Universal antiretroviral regimens: Thinking beyond one-pill-once-a-day

Jeffrey M. Jacobson, Charles W. Flexner

Research output: Contribution to journalReview article

Abstract

Purpose of review Poor adherence to oral antiretroviral treatment in a subpopulation of persons with HIV-1 infection interferes with the potential success of the drug regimens in treating the infection. Here, we review long-acting antiretroviral strategies currently in clinical development that could prove useful for the treatment of HIV-1 infection in individuals not succeeding with short-acting oral regimens. Recent findings Pharmaceutical nanotechnology has succeeded in creating two novel long-acting injectable antiretroviral compounds, carbotegravir and rilpivirine, which have completed early clinical trials demonstrating the safety, tolerability and prolonged antiretroviral activity. 4′-Ethynyl-2-fluoro-2′-deoxyadenosine (EFdA; MK8591) is a novel nucleoside reverse transcriptase inhibitor in early clinical development as a long-acting orally administered drug and in a long-acting polymer implant. Broadly neutralizing and cell-entry inhibitor monoclonal antibodies have demonstrated potent antiviral activity in early human trials; however, there is substantial baseline resistance. In addition, monotherapy leads to rapid resistance in those with baseline susceptibility. Summary Long-acting antiretroviral chemical compounds and monoclonal antibodies have demonstrated potent anti-HIV activity in the early-stage clinical investigations, and are actively being studied in advanced clinical trials for treatment and prevention. Strategies to manage toxicities and waning drug levels of chemical compounds, as well as primary and secondary resistance to current monoclonal antibodies are important considerations.

Original languageEnglish (US)
Pages (from-to)343-350
Number of pages8
JournalCurrent opinion in HIV and AIDS
Volume12
Issue number4
DOIs
StatePublished - Jul 1 2017

Keywords

  • HIV
  • HIV cell entry inhibitors
  • broadly neutralizing anti-HIV monoclonal antibodies
  • long-acting antiretroviral drugs
  • polymer implants

ASJC Scopus subject areas

  • Immunology
  • Hematology
  • Oncology
  • Oncology(nursing)
  • Infectious Diseases
  • Virology

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