildenafil	↑	=	=	↑	=	=	=	=
Prednisone	↑	=	=	↑	=	=	=	=
Coxib	=	=	=	=	=	=	=	=
Acetaminophen	=	=	=	=	=	=	=	=
Ibuprofen	=	=	=	=	=	=	=	E
Diclofenac	=	=	=	=	=	=	=	E
Codeine	↑	=	=	↑	=	=	=	=
Buprenorphine	↑	=	=	↑	=	=	=	=
Fentanyl	↑	=	=	↑	=	=	=	=
Morphine	↓	=	=	↑	=	=	=	=
Tramadol	↑	=	=	↑	=	=	=	=
Oxycodone	↑	=	=	↑	=	=	=	=

Figure 2. Role of interleukin7 (IL-7). IL-7 is a stromal cell-derived cytokine that provides continuous signals in all levels of lymphocytes maturation. Ag: antigen.

Tchkonia T, Zhu Y, van Deursen J, Campisi J, Kirkland J. Cellular senescence and the senescent secretory phenotype: therapeutic opportunities. J Clin Invest 2013; 123(3):966-72; PMID: 23454759; https://doi.org/10.1172/JCI64098

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BHIVA guidelines for the treatment of HIV-1-positive adults with ART 2015 (2016 interim update). Available at http://www.bhiva.org/HIV-1-treatment-guidelines.aspx

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