Current Diagnostic Methods for Human Immunodeficiency Virus

Current Diagnostic Methods for Human Immunodeficiency Virus Abstract: Detection of human immunodeficiency virus (HIV) infection is essential for diagnosis and monitoring of the infection. There are several different types of diagnostic tools available that are based on detection of HIV-specific antibodies, virus antigen, or nucleic acid. Sensitivities and specificities of assays utilized for HIV detection have improved. Newer HIV testing technologies such as third-generation enzyme immunoassay (EIA) which detect HIV-specific IgG and IgM antibodies, fourth-generation EIA which detect both anti-HIV antibodies and HIV p24 antigen, and nucleic acid-based tests (NATs) for HIV RNA, have significantly decreased the window period. This review study provides an overview of current technologies for the detection and monitoring of HIV infection and recent advances in the field of HIV diagnosis. Keywords: HIV diagnosis; HIV antibody test; human immunodeficiency virus; Immunoassay; Polymerase chain reaction (PCR) Introduction: Diagnosis of HIV infection contributes to evaluating the progression of disease, monitoring the effectiveness of antiretroviral therapy (ART), and prevention and control of HIV/AIDS. The diagnosis of HIV is associated with decrease in risky behaviors, reduced HIV transmission, and improved survival linked to increased case detection, earlier care and treatment. HIV-negative persons can also protect themselves from HIV when making sexual decisions by engaging in safer sex behaviors and sometimes, taking pre-exposure prophylaxis (PrEP). Early diagnosis of HIV infection provides an opportunity for risk reduction counseling and preventing further transmission of the disease, while late diagnosis of HIV infection is detrimental to infected patients and to the public health, and is associated with an increased rate of morbidity, mortality, and healthcare costs. Since the start of the epidemic, it is estimated that 78 million people have become infected with HIV and 35 million people have died from AIDS-related illnesses. In 2015, 2.1 million people became newly infected, 36.7 million people were living with HIV and 1.1 million people died from AIDS-related illnesses. New HIV infections have fallen by 6% since 2010. Sub-Saharan Africa, which bears the heaviest burden of HIV/AIDS worldwide, accounts for 65% of all new HIV infections. Other regions significantly affected by HIV/AIDS include Asia and the Pacific, Latin America and the Caribbean, and Eastern Europe and Central Asia (Table 1) [9]. The present study aims to conduct a narrative review to summarize and discuss the current diagnostic methods for HIV and recent developments. We start with a brief overview of HIV infection, follow by a description on the development of virological and immunological markers following HIV infection. Thereafter, we introduce current algorithms for laboratory HIV testing with different kind of current diagnostics techniques including various generations of enzyme immunoassays, rapid or point-of-care tests, and qualitative/quantitative PCR assays. Overview of HIV Infection: HIV-1 causes chronic infection which is usually characterized by progressive immune deficiency, a long period of clinical latency, and appearance of opportunistic infections [1, 2]. Characteristics of HIV include infection and viral replication in T lymphocyte expressing CD4 antigen. Qualitative defects in CD4 cell response and a gradual decline in their numbers increase the risk of opportunistic infections like Pneumocystis carinii pneumonia, and neoplasms such as Kaposis sarcoma and lymphoma [3-5]. HIV infection can disrupt functions of blood monocytes, tissue macrophages, and B lymphocytes, and also increase the potential of encapsulated bacteria for developing infections [6, 7]. Direct invasion of CD4 cells in the peripheral and central nervous systems can cause meningitis, peripheral neuropathy, and dementia [8]. The prognosis is variable between people infected with HIV-1. In adults, the average time between HIV exposure to AIDS stage is 10-11 years, but a remarkable proportion of individuals (~20%) progresses rapidly to AIDS within 5 years after HIV exposure. On the other hand, it is estimated that 12% of infected individuals will remain free of AIDS for 20 years [10]. Prophylaxis and in particular antiretroviral therapy (ART) significantly enhanced the overall prognosis of HIV disease against opportunistic infections [11]. The most common route of HIV infection is sexual transmission at the genital mucosa via direct contact with infected body fluids, such as blood, semen, and vaginal secretions. Infection may also occur via inoculation of infected blood, transfusion of infected blood products, transplantation of infected tissues, from an infected mother to her