title: Early protective effect of CCR-5 delta 32 heterozygosity on HIV-1 disease progression: relationship with viral load. The SEROCO Study Group.
abstract: OBJECTIVE
  To determine the influence of heterozygosity for the delta 32 mutant CCR-5 allele on HIV-1 disease progression.
  
  
  METHODS
  HIV-1 disease progression and serum viral load were analysed according to the C-C chemokine receptor (CCR)-5 genotype in 412 Caucasian patients (319 men and 93 women) with a known date of seroconversion, who were enrolled in the SEROCO cohort (median follow-up, 74 months).
  
  
  RESULTS
  The frequency of heterozygosity for the mutant allele was 17% and did not differ according to sex or risk factor of HIV infection. Heterozygotes were significantly less likely than patients with two functional alleles to have symptomatic primary infection. Their serum viral load was lower during the 6- to 24-month plateau phase after seroconversion. This difference persisted afterwards, although the rate of decline in CD4+ cells was similar. Kaplan-Meier survival curves showed slower progression to clinical AIDS in heterozygotes during the first 7 years following infection (P < 0.02), the two curves tending to join thereafter (overall log-rank test, P = 0.17). However, the interaction term with time did not reach significance in a Cox model. The overall relative risk of progression was 0.67 (95% confidence interval, 0.38-1.18) and was not influenced by adjustment for age at seroconversion or symptomatic primary infection. After adjustment for early viral load the relative risk was 0.83. Pneumocystis carinii pneumonia and toxoplasmosis were less likely to be the first AIDS-defining illness in heterozygotes than in the other patients (0 versus 24.7% of AIDS cases, P = 0.04), despite similar management.
  
  
  CONCLUSIONS
  Deletion of one CCR-5 gene allele appears to protect against HIV-1 disease progression, mainly during the early years of the infection. Heterozygosity for the deletion leads to persistently lower viral load, and also seems to protect against some opportunistic infections.
authors.forename: L
authors.initials: L
authors.lastname: Meyer
authors.forename: M
authors.initials: M
authors.lastname: Magierowska
authors.forename: J B
authors.initials: JB
authors.lastname: Hubert
authors.forename: C
authors.initials: C
authors.lastname: Rouzioux
authors.forename: C
authors.initials: C
authors.lastname: Deveau
authors.forename: F
authors.initials: F
authors.lastname: Sanson
authors.forename: P
authors.initials: P
authors.lastname: Debre
authors.forename: J F
authors.initials: JF
authors.lastname: Delfraissy
authors.forename: I
authors.initials: I
authors.lastname: Theodorou
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000235:genetics; D000163:Acquired Immunodeficiency Syndrome / Q000175:diagnosis; D000483:Alleles; D018791:CD4 Lymphocyte Count; D018450:Disease Progression; D005260:Female; D015658:HIV Infections / Q000453:epidemiology / Q000235:genetics*; D015497:HIV-1; D006801:Humans; D008297:Male; D011020:Pneumonia, Pneumocystis / Q000175:diagnosis; D012367:RNA, Viral / Q000032:analysis; D019713:Receptors, CCR5; D018121:Receptors, Cytokine / Q000235:genetics*; D015728:Receptors, HIV / Q000235:genetics*; D012307:Risk Factors; D012737:Sex Factors; D014123:Toxoplasmosis / Q000175:diagnosis; D019562:Viral Load
chemical_list: D012367:RNA, Viral; D019713:Receptors, CCR5; D018121:Receptors, Cytokine; D015728:Receptors, HIV