Data are limited regarding the immune status of CD40 ligand (CD40L)-deficient carriers and hematopoietic stem cell transplantation (HSCT) outcomes using them as donors for CD40L-deficient patients. Therefore, we studied the immune profiles of 7 carriers, 4 of whom were HSCT donors for family members with CD40L deficiency, and we characterized their HSCT outcomes. Immunoglobulin profiles, CD4, CD8, circulating T-follicular helper (cTfh) cells, and regulatory T cells (Tregs) in carriers were comparable to those in healthy controls. CD40L expression in carriers ranged from 37% to 78%. cTfh cells from carriers expressed higher CD40L compared with total CD4 cells or the memory CD4 compartment, suggesting a potential advantage to CD40L-expressing cTfh cells. Tregs had minimal CD40L expression in carriers and healthy controls. So we postulated that HSCT using donors who were CD40L carriers may result in excellent immune reconstitution without immune dysregulation. Four CD40L-deficient patients underwent HSCT from carriers who had CD40L expression from 37% to 63%. All patients engrafted, achieved excellent immune reconstitution with lack of opportunistic infections, graft-versus-host disease, and immune dysregulation; stable CD40L expression mimicked that of donors 1 to 5 years after HSCT. Immunoglobulin independence was achieved in 3 of the 4 patients. We demonstrated higher CD40L expression in the cTfh compartment of carriers and excellent immune reconstitution using donors who were CD40L carriers in CD40L-deficient patients.

Approximately 50% of people living with HIV (PLWH) in the United States are =50years old. Clinical trials of bictegravir/emtricitabine/ tenofovir alafenamide (B/F/TAF) demonstrated potent efficacy and favorable safety in older PLWH; however, real-world data would be useful to validate these results. Retrospective cohort study. We evaluated records from PLWH aged ≥50years at the Orlando Immunology Center who were switched to B/F/TAF between February 2018 and August 2019. Eligible patients had baseline HIV-1 RNA <50copies/mL and 48weeks of follow-up data. The primary endpoint was maintenance of HIV-1 RNA <50copies/mL at Week 48. The impact of switching to B/F/TAF on drug-drug interactions (DDIs) and safety parameters were also assessed. Three-hundred and fifty patients met inclusion criteria, median age was 57years, 20% were women, and 43% were non-White. Fifty-five percent of patients switched from integrase inhibitor-based regimens; the most common reason for switch was simplification. At Week 48, 330 (94%) patients maintained an HIV-1 RNA <50copies/mL and 20 (6%) had an HIV-1 RNA between 50 and 400copies/mL. One-hundred and forty potential DDIs were identified in 121 (35%) patients taking a boosting agent or rilpivirine at baseline that were resolved after switching to B/F/TAF. Treatment-related adverse events occurred in 51 (15%) patients (all Grade 1-2) and led to 8 discontinuations. In this real-world cohort, switching to B/F/TAF was associated with maintenance of virologic control, and avoidance of DDIs in a large proportion of patients. These data support use of B/F/TAF as a treatment option in older PLWH.