Antiretroviral therapy in HIV-infected elite controllers: impact on gut immunology, microbial translocation, and biomarkers of serious non-AIDS conditions.
Elite controllers (ECs) maintain undetectable HIV viral loads without antiretroviral therapy (ART) but are at increased risk of serious non-AIDS conditions (SNA). We assessed the impact of ART in ECs on gut immune dysfunction and biomarkers predicting SNA (blood CD4/CD8 ratio, plasma IL-6, D-dimer levels). At baseline, ECs had elevated IL-6 and D-dimer levels and reduced CD4/CD8 ratio compared with HIV-uninfected controls, but no difference in microbial translocation or gut CD4 subsets. ART increased CD4/CD8 ratio but did not normalize IL-6 and D-dimer levels. EC SNA pathogenesis may be independent of gut immune dysfunction, and resolution may require prolonged ART.
*Department of Medicine and Immunology, University of Toronto, Toronto, Ontario, Canada; †Maple Leaf Medical Clinic, Toronto, Ontario, Canada; ‡National Institutes of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD; and §Department of Gastroenterology, St. Michael's Hospital and the Li Ka Shing Knowledge Institute, Toronto, Ontario, Canada.
Connie J
CJ
Kim
Colin
C
Kovacs
Tae-Wook
TW
Chun
Gabor
G
Kandel
Brendan J W
BJ
Osborne
Sanja
S
Huibner
Kamnoosh
K
Shahabi
Feng-Yun
FY
Yue
Erika
E
Benko
Mario
M
Ostowski
Rupert
R
Kaul
D000328:Adult; D000368:Aged; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D018988:Bacterial Translocation; D015415:Biomarkers; D016516:CD4-CD8 Ratio; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis; D041981:Gastrointestinal Tract / Q000276:immunology*; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy*; D020276:HIV Long-Term Survivors; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged
D044966:Anti-Retroviral Agents; D015415:Biomarkers; D005338:Fibrin Fibrinogen Degradation Products; D015850:Interleukin-6; C036309:fibrin fragment D