Poccia F, Montesano C, Gioia C, Amicosante M, Agrati C, Topino S, Narciso P, Ippolito G, Pucillo LP, D'Offizi G; International Conference on AIDS.

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

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-gamma 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.

Publication Types:

• Meeting Abstracts

Keywords:

• AIDS Vaccines
• Acquired Immunodeficiency Syndrome
• Anti-HIV Agents
• Antigens, CD45
• Antiretroviral Therapy, Highly Active
• CD8-Positive T-Lymphocytes
• HIV
• HIV Antibodies
• HIV Infections
• HIV Protease Inhibitors
• HIV Seropositivity
• HIV-1
• Humans
• T-Lymphocyte Subsets
• T-Lymphocytes
• T-Lymphocytes, Cytotoxic
• Viremia
• drug therapy
• immunology
• therapy

Other ID:

• GWAIDS0015754

UI: 102253252

From Meeting Abstracts