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Updated: May 6, 2026
Amplification of Near Full-length HIV-1 Proviruses for Next-Generation Sequencing
Published on: October 16, 2018
Selection of epigenetically privileged HIV-1 proviruses during treatment with panobinostat and interferon-α2a
Marie Armani-Tourret1, Ce Gao1, Ciputra Adijaya Hartana2
1Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
Abstract:
CD4+ T cells with latent HIV-1 infection persist despite treatment with antiretroviral agents and represent the main barrier to a cure of HIV-1 infection. Pharmacological disruption of viral latency may expose HIV-1-infected cells to host immune activity, but the clinical efficacy of latency-reversing agents for reducing HIV-1 persistence remains to be proven. Here, we show in a randomized-controlled human clinical trial that the histone deacetylase inhibitor panobinostat, when administered in combination with pegylated interferon-α2a, induces a structural transformation of the HIV-1 reservoir cell pool, characterized by a disproportionate overrepresentation of HIV-1 proviruses integrated in ZNF genes and in chromatin regions with reduced H3K27ac marks, the molecular target sites for panobinostat. By contrast, proviruses near H3K27ac marks were actively selected against, likely due to increased susceptibility to panobinostat. These data suggest that latency-reversing treatment can increase the immunological vulnerability of HIV-1 reservoir cells and accelerate the selection of epigenetically privileged HIV-1 proviruses.
Insights
Latency-reversing agents like panobinostat may help cure HIV-1 by altering the viral reservoir. This study shows these drugs can make HIV-1-infected cells more vulnerable to immune attack, potentially accelerating viral clearance.
Area of Science:
- Virology
- Immunology
- Genetics
Background:
- Latent HIV-1 infection in CD4+ T cells persists despite antiretroviral therapy, hindering a cure.
- Latency-reversing agents aim to disrupt viral latency, potentially exposing infected cells to immune responses.
- The clinical effectiveness of latency-reversing agents in reducing HIV-1 persistence is unproven.
Purpose of the Study:
- To evaluate the clinical efficacy of panobinostat combined with pegylated interferon-α2a in altering the HIV-1 reservoir.
- To investigate the impact of latency-reversing treatment on the epigenetic landscape of HIV-1 proviruses.
Main Methods:
- A randomized-controlled human clinical trial was conducted.
- Panobinostat (a histone deacetylase inhibitor) and pegylated interferon-α2a were administered.
- Analysis of HIV-1 proviral integration sites and epigenetic marks (H3K27ac) was performed.
Main Results:
- Treatment induced a structural transformation of the HIV-1 reservoir cell pool.
- An overrepresentation of HIV-1 proviruses integrated in ZNF genes and regions with reduced H3K27ac marks was observed.
- Proviruses near H3K27ac marks were actively selected against, suggesting increased susceptibility.
Conclusions:
- Latency-reversing treatment can increase the immunological vulnerability of HIV-1 reservoir cells.
- This approach may accelerate the selection of epigenetically privileged HIV-1 proviruses.
- Further research is needed to confirm clinical efficacy for HIV-1 cure.
