Persistent HIV-1 transcription during ART: Time to reassess its significance?

C. line Fombellida-Lopez, Ben Berkhout, Gilles Darcis, Alexander O. Pasternak

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Purpose of reviewDespite suppressive antiretroviral therapy (ART), HIV-1 reservoirs persist and reignite viral replication if therapy is interrupted. Persistence of the viral reservoir in people with HIV-1 (PWH) is the main obstacle to an HIV-1 cure. The reservoirs are not transcriptionally silent, and viral transcripts can be detected in most ART-treated individuals. Here, we review the recent progress in the characterization of persistent HIV-1 transcription during ART.Recent findingsEvidence from several studies indicates that, although cell-associated unspliced (US) HIV-1 RNA is abundantly expressed in ART-treated PWH, intact full-length US transcripts are rare and most US RNA is derived from defective proviruses. The transcription- and translation-competent defective proviruses, previously considered irrelevant, are increasingly being linked to residual HIV-1 pathogenesis under suppressive ART. Recent data suggest a continuous crosstalk between the residual HIV-1 activity under ART and the immune system. Persistent HIV-1 transcription on ART, despite being mostly derived from defective proviruses, predicts viral rebound upon therapy interruption, suggesting its role as an indicator of the strength of the host antiviral immune response that is shaping the viral rebound.SummaryIn light of the recent findings, the significance of persistent HIV-1 transcription during ART for the long-term health of PWH and the cure research should be reassessed.
Original languageEnglish
Pages (from-to)124-132
Number of pages9
JournalCurrent opinion in HIV and AIDS
Volume19
Issue number3
DOIs
Publication statusPublished - 1 May 2024

Keywords

  • HIV-1 cure
  • HIV-1 reservoir
  • cell-associated HIV-1 RNA
  • defective proviruses
  • immune activation
  • residual HIV-1 pathogenesis

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