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Host Determinants in HIV Infection and Disease: Part 1: Cellular and Humoral Immune Responses*

Christine M. Hogan, MD; and Scott M. Hammer, MD
[+] Article, Author, and Disclosure Information

From the College of Physicians and Surgeons, Columbia University, New York, New York.

Part 2 of this review will appear in the 15 May 2001 issue.

Acknowledgment: The authors thank Brian-Fred Fitzsimmons, MD, for assistance with preparation of the figures.

Grant Support: Dr. Hammer is supported by grants AI46386 and AI48013 from the National Institute of Allergy and Infectious Diseases. Dr. Hogan is supported in part by Center for AIDS Research grant 5P30AI42848-03 from the National Institute of Health and the National Institute of Allergy and Infectious Diseases, and in part by the SmithKline Beecham Development Partners Junior Faculty Award.

Requests for Single Reprints: Christine M. Hogan, MD, Columbia University, College of Physicians and Surgeons, Division of Infectious Diseases, P & S Box 82, 630 West 168th Street, New York, NY 10032; e-mail, ch358@columbia.edu.

Current Author Addresses: Drs. Hogan and Hammer: Columbia University, College of Physicians and Surgeons, Division of Infectious Diseases, P & S Box 82, 630 West 168th Street, New York, NY 10032.

Ann Intern Med. 2001;134(9_Part_1):761-776. doi:10.7326/0003-4819-134-9_Part_1-200105010-00013
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The course of HIV infection varies widely among individuals. The median time from infection to development of AIDS is 8 to 10 years, but a small proportion of patients, probably no more than 5% to 10%, have been characterized as long-term nonprogressors. These persons have been identified among HIV-infected persons whose risk factors include sexual exposure, intravenous drug use, and transfusions (18). Strictly defined, long-term nonprogressors are those who, in the absence of treatment, remain asymptomatic and have normal CD4 cell counts and low or undetectable viral loads despite prolonged periods of infection with HIV. Of note, a substantial proportion of such patients described in the literature have subsequently demonstrated progressive immunodeficiency. In this review, the term long-term nonprogressors is used to mean true long-term nonprogressors and slow progressors. In contrast, perhaps 10% of all HIV-infected persons are rapid progressors who develop AIDS within 5 years of infection with HIV (6, 9). Identification of these patients has led to comparison of persons with different rates of disease progression in order to elucidate the factors that determine an individual's risk for progression. The interaction of numerous viral and host factors, such as viral virulence, host genetics, host immune response, and cytokine milieu is believed to determine the course of disease.


Grahic Jump Location
Figure 1. At the cellular level, CD8 cytotoxic T cells ( ), with the help of CD4 T-helper cells, lyse HIV-infected cells. Soluble factors and neutralizing antibodies inhibit viral replication. Macrophage-tropic HIV ( ) infects cells bearing CD4 and CCR5 co-receptor. T-tropic HIV ( ) infects cells bearing CD4 and CXCR4 co-receptor. Co-receptors and their ligands (regulated on activation, normal T expressed and secreted [ ]; macrophage inflammatory protein [ ]-1α; MIP-1β; and stromal cell–derived factor [ ]-1) are discussed in part 2 of this review. At the local level, mucosal CTLs and mucosal IgA may inhibit initial viral replication. Concomitant infections activate T cells, providing target cells for HIV to infect. Systemically, such inhibiting factors as CTLs, antibodies, interferon ( ), and interleukin ( )-16 are countered with such stimulating factors as tumor necrosis factor ( ), IL-1, IL-6, and co-infections. Interleukin-10 inhibits IL-6 and TNF-α. Cytokines are discussed in part 2 of this review. The rectangular bars indicate sites of inhibition. STD = sexually transmitted disease.
Schematic overview of host responses at the cellular, local, and systemic levels.+CTLs+R5X4RANTESMIPSDFIFNILTNF
Grahic Jump Location
Grahic Jump Location
Figure 2. An antigen-presenting cell presents an HIV epitope in association with an MHC class II molecule, which interacts with a CD4 T-helper cell whose T-cell receptor ( ) recognizes that particular epitope. The T-helper cell is then activated and stimulates the CD8 CTL. The CTL encounters an HIV epitope presented by an antigen-presenting cell in association with an MHC class I molecule. The activated CTL lyses the HIV-infected cell. IL-2 = interleukin-2.
Interactions among cytotoxic T-cell lymphocytes (CTLs), T-helper cells, and antigen-presenting cells.+TCR+
Grahic Jump Location




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