Substance-associated elevations in monocyte activation among methamphetamine users with treated HIV infection

Cherenack, Emily M.; Roach, Margaret; Riley, Elise D.; Oni, Olorunleke; Dilworth, Samantha E.; Shoptaw, Steven; Hunt, Peter W.; Roy, Sabita; Pallikkuth, Suresh; Pahwa, Savita

doi:10.1097/qad.0000000000001751

Cited by 40 publications

(33 citation statements)

References 29 publications

(33 reference statements)

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“…We also analyzed whether Cytomegalovirus (CMV) serostatus had an influence on Ag.pTfh frequency and function as CMV infection can significantly affect Ab responses to the influenza vaccine in aging and HIV infection [70–73]. In our study groups, CMV serostatus was higher in the HIV + individuals compared to HCs but did not correlate with age or Ab response to flu vaccination [74]. Although we did not measure CMV IgG titer in these participants, CMV serostatus did not show any association with Ag.pTfh frequency and function (not shown).…”

Section: Discussionmentioning

confidence: 99%

“…Study participants were selected from project FI nding N ovel D eterminants of Flu Responses (FIND), a substudy of FLORAH in which H1N1-specific Ab responses were determined in HIV + individuals and HCs of different ages [74]. Ab response to H1N1/09 vaccine antigen (H1N1 A/California/07/2009) was determined in serum by hemagglutination inhibition (HAI) assay [8,14,31].…”

Section: Methodsmentioning

confidence: 99%

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Dysfunctional peripheral T follicular helper cells dominate in people with impaired influenza vaccine responses: Results from the FLORAH study

et al. 2019

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Antigen-primed cluster of differentiation (CD) 4 + T follicular helper (Tfh) cells interact with B cells in the germinal centers (GCs) of lymph nodes to generate vaccine-induced antibody (Ab) responses. In the circulation, peripheral Tfh (pTfh) cells, a subset of memory CD4 T cells, serve as surrogates for GC Tfh because of several functional and phenotypic similarities between them. We investigated features of H1N1 influenza antigen-specific pTfh (Ag.pTfh) in virologically controlled HIV + volunteers on antiretroviral therapy (ART) and healthy control (HC) participants selected from a seasonal influenza vaccine responsiveness study. Selection of the participants was made based on age, defined as young (18–40 y) and old (>60 y) and on their classification as a vaccine responder (VR) or vaccine nonresponder (VNR). VRs demonstrated expansion of CD40L + and CD69 + Ag.pTfh, with induction of intracellular interleukin 21 (IL-21) and inducible costimulator (ICOS) post vaccination; these responses were strongest in young HC VRs and were less prominent in HIV + individuals of all ages. Ag.pTfh in VNRs exhibited dramatically different characteristics from VRs, displaying an altered phenotype and a cytokine profile dominated by cytokines IL-2, tumor necrosis factor alpha (TNF-α), or IL-17 but lacking in IL-21. In coculture experiments, sorted pTfh did not support the B cell IgG production in VNRs and were predominantly an inflammatory T helper 1 (Th1)/T helper 17 (Th17) phenotype with lower ICOS and higher programmed cell death protein 1 (PD1) expression. Induction of IL-21 and ICOS on Ag.pTfh cells are negatively affected by both aging and HIV infection. Our findings demonstrate that dysfunctional Ag.pTfh cells with an altered IL-21/IL-2 axis contribute to inadequate vaccine responses. Approaches for targeting inflammation or expanding functional Tfh may improve vaccine responses in healthy aging and those aging with HIV infection.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Dysfunctional peripheral T follicular helper cells dominate in people with impaired influenza vaccine responses: Results from the FLORAH study

et al. 2019

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“…We also observed concomitant elevations in soluble CD14 (sCD14), a clinically relevant plasma marker of monocyte activation [27], in those providing a urine sample that was reactive for stimulants. This partially reflects stimulation of monocytes with lipopolysaccharide leaking from the gastrointestinal tract [26]. The clinical relevance of these findings is supported by the fact that markers of systemic immune activation and inflammation are implicated in multiple, chronic medical conditions such as cardiovascular disease in people living with HIV, which have been identified as key risk factors for COVID-19 progression [28,29].…”

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confidence: 79%

“…There is increasing evidence from our team and others that meth use can induce gut-immune dysregulation, even among those with treated HIV infection [22][23][24][25][26]. In our prior bio-behavioral research conducted with MSM with treated HIV infection who use meth, those who provided a urine sample that was reactive for stimulants (i.e., meth or cocaine) displayed differential expression of genes and 2-directional perturbation of pathways relevant to systemic immune activation and inflammation [25].…”

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confidence: 99%

Double Jeopardy: Methamphetamine Use and HIV as Risk Factors for COVID-19

et al. 2020

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“…HPV infections are also known to follow sexual transmission routes, causing cervical, anal as well as oropharyngeal cancers [91] [92]. Those vulnerable people who engage in chemsex settings are at risk for connected disorders, e.g., by crystal meth [93]. Co-consumption of psychoactive drugs has both shortterm restrictions of cognitive self-control, disinhibition, as well as long-term consequences such as psychotic symptoms in the case of cannabis [94], drug addiction and the health consequences of addiction, including unemployment status.…”

Section: Comorbiditiesmentioning

confidence: 99%

The Disregarded HIV Prevention Strategies—Their Potential to Uphold the Pandemic, and the Challenges Facing Societies

Dennin¹,

Sinn²,

Du³

2018

WJA

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The ongoing spread of HIV after sobering news about the goal "End of AIDS" is not encouraging, apart from regional differences. We focus on the consequences of the two essentially failed HIV prevention strategies in certain countries. The first failed because the correct messages concerning preventive behavior did not reach the required levels of target populations to interrupt HIV infection chains. There was a lack of appropriate framework conditions for the target populations to engage in the required scale. The additional biomedical strategy "Treatment as Prevention" didn't achieve the breakthrough as was hoped. The consequences thereof affect the financial burden on societies, which can take several decades. We draw attention to the unbalanced principles of proportionality to which governments are committed, but which are practiced in favor of those vulnerable people; these people abuse their autonomy and contribute to the further spread of HIV at the expense of financial burdens, social and medical care systems; this behavior is tolerated, although the transmission of HIV is mostly preventable. We point to extreme tendencies, such as the chem-sex settings, whose unswayable participants engage in indirect violence against the societies. Another possible consequence of the still uncontrolled spread of HIV is the potential for HIV to increase its virulence.

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Substance-associated elevations in monocyte activation among methamphetamine users with treated HIV infection

Abstract: Monocyte activation is one plausible mechanism by which stimulant use may increase clinical HIV progression.

Cited by 40 publications

References 29 publications

Dysfunctional peripheral T follicular helper cells dominate in people with impaired influenza vaccine responses: Results from the FLORAH study

Dysfunctional peripheral T follicular helper cells dominate in people with impaired influenza vaccine responses: Results from the FLORAH study

Double Jeopardy: Methamphetamine Use and HIV as Risk Factors for COVID-19

The Disregarded HIV Prevention Strategies—Their Potential to Uphold the Pandemic, and the Challenges Facing Societies

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