HIV and cardiovascular disease: the role of inflammation

Dirajlal-Fargo, Sahera; Funderburg, Nicholas

doi:10.1097/coh.0000000000000755

Cited by 18 publications

(19 citation statements)

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“…Persistent immune activation plays a key role in HIV pathogenesis and co-morbidities (18)(19)(20) and may be a result of ongoing inflammation triggered by gut dysfunction and microbial translocation (21). Our findings support this hypothesis as well as earlier observations made by our group in adults living with HIV that 1) intestinal integrity markers like I-FABP do not improve overtime despite successful ART and that 2) fungal translocation as measured by BDG is associated with inflammation and immune activation (22).…”

Section: Discussionsupporting

confidence: 88%

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Persistent immune activation and altered gut integrity over time in a longitudinal study of Ugandan youth with perinatally acquired HIV

et al. 2023

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IntroductionPerinatally acquired HIV infection (PHIV) occurs during a critical window of immune development. We investigated changes in systemic inflammation and immune activation in adolescents with PHIV and those without HIV (HIV-) in Uganda.MethodsA prospective observational cohort study was performed in 2017-2021 in Uganda. All participants were between 10-18 years of age and without active co-infections. PHIVs were on ART with HIV-1 RNA level ≤400 copies/mL. We measured plasma and cellular markers of monocyte activation, T-cell activation (expression of CD38 and HLA-DR on CD4+ and CD8+), oxidized LDL, markers of gut integrity and fungal translocation. Groups were compared using Wilcoxon rank sum tests. Changes from baseline were examined with 97.5% confidence intervals on relative fold change. P values were adjusted for false discovery rate.ResultsWe enrolled 101 PHIV and 96 HIV-; among these, 89 PHIV and 79 HIV- also had measurements at 96 weeks. At baseline, median (Q1, Q3) age was 13 yrs (11,15), and 52% were females. In PHIV, median CD4+ cell counts were 988 cells/µL (638, 1308), ART duration was 10 yrs (8, 11), and 85% had viral load <50 copies/mL throughout the study, 53% of participants had a regimen switch between visits, 85% of whom switched to 3TC, TDF and DTG. Over 96 weeks, while hsCRP decreased by 40% in PHIV (p=0.12), I-FABP and BDG both increased by 19 and 38% respectively (p=0.08 and ≤0.01) and did not change in HIV- (p≥0.33). At baseline, PHIVs had higher monocyte activation (sCD14) (p=0.01) and elevated frequencies of non-classical monocytes (p<0.01) compared to HIV- which remained stable over time in PHIV but increased by 34% and 80% respectively in HIV-. At both time points, PHIVs had higher T cell activation (p ≤ 0.03: CD4+/CD8+ T cells expressing HLA-DR and CD38). Only in PHIV, at both timepoints, oxidized LDL was inversely associated with activated T cells(p<0.01). Switching to dolutegravir at week 96 was significantly associated an elevated level of sCD163 (β=0.4, 95% CI=0.14,0.57, p<0.01), without changes in other markers.ConclusionUgandan PHIV with viral suppression have some improvement in markers of inflammation over time, however T-cell activation remains elevated. Gut integrity and translocation worsened only in PHIV over time. A deeper understanding of the mechanisms causing immune activation in ART treated African PHIV is crucial.

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Section: Discussionsupporting

confidence: 88%

“…At both time points, markers of systemic inflammation hsCRP and IL6 were not different between the arms (p≥0. 19).…”

Section: Changes In Markers Of Systemic Inflammation Gut Integrity An...mentioning

confidence: 99%

Persistent immune activation and altered gut integrity over time in a longitudinal study of Ugandan youth with perinatally acquired HIV

et al. 2023

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“…HIV-mediated transactivation of transcription protein activates Nuclear Factor-Kappa B (NF-kB) and upregulates the expressions of inflammation cytokines and chemokines ( 53 ). Immune activation persists in PLWH under ART, and markers of inflammation (i.e.IL-6) predict mortality in atherosclerotic cardiovascular disease ( 54 ). BMI, a traditional risk factor for hypertension, also plays a positive role in PLWH.…”

Section: Discussionmentioning

confidence: 99%

Inflammation markers and the risk of hypertension in people living with HIV

Ouyang

Luo

et al. 2023

Front. Immunol.

