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Inflammation Persists Despite Early Initiation of ART in Acute HIV Infection
Netanya S. Utay1, Jintanat Ananworanich2, Suteera Pinyakorn3, Adam Rupert5, Duanghathai Sutthichom3, Suwanna Puttamaswin3, Bonnie M. Slike2, Nelson L. Michael2, Daniel C. Douek4, Irini Sereti4
1 University of Texas Medical Branch at Galveston, Galveston, TX, United States. 2 US Military HIV Research Program, Silver Spring, MD, United States. 3 South East Asia Research Collaboration with Hawaii, Bangkok, Thailand. 4 National Institutes of Health (NIH), Frederick, MD, United States. 5 Leidos Biomedical Research, Inc, Frederick, MD, United States.
Background: Biomarkers of microbial translocation, inflammation, coagulation and fibrosis predict morbidity and mortality in patients with chronic HIV infection. The effects of starting antiretroviral therapy (ART) in patients with acute HIV infection (AHI) on levels of these biomarkers in chronic treated infection are unknown and may illuminate the potential impact of early ART on clinical outcomes.
Methods: Subjects were diagnosed with acute HIV infection and initiated ART within 0-5 days per RV254 protocol. 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.
Results: 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. 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.
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.