Increased prevalence of the alpha-1-antitrypsin (A1AT) deficiency-related S gene in patients infected with human immunodeficiency virus type 1.

Large variation exists in susceptibility to infection with Human Immunodeficiency Virus Type 1 (HIV), and disease progression. These observations demonstrate a role for antiretroviral host factors. Several reports describe α1-antitrypsin (A1AT), the most abundant circulating serine protease inhibitor, as a potent suppressor of HIV infection and replication. We identified the normal (M) and most common deficiency-associated (S and Z) isoforms of the A1AT gene in patients infected with HIV from four multicenter cohorts. The level of disease progression in the patients was characterized and the patients were grouped into as elite controllers (EC), long-term non-progressors (LTNP), or progressors (Prog). No significant difference in the distribution of A1AT alleles was observed in the EC, LTNP, or Prog groups. However, significantly increased prevalence of the A1AT deficiency-associated S allele was observed in HIV-infected patients compared to the prevalence of S A1AT in the general population. These results suggest that deficiency in A1AT may be a risk factor for acquisition of HIV infection, but physiological A1AT concentrations do not affect disease progression after infection occurs.

A1AT polymorphisms may be associated with clinical characteristics of retrovirus infections in a mixed ethnic population from the Brazilian Amazon region.

OBJECTIVES: This study investigated the association of alpha-1-antrypsin deficiency (A1AT; S and Z polymorphisms) with HIV-1 and HTLV-1 infection. METHODS: Blood samples from 201 HIV-1-infected and 115 HTLV-1-infected individuals were examined and compared with those from 300 healthy controls. Genotyping of A1AT (S and Z) and quantification of plasma viral load were performed using RT-PCR, and the CD4+/CD8+ T-cell count was determined by flow cytometry. RESULTS: The wild-type MM genotype showed the highest frequency in each of the three groups investigated. SS and ZZ homozygous genotypes (variants) were observed only among HTLV-1 patients and controls, respectively. Genotype MS was significantly less frequent in HTLV-1-positive persons than in controls. Statistically significant differences were observed when comparing genotype frequencies between symptomatic and asymptomatic HTLV-1-infected persons. The distribution of plasma HIV-1 viral load among individuals with different genotypes of A1AT polymorphism also differed significantly. CONCLUSIONS: The results suggest that A1AT polymorphisms may be associated with human retrovirus infections when dealing with an ethnically mixed population from the Amazon region of Brazil.