HIV-1 Progression Definitions Figure 1. Distribution of protective and risk alleles and genetic score across clinical definitions of disease progression. Panel A. Participants fulfilled criteria for the definition of long term non-progressor elite controllers (LTNP-EC), LTNP viremic controllers (LTNP-VC), LTNP viremic non controllers (LTNP-NC), chronic progressors (P), and rapid progressors (RP). Analysis included genotyping for HLA-C-35 (rs9264942) (HLA- C), CCR5 D32 (rs333) and CCR2 V64I (rs1799864) and other polymorphisms in the CCR5 promoter region (rs2856758, rs2734648, rs1799987, rs1799988, rs1800023, rs1800024) that define protective (CCR5_H+) or risk haplotypes (CCR5_HHE or CCR5_P1), ZNRD1 rs9261174, and alleles in the HLA-A and HLA-B loci, including protective (HLA2A+, HLA2B+) and risk (HLA2A2, HLA2B2) alleles. For CCR5 haplotypes, the proportion of individuals carrying protective or risk genotypes are reported. The allelic frequency is represented for other genetic markers. For clarity, protective factors are represented on the positive Y-axis and risk factors on the negative Y-axis. The specific alleles and haplotypes considered are indicated in the text and Table S1. Panel B. Correlation between viral load and a simple additive genetic score that includes the most valuable genetic markers as explained in Materials and Methods section: The distribution of the various clinical definition groups in color coded (LTNP-EC, blue; LTNP-VC, dark green; LTNP-NC, light green; P, orange; RP, red). doi:10.1371/journal.pone.0011079.g001 the present study had viruses with sequence features associated with the presence of the more pathogenic X4 variant [7]. The study assessed also the host genetic determinants that associate with complete control of viral replication, as defined by the identification of ancestral viral populations –viruses that did not or minimally evolve from the founder ancestral sequence. Individuals carrying ancestral viruses have an enrichment of host protective viruses compared with those carrying modern viral. Viral dating methodology is a rapid approach to measure, within a given individual and in a single sample, viral evolution. This methodology has limitations [25] but it has shown it usefulness for the classification of LTNP [11,12]. Although there is a global control of viral replication which maintains the characteristic ancestral genotype, several reports have provided evidence of residual viral replication in elite controllers [21,22,26]. The contribution of this residual viremia to viral PLoS ONE | www.plosone.org 4 June 2010 | Volume 5 | Issue 6 | e11079