Human immunodeficiency virus type 1 long-term non-progressors: the viral, genetic and immunological basis for disease non-progression

Abstract

A small subset of human immunodeficiency virus type 1 (HIV-1)-infected, therapy-naive individuals--referred to as long-term non-progressors (LTNPs)--maintain a favourable course of infection, often being asymptomatic for many years with high CD4(+) and CD8(+) T-cell counts (>500 cells μl(-1)) and low plasma HIV-RNA levels (<10 ,000 copies ml(-1)). Research in the field has undergone considerable development in recent years and LTNPs offer a piece of the puzzle in understanding the ways that persons can naturally control HIV-1 infection. Their method of control is based on viral, genetic and immunological components. With respect to virological features, genomic sequencing has shown that some LTNPs are infected with attenuated strains of HIV-1 and harbour mutant nef, vpr, vif or rev genes that contain single nuclear polymorphisms, or less frequently, large deletions, in conserved domains. Studies have also shown that some LTNPs have unique genetic advantages, including heterozygosity for the CCR5-Δ32 polymorphism, and have been found with excitatory mutations that upregulate the production of the chemokines that competitively inhibit HIV-1 binding to CCR5 or CXCR4. Lastly, immunological factors are crucial for providing LTNPs with a natural form of control, the most important being robust HIV-specific CD4(+) and CD8(+) T-cell responses that correlate with lower viral loads. Many LTNPs carry the HLA class I B57 allele that enhances presentation of antigenic peptides on the surface of infected CD4(+) cells to cytotoxic CD8(+) T cells. For these reasons, LTNPs serve as an ideal model for HIV-1 vaccine development due to their natural control of HIV-1 infection.