HIV-1 specific antibody titers and neutralization among chronically infected patients on long-term suppressive antiretroviral therapy (ART): a cross-sectional study.
The majority of potent and broadly neutralizing antibodies against HIV-1 have been isolated from untreated patients with acute or chronic infection. To assess the extent of HIV-1 specific antibody response and neutralization after many years of virologic suppression from potent combination ART, we examined antibody binding titers and neutralization of 51 patients with chronic HIV-1 infection on suppressive ART for at least three years. In this cross-sectional analysis, we found high antibody titers against gp120, gp41, and the membrane proximal external region (MPER) in 59%, 43%, and 27% of patients, respectively. We observed significantly higher endpoint binding titers for gp120 and gp41 for patients with >10 compared to ≤ 10 years of detectable HIV RNA. Additionally, we observed higher median gp120 and gp41 antibody titers in patients with HIV RNA <50 copies/mL for ≤ 5 years. 22% of patients neutralized a HIV-1 primary isolate (HIV-1(JR-FL)) and 8% neutralized a HIV-2/HIV-1 MPER chimera. Significantly greater HIV-1(JR-FL) neutralization was found among patients with >10 years of detectable HIV RNA (8/20 [40.0%] versus 3/31 [9.7%] for ≤ 10 years, p = 0.02) and a trend toward greater neutralization in patients with ≤ 5 years of HIV RNA <50 copies/mL (7/20 [35.0%] versus 4/31 [12.9%] for >5 years, p = 0.08). All patients with neutralizing activity mediated successful phagocytosis of VLPs by THP-1 cells after antibody opsonization. Our findings of highly specific antibodies to several structural epitopes of HIV-1 with antibody effector functions and neutralizing activity after long-term suppressive ART, suggest continuous antigenic stimulation and evolution of HIV-specific antibody response occurs before and after suppression with ART. These patients, particularly those with slower HIV progression and more time with detectable viremia prior to initiation of suppressive ART, are a promising population to identify and further study functional antibodies against HIV-1.
Division of Gastroenterology, Northwestern University, Chicago, Illinois, United States of America ; Division of Infectious Diseases, University of California Irvine, Irvine, California, United States of America.
Johannes S
JS
Gach
Division of Infectious Diseases and Center for Global Health, Northwestern University, Chicago, Illinois, United States of America.
Chad J
CJ
Achenbach
Division of Infectious Diseases, University of California Irvine, Irvine, California, United States of America ; Institute of Applied Microbiology, University of Natural Resources and Applied Life Sciences Vienna, Vienna, Austria.
Veronika
V
Chromikova
Division of Infectious Diseases and Center for Global Health, Northwestern University, Chicago, Illinois, United States of America.
Baiba
B
Berzins
Division of Infectious Diseases and Center for Global Health, Northwestern University, Chicago, Illinois, United States of America.
Nina
N
Lambert
Division of Infectious Diseases, University of California Irvine, Irvine, California, United States of America.
Gary
G
Landucci
Division of Infectious Diseases, University of California Irvine, Irvine, California, United States of America.
Donald N
DN
Forthal
Université Pierre et Marie Curie-Paris, Hôpital Pitié-Salpêtrière, Paris, France.
Christine
C
Katlama
Division of Gastroenterology, Northwestern University, Chicago, Illinois, United States of America.
Barbara H
BH
Jung
Division of Infectious Diseases and Center for Global Health, Northwestern University, Chicago, Illinois, United States of America.
Robert L
RL
Murphy
D019380:Anti-HIV Agents / Q000627:therapeutic use*; D057134:Antibodies, Neutralizing / Q000097:blood*; D003430:Cross-Sectional Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015483:HIV Antibodies / Q000097:blood*; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood; D019562:Viral Load
D019380:Anti-HIV Agents; D057134:Antibodies, Neutralizing; D015483:HIV Antibodies; D012367:RNA, Viral