infant during pregnancy, or by reuse of contaminated needles [12]. The probability of transmission after a single exposure with an uncontrolled HIV source has been estimated to be 1/150 with needle sharing, 1/300 with occupational percutaneous exposure, 1/300-1/1000 with receptive anal intercourse, 1/500-1/1250 with receptive vaginal intercourse, 1/1000-1/3000 with insertive vaginal intercourse, and 1/3000 with insertive anal intercourse. The average risk is 12-50% for congenital (mother-to-child) transmission, 12% for breast-feeding, 90% for a contaminated blood transfusion, and 0.1-1.0% for nosocomial transmission [13]. The risk of HIV transmission during early or acute HIV infection appears to be greater than during chronic infection (251). Available data suggest that the viral load is an important predictor of the risk of heterosexual transmission, and patients with levels less than 1500 copies of HIV-1 RNA per milliliter are at lower risk of HIV transmission, whereas the probability of transmission is increased dramatically with increasing vira l loads (250). Laboratory markers for HIV-1 infection: Several immunological and virological blood markers can be monitored during the course of HIV infection. These markers appear highly consistent between different individuals in a chronological order and allows classification of HIV infection into distinct laboratory stages including eclipse period, seroconversion window period, acute HIV infection, and established HIV infection (Figure 1) [14, 15]. Shortly after exposure to HIV-1, no viral markers are consistently detectable in plasma, but low levels of HIV-1 RNA can be found intermittently [16]. This period is called the eclipse phase. About 10 days after infection, HIV-1 RNA becomes detectable by NAT in plasma and quantities rise to very high levels [17], which subsequently decline rapidly until reaching a set point, a stable level that may persist for years. This stable level of HIV RNA represents an equilibrium between HIV and host immune responses and is an important indicator of subsequent disease progression, and potential transmission of HIV. It has been shown that the higher HIV-1 RNA plasma level is associated with faster progression to AIDS [18]. The set point plasma HIV-1 RNA level can be a helpful clinical tool for determining the timing of initiation of antiretroviral therapy for HIV-infected patients. For instance, patients with high set point levels can be started on aggressive antiretroviral therapy and patient s with low set point levels can be monitored without initiating therapy [19]. HIV-1 p24 antigen is expressed and quantities rise to levels that can be measured by fourth-generation immunoassays within 17 days after infection (typical range 13-28 days) [15, 20]. Due to high titers of p24 antigen present in the sera of acutely infected patients during the interval prior to seroconversion, p24 Ag assay can be utilized to diagnose the primary HIV-1 infection [21]. Nevertheless, detection of p24 antigen is transient because, as antibodies begin to develop, they bind to the p24 antigen and form immune complexes that interfere with p24 Ag assay [22, 23]. The time interval between infection with HIV and the first detection of antibodies is known as the serological window period. The detection of HIV-specific antibodies indicates the end of the window period and the individual is known as seropositive [24]. The length of the window period depends on the design and the sensitivity of the immunoassay. Expression of IgM antibodies can be detected by immunoassays within 10 to 13 days after the appearance of viral RNA, 3 to 5 days after detection of p24 antigen, and peak between the 4th and the 5th week [15, 20, 25, 26]. Thereafter, the emergence of IgG antibodies occurs at about 3-4 weeks after infection and persist throughout the course of HIV infection [21]. Nevertheless, the immune responses are highly dependent on the ability of the individuals immune system to produce the antibodies. Approximately, 50% of patients within 3-4 weeks and about 100% of them within 6 months have detectable antibodies, although there are reports indicating that a small percentage of patients may require up to 6 months for the appearance of antibodies [27]. Laboratory HIV testing algorithms: Since 1989, the diagnostic algorithm for HIV testing recommended by CDC and the Association of Public Health Laboratories (APHL) relied on the confirmation of a repeatedly reactive HIV immunoassay with the more specific HIV-1 antibody test, either the HIV-1 Western blot or HIV-1 indirect immunofluorescence assay (IFA). The Western blot was previously considered to be the gold standard for the diagnosis of HIV infection by Clinicians [29, 30]. It should be noted that both the Western blot and IFA are first-generation assays that detect only IgG antibodies