AEGiS-14IAC: Expansion of pre-terminally differentiated CTL in HIV-infected persons presenting a rapid viral rebound during structured treatment interruption.

14th International AIDS Conference

Barcelona, Spain - July 7-12, 2002

Expansion of pre-terminally differentiated CTL in HIV-infected persons presenting a rapid viral rebound during structured treatment interruption.

Int Conf AIDS 2002 Jul 7-12; 14:(abstract no. ThOrB1442)

Poccia F, Montesano C, Gioia C, Amicosante M, Agrati C, Topino S, Narciso P, Ippolito G, Pucillo LP, D'Offizi G
National Institute for Infectious Diseases Lazzaro Spallanzani - IRCCS, Rome, Italy

BACKGROUND: Since structured antiretroviral treatments (STI) may boost anti-HIV specific immunity, we analysed the influence of STI on CD8 T cell dynamics and HIV viral rebound.

METHODS: Twenty-six chronically HIV-1 infected asymptomatic patients with undetectable HIV-RNA plasma during at least two years of HAART were divided in two groups: one group of patients with a rapid viral rebound and a second group of patients with a delayed viral rebound during STI. A clinical and immunological follow-up was performed at the suspension of HAART (t0), after 1 month from the suspension (t1), at the resumption of HAART (t2), and after 30 days from HAART-resumption (t3). HIV-specific CD8 T cell frequencies were measured by flow cytometry as intracellular cytokine-staining. Naive, central and effector memory CD8 T cell subsets were monitored using specific differentiation markers: CD45RA, CD27 and CCR7.

RESULTS: We observed a delayed viral rebound in a relevant fraction of our STI patients, presenting no significant changes in the immunological parameters during a prolonged drug-free period. In contrast, we observed a rapid expansion of circulating CD8 T lymphocytes in HIV-infected persons presenting a sustained viral rebound during STI. In these patients, the frequencies of CD8 T cells releasing IFN-γ after mitogen-induced or Gag-specific stimulation were both highly increased following HAART discontinuation. However, these CD8 T cells were mainly composed by pre-terminally differentiated CTL expressing a CCR7- CD45RA- phenotype and a reduced content of cytotoxic factors such as perforin.

CONCLUSION: These data indicate that an expansion of immature CTL with poor cytotoxic activity is associated to the failure to control viremia during STI. Thus, monitoring CD8 T cell dynamics during STI could be clinically relevant and useful to design new terapeutic strategies aimed to restore CTL effector funtions.

Keywords: AEGIS, HIV, HIV Infections, Antiretroviral Therapy, Highly Active, HIV-1, CD8-Positive T-Lymphocytes, Anti-HIV Agents, Antigens, CD8, HIV Seropositivity, T-Lymphocyte Subsets, Viremia, T-Lymphocytes, Antigens, CD45, HIV Protease Inhibitors, HIV Antibodies, Human, virology, therapy, immunology, drug therapy

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ThOrB1442