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Background: HIV treatment-based prevention modalities present new opportunities for women to make decisions around sex, intimacy, and prevention. The Universal test and treat (UTT) strategy, where widespread HIV testing is implemented and all people with HIV can access treatment, has the potential to change how sex is understood and HIV prevention incorporated into sexual relationships. We use the frame of sexual scripting to explore how women attribute meaning to sex relative to UTT in an HIV prevention trial setting. Exploring women's sexual narratives, we explored how HIV prevention feature in the sexual scripts for women who had access to UTT in South Africa (prior to treatment guideline changes) and increased HIV prevention messaging, compared to places without widespread access to HIV testing and immediate access to treatment., Methods: We employed a two-phased thematic analysis to explore longitudinal qualitative data collected from 71 women (18-35 years old) between 2016 and 2018 as part of an HIV prevention trial in the Western Cape Province, South Africa. Of the participants, 58/71 (82%) were from intervention communities while 13/71 (18%) lived in control communities without access to UTT. Twenty participants self-disclosed that they were living with HIV., Results: We found no narrative differences between women who had access to UTT and those who did not. HIV and HIV prevention, including treatment-based prevention modalities, were largely absent from women's thinking about sex. In their scripts, women idealised romantic sex, positioned sex as 'about relationships', and described risky sex as 'other'. When women were confronted by HIV risk (for example, when a partner disclosed his HIV-positive status) this created a point of disjuncture between this new perception of risk and their accepted relationship scripts., Conclusion: These findings suggest that HIV-negative women did not include their partners' use of antiretroviral therapy in their sexual partnership choices. For these women, the preventive benefits of UTT are experienced passively-through community-wide viral suppression-rather than through their own behaviour change explicitly related to the availability of treatment as prevention. We propose that prevention-based modalities should be made available and supported and framed as an intervention to promote relationship well-being., (© 2021. The Author(s).)

Purpose: Human epidermal growth factor receptor-2 (HER2) has been implicated in the progression of multiple tumor types, including breast cancer, and many downstream effectors of HER2 signaling are primary regulators of cellular metabolism, including Ras and Akt. A key downstream metabolic target of Ras and Akt is the 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 isozyme (PFKFB3), whose product, fructose-2,6-bisphosphate (F26BP), is a potent allosteric activator of a rate-limiting enzyme in glycolysis, 6-phosphofructo-1-kinase (PFK-1). We postulate that PFKFB3 may be regulated by HER2 and contribute to HER2-driven tumorigenicity., Methods: Immunohistochemistry and Kaplan-Meier analysis of HER2+ patient samples investigated the relevance of PFKFB3 in HER2+ breast cancer. In vitro genetic and pharmacological inhibition of PFKFB3 was utilized to determine effects on HER2+ breast cancer cells, while HER2 antagonist treatment assessed the mechanistic regulation on PFKFB3 expression and glucose metabolism. Administration of a PFKFB3 inhibitor in a HER2-driven transgenic breast cancer model evaluated this potential therapeutic approach in vivo., Results: PFKFB3 is elevated in human HER2+ breast cancer and high PFKFB3 transcript correlated with poorer progression-free (PFS) and distant metastatic-free (DFMS) survival. Constitutive HER2 expression led to elevated PFKFB3 expression and increased glucose metabolism, while inhibition of PFKFB3 suppressed glucose uptake, F26BP, glycolysis, and selectively decreased the growth of HER2-expressing breast cancer cells. In addition, treatment with lapatinib, an FDA-approved HER2 inhibitor, decreased PFKFB3 expression and glucose metabolism in HER2+ cells. In vivo administration of a PFKFB3 antagonist significantly suppressed the growth of HER2-driven breast tumors and decreased 18 F-2-deoxy-glucose uptake., Conclusions: Taken together, these data support the potential clinical utility of PFKFB3 inhibitors as chemotherapeutic agents against HER2+ breast cancer.