Anti-HIV Activity of Standard Combined Antiretroviral Therapy in Primary Cells Is Intensified by CCR5-Targeting Drugs

Matthew Weichseldorfer, Yvonne Affram, Alonso Heredia, Yutaka Tagaya, Francesca Benedetti, Davide Zella, Marvin Reitz, Fabio Romerio, Olga S. Latinovic

Research output: Contribution to journalArticlepeer-review

Abstract

The efficacy of combined antiretroviral therapy (cART) against HIV-1 is evidenced by reduction of plasma viremia, disease progression, viral transmission, and mortality. However, major challenges still remain in HIV-1 management, especially the emergence of resistant strains and the persistence of viral reservoirs, apparent after cART treatment interruption. Efforts are ongoing to explore the most effective means to intensify cART and successfully control residual viral replication. We anticipate that the reduction by cART of HIV-1 reservoirs could be further enhanced by combining cART with entry inhibitors and drugs that silence CCR5 expression. CCR5-targeting drugs are attractive option because of their low side effects when combined with other antiretroviral drugs. The concept that their inclusion would be effective has been supported by the reduction in two long terminal repeat unintegrated circular DNA, a marker for new infections, when CCR5-targeting drugs are added to standard antiretroviral treatment. This study is, in part, an extension of our previous study demonstrating greater preservation of human CD4+ T-cells and CD4+/CD8+ cell ratios in HIV-infected CD34+ NSG mice when CCR5-targeting drugs were included with standard cART. In this study, we treated HIV-1-infected cell cultures with cART or cART plus CCR5-targeting drugs (maraviroc and rapamycin). We found that treatment intensification with CCR5-targeting drugs led to a significant reduction of HIV-1 replication in peripheral blood ononuclear cells (PBMCs), as judged by measured viral DNA copies and p24 levels. Our data provide proof of principle for the benefit of adding CCR5-targeting drugs to traditional, standard cART to further lower viremia and subsequently reduce viral reservoirs in clinical settings, while potentially lowering side effects by reducing cART concentrations.

Original languageEnglish (US)
Pages (from-to)835-841
Number of pages7
JournalAIDS research and human retroviruses
Volume36
Issue number10
DOIs
StatePublished - Oct 1 2020
Externally publishedYes

Keywords

  • antiretroviral therapies
  • coreceptor
  • HIV/AIDS pathogenesis

ASJC Scopus subject areas

  • Immunology
  • Virology
  • Infectious Diseases

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