AEGiS-11IAC: Temporal relationship of changes in HIV load, HIV diversity, and cellular immunity to inflection points of CD4+ and CD3+ T cells in HIV-infected homosexual men.

11th International AIDS Conference

Vancouver, British Columbia — July 7-12, 1996

Temporal relationship of changes in HIV load, HIV diversity, and cellular immunity to inflection points of CD4+ and CD3+ T cells in HIV-infected homosexual men.

Int Conf AIDS 1996 Jul 7-12; 11:15 (abstract no. We.A.404)
Margolick JB, Rinaldo CR, Gupta P, Farzadegan H, Mullins JI; Dept. Molecular Microbiology and Immunology, Johns Hopkins School of Public Health, Baltimore, MD, USA. Fax: (410) 955-0105. E-mail: joe@statepi.shp.jhu.edu.

OBJECTIVE: To determine when changes in HIV (load and quasispecies diversity) and host immune system (T cell subsets, HIV-specific cytotoxic T lymphocyte (CTL) level) occur in relation to abrupt increases in the rate of decline of CD3+ (T) lymphocytes and CD4+ lymphocytes, termed inflection points (IP), in HIV-infected homosexual men.

METHODS: Cryopreserved peripheral blood mononuclear cells and plasma obtained at 6-month intervals from seroconversion to IP and/or AIDS were studied from MACS participants with IP of CD3+ and/or CD4+ T cells, or with no T cell decline. HIV RNA (in cells and plasma) and DNA (in cells) were measured by internally-controlled PCR; HIV diversity by heteroduplex mobility and tracking analyses; CTL-memory cells by stimulation with HIV antigen-expressing autologous B cells and lysis of HIVIIIB-infected autologous targets; and T cell subsets by 3-color flow cytometry.

RESULTS: HIV RNA in plasma and cells increased from low to high levels at or within 1 year of the IP. Memory CTL were detected in all subjects. The most common pattern of anti-gag, -pol, and -env CTL responses was decline at the IP, but decline 2 years before the IP was also seen. HIV diversity of subjects with IPs did not show a consistent pattern, but the subjects with the sharpest IPs demonstrated increasing diversity between seroconversion and the IP, followed by emergence of new variants within 1 year after the IP. There were no consistent changes in expression of CD45 isoforms, CD28, or the activation markers HLA-DR and CD38 by CD4+ or CD8+ T cells in relation to the IP.

CONCLUSIONS: These data suggest that increases in viral load, decreases in viral diversity, and loss of CTL memory cells are correlated in time with abrupt decreases in both CD3+ and CD4+ lymphocytes. Ongoing studies to define the relation of these changes to viral parameters and anti-HIV immune responses may help define mechanisms that are important in controlling HIV infection.

Keywords: AEGIS, Antigens, CD3, Antigens, CD4, HIV, CD4-Positive T-Lymphocytes, Antigens, CD8, Immunity, Cellular, HIV Infections, Viral Load, T-Lymphocytes, Cytotoxic, T-Lymphocyte Subsets, HIV Antigens, Antigens, Differentiation, Acquired Immunodeficiency Syndrome, Lymphocyte Activation, HLA-DR Antigens, NAD+ Nucleosidase, T10 antigen, Human, Male, immunology, ICA11

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