The estimated impact of the CCR-5 delta32 gene deletion on HIV disease progression varies with study design. Oslo HIV Cohort Study Group.

OBJECTIVES To study the impact of the genotype CCR-5 wild-type +/A32 on the progression rate to AIDS and death, and to discuss sources of bias according to study design. METHODS A prospective study of 310 HIV-positive subjects with follow-up time from study entry (prevalent cohort), and a prospective study of 105 HIV-positive subjects with well-defined time of HIV seroconversion, with follow-up time from the retrospectively assessed date of HIV seroconversion (retrospective incident cohort). RESULTS Slower progression to AIDS among subjects with CCR-5 +/delta32 than those with CCR-5 +/+ genotype was estimated in the prevalent cohort (P=0.07, log-rank test). Slower progression to death from any cause was also estimated for subjects with CCR-5 +/delta32 (P < 0.05, log-rank test). No differences in survival after AIDS diagnosis were seen (P=0.89, log-rank test). No differences in the progression rate to AIDS (P=0.82, log-rank test) or death (P=0.78, log-rank test) were estimated in the retrospective incident cohort. CONCLUSIONS The varying estimates of the impact of CCR-5 genotype on progression to AIDS in this and other studies, may be real and reflect differences in the dependence of HIV on the CCR-5 receptor, or may be due to systematic errors caused by study design. Several methodological difficulties occur when the factor studied, such as CCR-5 genotype, is associated both with the risk of being HIV-infected and the progression of disease.

[1]  P. Garred.  Chemokine-receptor polymorphisms: clarity or confusion for HIV-1 prognosis? , 1998, The Lancet.

[2]  J. Kaldor,et al.  Increased frequency of CCR‐5 Δ32 heterozygotes among long‐term non‐progressors with HIV‐1 infection , 1997 .

[3]  M. Carrington,et al.  CCR5-Δ32 gene deletion in HIV-1 infected patients , 1997, The Lancet.

[4]  H. Sheppard,et al.  CCR5-Δ32 gene deletion in HIV-1 infected patients , 1997, The Lancet.

[5]  R. Doms,et al.  Unwelcomed guests with master keys: how HIV uses chemokine receptors for cellular entry. , 1997, Virology.

[6]  A. Iversen,et al.  Dual effect of CCR5 Δ32 gene deletion in HIV-1-infected patients , 1997, The Lancet.

[7]  A. Iversen,et al.  Heterozygosity for a deletion in the CKR‐5 gene leads to prolonged AIDS‐free survival and slower CD4 T‐cell decline in a cohort of HIV‐seropositive individuals , 1997, AIDS.

[8]  J. Mascola,et al.  The role of viral phenotype and CCR-5 gene defects in HIV-1 transmission and disease progression , 1997, Nature Medicine.

[9]  P. Magnus,et al.  The impact of exposure group on the progression rate to acquired immunodeficiency syndrome. A comparison between intravenous drug users, homosexual men and heterosexually infected subjects. , 1997, Scandinavian journal of infectious diseases.

[10]  Steven M. Wolinsky,et al.  The role of a mutant CCR5 allele in HIV–1 transmission and disease progression , 1996, Nature Medicine.

[11]  Virginia Litwin,et al.  HIV-1 entry into CD4+ cells is mediated by the chemokine receptor CC-CKR-5 , 1996, Nature.

[12]  Stephen C. Peiper,et al.  Identification of a major co-receptor for primary isolates of HIV-1 , 1996, Nature.

[13]  M. T. Paixão,et al.  Expanded European AIDS case definition , 1993, The Lancet.

[14]  A Muñoz,et al.  Incubation period of human immunodeficiency virus. , 1993, Epidemiologic reviews.

[15]  R. Brookmeyer,et al.  The prevalent cohort study and the acquired immunodeficiency syndrome. , 1987, American journal of epidemiology.