against HIV proteins. Retrospective testing of specimens from high-risk individuals pointed that antibody testing alone may miss a significant percentage of HIV infections detectable by virologic tests such as HIV antigen and nucleic acid assays. In 2013, the CDC and the APHL released new guidelines on HIV testing that have led to the earlier diagnosis of HIV infection when compared with the previous diagnostic algorithm. The new recommended algorithm starts with a fourth-generation HIV-1/2 Ag/Ab immunoassay to screen for HIV infection that detects both HIV-1/2 antibodies and the HIV-1 antigen. When the result of initial immunoassay is nonreactive, further testing is not required for samples. Instead, testing with an HIV-1/HIV-2 antibody differentiation test is needed when the sample is reactive on the screening fourth-generation assay. Reactive results with the initial fourth-generation assay and the HIV-1/HIV-2 antibody differentiation immunoassay should be considered as reactive for HIV-1 antibodies, HIV-2 antibodies, or HIV antibodies, undifferentiated. Reactive results with the initial fourth-generation assay and nonreactive or indeterminate on the HIV-1/HIV-2 antibody differentiation immunoassay should be tested with an FDA-approved HIV-1 NAT to differentiate early HIV infection from a false-positive screening result [28] (Figure 2). HIV diagnostic tests: Serological diagnostic assays: Enzyme Immunoassays (EIA):Significant advances in the development of HIV immunoassays have been created since the discovery of HIV in 1983. Based on different design principles, HIV immunoassays are generally classified into generations. The earliest immunoassays (first-generation) are indirect EIAs that used coated viral lysate antigens derived from cell culture on a solid phase for antibody capture and an indirect format that detected antibody utilizing an enzyme-conjugated antihuman IgG [36]. Antibody can be detected within 8-10 weeks postinfection by first generation immunoassay. These assays have 99% sensitivity and 95-98% specificity for HIV infection. Second-generation immunoassays use synthetic peptide or recombinant protein antigens alone or in combination with viral lysates to bind HIV antibodies, and they use an indirect immunoassay format that employs conjugated antihuman IgG, which binds to IgG with high affinity, to detect IgG antibodies [37]. Utilizing recombinant anti gens in the second-generation assays improves sensitivity for HIV-1, HIV-1 group O, and HIV-2, allowing earlier detection of IgG antibodies. The sensitivity and specificity of second-generation assays have been reported to be ˃99.5% and ˃99%, respectively. First and second generation immunoassays can only detect IgG antibody to HIV. The window period was decreased to 4 to 6 weeks postinfection by second-generation assays. Third generation immunoassays also utilize synthetic peptide or recombinant antigens to bind HIV antibodies, but in an immunometric antigen sandwich format; HIV antibodies in the specimen bind to HIV antigens on the assay substrate and to antigens conjugated to indicator molecules. This allows detection of both IgM and IgG antibodies which leads to increase in sensitivity and specificity of the test. Lower sample dilutions and the ability to detect IgM antibodies (which are expressed before IgG antibodies) further decrease the window period to 2-3 weeks postinfection [38]. The reported sensitivity and specificity of third-generation assays is ˃99.5%. Combination or fourth-generation tests use synthetic peptide or recombinant protein antigens in the same antigen sandwich format as third-generation assays for the detection of IgM and IgG antibodies, and also monoclonal antibodies for the detection of p24 antigen [39]. Inclusion of p24 antigen capture allows the detection of HIV-1 infection before seroconversion and further decreases the window period. Most fourth-generation antigen/antibody immunoassays (termed combo assays) do not distinguish antibody reactivity from antigen reactivity [39]. Recent published data has shown that the fourth-generation assay was able to establish HIV infection in more than 80% of patients who tested NAAT positive but either nonreactive or indeterminate by other tests like Western blot, first to third generation immunoassays, and rapid tests [40-42]. Delaney et al. found that the fourth-generation immunoassay are able to detect HIV infection 1-3 weeks earlier than the first, second, and third generation immunoassay which cannot detect p24 antigen. The results of their study revealed that the median duration of the eclipse period was 11.5 days and 99% of specimens from HIV-infected patients could be reactive with Ag/Ab combination tests within 45 days of exposure. Moreover, for detection of antibodies by the IgG/IgM-sensitive and other plasma screening assays, 50 days or longer