Host and viral genetic correlates of clinical definitions of HIV-1 disease progression.
BACKGROUND
Various patterns of HIV-1 disease progression are described in clinical practice and in research. There is a need to assess the specificity of commonly used definitions of long term non-progressor (LTNP) elite controllers (LTNP-EC), viremic controllers (LTNP-VC), and viremic non controllers (LTNP-NC), as well as of chronic progressors (P) and rapid progressors (RP).


RESULTS
We re-evaluated the HIV-1 clinical definitions, summarized in Table 1, using the information provided by a selected number of host genetic markers and viral factors. There is a continuous decrease of protective factors and an accumulation of risk factors from LTNP-EC to RP. Statistical differences in frequency of protective HLA-B alleles (p-0.01), HLA-C rs9264942 (p-0.06), and protective CCR5/CCR2 haplotypes (p-0.02) across groups, and the presence of viruses with an ancestral genotype in the "viral dating" (i.e., nucleotide sequences with low viral divergence from the most recent common ancestor) support the differences among principal clinical groups of HIV-1 infected individuals.


CONCLUSIONS
A combination of host genetic and viral factors supports current clinical definitions that discriminate among patterns of HIV-1 progression. The study also emphasizes the need to apply a standardized and accepted set of clinical definitions for the purpose of disease stratification and research.
Casado
Concepción
C
Centro Nacional de Microbiología, Instituto de Salud Carlos III, Madrid, Spain.
Colombo
Sara
S
Rauch
Andri
A
Martínez
Raquel
R
Günthard
Huldrych F
HF
Garcia
Soledad
S
Rodríguez
Carmen
C
Del Romero
Jorge
J
Telenti
Amalio
A
López-Galíndez
Cecilio
C
D018450:Disease Progression; D015752:Genes, env; D015658:HIV Infections / Q000473:pathology* / Q000821:virology; D020276:HIV Long-Term Survivors; D015497:HIV-1 / Q000235:genetics*; D015235:HLA-B Antigens / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D010802:Phylogeny; D016133:Polymerase Chain Reaction; D054390:Receptors, CCR2 / Q000235:genetics; D019713:Receptors, CCR5 / Q000235:genetics; D012307:Risk Factors; D019562:Viral Load
C515334:CCR2 protein, human; D015235:HLA-B Antigens; D054390:Receptors, CCR2; D019713:Receptors, CCR5