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Abstract
CONSEQUENCES ON IMMUNE FUNCTIONS OF EARLY POST-EXPOSURE PROPHYLAXIS WITH HAART IN THE MODEL OF SHIV INFECTED MACAQUES.
LE GRAND R, BENHLASSAN K, BOSSUET C, THIÉBOT H, BOSQUET N, VASLIN B, DORMONT D
Objectives: To evaluate the consequences of HAART initiated within few hours after exposure to HIV in a non-human primate model for AIDS. Methods: Twelve macaques were exposed to the pathogenic SHIV89.6P (50AID50 intravenous injection). Monkeys were treated by the oral route, twice a day either with the association of AZT (4.5mg/kg), 3TC (2.5mg/kg) and Indinavir (20mg/kg), or a placebo. Treatment was started at 4 or 72 hours pi, and was continued until day 28 pi. Infection was followed sequentially in blood, and lymph nodes. Results: During primary infection, plasma viral load in macaques receiving HAART was at least 2 log lower than in controls. Seroconvertion occurred significantly earlier in 2 of 4 macaques in each HAART-treated group than in the placebo-controls. Whereas CD4+ T-cell decline was impressive both in PBMC and lymph nodes of placebo-treated macaques, only mild and transient CD4+ T-cell decline was noticed in HAART treated monkeys. Pre-existing response to recall antigens induced by vaccination with BCG and tetanous toxoid were rapidly depressed in placebo treated animals (proliferation assays, DTH and booster immunizations). These responses were preserved in HAART treated macaques. MIP-1?/ß and RANTES chemokine concentrations were significantly reduced in macaques which received HAART when compared to placebo controls. One year pi, HAART treated macaques maintained high CD4+ T-cell numbers whereas controls shown marked CD4+ T-cell depletion. Conclusions: Starting HAART within few hours after IV exposure, as recommended for treatment of accidental exposure to HIV, did not prevent from infection. Nevertheless, early HAART maintained during primary infection, improves the installation of the antiviral immune response, preserves the response to recall antigens and from the dramatic CD4+ T-cell depletion, even in the long term. New experiments are ongoing in order to evaluate the consequence of early treatment on CD8+ mediated antiviral response.
The 1st. IAS Conference on HIV Pathogenesis and Treatment
Abstract no.
89
Suggested Citation
"LEGRANDR, et al.
CONSEQUENCES ON IMMUNE FUNCTIONS OF EARLY POST-EXPOSURE PROPHYLAXIS WITH HAART IN THE MODEL OF SHIV INFECTED MACAQUES..
Oral Presentation:
The 1st. IAS Conference on HIV Pathogenesis and Treatment
:
Abstract no.
89"
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