Antiretroviral Laboratory Monitoring and Implications for HIV Clinical Care in the Era of COVID-19 and Beyond.

In the era of COVID-19, providers are delaying laboratory testing in people with HIV (PWH). The purpose of this study was to examine the clinical significance of renal, liver, and lipid testing. We reviewed the charts of 261 PWH who initiated care at an academic HIV clinic between January 1, 2016 and December 21, 2018. Analysis included one-sided binomial exact tests and multiple linear, Poisson, and Beta regression models. The most common abnormality was a glomerular filtration rate (GFR) <60 mL/min (10%). Age <40 years [estimated relative rate (rr) 0.017, 95% confidence interval (CI) 0.207 to 0.494], cobicistat (rr 0.284, 95% CI 0.128 to 0.63), and tenofovir alafenamide (rr 0.295 95% CI 0.151 to 0.573) were associated with a decreased risk of GFR <60 mL/min. An increased AST and ALT ≥2 × upper limit of normal (ULN) was found in 5% and 3%, respectively. Hepatitis C and use of darunavir and lopinavir were associated with increased AST or ALT. When a GFR was <60 mL/min or an AST or ALT was ≥2 × ULN, no action was taken in 53% of cases. In 18% of cases the only intervention was repeat testing. The most common interventions after lipid results were calculation of a 10-year cardiovascular risk score (31%) and addition of a statin (18%). Taking action after lipid results was strongly associated with age ≥40 (rr 7.37, 95% CI 3.0 to 18.3). Young PWH without hepatitis C rarely have renal, liver, or lipid test results that alter clinical care. Decreased testing should be considered.

Role of cystathionine ß-synthase in human breast Cancer.

Cystathionine ß-synthase (CBS) is an enzyme in the transulfuration pathway that can catalyze the condensation of homocysteine (Hcy) and cysteine (Cys) to hydrogen sulfide (H2S) and cystathionine (CTH). CBS-derived H2S is important in angiogenesis and drug resistance in colon and ovarian cancers, respectively. However, the mechanisms by which cancer cell-derived H2S is utilized by cancer cells as a protective agent against host-derived activated macrophages are not yet investigated. This study investigated the mechanistic role of CBS-derived H2S in the protection of human breast cancer (HBC) cells against activated macrophages. HBC patient-derived tissue arrays and immunoblot analysis of HBC cells exhibited significantly increased levels of CBS when compared with their normal counterparts. This was associated with increased levels of H2S and CTH. Silencing of CBS in HBC cells caused a significant decrease in the levels of H2S and CTH but did not affect the growth of these cells per se, in in vitro cultures. However CBS-silenced cells exhibited significantly reduced growth in the presence of activated macrophages and in xenograft models. This was associated with an increase in the steady state levels of reactive aldehyde-derived protein adducts. Exogenous addition of H2S countered the effects of CBS silencing in the presence of macrophages. Conversely overexpression of CBS in human breast epithelial (HBE) cells (which do not naturally express CBS) protected them from activated macrophages, which were otherwise susceptible to the latter.