Innate immune mechanisms of HIV control and reservoir regulation in elite and posttreatment controllers

PURPOSE OF REVIEW: Elite controllers (ECs) and posttreatment controllers (PTCs) provide complementary models of HIV remission, demonstrating that sustained viral control can occur in the absence of continuous antiretroviral therapy. Increasing evidence suggests that innate immune mechanisms may contribute to both viral suppression and reservoir regulation. RECENT FINDINGS: Recent studies have identified adaptive-like natural killer (NK) cell programmes, trained innate immune responses, enhanced dendritic-cell sensing pathways and distinct myeloid cell phenotypes associated with controller status. ECs and PTCs also exhibit favourable reservoir characteristics, including reduced frequencies of intact proviruses, restricted transcriptional activity and deep proviral latency. Emerging evidence suggests a relationship between innate immune programmes and reservoir regulation; however, direct mechanistic links remain incompletely understood. SUMMARY: Controllers represent a heterogeneous spectrum of remission phenotypes characterised by distinct innate immune signatures and reservoir landscapes. While innate immunity is increasingly associated with favourable reservoir characteristics, whether these programmes actively shape reservoir restriction or arise as a consequence of reduced viral persistence remains unresolved. Addressing this question may provide important insights for durable HIV remission and future cure strategies.