“HIV reservoir dynamics are driven by local inflammation and gut dysbiosis,” the investigators concluded.
HIV attacks its host’s immune system, including the gastrointestinal (GI) tract, causing cellular damage, microbial translocation, and inflammation. The GI tract is also known to be a source of HIV viral rebound after a patient ceases antiretroviral therapy (ART).
A new study, shared at the recent 30th Conference on Retroviruses and Opportunistic Infections (CROI 2023), studied the HIV dynamics between tissue reservoirs. The investigators evaluated biomarkers, viral reservoir characteristics, and microbiome composition associated with HIV viral dynamics.
The study population included 8 participants, recruited from the Last Gift cohort. The participants were nearly all male (n = 7) and White/Caucasian (n = 7).
The investigators performed HIV full envelope single genome sequencing in all participants, and measured HIV DNA levels via digital droplet (dd)PCR across 33 unique tissues (10-25 per participant).
Utilizing these models, the investigators inferred HIV dynamics, or number of estimated migration events, between the sampled tissues. They measured a panel of 44 cytokines perimortem in blood plasma.
The microbiome was characterized by GI tissues, using 16S-rDNA sequencing. The investigators utilized Bayesian hierarchical models to determine the association of viral migration between tissues with (1) HIV reservoir characteristics, (2) microbiome composition, and (3) soluble biomarkers. These models included predictors of the source and recipient tissues, whether the tissues are in the same biological system, and host- and tissue-level effects.
Bayesian discrete trait analyses (DTA) revealed that viral migration within, from, or toward GI tissues was associated with higher markers of inflammation and homeostasis. Viral migration related to GI tissues was also correlated with lower blood levels of ICAM1, a regulator of cellular inflammatory response.
The DTA showed strong associations between lower genetic distance between viral populations at anatomical sites and increased viral migration between the sites. Among GI tissues, viral diversity in source and recipient tissues was similarly positive correlated with viral migration.
In the gut microbiome, the investigators determined there was another marker of inflammation in the positive association between viral migration and the abundance of Fusobacteria in the source tissue, and Actinobacteria in the recipient tissue.
The investigators determined their study affirmed the impact of HIV reservoir composition on viral dynamics. “We showed that systemic inflammation and microbial gut environment also impacted HIV dynamics,” the study authors concluded, “Our approach provides a robust way to evaluate host and tissue level markets associated with directional HIV dispersal within host.”