Longitudinal study of humoral immune responses in HIV type 1 subtype CRF01_AE (E)-infected Thai patients with different rates of disease progression.
Identification of immune correlates associated with disease progression will provide information for HIV-1 vaccine design in countries such as Thailand, where the prevalent subtypes (B and CRF01_AE [E]) are characterized. In this study, plasma viral load and humoral immune responses were measured in 20 HIV-1 subtype E-infected Thai patients with different rates of disease progression, based on CD4(+) T cell decline and clinical symptoms. Nine progressors (PRs) and 11 slower progressors (SPs) were evaluated. CD4(+) T cell counts were inversely correlated with viral load (p = 0.004) and positively correlated with p24 Ab (p = 0.022). In progressors, p24 Ab showed a significant decrease (p < 0.001) over time. V3 and gp41 Ab did not change significantly in either group. Both CD4-binding site (CD4/gp120BS) and gp120 titers correlated positively with neutralizing antibody (NAb) against both a subtype E cell line-adapted virus (NP03) and a primary isolate (TH023). However, V3 Ab correlated only with NAb against NP03 (p < 0.001). Increased NAb over time was observed more frequently in SPs as compared with PRs, against both the TH023 (p = 0.004) and NPO3 (p = 0.004) viruses. Cross-clade antibody-dependent cellular cytotoxicity was demonstrated in both groups. These data suggest that in HIV-1 subtype E infection, declining p24 Ab titer is a predictive marker of disease progression, as described for subtype B. Furthermore, in subtype E-infected patients, slower progressors retain the immune competence to develop new antibody responses to Env over time; these evolving responses may contribute to prolonged survival during HIV-1 disease progression.
Chuenchitra
Thippawan
T
Armed Forces Research Institute of Medical Sciences, Bangkok 10400, Thailand.
Wasi
Chantapong
C
Louisirirojchanakul
Suda
S
Nitayaphan
Sorachai
S
Sutthent
Ruengpung
R
Cox
Josephine H
JH
De Souza
Mark S
MS
Brown
Arthur E
AE
Birx
Deborah L
DL
Polonis
Victoria R
VR
D000920:Antibody-Dependent Cell Cytotoxicity; D018791:CD4 Lymphocyte Count; D019742:Chemokines, CC / Q000097:blood; D004279:DNA, Viral / Q000097:blood; D018450:Disease Progression; D015686:Gene Products, env / Q000276:immunology; D015683:Gene Products, gag / Q000276:immunology; D015483:HIV Antibodies / Q000097:blood*; D015658:HIV Infections / Q000276:immunology / Q000503:physiopathology*; D015497:HIV-1 / Q000145:classification / Q000276:immunology*; D006801:Humans; D008137:Longitudinal Studies; D009500:Neutralization Tests; D013785:Thailand; D019562:Viral Load
D019742:Chemokines, CC; D004279:DNA, Viral; D015686:Gene Products, env; D015683:Gene Products, gag; D015483:HIV Antibodies