icon-folder.gif   Conference Reports for NATAP  
  ID Week
Oct 8-12 2014
Back grey_arrow_rt.gif
Acute Retroviral Syndrome Tied to Higher
HIV RNA and DNA in Blood, Colon, CSF

  IDWeek 2014, October 8-12, 2014, Philadelphia
Mark Mascolini
Compared with recently HIV-infected people without the acute retroviral syndrome (ARS), those with ARS had significantly higher levels of HIV RNA in blood, colon, and cerebrospinal fluid (CSF), higher HIV DNA in peripheral blood, and higher inflammatory marker levels, according to results of a 150-person comparison in Thailand [1]. People with ARS also had heightened CD8-cell activation in the sigmoid colon.
Most people with acute HIV infection go through ARS, noted the US-Thai collaborators who conducted this study. But much remains to be learned about virologic and immunologic changes in newly infected people with and without ARS. To address those issues, the researchers analyzed findings from an ongoing prospective study that enrolls people with acute HIV infection in Bangkok. When a person enters the cohort, clinicians use a standardized checklist to itemize symptoms. People with three or more qualifying symptoms are classified as having ARS.
Of the 97,920 people screened for HIV between May 2009 and February 2014, the researchers focused on 150 with acute HIV infection who began antiretroviral therapy. The most common symptoms were fever (94%), fatigue (81%), headache (72%), pharyngitis (60%), and myalgia (60%). Median number of ARS symptoms was 7. The investigators measured HIV RNA and DNA and numerous biomarkers in peripheral blood (75 people), colon tissue (42 people), and CSF (37 people).
Among the 150 study participants, 114 (76%) had ARS and 36 did not. Median age stood at 28 in the ARS group and 26 in the no-ARS group. Respective proportions of men were 95% and 92% and of men who have sex with men (MSM) 91% and 92%. Median days since HIV exposure was significantly longer in the ARS group (18 versus 14, P = 0.01).
Median HIV RNA when first measured was significantly higher with than without ARS in peripheral blood (5.7 versus 4.6 log10 copies/mL, P = 0.0003), colon (3.1 versus 1.7 log, P = 0.009), and CSF (3.6 versus 1.8 log, P = 0.006). Initial CD4 count in peripheral blood did not differ significantly between the two groups, but people with ARS had a significantly lower median colonic CD4 count (6.6 versus 11.8, P = 0.02). People with ARS had significantly higher median levels of two inflammatory markers: C-reactive protein (1.43 versus 0.64 mg/L, P = 0.004) and TNF-alpha (7.41 versus 4.71 pg/mL, P = 0.001).
At the baseline visit median total HIV DNA in peripheral blood was higher with than without ARS (145 versus 7.5 copies/million PBMCs, P = 0.02), as well as at week 24 (31 versus 0 copies/million PBMCs) and week 96 (11.5 versus 1.5 copies/million PBMCs). Median levels of the coagulation marker D-dimer were higher with than without ARS at the baseline visit (310 versus 179 ng/mL, P = 0.007) but not at week 24 (157 versus 154 ng/mL) or week 96 (158 versus 232 ng/mL). The median D-dimer level in healthy Thais is 165 ng/mL.
Median proportions of activated (HLA-DR+/CD38+) CD8 cells were higher in the ARS group at the baseline visit (8.7% versus 4.4%, P = 0.02) but not at week 24 (3.1% versus 3.3%) or week 96 (3.7% versus 3.2%). The median proportion of activated CD8 cells in healthy Thais is 3.7%.
Median baseline levels of CSF neopterin, an immune activation marker, were significantly higher with than without ARS (2410 versus 1101 pg/mL, P = 0.0001; median 651 pg/mL in healthy Thais). But CSF neopterin levels fell to normal levels in both groups at weeks 24 and 96 and did not differ significantly between groups at those points.
The researchers noted that their analysis is limited by the small sample size and lack of a comparison group not treated with antiretrovirals. They cautioned that results from this Thai group consisting mostly of MSM may not apply to other HIV populations. But with those limitations in mind they suggested that "patients with ARS may have poorer outcomes than those without ARS, particularly if they continue to display this unfavorable profile after treatment."
1. Crowell T, Fletcher JLK, Kroon E, et al. Acute retroviral syndrome is associated with gut mucosal CD4 depletion, inflammation and high viral and proviral burden in systemic and tissue compartments. IDWeek 2014. October 8-12, 2014, Philadelphia. Abstract 641.