Host and Viral Genetic Correlates of Clinical Definitions of HIV-1 Disease Progression

Abstract

BackgroundVarious 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).Methodology and Principal FindingsWe 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.ConclusionsA 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.

Phenotypic characterisation of Human Immunodeficiency Virus type 1 Envelope entry efficiency of transmitted/founder variants circulating in Mbeya, Tanzania

“…Overall, our results support the findings of Lassen et al, (2009) and Casado et al, (2013) who found that entry efficiency of viruses from seven ES and three LTNP, respectively were lower than those from chronic progressors, suggesting that viruses with poor entry could lead to viral control. In support, one of our PSV clones, 398, a LTNP with longitudinal viral loads below 2000 copies/ml (Casado et al, 2010) had the lowest entry efficiency. More importantly, we show that the effect of Env entry efficiency on disease progression is not restricted to ES and LTNP.…”

“…cavd.org). Analysis of longitudinal viral loads indicated that eight of the participants were progressors, and one was an LTNP based on classification by Casado et al, (2010). 2.2 PCR amplification and cloning of the env gene.…”

Comparative transcriptomics of extreme phenotypes of human HIV-1 infection and SIV infection in sooty mangabey and rhesus macaque

“…Transcriptome analysis also included 9 elite/viremic controllers (ECs) and 5 chronic progressors, as previously defined (5). Patient characteristics are detailed in Supplemental Table 1 (supplemental material available online with this article; doi:10.1172/JCI45235DS1).…”

“…The other extreme of the spectrum of disease - rapid progression - has been the subject of much less research. Rapid progressors (RPs) can be defined by a number of criteria - generally including progressive immunosuppression soon after seroconversion and, in many cases, high levels of viremia (4,5). Limited data suggest that the concurrence of viral and host factors contributes to the severity of early disease (6).…”

Unstimulated Primary CD4 + T Cells from HIV-1-Positive Elite Suppressors Are Fully Susceptible to HIV-1 Entry and Productive Infection

“…The dramatic impact of the CCR5 ⌬32 mutation on disease pathogenesis (18,21,29,44) initially suggested that this mutation accounted for the ability of individuals to control infection, but this mutation is present in only a minor fraction of ES (11,25,35,40).…”