were required and after 3 month of exposure, infection could be detected by all tests. Several studies have reported sensitivities of 100% for fourth-generation immunoassay, whereas other surveys reported transient sensitivities range from 62-89% when assessed against HIV RNA assays. This decreased sensitivity can be attributed to the presence of a second diagnostic window. This situation is rare but it can happen. Second diagnostic window period lies between the p24 antigen detection and the anti-HIV antibody detection, and is associated with reduction in the p24 antigen and antigen/antibody complexes levels, as well as a delay in HIV-specific antibody development which totally may affect the sensitivity of fourth-generation immunoassays. So, it is possible that many acute HIV infections have been missed using fourth-generation assays. Despite negative results from a fourth-generation immunoassay in high-risk populations with suspected acute HIV infection, it is needed to repeat the test on new blood samples obtained several days later, as well as testing for HIV anti body alone, p24 antigen or use of an HIV RNA assay. In 2015, an improved version of immunoassay, BioPlex 2200 HIV Ag-Ab screening test system, received FDA approval in HIV screening which detects both HIV antibody and the HIV-1 p24 antigen by providing separate results for each analyte. This test also provides separate results for HIV-1 and HIV-2 antibodies, so there is no need for a HIV-1/2 differentiation assay for antibody reactive samples. It was reported that the sensitivity and specificity of BioPlex 2200 HIV Ag-Ab assay were 100 and 99.5%, respectively [43]. HIV Confirmatory Tests:Screening tests must be highly sensitive to produce few false-negative results, whereas confirmatory assays are characterized with high specificity to produce few false-positive results [44]. If the result of a screening test is repeatedly reactive, this has to be confirmed by (at least) one confirmatory assay. Western blot or indirect IFA traditionally have been employed as confirmatory assay due to their higher specificity. The probability that both ELISA and Western blot would give false-positive results is extremely low (

Scuba Diving Essay -- Art

Scuba diving is a sport in which you can lose yourself to the beauty of the underwater world and escape gravity for a short time. You can wander among kelp forests or swim with sleek noble sharks. You can find a fortune in Spanish ducats or lose yourself in the beauty of the underwater realm. Some may say though that diving is an extreme sport and that it is too risky for anyone, it's just for the wild hooligans. Scuba Diving is a safe and enjoyable hobby despite the small risk involved. Haven't you ever wondered what it was like to swim with the fish? Or see why all of those people would want to were all that funny looking gear and go under the water? The going below the water is little like being above the water. While underwater there are forces and laws that dictate how your body will respond to being under so much pressure. The first rule regarding the pressure water puts on the air spaces in your body is Boyles Law. It says that as the pressure increases on a given mass of gas the volume will decrease. This rule explains the popping sensation you fell when you go up in an air plain and the squeeze you feel as you go under water (The Skin Divers Bible 37, 41). Another law is Dalton's law of partial Pressure. It says that pressure of mixed gasses is equal to the pressure exerted by the individual gas. So if a mixture of gas is say 5% carbon dioxide then it would account for 5% of the total pressure of the gas, because of this law the concentration of harmful gasses must be less when you are under water otherwise you can be poisoned or experience the effects of the gas that would only occur at a higher concentrati! on at sea lev el (47). And the last major law that governs you while underwater is Henry's law. It simply s... ...eatures feel like they are being attack they will usually fight back with painful and even deadly consequences (PADI Adventures 208-211). With all the mystic surrounding the sport of scuba diving many people would never dream about taking a class to get certified, and those people don't know what they are missing. Those people that would never consider diving most likely have only seen the dangers and risks of diving, but they have never really looked into the safety precaution and quality of the instruction needed to go diving. I hope that anyone who had previously decided against Scuba diving reconsider their choice, because they are missing out on some awe inspiring views and spectacular adventures. If you do nothing else in your lifetime at least take an introductory class to Scuba diving. It may just show you how safe and enjoyable the sport actually is.

