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Retroviruses have a single-stranded RNA genome that undergoes a special form of replication. Once the retrovirus has entered the host cell, an enzyme called reverse transcriptase synthesizes double-stranded DNA from the retroviral RNA genome. This DNA copy of the genome is then integrated into the host’s genome inside the nucleus via an enzyme called integrase. Consequently, the retroviral genome is transcribed into RNA whenever the host’s genome is transcribed, allowing the...
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Oral Combinational Antiretroviral Treatment in HIV-1 Infected Humanized Mice
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A new hypothesis on HIV cure.

Florian Hladik1

  • 1Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, 98109, USA ; Departments of Obstetrics and Gynecology, and Medicine, University of Washington, Seattle, Washington, 98195, USA.

F1000Research
|September 18, 2015
PubMed
Summary

Nucleoside reverse transcriptase inhibitors (NRTIs) might hinder human immunodeficiency virus (HIV) cure by supporting infected cell survival. This hypothesis suggests an HIV cure could be nearer than previously thought.

Keywords:
AIDSAntiretroviral drugsBerlin patientHIV LatencyIntegrase InhibitorsMucosaNRTIsTenofovir

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Area of Science:

  • Virology
  • Immunology
  • Pharmacology

Background:

  • Human immunodeficiency virus (HIV) establishes a persistent infection through integrated provirus in host cells.
  • Current antiretroviral therapies, including nucleoside reverse transcriptase inhibitors (NRTIs), suppress viral replication but do not eliminate the viral reservoir.
  • The long-term impact of NRTIs on the persistence of infected cells remains an area of active investigation.

Purpose of the Study:

  • To propose a novel hypothesis regarding the role of NRTIs in HIV persistence.
  • To suggest that NRTIs may inadvertently impede the eradication of HIV by promoting the survival of cells harboring integrated provirus.
  • To re-evaluate the potential for achieving an HIV cure in light of this hypothesis.

Main Methods:

  • This is an opinion article, presenting a hypothesis based on existing scientific literature and understanding of virology and pharmacology.
  • The rationale is built upon the known mechanisms of NRTI action and viral integration.
  • No new experimental data were generated; the focus is on theoretical interpretation.

Main Results:

  • The central hypothesis posits that NRTIs may prevent a complete HIV cure.
  • This prevention mechanism is proposed to occur through the enhancement of survival in cells containing integrated HIV provirus.
  • The implication is that a functional or sterilizing cure for HIV might be more attainable if this mechanism is addressed.

Conclusions:

  • NRTIs, while crucial for viral suppression, could paradoxically contribute to the persistence of the HIV reservoir.
  • Reconsidering the role of NRTIs in the context of HIV cure strategies is warranted.
  • The hypothesis, if validated, could significantly alter the landscape of HIV cure research and therapeutic development.