Oestradiol concentrations in trans women with HIV suppressed on unboosted integrase inhibitor regimens versus trans women without HIV taking oral oestradiol: a pilot study.

BACKGROUND: Feminizing hormone therapy (FHT) is essential to many trans women. Concern about negative drug interactions between FHT and ART can be an ART adherence barrier among trans women with HIV. OBJECTIVES: In this single-centre, parallel group, cross-sectional pilot study, we measured serum oestradiol concentrations in trans women with HIV taking FHT and unboosted integrase strand transfer inhibitor (INSTI)-based ART versus trans women without HIV taking FHT. METHODS: We included trans women with and without HIV, aged ≥18 years, taking ≥2 mg/day of oral oestradiol for at least 3 months plus an anti-androgen. Trans women with HIV were on suppressive ART ≥3 months. Serum oestradiol concentrations were measured prior to medication dosing and 2, 4, 6 and 8 h post-dose. Median oestradiol concentrations were compared between groups using Wilcoxon rank-sum tests. RESULTS: Participants (n = 8 with HIV, n = 7 without) had a median age of 32 (IQR: 28, 39) years. Among participants, the median oral oestradiol dose was 4 mg (range 2-6 mg). Participants had been taking FHT for a median of 4 years (IQR: 2, 8). Six trans women with HIV were taking bictegravir/emtricitabine/tenofovir alafenamide and two were taking dolutegravir/abacavir/lamivudine. All oestradiol concentrations were not significantly different between groups. Eleven (73%) participants had target oestradiol concentrations in the range 200-735 pmol/L at C4h (75% among women with HIV, 71% among those without HIV). CONCLUSIONS: Oestradiol concentrations were not statistically different in trans women with HIV compared with those without HIV, suggesting a low probability of clinically relevant drug-drug interactions between FHT and unboosted INSTI-based ART.

The globoseries glycosphingolipid SSEA-4 is a marker of bone marrow-derived clonal multipotent stromal cells in vitro and in vivo.

The therapeutic potential of multipotent stromal cells (MSC) may be enhanced by the identification of markers that allow their discrimination and enumeration both in vivo and in vitro. Here, we investigated the ability of embryonic stem cell-associated glycosphingolipids to isolate human MSC from both whole-bone-marrow (BM) and stromal cell cultures. Only SSEA-4 was consistently expressed on cells within the CD45loCD105hi marrow fraction and could be used to isolate cells with the capacity to give rise to stromal cultures containing MSC. Human stromal cultures, generated in either the presence or absence of serum, contained heterogeneous cell populations discriminated by the quantity of SSEA-4 epitopes detected on their surface. A low level of surface SSEA-4 (SSEA-4lo) correlated with undetectable levels of the α2,3-sialyltransferase-II enzyme required to synthesize SSEA-4; a reduced proliferative potential; and the loss of fat-, bone-, and cartilage-forming cells during long-term culture. In vitro, single cells with the capacity to generate multipotent stromal cultures were detected exclusively in the SSEA-4hi fraction. Our data demonstrate that a high level of surface epitopes for SSEA-4 provides a definitive marker of MSC from human BM.