Azzoni L, Chehimi J, Farabaugh M, Herman C, Mounzer K, Kostman J, Montaner LJ; Conference on Retroviruses and Opportunistic Infections (11th : 2004 : San Francisco, Calif.).

Program Abstr Conf Retrovir Oppor Infect 11th 2004 San Franc Calif. 2004 Feb 8-11; 11: abstract no. 240.

Wistar Inst., Philadelphia, USA

BACKGROUND: Cross-sectional studies have shown that innate immunity effectors [Natural Killer (NK) cells, plasmacytoid and myeloid Dendritic Cells (PDC, MDC] are depleted and impaired in viremic HIV+ individuals. Here we address the longitudinal changes in innate immunity effectors in HIV+ patients initiating ART and maintaining suppression <50 c/ml for 32 weeks.METHODS: NK and DC frequencies and functions (NK cytotoxicity, MLR, LPA, phagocytosis and cytokine secretion) were assessed in 18 therapy-naive HIV+ individuals initiating ART (CD4 counts median 233 cells/mm3, interquantile range IQR 161; serum HIV RNA 19337, IQR 46478). Follow-up was up to 32 weeks after reaching <50 copies/mL. A control group of 14 healthy individuals was used as a reference. Friedman paired ANOVA, Kruskal-Wallis' ANOVA and Spearman correlations tests were applied.RESULTS: As expected, ART increased CD4 cells over 32 weeks (median 499 cells/mm3 at week 32). Spontaneous, IFN-alpha and CpG-2216-induced cytotoxicity, depleted at baseline, increased over time on ART, but did not reach uninfected control levels. Accordingly, NK phenotypes CD16+/56+/[161+], depleted at baseline, remained low, independent of ART; other NK phenotypes (i.e. CD161+/56-/16+), higher in HIV+ individuals, were also not normalized by ART. Although their frequency increased over time on ART, CD123+ PDC remained depleted in HIV+ individuals. In parallel, PDC functional correlates (IFN-alpha secretion upon Influenza virus PR8 or CPG-2216-stimulation) increased on treatment, but remained significantly lower than control levels, indicating that PDC functional recovery on ART does occur but is only partial. MDC functional correlates (MLR responses and HMW dextran phagocytosis) showed a trend to increase over time on HAART, even though MDC frequencies were not significantly different between HIV+ individuals and uninfected controls, suggesting an increased in MDC function. Consistent with this observation and with the restoration of CD4 cells, LPA responses to CMV and HIV p24 also increased over time on ARTCONCLUSIONS: We found that 32 weeks of ART-mediated viral suppression result in the reconstitution of adaptive immune function, yet NK subsets and PDC remain depleted and/or functionally impaired, thus failing to completely restore innate immunity functions.

Publication Types:

• Meeting Abstracts

Keywords:

• Acquired Immunodeficiency Syndrome
• Anti-HIV Agents
• Antiretroviral Therapy, Highly Active
• CD161 antigen
• CD4-Positive T-Lymphocytes
• Cross-Sectional Studies
• Dendritic Cells
• FCGR3B protein, human
• HIV
• HIV Infections
• HIV Seropositivity
• Humans
• Immunity, Natural
• Interferon-alpha
• Killer Cells, Natural
• Lectins, C-Type
• Myeloid Cells
• Receptors, IgG
• drug therapy
• immunology
• therapy

Other ID:

• GWAIDS0031561

UI: 102271198

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