Current Issue : October - December Volume : 2019 Issue Number : 4 Articles : 5 Articles
While extensive research efforts have decreased human immunodeficiency virus (HIV)\ntransmissions and mortalities, new challenges have arisen in the fight to eradicate HIV. Drug\nresistance to antiretroviral therapy threatens infected individuals, while the prevalence of heterosexual\ntransmission creates an urgent need for therapies effective in the female reproductive tract (FRT)\nmucosa. We screened a library of 2095 small molecule compounds comprising a unique chemical\nspace, purchased from Asinex Corporation, for antiviral activity against human immunodeficiency\nvirus type 1 (HIV-1) strain BaL and identified several molecular representatives of a unique class of\nHIV-1 inhibitors, which we termed â??Avirulins.â?We determined that Avirulins were active against\nclinical isolates of HIV-1 from genetically variant subtypes, several of which have reduced sensitivity\nto other antivirals. Avirulins displayed specific dose-dependent inhibition of the HIV-1 drug target,\nreverse transcriptase (RT). Avirulins were effective against several nucleoside RT-inhibitor resistant\nstrains of HIV-1, as well as one nonnucleoside RT-inhibitor resistant strain containing a 106A mutation,\nsuggesting a noncompetitive mechanism of action. Drugs, which are damaging to the FRT, can increase\nthe risk of HIV-1 transmission. We therefore explored the cytotoxicity of Avirulins against epithelial\ncells derived from the FRT and found no significant toxicity, even at the highest concentrations tested.\nImportantly, Avirulin antiviral activity was not diminished in human cervicoâ??vaginal fluid, suggesting\nretained potency in the milieu of the FRT. Based on these promising results, Avirulins should be\nvaluable chemical scaffolds for development into next-generation treatments and preventatives that\ntarget HIV-1....
Hundreds of billions of dollars have been spent for over three decades in the search for an\neffective human immunodeficiency virus (HIV) vaccine with no success. There are also at least two\nother sexually transmitted viruses, for which no vaccine is available, the herpes simplex virus (HSV)\nand the hepatitis C virus (HCV). Traditional textbook explanatory paradigm of rapid mutation of\nretroviruses cannot adequately address the unavailability of vaccine for many sexually transmissible\nviruses, since HSV and HCV are DNA and non-retroviral RNA viruses, respectively, whereas eective\nvaccine for the horsefly-transmitted retroviral cousin of HIV, equine infectious anemia virus (EIAV),\nwas found in 1973. We reported earlier the highly disordered nature of proteins in outer shells of\nthe HIV, HCV, and HSV. Such levels of disorder are completely absent among the classical viruses,\nsuch as smallpox, rabies, yellow fever, and polio viruses, for which efficient vaccines were discovered.\nThis review analyzes the physiology and shell disorder of the various related and non-related viruses\nto argue that EIAV and the classical viruses need harder shells to survive during harsher conditions\nof non-sexual transmissions, thus making them vulnerable to antibody detection and neutralization.\nIn contrast, the outer shell of the HIV-1 (with its preferential sexual transmission) is highly disordered,\nthereby allowing large scale motions of its surface glycoproteins and making it difficult for antibodies\nto bind to them. The theoretical underpinning of this concept is retrospectively traced to a classical\n1920s experiment by the legendary scientist, Oswald Avery. This concept of viral shapeshifting has\nimplications for improved treatment of cancer and infections via immune evasion....
Background: Presence of isolated anti-HBc antibody is common in HIV-infected patients in endemic areas and could\nbe caused by prior HBV infection with loss of anti-HBs antibody. The role of vaccination in these patients remains\ncontroversial and is based largely on limited and low quality data. We, therefore, conducted this study to determine\nimmunogenicity and safety of 4 vs. 3 standard doses of HBV vaccination in HIV-infected adults with isolated anti-HBc\nantibody.\nMethods: An open-label, randomized controlled trial was conducted among HIV-infected patients visiting HIV clinic\nof the Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand between July and September 2017.....................
