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New treatment opportunities are emerging in the field of lipid-lowering therapy through gene-silencing approaches. Both antisense oligonucleotide inhibition and small interfering RNA technology aim to degrade gene mRNA transcripts to reduce protein production and plasma lipoprotein levels. Elevated levels of LDL, remnant lipoproteins, and lipoprotein(a) all cause cardiovascular disease, whereas elevated levels of triglyceride-rich lipoproteins in some patients can cause acute pancreatitis. The levels of each of these lipoproteins can be reduced using gene-silencing therapies by targeting proteins that have an important role in lipoprotein production or removal (for example, the protein products of ANGPTL3, APOB, APOC3, LPA, and PCSK9). Using this technology, plasma levels of these lipoproteins can be reduced by 50-90% with 2-12 injections per year; such dramatic reductions are likely to reduce the incidence of cardiovascular disease or acute pancreatitis in at-risk patients. The reported adverse effects of these new therapies include injection-site reactions, flu-like symptoms, and low blood platelet counts. However, newer-generation drugs are more efficiently delivered to liver cells, requiring lower drug doses, which leads to fewer adverse effects. Although these findings are promising, robust evidence of cardiovascular disease reduction and long-term safety is needed before these gene-silencing technologies can have widespread implementation. Before the availability of such evidence, these drugs might have roles in patients with unmet medical needs through orphan indications. [ABSTRACT FROM AUTHOR]

Altered coagulation has been reported in people living with HIV (PLWH) with ongoing viral replication and may predispose to cardiovascular diseases. However, less is known about coagulation in PLWH with undetectable viral replication. In a cross-sectional observational study, we investigated whether HIV infection with undetectable viral replication is independently associated with activated partial thromboplastin time (APTT) and coagulation factor II–VII–X concentrations out of reference. Logistic regression analyses were used to assess the association of HIV infection with APTT and coagulation factor II–VII–X, after adjusting for age, sex, smoking status, alcohol consumption, BMI, diabetes and hsCRP. 936 PLWH with undetectable viral replication from the Copenhagen Co-morbidity in HIV infection study (COCOMO-study) and 2955 uninfected controls were included. Higher prevalence of short APTT was found in PLWH compared to controls (13.5% vs. 7.6%, P < 0.001). Furthermore, higher prevalence of low coagulation factor II–VII–X was found in PLWH than in controls (9.6% vs. 7.4%, P = 0.022). HIV was independently associated with short APTT (adjusted odds ratio (aOR) 2.3 (95% CI 1.7–2.9), P < 0.001) and low coagulation factor II–VII–X (aOR 1.4 (95% CI 1.0–1.9), P = 0.046). Few participants among PLWH and controls had both short APTT and low coagulation factor II–VII–X, 2.1% vs. 0.8%, respectively. We found evidence of both procoagulant (short APTT) and anticoagulant (low coagulation factor II–VII–X) alterations in PLWH with undetectable viral replication, and our findings suggest that two different coagulation phenotypes exist in participants with treated HIV infection. [ABSTRACT FROM AUTHOR]