HIV maintains an evolving and dispersed population among multiple tissues during suppressive cART with periods of rapid expansion corresponding to the onset of cancer.

Rose, R; Lamers, S; Nolan, D; Maidji, E; Faria, N; Pybus, O; Dollar, J; Maruniak, S; McAvoy, A; Salemi, M; Stoddart, C; Singer, E; McGrath, M

Journal article

HIV maintains an evolving and dispersed population among multiple tissues during suppressive cART with periods of rapid expansion corresponding to the onset of cancer.

Abstract:: While combined antiretroviral therapy (cART) can result in undetectable plasma viral loads, it does not eradicate HIV infection. Furthermore, HIV-infected individuals while on cART remain at an increased risk of developing serious co-morbidities, such as cancer, neurological disease, and atherosclerosis, suggesting that during cART, tissue-based HIV may contribute to such pathologies.

We obtained DNA and RNA env, nef and pol sequences using single genome sequencing from post mortem tissues of three HIV+/cART+ individuals with undetectable viral load and metastatic cancer at death, and performed time-scaled Bayesian evolutionary analyses. We used a sensitive in situ hybridization technique to visualize HIV gag-pol mRNA transcripts in cerebellum and lymph node tissues from one patient.

Tissue-associated virus evolved at a similar rate in cART+ and cART- patients. Phylogenetic trees were characterized by two distinct features: 1) branching patterns consistent with constant viral evolution and dispersal amongst tissues; and 2) very recently derived clades containing both DNA and RNA sequences from multiple tissues. Cancer diagnoses were temporally associated with diversification of viral lineages. Rapid expansion of virus near death corresponded to wide-spread metastasis. HIV RNA+ cells clustered in cerebellum tissue but were dispersed in lymph node tissue, mirroring the evolutionary patterns observed for that patient. Activated, infiltrating macrophages were associated with HIV-expressing cells.

Our data provide evidence that tissues serve as a sanctuary for wild-type HIV during cART and suggest the importance of macrophages as an alternative reservoir and mechanism of virus spread.

Publication status:: Published

Peer review status:: Peer reviewed

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APA Style

Rose, R., Lamers, S., Nolan, D., Maidji, E., Faria, N., Pybus, O., Dollar, J., Maruniak, S., McAvoy, A., Salemi, M., Stoddart, C., Singer, E., & McGrath, M. (2016). HIV maintains an evolving and dispersed population among multiple tissues during suppressive cART with periods of rapid expansion corresponding to the onset of cancer. Journal of Virology, 90(20), 8984–8993.

MLA Style

Rose, R., et al. “HIV Maintains an Evolving and Dispersed Population among Multiple Tissues during Suppressive CART with Periods of Rapid Expansion Corresponding to the Onset of Cancer.” Journal of Virology, vol. 90, no. 20, American Society for Microbiology, 2016, pp. 8984–93.

Chicago Style

Rose, R, S Lamers, D Nolan, E Maidji, N Faria, O Pybus, J Dollar, et al. 2016. “HIV Maintains an Evolving and Dispersed Population among Multiple Tissues during Suppressive CART with Periods of Rapid Expansion Corresponding to the Onset of Cancer.” Journal of Virology 90 (20): 8984–93.
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