AEGiS-13IAC: Effects of in vivo IL-2 administration on in vitro CC-chemokine production and viral isolation in HIV-infected individuals receiving HAART.

13th International AIDS Conference

Durban, South Africa - July 9-July 14, 2000

Effects of in vivo IL-2 administration on in vitro CC-chemokine production and viral isolation in HIV-infected individuals receiving HAART.

Int Conf AIDS 2000 Jul 9-14; 13:(abstract no. WeOrB490)

Oliva A, Kinter A, Rabin R, Farber J, Metcalf J, Li Y, Romano J, Lane HC, Fauci AS
A.Oliva, IRCCS L. Spallanzani, Via Portuense, 292, 00149 Rome, Italy, E-mail: alecrazy@yahoo.com

BACKGROUND: Exposure of PBMC or CD4+ T cells to IL-2 in vitro results in various, frequently opposing effects on HIV replication such as elevation of the expression of the HIV coreceptor/CC-chemokine receptor CCR5 as well as increased production of HIV inhibitory factors.

METHODS: Whole blood was obtained from HIV-infected subjects receiving HAART (viral load >50 copies/ml) 1 day prior to receiving IL-2 and on day 4 and day 30 post-IL-2 treatment. The samples were analyzed to evaluate the expression of CCR5 and CXCR4, of CCR5 ligand chemokines and to isolate endogenous virus from CD8-depleted PBMC cultures.

RESULTS: The expression of CCR5 on CD4+, but not CD8+, T cells was found to be significantly enhanced, compared to pretreatment (1.55%), at both day 4 (17.52%, p>0.01) and day 30 (21.55% p>0.01) post administration of IL-2. This increase in CCR5 expression did not correlate with a higher frequency of viral isolation from CD8-depleted PBMC cultures. Viral isolation was more frequent (55.5%) in CD8-depleted cultures from a control group, matched for CD4, viral load and duration of HAART than in the group receiving HAART+IL-2 (16.6%). Spontaneous CC-chemokine (MIP-1a, MIP-1b and RANTES) production after an average of 5.3 IL-2 cycles was dramatically higher (p>0.05) in the PBMCs of the HAART+IL-2 group (mean levels of MIP-1a = 3459.87 pg/ml; MIP-1b = 4590.67 pg/ml; RANTES = 1682.35 pg/ml) as compared to the HAARTalone group (mean levels of MIP-1a = 65.85 pg/ml; MIP-1b = 130.45 pg/ml; RANTES = 652.85 pg/ml). Constitutive RANTES and MIP-1b mRNA expression in PBMCs at the same time point was higher in the HAART+IL-2 patients (MIP-1b = 3.75 ó Ç Ö 105 copies/10000 cells; RANTES = 3.85 ó Ç Ö 105/10000 cells) than in the HAART only patients (MIP-1b = 1.65 ó Ç Ö 105 copies/10000 cells; RANTES = 2.14 ó Ç Ö 105/10000 cells).

CONCLUSIONS: These data suggest that the combination of IL-2 plus HAART may improve host defenses against HIV in patients receiving HAART, by increasing CC-chemokine production and reducing viral replication and spread.

Keywords: AEGIS, Antiretroviral Therapy, Highly Active, HIV, HIV Infections, Chemokines, CC, Interleukin-2, Viral Load, RANTES, Macrophage Inflammatory Protein-1, Anti-HIV Agents, Virus Replication, HIV Protease Inhibitors, HIV Seropositivity, Receptors, Chemokine, T-Lymphocytes, Case-Control Studies, In Vitro, Human, virology, organization & administration
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WeOrB490