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Retrovirus Life Cycles01:10

Retrovirus Life Cycles

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 retrovirus to...

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An Affordable HIV-1 Drug Resistance Monitoring Method for Resource Limited Settings
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Published on: March 30, 2014

Optimizing HIV-1 Genotypic Resistance Testing for Low- and Middle-Income Countries: High-Impact HIV-1 Mutations

Robert W Shafer1, Kaiming Tao1, Tom Loosli2

  • 1Division of Infectious Diseases, Department of Medicine, Stanford University Stanford, Stanford, CA 94305, USA.

Viruses
|June 26, 2026
PubMed
Summary

HIV drug resistance testing is crucial for managing treatment failure in low- and middle-income countries. Identifying specific drug-resistance mutations (DRMs) guides the development of effective HIV assays for diverse patient populations.

Keywords:
Antiretroviral drugsHIV drug resistanceHIV mutations

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Area of Science:

  • Infectious Diseases
  • Virology
  • Public Health

Background:

  • Drug resistance testing can significantly improve HIV management in low- and middle-income countries (LMICs).
  • The World Health Organization (WHO) has defined target product profiles (TPPs) for genotypic resistance testing in two priority scenarios.
  • These scenarios address virological failure on integrase strand transfer inhibitor (INSTI)-based regimens and treatment failure in heavily treated individuals, including children.

Purpose of the Study:

  • To identify key drug-resistance mutations (DRMs) impacting clinical management for PLWH in WHO TPP scenarios.
  • To inform the development of diagnostic assays for HIV drug resistance.
  • To guide the interpretation of sequence-based HIV resistance testing.

Main Methods:

  • Reviewed HIV-1 DRM prevalence and in vitro susceptibility data from the Stanford HIV Drug Resistance Database.
  • Focused on mutations associated with nucleoside RT inhibitors (NRTIs), nonnucleoside RT inhibitors (NNRTIs), protease inhibitors (PIs), INSTIs, and lenacapavir.
  • Analyzed data relevant to the WHO TPP scenarios for HIV drug resistance testing.

Main Results:

  • In INSTI-regimen failure, key DRMs include NRTI mutations K65R, M184V/I and INSTI mutations G118R, N155H, Q148H/K/R, R263K.
  • For heavily treated patients, a wider range of DRMs are relevant, including those affecting PIs (e.g., darunavir) and NNRTIs (e.g., etravirine, doravirine).
  • For PrEP failures, relevant DRMs include NRTI and INSTI mutations similar to scenario 1, plus capsid mutations seen with lenacapavir.

Conclusions:

  • HIV drug resistance testing is increasingly vital in LMICs due to rising INSTI use and complex treatment cases.
  • While sequence-based assays offer comprehensive data, targeted assays for individual DRMs are highly valuable for the defined WHO TPP scenarios.
  • These findings support the development and implementation of tailored HIV resistance testing strategies.