Anti-CD4 monoclonal antibody, clone DWT5 [R-PE]

Background: Rapid antiretroviral therapy (ART), ideally initiated within twenty-four hours of diagnosis, may be crucial in efforts to increase virologic suppression and reduce HIV transmission. Recent studies, including demonstration projects in large metropolitan areas such as Atlanta, Georgia; New Orleans, Louisiana; San Francisco, California; and Washington D.C., have demonstrated that rapid ART initiation is a novel tool for expediting viral suppression in clinical settings. Here we present an evaluation of the impact of a rapid ART initiation program in a community-based clinic in Jackson, MS. Methods: We conducted a retrospective chart review of patients who were diagnosed with HIV at Open Arms Healthcare Center or were linked to the clinic for HIV care by the Mississippi State Department of Health Disease Intervention Specialists from January 1, 2016 to December 31, 2018. Initial viral load, CD4+ T cell count, issuance of an electronic prescription (e-script), subsequent viral loads until suppressed and patient demographics were collected for each individual seen in clinic during the review period. Viral suppression was defined as a viral load less than 200 copies/mL. Rapid ART initiation was defined as receiving an e-script for antiretrovirals within seven days of diagnosis. Results: Between January 1, 2016 and December 31, 2018, 70 individuals were diagnosed with HIV and presented to Open Arms Healthcare Center, of which 63 (90%) completed an initial HIV counseling visit. Twenty-seven percent of patients were provided with an e-script for ART within 7 days of diagnosis. The median time to linkage to care for this sample was 12 days and 5.5 days for rapid ART starters (p < 0.001). Median time from diagnosis to viral suppression was 55 days for rapid ART starters (p = 0.03), a 22 day decrease from standard time to viral suppression. Conclusion: Our results provide a similar level of evidence that rapid ART initiation is effective in decreasing time to viral suppression. Evidence from this evaluation supports the use of rapid ART initiation after an initial HIV diagnosis, including same-day treatment.

Background and Aims The augmenter of liver regeneration (ALR) protein is critical for lipid homeostasis and mitochondrial function. We investigated high-fat/high-carbohydrate (HF/HC) diet-induced nonalcoholic fatty liver disease (NAFLD) in wild-type (WT), hepatocyte-specific ALR-knockout (ALR-H-KO), and ALR-heterozygous (ALR-H-HET) mice. ALR was measured in serum of human nonalcoholic steatohepatitis (NASH) and NASH-induced cirrhosis (serum and liver). Approach and Results HF/HC feeding decreased ALR expression in all groups of mice. The otherwise normal ALR-H-HET mice gained more weight and steatosis than WT mice when challenged metabolically with the HF/HC diet; ALR-H-KO mice gained the least weight and had the least steatosis. These findings were consistent with correspondingly increased triglycerides and cholesterol and altered expression of carnitine palmitoyltransferase 1a, sterol regulatory element-binding protein, acetyl coenzyme A carboxylase, and fatty acid synthase. All HF/HC-fed mice developed insulin resistance, the magnitude being lower in ALR-H-KO mice. HF/HC-fed ALR-H-HET mice were more resistant to glucose challenge than WT or ALR-H-KO mice. The frequency of tumor necrosis factor alpha-producing, interleukin 6 (IL6)-producing, and IL17-producing cells was greater in ALR-H-KO than ALR-H-HET and lowest in WT mice. HF/HC feeding did not increase their number in ALR-H-KO mice, and the increase in ALR-H-HET was greater than that in WT mice except for IL17 cells. Cluster of differentiation 25-positive (CD25(+)) forkhead box P3-positive CD4(+) regulatory T-cell frequency was lower in ALR-H-HET than WT mice and further reduced in ALR-H-KO mice; HF/HC reduced regulatory T-cell frequency only in WT mice. HF/HC-fed ALR-H-HET, but not WT, mice developed fibrosis; and ALR-H-KO mice progressed to cirrhosis. White adipose tissue of HF/HC-fed ALR-deficient mice developed strong inflammation, indicating bidirectional interactions with the liver. Hepatic and serum ALR levels were significantly reduced in patients with NASH-cirrhosis. Serum ALR was also significantly lower in patients with NASH. Conclusions Hepatic ALR deficiency may be a critical predisposing factor for aggressive NAFLD progression.