Overview of HIV Infection and Disease

For more information about HIV/AIDS and its prevention and treatment, visit the CDC web site devoted to the subject.

Course of Infection

Exposure to human immunodeficiency virus (HIV) does not have a single common outcome in all individuals. Even in the absence of antiviral drug treatment, several classes of clinical progression have been defined. Rapid progressors are individuals who develop the symptoms of AIDS, or end-stage HIV disease, within 2-3 years after infection. (Phair et al., 1992; reviewed in Haynes et al., 1996) About 10% of individuals who become HIV-positive fit this profile. A second group, denoted typical progressors, consists of individuals who develop end-stage disease within approximately 10 years after seroconversion. The third broad category of HIV-positive individuals consists of those who have normal CD4+ T cell counts after more than a decade of HIV seropositivity without drug treatment. (Buchbinder et al., 1994; Sheppard et al., 1993; Learmont et al., 1992) Approximately 10% of HIV-positive individuals appear to fit this profile. Such individuals also tend to have low or undetectable levels of HIV in their blood (Pantaleo et al., 1995). A fourth category is composed of individuals who are multiply-exposed but HIV-negative.

Courses of HIV Disease Progression
linked from Report of the NIH Panel to Define Principles of Therapy of HIV Infection.
April 24, 1998 / 47(RR-5);1-41.

Much research has been devoted to each of these groups, as each has a potential "lesson" for the understanding and treatment of HIV. The ability to predict rapid progression to end-stage disease would be greatly helpful in designing appropriate therapeutic strategies. In addition, identification of controllable factors that may cause rapid progression would open a window for intervention to prevent such an event. Typical progressors are of course of great interest because they represent the majority of the HIV-infected population, so an understanding of events in their disease progression is applicable to the largest number of people.

Non-progressors and Multiply-Exposed but HIV-negative Individuals

Non-progressors and multiply-exposed but HIV-negative individuals have been the subject of special interest, as researchers would like to know why these people do not develop HIV disease and if it is possible to engineer similar protection for others. Some, but not all, multiply-exposed HIV-negative individuals are homozygous for a mutation in the HIV co-receptor CCR5, a molecule that is required for HIV entry into macrophages (Samson et al., 1996; Liu et al., 1996; Dean et al., 1996; Huang et al., 1996). In addition, a recent study of multiply-exposed seronegative individuals found that 41% of those tested had cytotoxic T lymphocyte (CTL) activity against HIV antigens, while none of the low-risk and likely unexposed control subjects did (Bernard et al., 1999). This correlation suggests that a protective CTL response may be another means by which individuals resist infection by HIV. It is worth noting that a protective antibody response would constitute another potential mechanism by which HIV infection could be prevented, but individuals possessing such a response would by generally seroconvert and thus manifest themselves as non-progressors rather than multiply-exposed but HIV-negative. One exception to this has been observed in some multiply-exposed HIV-negative individuals who have strong mucosal IgA responses that are specific for HIV antigens (Mazzoli et al., 1996; Beyrer et al., 1999).



Bernard NF, Yannakis CM, Lee JS, Tsoukas CM. Human Immunodeficiency Virus (HIV)-Specific Cytotoxic T Lymphocyte Activity in HIV-Exposed Seronegative Persons. JID 1999; 179:538-47.

Beyrer C, Artenstein AW, Rugpao S, Stephens H, VanCott TC, Robb ML, Rinkaew M, Birx DL, Kamboonruang C, Zimmerman PA, Nelson KE, Natpratan C. Epidemiologic and Biologic Characterization of a Cohort of Human Immunodeficiency Virus Type 1 Highly Exposed, Persistently Seronegative Female Sex Workers in Thailand. JID 1999; 179: 59-67.

Buchbinder SP, Katz MH, Hessol NA, O'Malley PM, Holmberg SD. Long-term HIV-1 infection without immunologic progression. AIDS 1994 Aug;8(8):1123-8.

Dean M, Carrington M, Winkler C, Huttley GA, Smith MW, Allikmets R, Goedert JJ, Buchbinder SP, Vittinghoff E, Gomperts E, Donfield S, Vlahov D, Kaslow R, Saah A, Rinaldo C, Detels R, O'Brien SJ. Genetic restriction of HIV-1 infection and progression to AIDS by a deletion allele of the CKR5 structural gene. Hemophilia Growth and Development Study, Multicenter AIDS Cohort Study, Multicenter Hemophilia Cohort Study, San Francisco City Cohort, ALIVE Study. Science 1996 Sep 27;273(5283):1856-62.

Haynes BF, Pantaleo G, Fauci AS. Towards an Understanding of the Correlates of Protective Immunity to HIV Infection. Science 1996; 271(5247):324-8.

Huang Y, Paxton WA, Wolinsky SM, Neumann AU, Zhang L, He T, Kang S, Ceradini D, Jin Z, Yazdanbakhsh K, Kunstman K, Erickson D, Dragon E, Landau NR, Phair J, Ho DD, Koup RA. The role of a mutant CCR5 allele in HIV-1 transmission and disease progression. Nat Med 1996 Nov;2(11):1240-3.

Learmont J, Tindall B, Evans L, Cunningham A, Cunningham P, Wells J, Penny R, Kaldor J, Cooper DA. Long-term symptomless HIV-1 infection in recipients of blood products from a single donor. Lancet 1992 Oct 10;340(8824):863-7.

Liu R, Paxton WA, Choe S, Ceradini D, Martin SR, Horuk R, MacDonald ME, Stuhlmann H, Koup RA, Landau NR. Homozygous defect in HIV-1 coreceptor accounts for resistance of some multiply-exposed individuals to HIV-1 infection. Cell 1996 Aug 9;86(3):367-77.

Mazzoli S, Trabattoni D, Lo Caputo S, Piconi S, Ble C, Meacci F, Ruzzante S, Salvi A, Semplici F, Longhi R, Fusi ML, Tofani N, Biasin M, Villa ML, Mazzotta F, Clerici M. HIV-specific mucosal and cellular immunity in HIV-seronegative partners of HIV-seropositive individuals. Nat Med 1997 Nov;3(11):1250-7.

Pantaleo G, Menzo S, Vaccarezza M, Graziosi C, Cohen OJ, Demarest JF, Montefiori D, Orenstein JM, Fox C, Schrager LK, et al. Studies in subjects with long-term nonprogressive human immunodeficiency virus infection. N Engl J Med 1995 Jan 26;332(4):209-16.

Phair J, Jacobson L, Detels R, Rinaldo C, Saah A, Schrager L, Munoz A. Acquired immune deficiency syndrome occurring within 5 years of infection with human immunodeficiency virus type-1: the Multicenter AIDS Cohort Study. J Acquir Immune Defic Syndr 1992;5(5):490-6.

Samson M, Libert F, Doranz BJ, Rucker J, Liesnard C, Farber CM, Saragosti S, Lapoumeroulie C, Cognaux J, Forceille C, Muyldermans G, Verhofstede C, Burtonboy G, Georges M, Imai T, Rana S, Yi Y, Smyth RJ, Collman RG, Doms RW, Vassart G, Parmentier M. Resistance to HIV-1 infection in caucasian individuals bearing mutant alleles of the CCR-5 chemokine receptor gene. Nature 1996 Aug 22;382(6593):722-5.

Sheppard HW, Lang W, Ascher MS, Vittinghoff E, Winkelstein W. The characterization of non-progressors: long-term HIV-1 infection with stable CD4+ T-cell levels. AIDS 1993 Sep;7(9):1159-66.


Unless otherwise noted, all contents are Copyright © 1999 by Peter Kasson.