Prenuptial Agreement

What to do/say to make her willing for signing the prenup The easiest way to convince your girlfriend to sign is by making it clear that it's to protect both of you, not just you. And make sure to explain that you in no way expect to get a divorce in the future. Don't lead her to believe that you're planning your exit strategy. Explain that this is simply a â€Å"just in case† plan. It's a good idea to bring up the prenup issue early on in the relationship, and definitely before getting engaged, in order to gauge her feelings about the issue. Ask her what she knows about prenups. Make her understand that it's not you against her; you both have input when it comes to the contract. Make her understand that it's not about her getting nothing if you part ways. Don't leave her with doubts. Ask her to be logical about the situation. Although this will likely be difficult for her (it is for most women), if she really cares for you, she'll put forth the effort. You can include a clause about cheating, if she begins to question your fidelity. Keep in mind that if you agree to do this, then she should have no problem attesting that she'll remain faithful as well. Ask her to get legal advice she will eventually see the benefits of a prenup on her own. Tell her you love her, and that this is just for insurance. Read more: http://www.askmen.com/money/how_to_150/190_how_to.html#ixzz2XN57hR2j

Ethics Reflection Paper - Free Essay Example

Sample details Pages: 3 Words: 1046 Downloads: 1 Date added: 2017/09/13 Category Advertising Essay Did you like this example? Ethics Reflection Paper Lourdes Munoz STR/581 Strategic Planning Implementation September 2nd, 2010 Gary Solomon Abstract Ethics and Social responsibility resides in an important set of our own personal values. When it comes to Business matter and operation the customer must feel confidence and this has been taken for granted several times on recent corporate scandals and collapses, a perfect example of missed conducted ethic and responsibility is Enron. Is extremely important for companies to incorporate ethics and responsibilities to their strategic planning. Strategic planning using ethics and responsibility corresponds to company who are engaged with customer face to face or their involvement is not physical or direct, developing a relationship with their clients. On this paper analyzes the ethics and social responsibility, how these applies to a company stakeholders and strategy planning. The paper will also develop on the perspective and evolvement of personal ethics throughout the master degree. The Role Of Ethics and Social Responsibility in Strategic Planning Don’t waste time! Our writers will create an original "Ethics Reflection Paper" essay for you Create order In order to be successful, companies must contemplate on what ethics and social responsibility may the business should take critical part. On the strategic planning the ethical responsibility and social responsibility must imply profit decisions to receive a maximum benefits in other words is a success if these roles are incorporated. Within the business perspective, businesses are likely to have high-quality ethical values and act of socially responsibility. Ethics is not just talking about the right thing is actually doing what is right. The Role of Ethics The values of ethics reinforce the companies mission, visions and goals building a direction and a framework. The ethics of a company can be use as a guideline to create a truss to the entire organization into one general loop, managing the action of the organizations employees, and avoiding differences the strategic plan designed. The values of Ethics responsibility makes sure that the strategic plan is prepared basically for the best interest of the stakeholders, weather the employees or customers or even vendors may operate. What is ethics? According to authors Andre and Velasquez, ethics has two parts. First, it refers to well base standards of right and wrong behavior. What individuals ought to do, usually in terms of rights, obligations, and benefits to society, fairness, or specific virtues. Second, it refers to continually examining our moral beliefs and moral conduct, and striving to live up to these well based standards (Andre, C, Velesquez, M. , 1987). Many