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Peripheral blood HIV-1 DNA dynamics in antiretroviral-treated HIV/HCV co-infected patients receiving directly-acting antivirals.

Peripheral blood HIV-1 DNA dynamics in antiretroviral-treated HIV/HCV co-infected patients receiving directly-acting antivirals.
Author Information (click to view)

Rozera G, Fabbri G, Lorenzini P, Mastrorosa I, Timelli L, Zaccarelli M, Amendola A, Vergori A, Plazzi MM, Cicalini S, Antinori A, Capobianchi MR, Abbate I, Ammassari A,


Rozera G, Fabbri G, Lorenzini P, Mastrorosa I, Timelli L, Zaccarelli M, Amendola A, Vergori A, Plazzi MM, Cicalini S, Antinori A, Capobianchi MR, Abbate I, Ammassari A, (click to view)

Rozera G, Fabbri G, Lorenzini P, Mastrorosa I, Timelli L, Zaccarelli M, Amendola A, Vergori A, Plazzi MM, Cicalini S, Antinori A, Capobianchi MR, Abbate I, Ammassari A,

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PloS one 2017 10 2712(10) e0187095 doi 10.1371/journal.pone.0187095
Abstract
BACKGROUND
Aim was to determine the dynamics of peripheral blood mononuclear cells (PBMC)- associated total HIV-1 DNA in successfully ART-treated HIV/HCV co-infected patients receiving DAA treatment and to explore possible virological hypotheses underlying the phenomenon.

METHODS
Longitudinal, single-centre study measuring total HIV-1 DNA before the start of DAA, at the end of treatment (EOT), and 3 months after treatment. Univariable and multivariable analyses were used to assess factors associated with HIV-1 DNA increase ≥0.5 Log copies/million PBMC. Episomal 2-LTR forms, residual HIV-1 viremia and proviral DNA quasispecies evolution were also investigated.

RESULTS
119 successfully ART-treated HIV/HCV co-infected patients were included. Median baseline HIV-1 DNA was 3.84 Log copies/million PBMC (95%CI 3.49-4.05), and no significant variation with respect to baseline was found at EOT and after 3 months of DAA termination. In 17% of cases an increase ≥0.5 Log copies/million PBMC was observed at EOT compared to baseline. HIV-1 DNA increase was independently associated with lower baseline HIV-1 DNA, longer HIV suppression, raltegravir-based ART and previous exposure to interferon/ribavirin for HCV treatment. In none of the patients with HIV-1 DNA increase, 2-LTR forms were detected at baseline, while in 2 cases 2-LTR forms were found at EOT, without association with residual HIV-1 RNA viremia. No evidence of viral evolution was observed.

CONCLUSIONS
In successfully ART-treated HIV/HCV co-infected patients receiving DAA, PBMC-associated total HIV-1 DNA was quite stable over time, but some patients showed a considerable increase at EOT when compared to baseline. A significantly higher risk of HIV DNA increase was found, in presence of lower cellular HIV reservoir at baseline. Activation of replicative-competent virus generating new rounds of viral replication seems unlikely, while mobilization of cell-associated HIV from tissue reservoirs could be hypothesized.

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