AEGiS-13IAC: Initiating a four weeks long oral HAART 4 hours after intravenous exposure of macaques with SHIV896P preserves from acute CD4+ cell decline.

13th International AIDS Conference

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

Initiating a four weeks long oral HAART 4 hours after intravenous exposure of macaques with SHIV896P preserves from acute CD4+ cell decline.

Int Conf AIDS 2000 Jul 9-14; 13:(abstract no. MoOrA102)

Vaslin B, Neildez O, Larghero J, Thiebot H, Benlhassan K, Dereuddre-Bosquet N, Clayette P, Dormont D, Le Grand R
B. Vaslin, Commissariat a l' Energie Atomique, DSV/DRM/SNV, 60-68 Av. Division Leclerc, BP 6, 92265 Fontenay aux Roses, France, Tel.: +33 1 146 547 374, Fax: +33 1 146 547 726, E-mail: vaslin@davidf.cea.fr

OBJECTIVES: To evaluate the consequences of initiating HAART within few hours after HIV exposure, using a non human primate model for AIDS.

METHODS: Twelve cynomolgus macaques were exposed to the pathogenic SHIV89.6p chimera (50AID50 intravenous injection). Monkeys were treated oraly twice a day at 8 hours intervals either with the association of AZT (4.5 mg/kg), 3TC (2.5 mg/kg) and Indinavir (20 mg/kg) (group 1 and 2), or a placebo (group 3). Treatment was started 4 hours PI in group 1 and 3, 72 hours PI in group 2, and was continued until day 28 PI. Virologic, immunologic, and hematologic parameters were followed sequentially in blood, and lymphnodes.

RESULTS: During acute primary infection, plasmatic virus loads of macaques receiving early HAART were on average 2 logs lower than placebo's. Seroconvertion occurred earlier in 2/4 macaques in each HAART treated groups (week 1 and 2) than in placebos (week 5). Whereas CD4+ T-cell decline was impressive both in PBMC and lymphnodes of placebo treated macaques, mild and transient CD4+ T-cell decline was noted in PBMC of HAART treated monkeys, which exhibit no significant changes of T lymphocyte populations in LNMCs. Preexisting recall antigen responses of PBMC were more rapidly depressed in placebo treated animals than in HAART treated ones. One year PI, early HAART treated macaques maintained high CD4+ T-cell numbers whereas placebo treated monkeys shown marked CD4+ T-cell depletion.

CONCLUSIONS: Starting HAART within few hours after IV exposure, as recommended for treatment of accidental percutaneous exposures to blood of human health care workers, did not prevent infection or erradicate virus. Nevertheless, treatment limits both virus replication and CD4+ T-cell decline during acute primary infection. Consequences on immune responses were 1/ delay the decline of recall antigen responses, 2/ favor earlier seroconvertion. Early transient HAART favors the installation of the immune response in the context of low CD4+ T-cell depletion which may ensure a better immune control of virus replication and retard progression on the long term.

Keywords: AEGIS, Antiretroviral Therapy, Highly Active, CD4-Positive T-Lymphocytes, Macaca, Simian Acquired Immunodeficiency Syndrome, HIV Infections, T-Lymphocytes, Acquired Immunodeficiency Syndrome, Antigens, CD4, Zidovudine, Virus Replication, Macaca mulatta, Macaca fascicularis, Animal, Human, immunology, virology
000709
MoOrA102