Host Determinants in HIV Infection and Disease: Part 2: Genetic Factors and Implications for Antiretroviral Therapeutics*

15 May 2001 | Volume 134 Issue 10 | Pages 978-996

The course of HIV infection varies widely among individuals. Immunologic and genetic studies of long-term nonprogressors and exposed yet uninfected persons have helped to elucidate the mechanisms by which some persons are protected from HIV acquisition or have slow rates of disease progression. This two-part review describes what is currently known about host factors in HIV-1 infection. Studies for inclusion were identified by a systematic search of PubMed for English-language literature published from 1988 through June 2000. Abstracts of presentations at major meetings convened in 2000 were also included if appropriate. The first part of the review discussed cellular and humoral immunity to HIV infection. This second part describes genetic host factors—namely, inheritance of mutant chemokine receptors or ligands, such as CCR5-32, CCR2-V64I, stromal cell–derived factor-1 3', and CCR5 promoter polymorphisms, as well as HLA type—that affect susceptibility to infection and subsequent clinical course. Soluble inhibitory factors, the cytokine milieu, and concomitant infections also affect outcome. Knowledge of host responses is increasingly being applied to new therapeutic strategies, including early treatment, immune modulation, structured treatment interruptions, therapeutic vaccination, and new chemotherapeutic agents, as well as to vaccine development.

Author and Article Information

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

Part 1 of this review was published in the 1 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, Division of Infectious Diseases, Columbia University, College of Physicians and Surgeons, P & S Box 82, 630 West 168th Street, New York, NY 10032; e-mail, ch358{at}columbia.edu.

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