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 alpha 1-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. J. Med. Virol. 86:23-29, 2014. (c) 2013 Wiley Periodicals, Inc.