RESUMO
BACKGROUND: Pre-exposure prophylaxis (PrEP) is effective for human immunodeficiency virus (HIV) prevention in risk groups. We assessed PrEP uptake and 12-month retention among men who have sex with men (MSM) and transgender women (TGW) in Myanmar during the coronavirus disease 2019 pandemic and a political crisis. METHODS: Using prospectively collected data, we assessed the proportion of persons eligible, initiated and retained 12 months on PrEP. We calculated HIV and syphilis incidence among those initiated on PrEP. Predictors of compliance to scheduled visits were assessed with fractional logistic regression. RESULTS: Among 652 persons screened between July and December 2020, 85.3% were eligible and 38.8% initiated PrEP. The daily pill burden was the main reason (86.5%) for refusing PrEP. A history of HIV post-exposure prophylaxis (PEP) and having an HIV-positive partner not on anti-retroviral therapy (ART) was associated with PrEP uptake (p<0.05). The 12-month retention among those initiating PrEP was 43.0%. Age ≥25 y, a history of PEP and having an HIV-positive partner not on ART predicted better compliance with scheduled visits (p<0.05). HIV incidence among PrEP initiators was 3.1 per 100 person-years (95% confidence interval [CI] 1.3 to 7.4) and syphilis incidence was 17.6 per 100 person-years (95% CI 12.3 to 25.1). CONCLUSIONS: A PrEP program for MSM and TGW in Myanmar was implemented successfully under difficult circumstances. Alternative strategies are needed addressing PrEP uptake and retention.
RESUMO
Three murine glioma cell lines (GL261, CT2A, and ALTS1C1) were modified to downregulate the expression of the murine LDH-A gene using shRNA, and compared to shRNA scrambled control (NC) cell lines. Differences in the expression of LDH-A and LDH-B mRNA, protein and enzymatic activity, as well as their LDH isoenzyme profiles, were observed in the six cell lines, and confirmed successful LDH-A KD. LDH-A KD (knock-down) resulted in metabolic changes in cells with a reduction in glycolysis (GlycoPER) and an increase in basal respiratory rate (mitoOCR). GL261 cells had a more limited ATP production capacity compared to CT2A and ALTS1C1 cells. An analysis of mRNA expression data indicated that: (i) GL261 LDH-A KD cells may have an improved ability to metabolize lactate into the TCA cycle; and (ii) that GL261 LDH-A KD cells can upregulate lipid metabolism/fatty acid oxidation pathways, whereas the other glioma cell lines do not have this capacity. These two observations suggest that GL261 LDH-A KD cells can develop/activate alternative metabolic pathways for enhanced survival in a nutrient-limited environment, and that specific nutrient limitations have a variable impact on tumor cell metabolism and proliferation. The phenotypic effects of LDH-A KD were compared to those in control (NC) cells and tumors. LDH-A KD prolonged the doubling time of GL261 cells in culture and prevented the formation of subcutaneous flank tumors in immune-competent C57BL/6 mice, whereas GL261 NC tumors had a prolonged growth delay in C57BL/6 mice. In nude mice, both LDH-A KD and NC GL261 tumors grew rapidly (more rapidly than GL261 NC tumors in C57BL/6 mice), demonstrating the impact of an intact immune system on GL261 tumor growth. No differences between NC and KD cell proliferation (in vitro) or tumor growth in C57BL/6 mice (doubling time) were observed for CT2A and ALTS1C1 cells and tumors, despite the small changes to their LDH isoenzyme profiles. These results suggest that GL261 glioma cells (but not CT2A and ALTS1C1 cells) are pre-programmed to have the capacity for activating different metabolic pathways with higher TCA cycle activity, and that this capacity is enhanced by LDH-A depletion. We observed that the combined impact of LDH-A depletion and the immune system had a significant impact on the growth of subcutaneous-located GL261 tumors.