Targeting inhibitory immune checkpoint receptor pathways has shown remarkable success in improving anticancer T cell responses for the elimination of tumors. Such immunotherapeutic strategies are being pursued for HIV remission. Metformin has shown favorable clinical outcomes in enhancing the efficacy of programmed cell death-1 (PD-1) blockade and restoring antitumor T cell immunity. Furthermore, monocytes are known to be a strong predictor of progression-free survival in response to anti-PD-1 immunotherapy. In a single-arm clinical trial, we evaluated the immunological effects over an 8-week course of metformin therapy in seven euglycemic, virally suppressed HIV-infected participants on combination antiretroviral therapy (cART). We assessed changes in peripheral HIV-Gag-specific T cell responses to immune checkpoint blockade (ICB) with anti-PD-L1 and anti-T cell immunoreceptor with immunoglobulin and ITIM domain (TIGIT) monoclonal antibodies (mAbs) and changes in CD8 T cell and monocyte subsets using flow cytometry. Study participants were all male, 71% (5/7) Caucasian, with a median age of 61 years, CD4 count of 739 cells/lL, and plasma HIV RNA of <50 copies/mL on stable cART for >1 year. Ex vivo polyfunctional HIV-Gag-specific CD8 T cell responses to anti-PD-L1 mAb significantly improved (p < .05) over the 8-week course of metformin therapy. Moreover, frequencies of both intermediate (CD14 + CD16 + ; r = 0.89, p = .01) and nonclassical (CD14 low CD16 + ; r = 0.92, p = .01) monocytes at entry were predictive of the magnitude of the anti-HIV CD8 T cell responses to PD-L1 blockade. Collectively, these findings highlight that 8-week course of metformin increases the polyfunctionality of CD8 T cells and that baseline monocyte subset frequencies may be a potential determinant of PD-L1 blockade efficacy. These data provide valuable information for HIV remission trials that utilize ICB strategies to enhance anti-HIV CD8 T cell immunity.

Objectives: Describe the ultrasound features of benign asymptomatic adnexal masses submitted to surgical excision and prospectively assess the diagnostic performance of simple rules model to predict benignity. Methods: Observational study between January 2013 and December 2017, including asymptomatic women from a tertiary hospital with an adnexal mass diagnosed on a transvaginal grey scale and colour Doppler ultrasound by a skilled sonographer, before surgery. A standardised examination technique and predefined definitions of ultrasound characteristics based on IOTA terminology were used. Women with histological diagnosis of malignancy or presence of endometriotic tissue in the adnexal lesion were excluded. Results: Of the 93 women submitted to surgical excision, 79 (84%) were included in the study. Morphological description of the lesions included: 40 unilocular, 12 multilocular, 11 solid, 8 unilocular solid and 8 multilocular solid. Vascularisation was colour score-1 in 62 cases with no colour score-4 cases. For the cystic lesions (median diameter of 78mm), the cyst content was: anechoic in 27 cases, low-level in 25, mixed in 13 and ground glass in 6 cases. The presence of papillary projections was observed in 6 unilocular solid and 5 multilocular solid lesions, with a maximum of 2 projections, with no vascularisation. For the solid lesions (median dimeter of r 49mm) acoustic shadows, regular contours and colour score-1 were present in all cases. No ascites was described. When using the simple rules, all tumours were classified as benign. Conclusions:The results demonstrate the high diagnostic accuracy of simple rules risk calculation system regarding benign asymptomatic adnexal masses in these population.