Ling B, Veazey RS, Martin LN, Luckay A, Marx PA; Conference on Retroviruses and Opportunistic Infections.

Program Abstr 8th Conf Retrovir Oppor Infect Conf Retrovir Oppor Infect 8th 2001 Chic Ill. 2001 Feb 4-8; 8: 70 (abstract no. 92).

Aaron Diamond AIDS Res Ctr, Rockefeller Univ, New York, NY.

Background: The predominant human immunodeficiency virus (HIV) models are simian immunodeficiency virus (SIV) and simian-human hybrid viruses in rhesus macaques of Indian origin (Ind Rh). The model has significant limitations; Ind Rh are in short supply, develop AIDS more rapidly than humans and have viral plasma loads 1000 fold higher. A model that closely mimics HIV virus loads and time to disease will have more predictive value for HIV/AIDS. Anecdotal evidence suggested that SIV-infected rhesus macaques of Chinese origin (Ch Rh sub-species) progress to AIDS more slowly than infected Ind Rh. We tested the hypothesis that a more slowly progressing model would have lower virus loads, slower CD4 cell decline and fewer rapid progressors. These features more closely model HIV pathogenesis in humans. Methods: SIV pathogenesis was measured by bDNA, flow cytometry for intestinal/peripheral lymphocyte phenotypes and SIV antibody. Results: 10 Ch Rh and 4 Ind Rh were infected with SIVmac239 clone. Peak virus loads at 14 days post-infection (PI) were 10 fold lower in Ch Rh compared to 4 In Rh controls. The set point at 60 days PI was lower in Ch Rh and was completely within the range of set points found in untreated HIV+ humans. A retrospective analysis of 18 In Rh confirmed differences in viral load. CD4/CD8 ratios were higher in Ch Rh. All Ch Rh were chronically infected at 8 months PI, with no rapid progressors. A detailed analysis of intestinal and peripheral lymphocyte phenotypes revealed no differences except that baseline levels of CD4+ naive cells (CD4+ CD45+ CD62L+) were higher in Ch Rh. A trend of higher SIV antibody titers was found in infected Ch Rh. Conclusion: The new model offers significant advantages because it more closely mimics early HIV pathogenesis. Long term clinical follow-up is in progress.

Publication Types:

• Meeting Abstracts

Keywords:

• AIDS Vaccines
• Acquired Immunodeficiency Syndrome
• Animals
• Antigens, CD45
• CD4-Positive T-Lymphocytes
• HIV
• HIV Antibodies
• HIV Infections
• HIV Seropositivity
• Humans
• Macaca mulatta
• Models, Biological
• Simian Acquired Immunodeficiency Syndrome
• Simian immunodeficiency virus
• Viral Load
• immunology

Other ID:

• GWAIDS0006376

UI: 102243872

From Meeting Abstracts