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Medications for opioid use disorder shape immune responses during chronic HIV infection

Jack A Collora1, Savannah F Steinhauser1, Timothy C Davenport1

  • 1Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT 06519, USA.

Cell Reports. Medicine
|June 3, 2025
PubMed

Insights

Medications for opioid use disorder (MOUDs) impact immune responses in people living with HIV (PLWHs). Naltrexone and buprenorphine improved immune function and decreased HIV expression in a small study.

Area of Science:

  • Immunology
  • Infectious Diseases
  • Pharmacology

Background:

  • People living with HIV (PLWHs) have a higher risk of opioid use disorder (OUD).
  • The effects of medications for opioid use disorder (MOUDs) on immune responses in PLWHs are not well understood.

Purpose of the Study:

  • To investigate how different MOUDs (methadone, buprenorphine, naltrexone) affect immune profiles in PLWHs with OUD.
  • To assess changes in HIV expression in response to MOUD initiation.

Main Methods:

  • Single-cell DOGMA-seq was used to profile 29,462 peripheral blood immune cells from 12 PLWHs.
  • Immune cell profiles were analyzed before and 3 months after initiating methadone, buprenorphine, or naltrexone.

Main Results:

  • Naltrexone increased type I interferon (IFN) responses, while buprenorphine increased tumor necrosis factor (TNF) responses in cytotoxic T cells.
  • HIV+ cells upregulated PTPN13 and TAF5L, genes associated with HIV replication.
  • Methadone showed a trend towards increased HIV RNA expression, whereas buprenorphine and naltrexone showed a trend towards decreased HIV RNA expression.

Conclusions:

  • MOUDs can modulate immune responses in PLWHs.
  • Buprenorphine and naltrexone may offer benefits by improving immune responses and reducing HIV expression.
Keywords:
AP-1DOGMA-seqHIV reservoirMOUDOUDTNFcytotoxic T lymphocytesmedications for opioid use disorderopioid use disordersingle-cell ATAC-seqsingle-cell RNA-seqsingle-cell multiomics

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