In 2016, the Prevention Access Campaign, a health equity initiative with the goal of ending the HIV/AIDS pandemic as well as HIV-related stigma, launched the Undetectable = Untransmittable (U = U) initiative. 1 U = U signifies that individuals with HIV who receive antiretroviral therapy (ART) and have achieved and maintained an undetectable viral load cannot sexually transmit the virus to others. This concept, based on strong scientific evidence, has broad implications for treatment of HIV infection from a scientific and public health standpoint, for the self-esteem of individuals by reducing the stigma associated with HIV, 2 and for certain legal aspects of HIV criminalization. 3 In this Viewpoint, we examine the underlying science-based evidence supporting this important concept and the behavioral, social, and legal implications associated with the acceptance of the U = U concept.A major breakthrough in HIV/AIDS therapeutics came in 1996 with the advent of 3-drug combinations of antiretrovirals, including the newly developed protease inhibitors. These therapeutic regimens resulted in substantial decreases in viral load in a high percentage of patients, usually below the level of detection in plasma and sustained for extended periods. 2 Although not appreciated at the time, the accomplishment of a sustained, undetectable viral load was likely the definitive point when the U = U concept became a reality. Proof of that concept would await further clinical trials and cohort studies. Based on a review of scientific data, a statement from Switzerland in 2008 indicated that individuals with HIV who did not have any other sexually transmitted infection, and achieved and maintained an undetectable viral load for at least 6 months, did not transmit HIV sexually. 4 This was the first declaration of the U = U concept, but it was not universally embraced because it lacked the rigor of randomized clinical trials.In 2011, the HIV Prevention Trials Network (HPTN) study 052 compared the effect of early with delayed initiation of ART in the partner with HIV among 1763 HIVdiscordant couples, of whom 98% were heterosexual. The finding of a 96.4% reduction in HIV transmission in the early-ART group, vs those in the delayed group, provided the first evidence of treatment as prevention in a randomized clinical trial. 5 At that point, the study could not address the durability of the finding or provide a precise correlation of the lack of transmissibility with an undetectable viral load. Importantly, after 5 additional years of follow-up, the durable, protective effect of early ART to maintain viral suppression and prevent HIV transmission was validated. There were no linked transmissions when viral load was durably suppressed by ART. 6
The cellular receptor for murine coronavirus mouse hepatitis virus (MHV)-A59 is a member of the carcinoembryonic antigen (CEA) family of glycoproteins in the immunoglobulin superfamily. We isolated a cDNA clone (MHVR1) encoding the MHV receptor. The sequence of this clone predicts a 424-amino-acid glycoprotein with four immunoglobulinlike domains, a transmembrane domain, and a short intracytoplasmic tail. MHVR, is closely related to the murine CEA-related clone mmCGM, (Mus musculus carcinoembryonic antigen gene family member). Western blot (immunoblot) analysis performed with antireceptor antibodies detected a glycoprotein of 120 kDa in BHK cells stably transfected with MHVR,. This corresponds to the size of the MHV receptor expressed in mouse intestine and liver. Human and hamster fibroblasts transfected with MHVR1 became susceptible to infection with MHV-A59. Like MHV-susceptible mouse fibroblasts, the MHVR,-transfected human and hamster cells were protected from MHV infection by pretreatment with monoclonal antireceptor antibody CCL. Thus, the 110to 120-kDa CEA-related glycoprotein encoded by
PCR is a technology born of the modern molecular biology era. The enzyme used for PCR, Taq DNA polymerase, supplied with the 10x buffer, is purchased as a cloned product, and the nucleoside triphosphates are ultrapure, buffered, and available at a convenient concentration. Yet, with all of these commercially available starting materials, PCR still fails, particularly for the novice. Assuming that all of the reagents have been added in the proper concentrations, two critical PCR components are left to the researcher. The first is the nucleic acid template, which should be of sufficient quality and PARAMETERS USED IN BASIC PCR PRIMER DESIGN Primer design is aimed at obtaining a balance between two goals: specificity and efficiency of amplification. Specificity is defined as the frequency with which a mispriming event occurs. Primers with mediocre to poor specificity tend to produce PCR products with extra unrelated and undesirable ampli-$30 PCR Methods and Applications
Mouse hepatitis virus-A59 (MHV-A59), a murine coronavirus, can utilize as a cellular receptor MEIVR, a murine glycoprotein in the biliary glycoprotein (BGP) subfamily of the carcinoembryonic antigen (CEA) family in the immunoglobulin superfamily (G.
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