For the estimated 38 million people living with HIV worldwide, viral suppression via antiretroviral therapy is no longer the finish line — chronic immune aging, persistent inflammation, and co-infections like cytomegalovirus (CMV) continue to erode healthspan even in well-controlled patients. A newer injectable formulation of two established antiretrovirals may offer an additional biological advantage beyond convenience.
This prospective observational study enrolled 37 people with HIV who switched to long-acting injectable cabotegravir plus rilpivirine (CAB/RPV-LA) and compared them against nine participants who remained on daily oral ART over a 72-week follow-up. T-cell immune activation was quantified using the CD38+HLA-DR+ phenotype, and immune senescence via CD28−CD57+ expression — both established surrogates for accelerated immunological aging. Among those on the injectable regimen, CD8 T-cell counts declined significantly by week 72 relative to baseline and week 4, a pattern associated with reduced immune hyperactivation. CMV-specific cellular and humoral responses were also characterized to disentangle the contribution of this co-infection to observed T-cell alterations.
The finding is incremental but mechanistically meaningful. CD8 T-cell expansion and senescence are hallmarks of chronic HIV and CMV dual infection, and are independently associated with cardiovascular disease, frailty, and non-AIDS mortality in aging HIV-positive populations. This study adds to a modest but growing body of evidence suggesting that long-acting injectable ART may exert immunomodulatory effects beyond pharmacokinetic advantages — potentially by reducing low-level viral blips or reservoir reactivation events that continuously stimulate immune activation. Key limitations are substantial: the sample is small (37 vs. 9), the control arm was not randomized, and the 72-week horizon cannot establish durability. Causality remains unconfirmed. Larger, randomized trials tracking clinical endpoints — not just biomarkers — are needed before immune aging benefits can be attributed specifically to the injectable delivery format rather than to drug formulation differences.