HIV-1 diversity in viral reservoirs obtained from circulating T-cell subsets during early ART and beyond. Â PLoS Pathogens
Individuals living with HIV carry persistent virus reservoirs that can remain hidden even during effective antiretroviral therapy (ART). These reservoirs can potentially reactivate, leading to renewed infection. In a recent study published in PLOS Pathogens, Zhang et al. explored the genetic diversity and dynamics of HIV reservoirs in different immune cell subsets among individuals who began ART shortly after their HIV diagnosis. Using advanced sequencing methods, the researchers analyzed how virus variants evolve within these reservoirs over time.
The study revealed two main reservoir patterns:
• In individuals who started ART early after infection, the HIV reservoir typically consisted of only one or a few virus variants, which remained relatively stable over extended periods.
• Individuals who initiated treatment later or had a compromised immune system displayed reservoirs with higher genetic diversity, containing multiple virus variants that frequently changed over time.
Furthermore, the researchers found that replication-competent viruses predominantly persisted in less differentiated T-cell subsets, such as naïve and central memory T-cells. In contrast, more differentiated subsets (transitional and effector memory T-cells) mainly harbored genetically diverse but mostly defective viral variants. Despite being defective, these variants could potentially recombine or reactivate, posing future health risks.
In conclusion, these findings by Zhang et al. highlight the significant advantage of initiating ART early after HIV infection. Early therapy not only preserves immune function but also limits the formation of genetically diverse and potentially harmful viral reservoirs. By restricting the complexity and size of these reservoirs, early intervention may reduce the risk of future HIV reactivation, thus improving long-term clinical outcomes. These insights emphasize the need for continued efforts to promote early diagnosis and timely initiation of ART to effectively manage HIV infection.