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Inflammation Persists Despite Early ART in Acute HIV
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At CROI 2015, this oral talk was presented: "Inflammation Persists Despite Early Initiation of ART in Acute HIV Infection"
[http://www.croiwebcasts.org/console/player/25573?mediaType=slideVideo&]. They found: despite suppressive ART in acute infection inflammation persists with some improvements in general but not to levels of uninfected individuals (see slide just below).
program abstract: Subjects were diagnosed with acute HIV infection and initiated ART within 0-5 days per RV254 protocol. Twenty subjects were diagnosed in 4th generation (4thG) stage 1 (median 12 days post-acquisition), 15 in stage 2 (16 days) and 43 in stage 3 (18 days). All week 0 biomarker levels were significantly higher in HIV+ than HIV- subjects (see table). I-FABP increased by week 2 and remained elevated regardless of 4thG stage. Other biomarkers did not decrease in individuals diagnosed in 4thG1 until week 12. sCD14, CRP and HA decreased by week 2 in individuals diagnosed in 4thG2, and sCD14, CRP, HA and D-dimer decreased by week 2 in individuals diagnosed in 4thG3. HIV+ subjects had significantly higher levels of all biomarkers except D-dimer after 48 and after 96 weeks of ART compared to HIV- subjects.
Plasma levels of D-dimer, C-reactive protein (CRP), hyaluronic acid (HA), soluble CD14 (sCD14) and intestinal fatty acid binding protein (I-FABP, a marker of enterocyte turnover) were measured by ELFA (D-Dimer), Mesoscale (CRP) and ELISA (HA, sCD14, I-FABP) from 109 HIV-uninfected (HIV-) and 78 AHI Thai participants at diagnosis (week 0), weeks 2, 12, 24, 36, 48 and 96. Median values were compared between HIV+ and HIV- groups by Mann-Whitney test and longitudinal within-group comparisons by Wilcoxon matched-pairs signed rank test..
Median age was 28 years (range 24-33) for HIV+ subjects and 27 years (22-37) for HIV- subjects. 92.3% of HIV+ subjects and 77.1% of HIV- subjects were male. Median time since HIV acquisition was 16 days (12-22), CD4 T-cell count 384 (293-525) cells/mm3 and HIV RNA 5.6 (5.1-6.3) log10copies/mL.
· All week 0 biomarker levels were significantly higher in HIV+ than HIV- subjects (see table).
· I-FABP increased by week 2 and remained elevated regardless of 4thG stage.
· Other biomarkers did not decrease in individuals diagnosed in 4thG1 until week 12.
· sCD14, CRP and HA decreased by week 2 in individuals diagnosed in 4thG2, and sCD14, CRP, HA and D-dimer decreased by week 2 in individuals diagnosed in 4thG3.
· HIV+ subjects had significantly higher levels of all biomarkers except D-dimer after 48 and after 96 weeks of ART compared to HIV- subjects.
Conclusions: Enterocyte turnover increases after initiation of ART during acute infection and persists into chronic infection. Biomarkers of inflammation, microbial translocation and fibrosis decrease, but remain elevated compared to HIV- controls with the exception of D-dimer. Together, these data suggest that the inflammatory damage caused by HIV may not be completely prevented by starting ART during acute HIV infection.
This was a followup from CROI 2014 where the authors reported: Biomarkers of inflammation, coagulation and fibrosis are elevated in AHI (acute HIV) before seroconversion. The temporal course of these biomarkers suggests that peak viral burden and inflammation trigger a pro-thrombotic and pro-fibrotic response. During acute infection you can see (Figures 2 & 3 below) inflammation markers increased but lower in earliest stage (4) of acute infection and increased markers for microbial translocation (damaged gut).
AND then at CROI 2015 Ken Lichtenstein reported this poster from the SUN Study group (see below): "Inflammatory Biomarkers Decline but Do Not Normalize after 10 Years of cART"
2014 CROI
Inflammation in Acute HIV Infection Correlates with Blood and Gut CD4 T-cell Loss and HIV Viral Burden
http://www.natap.org/2014/CROI/croi_188.htm
"these data suggest that days matter when halting viral replication to reduce the viral reservoir, intestinal CD4 depletion, and inflammation......Plasma levels of biomarkers of inflammation, microbial translocation (MT), fibrosis and coagulation correlated positively with plasma HIV viremia.....and with sigmoid HIV DNA levels"
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