Herpes simplex virus type 2 serostatus is not associated with inflammatory or metabolic markers in antiretroviral therapy-treated HIV.
Systemic inflammation and immune activation may persist in HIV-infected persons on suppressive combination antiretroviral therapy (cART) and contribute to adverse health outcomes. We compared markers of immune activation, inflammation, and abnormal glucose and lipid metabolism in HIV-infected adults according to herpes simplex virus type 2 (HSV-2) serostatus in a 6-month observational cohort study in Toronto, Canada. HIV-infected adults on suppressive (viral load <50 copies/ml) cART were categorized as HSV-2 seropositive or seronegative using the HerpeSelect ELISA, and underwent study visits at baseline, 3 months, and 6 months. The primary outcome was the median percentage of activated (CD38(+)HLADR(+)) CD8 T cells. Secondary outcome measures included additional immune (activated CD4, regulatory T cells) and inflammatory (hsCRP, D-dimer, IL-1b, IL-6, MCP-1, TNF, sICAM-1, sVCAM-1, Ang1/Ang2 ratio) markers. Metabolic outcomes included the proportion with impaired fasting glucose/impaired glucose tolerance/diabetes, insulin sensitivity (calculated using the Matsuda index), insulin resistance (homeostasis model assessment of insulin resistance), and fasting lipids. The impact of HSV-2 on each outcome was estimated using generalized estimating equation regression models. Of 84 participants, 38 (45%) were HSV-2 seropositive. HSV signs and symptoms were uncommon. Aside from D-dimer, which was more often detectable in HSV-2 seropositives (adjusted odds ratio=3.58, 95% CI=1.27, 10.07), HSV-2 serostatus was not associated with differences in any other immune, inflammatory cytokine, acute phase reactant, endothelial activation, or metabolic markers examined in univariable or multivariable models. During the study, CD8 and CD4 T cell activation declined by 0.16% and 0.08% per month, respectively, while regulatory T cells increased by 0.05% per month. HSV-2 serostatus was not consistently associated with immune activation, inflammatory, or lipid and glucose metabolic markers in this cohort of HIV-infected adults on suppressive cART.
1 Department of Medicine, University of Toronto , Toronto, Canada .
Darrell H S
DH
Tan
Janet M
JM
Raboud
Leah
L
Szadkowski
Tae Joon
TJ
Yi
Brett
B
Shannon
Rupert
R
Kaul
W Conrad
WC
Liles
Sharon L
SL
Walmsley
D051997:ADP-ribosyl Cyclase 1 / Q000032:analysis; D000328:Adult; D044966:Anti-Retroviral Agents / Q000627:therapeutic use; D000914:Antibodies, Viral / Q000097:blood*; D018414:CD8-Positive T-Lymphocytes / Q000737:chemistry / Q000276:immunology*; D002170:Canada / Q000453:epidemiology; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy / Q000473:pathology*; D006684:HLA-DR Antigens / Q000032:analysis; D006558:Herpes Genitalis / Q000276:immunology*; D018258:Herpesvirus 2, Human / Q000276:immunology*; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis; D008875:Middle Aged; D011446:Prospective Studies; D018746:Systemic Inflammatory Response Syndrome / Q000209:etiology*; D016176:T-Lymphocyte Subsets / Q000276:immunology
D044966:Anti-Retroviral Agents; D000914:Antibodies, Viral; D006684:HLA-DR Antigens; D008562:Membrane Glycoproteins; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1