Switching to Dolutegravir/Lamivudine Two-Drug Regimen: Durability and Virologic Outcomes by Age, Sex, and Race in Routine US Clinical Care

Gerald Pierone Jr,1 Laurence Brunet,2 Jennifer S Fusco,2 Cassidy E Henegar,3 Supriya Sarkar,3 Jean Van Wyk,4 Vani Vannappagari,3 Michael B Wohlfeiler,5 Gregory P Fusco2 1Department of Adult Primary Care, Whole Family Health Center, Vero Beach, FL, USA; 2Department of Epidemiology, Epividian, Raleigh, NC, USA; 3Epidemiology and Real World Evidence, ViiV Healthcare, Research Triangle Park, NC, USA; 4Global Medical, ViiV Healthcare, Brentford, UK; 5Department of Medicine, AIDS Healthcare Foundation, Miami, FL, USACorrespondence: Laurence Brunet, Epividian, 150 Fayetteville Street, Suite 2300, Raleigh, NC, 27601, USA, Tel +1-919-827-0010, Email [email protected]: Two-drug regimens (2DR) may address drug–drug interactions and toxicity concerns. Dolutegravir/lamivudine (DTG/3TC) 2DR was approved in the US for both treatment-naïve and treatment-experienced individuals with a viral load < 50 copies/mL. This study describes real-world DTG/3TC 2DR treatment outcomes among treatment-experienced individuals, stratified by age, sex, and race.Methods: From the OPERA® cohort, people with HIV with a viral load < 50 copies/mL who switched from a commonly used three-drug regimen to DTG/3TC 2DR as per the label between April 8, 2019 and April 30, 2021 were included. Incidence rates (Poisson regression) for loss of virologic control (first viral load ≥ 50 copies/mL), confirmed virologic failure (2 viral loads ≥ 200 copies/mL or discontinuation after 1 viral load ≥ 200 copies/mL), and DTG/3TC 2DR discontinuation were estimated overall and stratified by age, sex, and race.Results: The 787 individuals included were followed for a median of 13.6 months (IQR: 8.2, 22.3). Confirmed virologic failure occurred in ≤ 5 individuals. Loss of virologic control occurred at a rate of 14.0 per 100 person-years (95% CI: 11.7, 16.8). DTG/3TC 2DR discontinuation occurred at a rate of 17.5 per 100 person-years (95% CI: 15.0, 20.3); 4% discontinued for treatment-related reasons (viremia, adverse diagnosis, side effect, lab abnormality). For all outcomes, incidence rates were comparable across strata of age, sex, and race.Conclusion: This descriptive study demonstrates that DTG/3TC 2DR is an effective and well-tolerated treatment option for people with HIV with a viral load < 50 copies/mL at switch, regardless of their age, sex, or race.Keywords: antiretroviral therapy, cohort, electronic health records, suppressed, viral loa

HMGA1 overexpression in adipose tissue impairs adipogenesis and prevents diet-induced obesity and insulin resistance

High-Mobility-Group-A1 (HMGA1) proteins are non-histone proteins that regulate chromatin structure and gene expression during embryogenesis, tumourigenesis and immune responses. In vitro studies suggest that HMGA1 proteins may be required to regulate adipogenesis. To examine the role of HMGA1 in vivo, we generated transgenic mice overexpressing HMGA1 in adipose tissues. HMGA1 transgenic mice showed a marked reduction in white and brown adipose tissue mass that was associated with downregulation of genes involved in adipogenesis and concomitant upregulation of preadipocyte markers. Reduced adipogenesis and decreased fat mass were not associated with altered glucose homeostasis since HMGA1 transgenic mice fed a regular-chow diet exhibited normal glucose tolerance and insulin sensitivity. However, when fed a high-fat diet, overexpression of HMGA1 resulted in decreased body-weight gain, reduced fat mass, but improved insulin sensitivity and glucose tolerance. Although HMGA1 transgenic mice exhibited impaired glucose uptake in adipose tissue due to impaired adipogenesis, the increased glucose uptake observed in skeletal muscle may account for the improved glucose homeostasis. Our results indicate that HMGA1 plays an important function in the regulation of white and brown adipogenesis in vivo and suggests that impaired adipocyte differentiation and decreased fat mass is not always associated with impaired whole-body glucose homeostasis

Diabetic nephropathy

<p>Abstract</p> <p>Diabetic nephropathy is the leading cause of chronic renal disease and a major cause of cardiovascular mortality. Diabetic nephropathy has been categorized into stages: microalbuminuria and macroalbuminuria. The cut-off values of micro- and macroalbuminuria are arbitrary and their values have been questioned. Subjects in the upper-normal range of albuminuria seem to be at high risk of progression to micro- or macroalbuminuria and they also had a higher blood pressure than normoalbuminuric subjects in the lower normoalbuminuria range. Diabetic nephropathy screening is made by measuring albumin in spot urine. If abnormal, it should be confirmed in two out three samples collected in a three to six-months interval. Additionally, it is recommended that glomerular filtration rate be routinely estimated for appropriate screening of nephropathy, because some patients present a decreased glomerular filtration rate when urine albumin values are in the normal range. The two main risk factors for diabetic nephropathy are hyperglycemia and arterial hypertension, but the genetic susceptibility in both type 1 and type 2 diabetes is of great importance. Other risk factors are smoking, dyslipidemia, proteinuria, glomerular hyperfiltration and dietary factors. Nephropathy is pathologically characterized in individuals with type 1 diabetes by thickening of glomerular and tubular basal membranes, with progressive mesangial expansion (diffuse or nodular) leading to progressive reduction of glomerular filtration surface. Concurrent interstitial morphological alterations and hyalinization of afferent and efferent glomerular arterioles also occur. Podocytes abnormalities also appear to be involved in the glomerulosclerosis process. In patients with type 2 diabetes, renal lesions are heterogeneous and more complex than in individuals with type 1 diabetes. Treatment of diabetic nephropathy is based on a multiple risk factor approach, and the goal is retarding the development or progression of the disease and to decrease the subject's increased risk of cardiovascular disease. Achieving the best metabolic control, treating hypertension (<130/80 mmHg) and dyslipidemia (LDL cholesterol <100 mg/dl), using drugs that block the renin-angiotensin-aldosterone system, are effective strategies for preventing the development of microalbuminuria, delaying the progression to more advanced stages of nephropathy and reducing cardiovascular mortality in patients with diabetes.</p