Human genetics of HIV infection

Area of Science:

• Genetics and Immunology
• Virology
• Public Health

Background:

• Human Immunodeficiency Virus Type 1 (HIV-1) remains a global health concern with significant variability in infection susceptibility, viral load, and disease progression.
• Host genetic factors play a crucial role in controlling HIV-1, with known associations at CCR5 and HLA class I loci.

Purpose of the Study:

• To review the current understanding of host genetic factors influencing HIV-1 control and progression.
• To highlight emerging research on somatic genetic variation, aging, and their impact on individuals living with HIV-1.
• To discuss the implications of genetic research for precision HIV-1 medicine and future therapeutic strategies.

Main Methods:

• Review of existing literature on host genetic factors and HIV-1.
• Analysis of recent studies on germline and somatic genetic variations.
• Examination of aging-related processes and their association with HIV-1 infection.
• Discussion of polygenic risk scores in the context of HIV-1 comorbidities.

Main Results:

• Established genetic loci like CCR5 and HLA class I influence HIV-1 control through immune responses.
• Emerging population-specific associations and novel pathways affecting viral replication are being identified.
• HIV-1 infection is linked to genomic instability, accelerated aging, and clonal hematopoiesis, potentially increasing comorbidity risk.
• Polygenic risk scores show promise for predicting non-communicable diseases in treated HIV-1 populations.

Conclusions:

• Host genetic variation, including germline and somatic factors, is critical for understanding HIV-1 outcomes.
• Aging processes and genetic predispositions interact to influence health in people living with HIV-1.
• Future research focusing on host genetics will be essential for advancing precision HIV-1 medicine, optimizing therapies, and managing the viral reservoir.