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Clonal Hematopoiesis Is Associated With Low CD4 Nadir and Increased Residual HIV Transcriptional Activity in Virally Suppressed Individuals With HIV.

ABSTRACT: Clonal hematopoiesis, a common age-related phenomenon marked by expansion of cells with clonal hematopoiesis driver mutations, has been associated with all-cause mortality, cancer, and cardiovascular disease. People with HIV (PWH) are at risk for non-AIDS-related comorbidities such as atherosclerotic cardiovascular disease and cancer. In a cross-sectional cohort study, we compared clonal hematopoiesis prevalence in PWH on stable antiretroviral therapy with prevalence in a cohort of overweight individuals and a cohort of age- and sex-matched population controls. The prevalence of clonal hematopoiesis adjusted for age was increased and clone size was larger in PWH compared to population controls. Clonal hematopoiesis is associated with low CD4 nadir, increased residual HIV-1 transcriptional activity, and coagulation factors in PWH. Future studies on the effect of clonal hematopoiesis on the HIV reservoir and non-AIDS-related comorbidities are warranted.

SUBMITTER: van der Heijden WA

PROVIDER: S-EPMC9016425 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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Clonal Hematopoiesis Is Associated With Low CD4 Nadir and Increased Residual HIV Transcriptional Activity in Virally Suppressed Individuals With HIV.

van der Heijden Wouter A WA van Deuren Rosanne C RC van de Wijer Lisa L van den Munckhof Inge C L ICL Steehouwer Marloes M Riksen Niels P NP Netea Mihai G MG de Mast Quirijn Q Vandekerckhove Linos L de Voer Richarda M RM van der Ven Andre J AJ Hoischen Alexander A

The Journal of infectious diseases 20220401 8

Clonal hematopoiesis, a common age-related phenomenon marked by expansion of cells with clonal hematopoiesis driver mutations, has been associated with all-cause mortality, cancer, and cardiovascular disease. People with HIV (PWH) are at risk for non-AIDS-related comorbidities such as atherosclerotic cardiovascular disease and cancer. In a cross-sectional cohort study, we compared clonal hematopoiesis prevalence in PWH on stable antiretroviral therapy with prevalence in a cohort of overweight in ...[more]

PMID: 34417800

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Project description:BackgroundThe longitudinal rate and profile of cognitive decline in persons with stable, treated, and virally suppressed HIV infection is not established. To address this question, the current study quantifies the rate of cognitive decline in a cohort of virally suppressed HIV+ persons using clinically relevant definitions of decline, and determine cognitive trajectories taking into account historical and baseline HAND status.MethodsNinety-six HIV+ (clinically stable and virally undetectable) and 44 demographically comparable HIV- participants underwent standard neuropsychological testing at baseline and 18-months follow-up. We described clinically relevant cognitive trajectories based on standard definitions of historical and baseline HAND status and cognitive decline. Historical, moderate to severe HAND was formally diagnosed at the start of the cART era in 15/96 participants based on clinical neurological and neuropsychological assessment. The same standard of care has been applied to all participants at St. Vincent's Hospital Infectious Disease Department for the duration of their HIV infection (median of 20 years).ResultsRelative to HIV- controls (4.5%), 14% of HIV+ participants declined (p = .11), they also scored significantly lower on the global change score (p = .03), processing speed (p = .02), and mental flexibility/inhibition (p = .02) domains. Having HAND at baseline significantly predicted cognitive decline at follow up (p = .005). We determined seven clinically relevant cognitive trajectories taking into account whether participant has a history of HAND prior to study entry (yes/no); their results on the baseline assessment (baseline impairment: yes/no) and their results on the 18-month follow up (decline or stable) which in order of prevalence were: 1) No HAND history, no baseline impairment, 18-month follow-up stable (39%), 2) No HAND history, baseline impairment, 18-month follow-up stable (35%), 3) History of HAND; baseline impairment, 18-month follow-up stable (9%) 4) No history of HAND, baseline impairment, 18-month follow-up decline (7%), 5) History of HAND, no baseline impairment, 18-month follow-up stable (3%), 6) No HAND history, no baseline impairment, 18-month follow-up decline (3%) 7) History of HAND, baseline impairment, 18-month follow-up decline (3%). There was no relationship between cognitive decline (taking into account historical and baseline HAND) and traditional HIV disease biomarkers.ConclusionsDespite long-term viral suppression, we found mostly subclinical levels of decline in psychomotor speed and executive functioning (mental flexibility and cognitive inhibition); well-established markers of HAND progression. Moreover, 57% of our cohort is undergoing slow evolution of their disease, challenging the notion of prevalent neurocognitive stability in virally suppressed HIV infection.

Project description:ObjectiveInflammation may contribute to brain white matter health in people living with HIV who report cognitive symptoms despite adherence to combination antiretroviral therapy and viral suppression. We explored relationships between diffusion tensor imaging (DTI) metrics of white matter, plasma biomarkers of immune activation, and cognitive function in the HIV-infected population.DesignRetrospective study of older adults living with HIV who are combination antiretroviral therapy adherent, virally suppressed, and self-report cognitive symptoms.MethodsMRI, blood draws, and standardized neuropsychological test scores were collected from HIV-infected individuals. DTI metrics (fractional anisotropy, mean diffusivity, radial diffusivity, axial diffusivity) and plasma biomarkers (soluble CD163, soluble CD14, neopterin, IFN γ-induced protein 10, monocyte chemoattractant protein 1) were quantified. Statistical analysis explored associations between biomarker levels or neuropsychological test scores and DTI metrics using region of interest analyses and a voxelwise approach.ResultsA total of 43 participants with median (interquartile range) age of 64 (62-66 years), CD4 cell count of 600 (400-760 cell/μl) who were all virally suppressed (<100 copies/ml) were selected. Higher levels of monocyte chemoattractant protein 1 associated with lower fractional anisotropy and higher mean diffusivity (P < 0.05) across white matter tracts including corpus callosum, corona radiata, and superior longitudinal fasciculus. Higher neopterin associated with higher mean diffusivity in the genu of corpus callosum, and higher soluble CD14 associated with lower fractional anisotropy in the bilateral superior corona radiata (P < 0.05). Worse global performance and speed domain scores associated with higher mean diffusivity and lower fractional anisotropy, and worse executive domain scores associated with lower fractional anisotropy (P < 0.05).ConclusionElevated inflammatory plasma biomarkers link to white matter abnormalities among virally suppressed individuals. DTI abnormalities associate to cognitive performance. We conclude that inflammatory processes impact clinically relevant brain health indices despite viral suppression.

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Clonal Hematopoiesis Is Associated With Low CD4 Nadir and Increased Residual HIV Transcriptional Activity in Virally Suppressed Individuals With HIV.

Publications

Clonal Hematopoiesis Is Associated With Low CD4 Nadir and Increased Residual HIV Transcriptional Activity in Virally Suppressed Individuals With HIV.

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