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Inflammation Associated with Heart Disease,
Cancers, Diabetes, Viral Load & CD4 Count
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Download the PDF here
Inflammation markers associated with AIDS & Non-AIDS Events (cancers, heart disease, diabetes) independent of CD4
"HIV-1 RNA level correlated" with inflammation markers.
"baseline CD4 was inversely but not strongly correlated with inflammation marker levels of IL-6, sTNF...."
"the change in CD4 count from baseline to week 24 was inversely correlated with baseline to week 24 changes" in levels of inflammation markers
CD4 & Viral load were associated with inflammation markers" so the suggestion is I think (from Jules) that immunodeficiency & viral replication contribute strongly to inflammation which is a strong causation factor for AIDS & Non-AIDS events.
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Associations of Inflammatory Markers with AIDS and non-AIDS Clinical Events after Initiation of Antiretroviral Therapy: AIDS Clinical Trials Group A5224s, a substudy of ACTG A5202 - pdf attached
JAIDS Journal of Acquired Immune Deficiency Syndromes Oct 10 2013
McComsey, Grace A; Kitch, Douglas; Sax, Paul E; Tierney, Camlin; Jahed, Nasreen C; Melbourne, Kathleen; Ha, Belinda; Brown, Todd T; Bloom, Anthony; Fedarko, Neal; Daar, Eric S
"we showed that higher levels of several inflammatory biomarkers were associated independently of CD4 with increased risk of AIDS or non-AIDS events. Larger and longer studies should investigate the use of these markers as predictors of clinical endpoints, especially during long-term viral suppression on ART."
"several studies have linked a single measurement of an inflammatory
marker to subsequent mortality10-12, myocardial infarction risk13, and increased intima media thickness14-15 (a marker of vascular disease)."
"We showed that higher pre-ART and on-ART levels of several inflammatory biomarkers were associated independently of CD4 count with increased risk of progression to AIDS and/or non-AIDS events.....IL-6 is associated with increased risk of AIDS-defining event....we found that higher baseline hsCRP is associated increased rate of progression to non-AIDS event. When we combined progression to AIDS and non-AIDS events baseline hsCRP and IL-6 were associated with increased risk of clinical progression. It was notable in our study that overall, in both unadjusted and CD4- or HIV-1 RNA- adjusted analyses, time-updated levels in markers of TNF-a levels (levels of TNF-a or its soluble receptors), were associated with clinical"
"269 subjects were enrolled in A5224s.....(70%) had HIV-1 RNA<50 copies/mL......85% were male, 48% white non-Hispanics, and among 205 subjects with available data, 41% were smokers. Among subjects who had screening HIV-1 RNA ≥100,000 copies/mL, 56% on TDF/FTC and 60% on ABC/3TC had HIV-1 RNA <50 copies/mL.....hiv RNA & CD4 correlated with elevated inflammation markers......Baseline hsCRP was significantly associated with developing a non-AIDS-event, and there was a trend for an association with IL-6. Adjustment for ART assignment and for baseline HIV-1 RNA levels did not change either of the results. Adjustment for baseline CD4 did not change the hsCRP results"
Abstract
Background: The association of inflammatory biomarkers with clinical events after antiretroviral therapy (ART) initiation is unclear.
Methods: A5202 randomized 1857 treatment-naive subjects to abacavir/lamivudine or tenofovir-DF/emtricitabine with efavirenz or atazanavir/ritonavir. Substudy A5224s measured inflammatory biomarkers on subjects with available plasma from baseline and weeks 24 or 96. An exploratory analysis of the association of hsCRP, IL-6, sTNF-RI, sTNF-RII, TNF-[alpha], sVCAM-1, and sICAM-1 with times to AIDS and to non-AIDS events used Cox proportional hazards models.
Results:
Analysis included 244 subjects; 85% male, 48% white non-Hispanic, with median age 39 years, HIV-1 RNA 4.6 log10 copies/mL, and CD4 240 cells/[micro]L. Overall, 13 AIDS events (9 opportunistic infections; 3 AIDS-cancers, 1 recurrent bacterial pneumonia) and 18 non-AIDS events (6 diabetes, 4 cancers, 3 cardiovascular, 5 pneumonias) occurred.....a total of 15 bone fractures occurred during the study, all of which were associated with a trauma.
Higher baseline IL-6, sTNF-RI, sTNF-RII, and sICAM-1 were significantly associated with increased risk of AIDS-defining events.
Adjustment for baseline HIV-1 RNA did not change results, while adjusting for baseline CD4 count left only sTNF-RI and sICAM-1 significantly associated with increased risk. Time-updated values of IL-6, sTNFR-I and II, and sICAM-1 were also associated with an increased risk. For non-AIDS events, only higher baseline hsCRP was significantly associated with increased risk, while higher IL-6 was marginally associated with higher risk. Analyses of time-updated biomarker values showed TNF-[alpha] to be significantly associated with increased risk, even after adjustment for ART, and CD4 count or HIV-1 RNA.
Conclusion: Higher levels of several inflammatory biomarkers were independently associated with increased risk of AIDS and non-AIDS events.
At baseline HIV-1 RNA level correlated with levels of IL-6 (r = 0.17 , p=0.008), sVCAM-1 (r = 0.45 , p<0.001), sICAM-1 (r = 0.26 , p<0.001), sTNF-RII (r = 0.52 , p<0.001), sTNFRI (r = 0.43 , p<0.001), and TNF-a (r = 0.38 , p<0.001), but not with hsCRP (r = 0.04 , p=0.49). Only for sTNFR-I was mean change from baseline to week 24 significantly different between subjects who at week 24 were virologically suppressed (<50 copies/mL) or not (estimated mean (SD) -0.18 (0.23) vs. -0.12 (0.17) pg/mL; p=0.018).
The mean (SD) change from baseline to week 96 in sTNFR-II, sVCAM-1, and TNF-a were statistically significantly different between subjects who were virologically suppressed (<50 copies/mL) or not (-0.73 (0.43) vs. -0.52 (0.56) pg/mL; p=0.019 and -0.53 (0.33) vs. -0.25 (0.42) ng/mL; p<0.001, and -0.75 (0.42) vs. -0.37 (0.52) pg/mL; p<0.001, respectively).
"....baseline CD4 was inversely but not strongly correlated with level of IL-6, sTNF...."
"the change in CD4 count from baseline to week 24 was inversely correlated with baseline to week 24 changes in levels of sVCAM-1
0.40, p<0.001), sICAM-1 (r = -0.22, p =0.001), sTNF-RII (r = -0.36, p<0.001), sTNF-RI (r= -0.16, p=0.015), and TNF-a (r = -0.29, p<0.001). Similarly, the change in CD4 count from baseline to week 96 was correlated with baseline to week 96 changes in levels of
sVCAM-1 (r = -0.36, p<0.001), sTNF-RII (r = -0.23, p=0.001), sTNF-RI (r =-0.14, p=0.046), and TNF-a (r = -0.22, p=0.001). Notably, neither baseline nor changes in CD4 count correlated with baseline or changes in hsCRP levels (r ≤ 0.07; p ≥ 0.31)."
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