companies around the world have left their customers in a state of frustration or distrust to specific businesses resulting in an analysis from regulatory authorities and government. Creating a high standard on ethical issues and integrating ethics to the strategic planning can build a great corporate image for stakeholders and the organization. Integrating to the strategic planning a disciplinary policy to manage integrity in the business. There are specific strategies to incorporate to a plan for ethical manners and the first will be to be explicit on the ethical goals and criteria of the company. Second to demonstrate the commitment to the first one. Third, to communicate and train employees in order to behave and act using their criteria making decisions for the company based on their goals. Four monitor the employees’ behavior and decisions in the company. For last, maintain on-going proactive integrity continuity management (Valentino, 2007). This may ensure the company’s stakeholders best interest and will address their needs. The Role of Social Responsibility The Role of Social Reponsability is a major element to a strategic planning in a business. This demand has been marked by numerous claims linking corporate social responsibility to a firm’s profits, particularly in professional publications (Kanter, 1999). A social responsibility can be an example of ethical behavior. It’s attractive to general society. A business on the other side not very often can afford to go around and do good deeds if is not potential to receive a profitable benefit. Sometimes companies go beyond what is optional intending to create a benefit for others beside the company. A good example of a socially responsible behavior could be a company raising money for a research on a disease or raise money for a cause or make a requirement for their employees to volunteer in a community service. My Ethical Perspective My ethical perspective has expanded via this program, as I have understood the relationship involving ethics and its repercussion in a business. I have understood the meaning of ethics in terms of help to the stakeholders of an organization and the significance in the organizations day-to-day process. The program has qualified to identify the relationship concerning ethics and the different mechanism of the strategic plan of the organization. The upcoming of our organizations, the people they stand for, and the wider society that can only be build up by push in ethics into the strategic planning process. Ethics are central the overall management of the firm. Conclusion There are many things an organization can do to assist good ethical behavior and social responsibility. The best thing is to make sure the employees understand the companies’ values and culture of the organization and promotes it. Allowing employees to address to their managers regarding ethical behavior can be a great solution and this must be a concern and a result of ambiguous decisions about the right thing to do. Must well known companies include a code of ethics written and handle them to their new employees, by developing brochures with the companies mission statements ad beliefs. References Andre, C. Velesquez, M. (1987). What is Ethics? Issues in Ethics, 1, Fall 1987. Retrieved September 1, 2010 from https://www. scu. edu/ethics/publications/iie/v1n1/whatis. html Kanter R. M. (1999, December 14). From Spare Change to Real Change. Harvard Business Review 77 (3), 122-132. Retrieved September 1, 2010 from https://hbswk. hbs. edu/item/2974. html Lessons from the Enron Scandal On March 5, 2002, Kirk Hanson, executive director of the Markkula Center for Applied Ethics, was interviewed about Enron by Atsushi Nakayama, a reporter for the Japanese newspaper Nikkei, Santa Clara University, Retrieved September 1, 2010 from https://www. cu. edu/ethics/publications/ethicalperspectives/enronlessons. html Valentino, B. (2007, September 3). MBA Toolkit For CSR: Strategic Planning And Corporate Social Responsibility. Retrieved September 1, 2010 from https://www. chinacsr. com/en/2007/09/03/1652-mba-toolkit-for-csr-strategic-planning-and-corporate-social-responsibility/. Williams Institute: Ethical Choices in the Workplace, University Of Phoenix assessment week 1, strategic planning and implementation STR/581