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BackgroundThe incidence of hypertension is high in people living with HIV (PLWH). High-sensitivity C-reactive protein (hsCRP), systemic inflammation response index (SIRI), and neutrophil-to-monocyte ratio (NMR) are considered economic and convenient parameters that reflect the levels of inflammation in patients. Our aim was to explore whether indirect inflammation markers are associated with hypertension in PLWH.MethodsThis was a case-control study. The case group (hypertension) comprised PLWH with hypertension, and the control group (non-hypertension) comprised sex- and age-(± 3 years)-matched PLWH without hypertension. Demographic parameters, hsCRP, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune- inflammation index (SII), SIRI, lymphocyte-to-monocyte ratio (LMR), platelet-to-neutrophil ratio (PNR), platelet-to-monocyte ratio (PMR), NMR, time to HIV diagnosis, antiretroviral therapy (ART) duration, recent CD4+ and CD8+ cell counts, recent CD4+/CD8+ ratio, recent HIV viral load (HIV-RNA),and recent ART regimen were obtained from the patients’ electronic medical records. A t-test or Wilcoxon rank-sum test was performed to compare differences between the two groups, and conditional logistic regression was used to analyze the risk factors of hypertension. Correlations between inflammation markers and CD4+ cell counts, CD8+ cell counts, and CD4+/CD8+ ratio were analyzed using Spearman’s correlation.ResultsIn the hypertension group, body mass index (BMI), hsCRP, NLR, SII, SIRI, NMR, time to HIV diagnosis, ART duration, CD4+ and CD8+ cell counts, and CD4+/CD8+ ratio, the ratio of HIV-RNA < 100 copies/mL were all higher than those in the non-hypertension group, while the PNR was lower than that in the non-hypertension group. ART duration, CD4+ cell counts, HIV-RNA < 100 copies/mL, hsCRP, SIRI, and NMR were positively associated with hypertensive risk in PLWH. CD8+ cell counts and CD4+/CD8+ ratio was negatively associated with hypertensive risk in PLWH. SIRI was negatively correlated with CD4+ cell counts and CD8+ cell counts, but positively correlated with CD4+/CD8+ ratio.ConclusionsWe identified positive associations between inflammation markers hsCRP, SIRI, NMR and hypertensive risk in PLWH. Alleviating inflammation may help control or delay the occurrence of hypertension in PLWH.

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“…People living with HIV have an increasing life expectancy, which increases exposure to age-related risk factors that can be potentiated by the deleterious factors of HIV infection [ 10 , 12 , 13 ]. It is also possible to observe an increase in the incidence or worsening of age-related chronic inflammatory diseases such as cardiovascular diseases [ 42 ], diabetes [ 43 ], hypertension [ 44 ], metabolic syndrome [ 45 ], tuberculosis [ 46 ], and possibly periodontitis [ 5 , 47 , 48 ].…”

Section: Discussionmentioning

confidence: 99%

Factors Associated with Periodontitis in Patients with and without HIV

Pereira

Amorim

Sampaio

et al. 2023

International Journal of Dentistry

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Purpose. The aim of this study was to compare clinical periodontal conditions in HIV-positive people on HAART with an HIV-negative group, in addition to investigating factors associated with periodontitis in the entire sample. Methods. This was a cross-sectional study. Data were collected by oral clinical examination for the diagnosis of periodontitis, review of medical records, and application of a questionnaire containing personal data, deleterious habits, and oral hygiene habits for the other variables. The results were analyzed by Pearson’s χ2 test and Student’s t-test. A logistic regression model was constructed for the multivariate analysis and periodontitis was defined as a dependent variable. The analysis was performed on the entire sample (HIV+ and HIV−) and also on the group consisting of only people living with HIV. Results. Individuals older than 43 years old and with HIV were more likely to develop moderate and severe periodontitis (47.80 and 4.84 times, respectively). When analyzing only HIV+, in addition to age (OR = 2.795; CI = 1.080−7.233), the use of nonnucleoside reverse transcriptase inhibitors (NNRTIs) (OR = 2.841; CI = 1.135−7.112) was also associated with moderate and severe periodontitis. Conclusion. It was possible to observe a higher prevalence of periodontitis among individuals with HIV, showing an association between the virus, advanced age, and moderate or severe periodontitis.

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HIV and cardiovascular disease: the role of inflammation

Cited by 18 publications

References 98 publications

Persistent immune activation and altered gut integrity over time in a longitudinal study of Ugandan youth with perinatally acquired HIV

Persistent immune activation and altered gut integrity over time in a longitudinal study of Ugandan youth with perinatally acquired HIV

Inflammation markers and the risk of hypertension in people living with HIV

Factors Associated with Periodontitis in Patients with and without HIV

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