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ART does not reverse all residual inflammation in HIV
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Although early ART normalized the coagulation cascade and some inflammatory biomarkers in patients with HIV, treatment was not associated with normalization of fibrosis biomarkers, monocyte activation, enterocyte turnover or acute phase response, according to data published in Clinical Infectious Diseases.
“Initiation of ART at high CD4 T-cell counts and/or within the first year of seroconversion results in more robust immune restoration and less chronic immune activation, whereas lower nadir CD4 T-cell counts are associated with higher risk of serious non-AIDS events,” Irini Sereti, MD, of the laboratory of immunoregulation at the National Institute of Allergy and Infectious Diseases, NIH, and colleagues wrote. “However, whether ART initiation during acute HIV infection could eliminate increased inflammation in chronic HIV infection remains unknown.”
Researchers obtained plasma samples from patients with acute HIV infection and chronic HIV as they started ART, along with uninfected patients from the Thai Red Cross Anonymous Clinic in Bangkok, Thailand (n = 247). Sereti and colleagues measured inflammation biomarkers, enterocyte turnover, monocyte activation, coagulation cascade activation and fibrosis, at baseline and during 96 weeks of treatment.
Patients with acute HIV infection had elevated C-reactive protein, TNF, soluble IL-6 receptor, intestinal fatty acid binding protein, soluble CD14, coagulation cascade activation and fibrosis, the researchers reported. ART was associated with normalized TNF, soluble IL-6 receptor and coagulation cascade activation levels, but increased intestinal fatty acid binding protein. ART also lowered C-reactive protein, soluble CD14 and hyaluronic acid levels, but these remained elevated compared with patients without HIV. Increased CD4 T-cell counts were associated with decreases in soluble CD14 and C-reactive protein levels, Sereti and colleagues wrote.
After 2 weeks of ART, median C-reactive protein levels fell in all patients with acute HIV infection (P = .0009), mainly in the 4th generation IA stage 2 and 4th generation IA stage 3 groups. Patients with acute infections had lower median C-reactive protein levels than participants with chronic infections at week 48 (P < .0001), but these levels were still higher than those of participants who did not have HIV at 96 weeks (P = .04). After 48 weeks, the acute patients’ TNF levels rose (P = .0008), but decreased to levels similar to those of non-infected participants by 96 weeks.
Patients had varying soluble IL-6 receptor (sIL-6R) levels throughout the study, but participants with acute and chronic infections had similar levels by week 96, Sereti and colleagues wrote. In both groups, patients’ sIL-6R levels decreased after 24 and 96 weeks (P < .001). After 96 weeks, all patients with HIV had sIL-6R levels similar to those of the non-infected patients. The data indicated ART normalized TNF levels and mediators of IL-6 signaling, but did not normalize C-reactive protein levels,” the researchers reported.
“In conclusion, initiation of ART during acute HIV infection is insufficient to resolve the chronic inflammation associated with increased all-cause morbidity and mortality in treated HIV infection. Initiating ART during acute infection, however, attenuates inflammation to a greater extent than initiating ART in chronic HIV infection,” Sereti and colleagues wrote. “Whether persistent residual inflammation will translate into increased end-organ disease remains to be determined. If so, further interventions to attenuate inflammation even among patients treated in acute HIV infection may be necessary to optimize clinical outcomes.” – by Andy Polhamus
Disclosure: Sereti reports no relevant financial disclosures. Please see the full study for a complete list of all other researchers’ relevant financial disclosures.
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