SUMMARY The pursuit of timely, cost-effective, accurate, and noninvasive diagnostic methodologies is an endeavor of urgency among clinicians and scientists alike. Detecting pathologies at their earliest stages can significantly affect patient discomfort, prognosis, therapeutic intervention, survival rates, and recurrence. Diagnosis and monitoring often require painful invasive procedures such as biopsies and repeated blood draws, adding undue stress to an already unpleasant experience. The discovery of saliva-based microbial, immunologic, and molecular biomarkers offers unique opportunities to bypass these measures by utilizing oral fluids to evaluate the condition of both healthy and diseased individuals. Here we discuss saliva and its significance as a source of indicators for local, systemic, and infectious disorders. We highlight contemporary innovations and explore recent discoveries that deem saliva a mediator of the body's physiological condition. Additionally, we examine the current state of salivary diagnostics and its associated technologies, future aspirations, and potential as the preferred route of disease detection, monitoring, and prognosis.

Tigecycline was effective in most of these 25 patients when used alone or in combination with other antimicrobials for VAP and/or bacteremia caused by multidrug-resistant A. baumannii. The emergence of a resistant strain while one patient was receiving therapy, however, is concerning.

Imagine a time where your health status could be available to you without the pain, discomfort and inconvenience of a physical examination. Distant vision of an inconceivable future or impending reality with potentially immeasurable impact? Recent advancements in the field of molecular diagnostics indicate this is not only possible, but closer than we think. Novel discoveries and substantial advancements have revealed that saliva may contain real-time information describing our overall physiological condition. Researchers are now reporting that, like blood and tissue biopsies, oral fluids could be a source of biochemical data capable of detecting certain diseases. What is even more intriguing is that this phenomenon not only applies to local disorders like oral cancer and Sjögren's syndrome, but distant pathologies like autoimmune, cardiovascular and metabolic diseases as well as viral/bacterial infections and even some cancers. These revelations have provided a foundation for the burgeoning field of salivary diagnostics and hence spurred the onset of investigations poised at deciphering the salivary milieu. This paper overviews salivary diagnostics from biomarker development to the multitude of techniques utilized in identifying saliva-based molecular indicators of disease. In doing so, we present oral fluids as an easily accessible noninvasive alternative to traditional diagnostic avenues and not just an essential component of the digestive process. Determining saliva as a credible means of evaluating health status represents a considerable leap forward in health care, one that could lead to enormous translational advantages and significant clinical opportunities.

Ritonavir is commonly used as a pharmacokinetic booster for antiretroviral regimens in the management of human immunodeficiency virus infections. Limitations to ritonavir boosting include increased pill burden, adverse effects, and a wide range of clinically significant drug-drug interactions. Cobicistat is a new pharmacokinetic booster that is a selective inhibitor of cytochrome P450 3A, the main metabolizing pathway of several antiretrovirals. Cobicistat has been studied as a booster for elvitegravir, a second-generation integrase inhibitor, and protease inhibitors. Based on successful clinical trials, a new single-tablet regimen of elvitegravir, cobicistat, emtricitabine, and tenofovir has been approved for the management of treatment-naïve patients. Additional studies are underway investigating the safety and efficacy of cobicistat-boosted protease inhibitor regimens for both treatment-naïve and treatment-experienced patients. Cobicistat is well tolerated and may become a preferred booster for antiretroviral regimens, as it can be coformulated with several agents to create simpler regimens.

Background Switching from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF) containing antiretroviral therapy (ART) can improve renal function and bone mineral density in people with HIV (PWH). The switch can also negatively influence cholesterol, but changes in body mass index (BMI), and atherosclerotic cardiovascular disease (ASCVD) risk are unknown. Setting An urban, academic medical center Methods This retrospective observational study evaluated BMI and ASCVD risk score changes in virologically suppressed PWH who switched from TDF to TAF without switching other ART regimen components. Adults on TDF for ≥ 1 year with two consecutive HIV RNA values <200 copies/mL prior to a TAF switch were included. Body weight, BMI, cholesterol and ASCVD risk score were collected for the year prior to and following the switch. Pre and post switch values were compared with the Wilcoxon signed-rank test. Changes in BMI and ASCVD scores were modeled using generalized estimating equations regression. Results 110 patients were included. In unadjusted analyses, there were significant increases in weight, BMI, total cholesterol, LDL, HDL, and ASCVD risk score in the year after switching from TDF to TAF (each p ≤ 0.01). In regression models, switching from TDF to TAF was associated with a 0.45 kg/m2 increase in BMI (95% CI: 0.14, 0.76) and a 13% increase in ASCVD risk score (95% CI: 4%, 23%). Conclusion We observed significant BMI and ASCVD score increases in PWH one year after switching from TDF to TAF. The mechanism of changes is unclear and requires additional study.

No abstract

The first two integrase strand transfer inhibitors (INSTIs) approved for treatment of patients infected with human immunodeficiency virus (HIV) were raltegravir and elvitegravir. Both raltegravir and elvitegravir are now guideline-preferred agents as part of an antiretroviral regimen for treatment-naive patients. However, raltegravir is dosed twice/day. Elvitegravir is available in a single-tablet regimen and dosed once/day because it is administered with the pharmacokinetic booster cobicistat, a potent CYP3A4 inhibitor that can lead to clinically significant drug-drug interactions. In addition, raltegravir and elvitegravir have a low genetic barrier to resistance and are associated with cross-resistance. Dolutegravir is a new-generation INSTI administered once/day without a pharmacokinetic booster and can be coformulated in a single-tablet regimen. Phase III studies have demonstrated the efficacy and safety of dolutegravir for treatment-naive and treatment-experienced patients. Compared with other INSTIs, dolutegravir has a higher genetic barrier to resistance. Dolutegravir was approved by the U.S. Food and Drug Administration in August 2013 and joins raltegravir and elvitegravir as guideline-preferred agents for the management for HIV-infected treatment-naive patients.

No abstract