Background: Individuals with two copies of the apolipoprotein-1 (APOL1) gene risk variants are at high risk (HR) for\nnon-diabetic kidney disease. The presence of these risk variants is highest in West Africa, specifically in Nigeria.\nHowever, there is limited availability of dialysis and kidney transplantation in Nigeria, and most individuals will die\nsoon after developing end-stage renal disease. Blocking the renin angiotensin aldosterone system with angiotensinconverting\nenzyme inhibitors (ACEi) is a well-recognized strategy to slow renal disease progression in patients with\ndiabetes mellitus with chronic kidney disease (CKD) and in patients with HIV-associated nephropathy. We propose\nto determine whether presence of the APOL1 HR genotype alters or predicts responsiveness to conventional\ntherapy to treat or prevent CKD and if addition of an ACEi to standard combination antiretroviral therapy (ART)\nreduces the risk of kidney complications among non-diabetic Nigerian adults.\nMethods/design: We will screen 2600 HIV-positive adults who have received ART to (1) determine the prevalence\nof APOL1 risk variants and assess whether APOL1 HR status correlates with prevalent albuminuria, estimated\nglomerular filtration rate (eGFR), and/or prevalent CKD; (2) assess, via a randomized, placebo-controlled trial (RCT) in\na subset of these participants with microalbuminura (n = 280) whether addition of the ACEi, lisinopril, compared to\nstandard of care, significantly reduces the incidence or progression of albuminuria; and (3) determine whether the\nAPOL1 HR genotype is associated with worse kidney outcomes (i.e. eGFR slope or regression of albuminuria) among\nparticipants in the RCT.\nConclusions: This study will examine the increasing prevalence of kidney diseases in HIV-positive adults in a West\nAfrican population, and the relationship between these diseases and the APOL1 high-risk genotype. By evaluating\nthe addition of an ACEi to the care of individuals with HIV infection who have albuminuria, our trial will provide\ndefinitive evidence to guide strategies for management and clinical care in this population, with the goal of\nreducing HIV-related kidney complications....
Background. In 2016, the Kenyan Ministry of Health (MOH) released guidelines that recommend preexposure prophylaxis (PrEP)\nfor persons with substantial ongoing HIV risk, including those in HIV serodiscordant partnerships. Estimates of the costs of\ndelivering PrEP within Kenyan public health facilities are needed for planning for PrEP scale up. Methods. We estimated the\nincremental annual costs of providing PrEP to HIV uninfected partners as a time-limited â??bridgeâ? until the infected partner is\nvirally suppressed on ART within HIV serodiscordant couples as part of routine clinic care inThika, Kenya. Costs were collected\nfrom the Partners Demonstration Project, a prospective evaluation of integrated delivery of preexposure prophylaxis (PrEP) and\nantiretroviral therapy (ART) to high-risk HIV serodiscordant couples. We conducted time and motion studies to distinguish\nbetween activities related to research, routine clinical care, and PrEP delivery. Costs (2015 US dollars) were collected from the\nMOH perspective and divided into staff, transportation, equipment, supplies, buildings and overhead, and start-up. Results. PrEP\nrelated activities conducted during the screening, enrollment, and follow-up visits took an average of 13 minutes, 51 minutes, and\n12 minutes, respectively. Assuming a staff structure of 3 counselors, 1 nurse, and 2 clinicians, we estimate that 3,178 couples can\nbe screened, 1,444 couples offered PrEP and ART, and 6,138 couples followed up annually in an average HIV care clinic. Using\ncosts incurred by the MOH for personnel, drug, and laboratory tests, we estimate that the incremental cost of offering PrEP to\nHIV uninfected partners within existing ART programs is $86.79 per couple per year. Personnel and PrEP medication made up the\nlargest portion of the costs.We estimate that the total cost toMinistry of Health of delivering integrated PrEP and ART program in\npublic health facilities is $250.19 per HIV serodiscordant couple per year. Conclusions. Time-limited provision of PrEP to the HIV\nuninfected partner within HIV serodiscordant couples can be an affordable delivery model implemented in HIV care programs in\nKenya and similar settings. These costs can be used for budgetary planning and cost effectiveness analyses....
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