AEGiS-13IAC: Early HAART in macaques infected by pathogenic lentivirus characterization of virologic parameters.

13th International AIDS Conference

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

Early HAART in macaques infected by pathogenic lentivirus characterization of virologic parameters.

Int Conf AIDS 2000 Jul 9-14; 13:(abstract no. MoOrA105)

Bossuet C, Neildez O, Vaslin B, Feuillat C, Roques P, Sellier P, Dormont D, Le Grand R
C. Bossuet, Cea Service De Neurovirologie DSV/DRM/SNV, 6068 Avenue De La Division Leclerc, Fontenay Aux Roses 92265 BP6, France, Tel.: +33 1 041 654 9469, Fax: +33 1 014 651 7726, E-mail: bossuet@dsvidf.cea.fr

OBJECTIVES: In order to evaluate the efficacy of highly active antiretroviral therapy (HAART) after accidental exposure to HIV, we characterized DNA cellular viral loads and viral mRNA expression in peripheral blood mononulcear cells (PBMC) and lymph nodes mononuclear cells (LNMC) during the primary infection of macaques with a pathogenic simian/human immunodeficiency virus (SHIV) chimera. Materials and

METHODS: Three groups of four macaques were infected intravenously with a low dose (50 MID50 ) of pathogenic SIVmac 239 chimera (SHIV 89.6 P) expressing the env gene of HIV-1 89.6 primary isolate. Animals were treated twice a day at 8 h intervals and by the oral route with placebo or the combination of AZT (4.5 mg/kg), 3 TC (2.5 mg/kg) and indinavir (20 mg/kg). Treatment was initiated at 4 h or 72 h p.i. and continued until day 28 p.i. Follow-up included hematological, virological and immunological parameters. Viral DNA copy number was estimated in PBMC and LNMC, using a quantitative PCR assay. Expression of viral mRNA coding structural proteins was evaluated in PBMC and LNMC using a quantitative RT-PCR assay amplifying the gag gene.

RESULTS: Treatment with AZT/3TC/IDV did not protect from SHIV 89.6 P intraveinous infection. However, HAART significantly reduced and delayed plasma and cellular (PBMC and LNMC) viral load during primary infection. In placebo treated animals, number of viral DNA copies was higher in PBMC than LNMC. By contrast, during HAART treatment, higher viral load was detected in LNMC than in PBMC. Expression of gag viral mRNA was evaluated at day 8 and 15 p.i. In PBMC and LNMC, a significant lower mRNA expression was observed in HAART treated animals than in placebo treated animals

CONCLUSION: Althougth early initiation of HAART does not protect from IV infection, the significantly limited cellular viral load and viral mRNA expression in blood and lymphoid tissues may be of good prognosis for long lasting evolution of infection and disease.

Keywords: AEGIS, Antiretroviral Therapy, Highly Active, Viral Load, Macaca, HIV-1, HIV Infections, Zidovudine, DNA, Viral, Lamivudine, Lymph Nodes, Macaca fascicularis, Animal, Human, virology, pathogenicity
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MoOrA105