Correlation between breadth of memory HIV-specific cytotoxic T cells, viral load and disease progression in HIV infection.
BACKGROUND
Memory cytotoxic T lymphocytes (CTL) should play a key role in controlling HIV infection. The correlations between the breadth and specificities of memory CTL and virus production and disease progression are still unknown, but are of major importance for vaccine strategies.


METHODS
One-hundred and forty-eight chronically-infected patients, enrolled before the advent of highly active antiretroviral therapy, were followed-up prospectively over 5 years. Memory CTL were tested in vitro against autologous target cells expressing Env, Gag, Pol, Nef, Vif, Rev or Tat HIV-LAI sequences.


RESULTS
At entry, an HIV-specific CTL response was detected against at least one viral protein in 77% cases, with Pol and Gag recognized in 57% each, Env and Nef in 36% and 30%, Vif, Rev and Tat in 14%, 10% and 5% of cases respectively. The same pattern was observed over time with some individual variations in responder status. Multivariate analysis of longitudinal data showed that the average number of recognized proteins of two at entry significantly decreased over time with the average loss of one protein per 7 years. The number of recognized proteins was negatively associated with viral load (P < 0.05), and with occurrence of opportunistic infection (P < 0.01), and significantly correlated with CD8 cell counts (P < 0.05) but not with CD4 cell counts.


CONCLUSIONS
The breadth of HIV antigens recognized by memory CTL is a major correlate of immune control of HIV-replication and disease progression.
Chouquet
Cécile
C
INSERM EMI 0214, Laboratoire d'Immunologie Cellulaire et Tissulaire, Centre Hospitalier Pitié-Salpétrière, Institut Pasteur, 25 rue du Dr. Roux, 75015 Paris, France.
Autran
Brigitte
B
Gomard
Elisabeth
E
Bouley
Jean-Marc
JM
Calvez
Vincent
V
Katlama
Christine
C
Costagliola
Dominique
D
Rivière
Yves
Y
D000328:Adult; D002908:Chronic Disease; D015331:Cohort Studies; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology*; D008297:Male; D011446:Prospective Studies; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000821:virology; D019562:Viral Load