Kaslow R, Koup R, Zimmerman P, Dean M, Naik E, Enger C, Carrington M, Goedert J, Saah A, Giorgi J, Phair J, Rinaldo C; Conference on Retroviruses and Opportunistic Infections.
Program Abstr 4th Conf Retrovir Oppor Infect Conf Retrovir Oppor Infect 4th 1997 Wash DC. 1997 Jan 22-26; 4th: 69 (abstract no. 22).
Birmingham, AL.
Introduction: HSP (including class I, class II and TAP alleles) exerts a strong effect on the course of HIV-1 infection. Heterozygosity for a 32-bp deletion (delta32) in the chemokine receptor gene, CCR5, is also reported to influence the course. Although these genes are not linked physically, we searched for biologically additive or synergistic effects on progression of HIV-1 infection in gay men. Methods: In MACS (N=133) and DCG (N=98) seroconverters we analyzed time to AIDS, for 3 HSP categories (less than or equal to -1 = risk, 0=neutral, and greater than or equal to 1=protection) and 2 CKR5delta32 patterns (single delta present or absent). Men were typed serologically for class I and by SSCP or SSO for class II and TAP markers. 3 laboratories amplified the N-terminal portion of CCR5 with different primers to detect the delta32. Results: The relationship of AIDS-free time to presence of the CCR5delta32 was much weaker and less consistent than to the HSP. The frequency of delta32 heterozygotes did not differ according to HSP distribution; there was no concurrence of delta32 with HSP group or with individual HLA markers. CCR5delta32 prevalence in the MACS ranged from 12.5% in men with AIDS in less than 3 yrs to 27.7% in men with no AIDS in 6-12 yrs, p=0.1) while no such trend was seen in the DCG. However, in the MACS, DCG and combined cohorts, the weak protective effect was more consistent in the HSP=0 subgroup, i.e. in the absence of the strong HSP effect. Conclusion: Compared with the composite HLA profile, CCR5delta32 made only small differences in the rate of progression of HIV-1 infection. More extended evaluation of chemokine receptor variants may be needed to discern a more significant contribution to the outcome of HIV-1 infection.
Publication Types:
Keywords:
- Acquired Immunodeficiency Syndrome
- Alleles
- Disease Progression
- HIV Infections
- HLA Antigens
- HSP70 Heat-Shock Proteins
- Heat-Shock Proteins
- Heterozygote
- Homosexuality, Male
- Humans
- Male
- Receptors, CCR5
- Receptors, Chemokine
- genetics
- immunology
Other ID:
UI: 102223305
From Meeting Abstracts