Association of HLA types A1-B8-DR3 and B27 with rapid and slow progression of HIV disease

Abstract

SummaryWe examined how HLA types A1-B8-DR3 and B27 were related to progression of clinical disease and rate of loss of CD4 lymphocytes in the Edinburgh City Hospital cohort of HIV-positive patients, mainly injection drug users. Patients (n = 692) were prospectively followed from 1985 through March 1994. Accurately estimated seroconversion times were determined retrospectively for a subgroup of 313 (45%). Of 262 patients (39%) who were fully or partially HLA typed, 155 (50%) had known seroconversions. Of 34 patients typed positive for A1-B8-DR3, 29 progressed to CDC stage IV, 22 to AIDS and 20 died. Twelve patients were typed positive for B27; six of these progressed to CDC stage IV, one to AIDS and none died. In a proportional hazards analysis of the 313 patients with known seroconversions, A1-B8-DR3 was significantly associated with covariate-adjusted relative risks of 3.7 (95% Cl 1.9-7.2), 3.1 (1.6-6.0) and 1.9 (1.1-3.2) for progression from seroconversion to death, AIDS and CDC stage IV, respectively. Events for B27 were too rare to include B27 in analyses to death and AIDS, but B27 was significantly associated with slower progression to CDC stage IV (0.3, Cl 0.1 -0.9). Random effects growth curve models were used to estimate individual rates of loss of square root CD4 count and loss of CD4 percentage, for 603 and 617 patients, respectively. A1-B8-DR3 was associated with rapid loss of both markers ( p = 0 . 0 2 and p = 0.01, respectively); B27 was associated with slow loss of both markers ( p = 0 . 0 4 and p< 0.005).

Mhc class I haplotypes associated with survival time in simian immunodeficiency virus (SIV)-infected rhesus macaques

“…Several studies have shown (1) a temporal relationship between the decline of viral load and the emergence of CTL responses in both infected humans and infected monkeys, [3][4][5][6] (2) an increase of viral load after the appearance of CTL-escape HIV/SIV mutants during chronic and acute infection [7][8][9][10][11][12][13] and (3) a dramatic rise of viral load after CD8 þ T-cell depletion. [14][15][16] Additional indirect evidence for a CTL effect upon viral replication came from genetic association studies showing that Mhc class I alleles are strongly associated with survival time in HIV-infected humans [17][18][19][20] .…”

Early participation in an HIV cohort study slows disease progression and improves survival

“…Pronounced differences in rates of progression to the acquired immunodeficiency syndrome (AIDS) and in survival exist amongst patients infected with the human immunodeficiency virus (HIV) [1][2][3][4]. A considerable proportion of the variation in progression rates will be due to factors which cannot be modified by medical interventions, e.g.…”

Differential CD4+versus CD8+T-Cell Responses Elicited by Different Poxvirus-Based Human Immunodeficiency Virus Type 1 Vaccine Candidates Provide Comparable Efficacies in Primates

“…Recent approaches have focused on vaccines capable of inducing potent CD8 ϩ T-cell responses to control the virus load, to reduce transmission, and to slow disease development (26,53). Evidence from both humans and nonhuman primates for the role of T-cell responses in the control of HIV includes the correlation between HIV-specific CD8 ϩ T cells and the control of plasma viremia (51,52,99); the association of certain restricting major histocompatibility complex (MHC) class I alleles, conserved T-cell epitopes, and slow disease progression (14,27,28,48,55,59,61,64,70,72,90,100); and the rapid increase in viral load after experimental CD8 ϩ lymphocyte depletion in simian immunodeficiency virus (SIV)-or simian-human immunodeficiency virus (SHIV)-infected rhesus macaques (2,54,86), providing a strong rationale for the development of T-cell-based vaccines. Recently the quality of the HIV-specific CD8 ϩ T cells associated with the control of HIV-1 virus loads in human long-term nonprogessors has been described, revealing characteristics of a polyfunctional profile simultaneously capable of degranulation and of producing gamma interferon (IFN-␥), interleukin-2 (IL-2), tumor necrosis factor alpha (TNF-␣), and macrophage inflammatory protein 1-␤ (9).…”