Abstract
Over the past four decades, research on the natural history of HIV infection has described how HIV wreaks havoc on human immunity and causes AIDS. HIV host genomic research, which aims to understand how human genetic variation affects our response to HIV infection, has progressed from early candidate gene studies to recent multi-omic efforts, benefiting from spectacular advances in sequencing technology and data science. In addition to invading cells and co-opting the host machinery for replication, HIV also stably integrates into our own genome. The study of the complex interactions between the human and retroviral genomes has improved our understanding of pathogenic mechanisms and suggested novel preventive and therapeutic approaches against HIV infection.
Highlights
Abstract | Over the past four decades, research on the natural history of HIV infection has described how HIV wreaks havoc on human immunity and causes AIDS
These findings were soon validated and expanded by other genome-wide association studies (GWAS) performed in independent cohorts, which demonstrated that the genetic architecture of HIV Set point viral load (spVL) is comparable between the general popu lation of PLWH16,28–30 and a particular group of individuals able to maintain low viral loads for prolonged periods of time in the absence of antiretroviral therapy (ART), the so-called HIV controllers[17,31]
With the accepted knowledge that people living with HIV (PLWH) who do not have detectable plasma viral loads cannot transmit the virus to others[90], the Joint United Nations Programme on HIV/AIDS (UNAIDS) set an ambitious 90–90–90 target[91], where 90% of infected people know their status, 90% of those are on antiviral therapy and 90% of those are suppressing the virus below the level of detection
Summary
The spectrum of interrogated variants was limited by early DNA genotyping arrays, yet genome-wide significant associations were identified in the HLA class I region, the most polymorphic locus in the human genome, known to have a crucial role in the modulation of T cell immunity (see ‘HLA variation in HIV control’, below) These findings were soon validated and expanded by other GWAS performed in independent cohorts, which demonstrated that the genetic architecture of HIV spVL is comparable between the general popu lation of PLWH16,28–30 and a particular group of individuals able to maintain low viral loads for prolonged periods of time in the absence of ART, the so-called HIV controllers[17,31]. The identification of additional genetic determinants of individual susceptibility to HIV infection will require increased sample sizes (ideally in the thousands) as well as the use of sequencing approaches to characterize the rare functional variants that are not interrogated in studies based on genotyping arrays
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