Biology of AIDS and STDs - Assignment Example

BIOLOGY OF AIDS AND STDs Answer Seven different programs to prevent HIV transmission among those carried out by the Centers for Disease Control and Prevention (CDC): 1) A program of HIV testing in both medical and non-medical settings, was to identify persons who were not aware of their own HIV infection. This facilitated getting them into treatment services. 2) Implemented new models for diagnosing HIV infections outside medical settings. Some persons infected with HIV did not have access to traditional medical settings. 3) Prevented new infections by working with people diagnosed with HIV and their partners with treatment services within and outside traditional medical settings. 4) Further decreased mother to child HIV transmission, by monitoring breast feeding given to the infant as the only food, which had to be terminated after 4 to 6 months, followed by only weaning foods1. 5) The Advancing HIV Prevention Initiative focused on people at greatest risk for transmitting HIV and their partners; members of racial and ethnic minorities were disproportionately represented among these. 6) Directly-funded community-based organizations were required to use CDC-developed protocols and procedures for targeted outreach, health education and risk reduction, voluntary counseling and testing services, partner counseling and referral services. 7) 2The CDC provided information and social support to groups at risk for HIV, such as: peer outreach for gay men, street outreach for injection-drug users, education programs for youth in and out of school and faith-based initiatives in African-American communities. Answer 2: Screening tests for HIV are based on HIV antigens or antibodies directed towards these antigens (George; Schochetman 1994: p.57). These are used for blood donor screeningand medical diagnosis. Enzyme immune assay (EIA) or standard indirect enzyme linked immunosorbent assay (ELIZA) technology, with an enzyme-labelled second antibody is used as an initial screening test. Confirmatory tests are done to re-affirm the presence of the AIDS virus, by using a second test such as the Western blot test. Other examples of confirmatory tests are: 1) Radioimmunoprecipitation assay. 2) Dot-blot immunobinding assay. 3) Immunofluorescence assay. 4) Nucleic acid testing 5) Polymerase chain reaction (CDC). The terms used to measure the effectiveness of each of the diagnostic tests are: The sensitivity of a test is the probability that it will produce a true positive result when used on an infected population. The specificity of a test is the probability that a test will produce a true negative result when used on a noninfected population. The positive predictive value of a test is the probability that a person is infected when a positive test result is observed. In practice, predictive values should only be calculated from cohort studies or studies that legitimately reflect the number of people in that population who are infected with the disease of interest at that time. This is because predictive values are inherently dependent upon the prevalence of infection. The negative predictive value of a test is the probability that a person is not infected when a negative test result is observed. This measure of accuracy should only be used if prevalence is available from the data. The positive DLR represents the odds ratio that a positive test result will be observed in an infected population compared to the odds that the same result will be observed among a noninfected population. The negative DLR represents the odds ratio that a negative test result will be observed in an infected population compared to the odds that the same result will be observed among a noninfected population. Answer 3. The four different types of outcomes from an HIV vaccine: first, the infection is rapidly controlled and there is no disease. Second, the virus is fully eliminated thus achieving sterilizing immunity, and third: this low-grade, transient subclinical infection serves as a natural booster to the immune system. There is prolonged antibody production lasting for several years after infection or vaccination. Although very little neutralizing antibody is generated during the course of human immunodeficiency virus (HIV) infection, there is evidence suggesting that immunization with the right form of HIV envelope protein can induce neutralizing antibody that may be useful in conferring protective immunity. Thus the right strategy for an HIV vaccine would be to stimulate both the humoral and cellular arms of the immune system (Kaufmann, et al, 2002: p.178). The characteristics of an ideal vaccine are: The vaccine would be 100% safe to the recipient. An ideal vaccine should not retain any potential to cause the disease it is charged to protect against. An ideal vaccine should not lead to any vaccine-associated disease, particularly ones which are not characteristics of the wild pathogen. These can include: 1) allergic responses in recipients 2) significant local inflammation, etc3. Answer 4: The five major strategies that have been used for vaccine design are: 1) A high frequency of polyfunctional T-cells, especially those with the ability to secrete interleukin-2 and to proliferate. 2) T cells whose antigen receptors show high functional avidity for viral epitopes. 3) T cells that target epitopes where viral fitness constraints curb their ability to mutate. 4) T cells with recognition properties that are better able to detect escape mutations and viral quasispecies and 5) T cells at mucosal surfaces which are the first T cells likely to come into contact with HIV infected cells. All of these principles will guide critical aspects of vaccine design, including the route of immunization, mode of antigen presentation, antigen dose and persistence, and use of immunomodulatory adjuvants (Douek, et al, 2006: p.680). New technology such as prime-boost regimens, genetic immunization, expression library immunization, and recombinant viruses will aid in the discovery and/or delivery of vaccines (Kaufmann, et al, 2002: p.50). Answer 5. The first step in preparing for AIDS vaccine efficacy trials is to conduct a thorough assessment of strengths, assets and needs for infrasructure and training, and to determine whether a population at sufficiently high risk of HIV infection is accessible, and is willing to participate (Gust, et al, 2007: p.41). Major phases of clinical trials for vaccine testing: accumulation of data from many thousands of HIV infected individuals worldwide that identify preferentially targetted epitopes, the timing and nature of epitope escape, epitope-specific T-cell clonage usage, and HLA type and disease outcome should allow us to predict the nature of the T cell response that we need to elicit with a vaccine to prevent disease. The principles established could be incorporated in a successful vaccine (Douek, et al, 2006: p. 677). Answer 6 There are four major categories of FDA approved ARV drugs: 1) Nucleoside reverse transcriptase inhibitors work by blocking Step 4 of the HIV Life Cycle (The HIV genetic code (RNA) is changed into DNA). Drugs in use in this category include: AZT, ddl, d4T, etc. 2) Another class of drugs blocks the same step of the Life Cycle, but in a different way. This class is the non-nucleoside reverse transcriptase inhibitors or NNRTIs, they have been approved. The drugs in this category include: nevirapine, delavirdine. 3) The third class of anti-retroviral drugs block Step 10 of the Life Cycle where the raw material for the new HIV is cut into specific pieces. Ten protease inhibitors are being used. The drugs include Saqinavir and Indinavir. 4) The newest class of ARV drugs include fusion inhibitors. They prevent HIV from attaching to a cell by blocking Step 2 of the life cycle. One fusion inhibitor has been approved. The drug in this class is Enfuvirtide. Major side-effects associated with these drugs are: fatigue, anemia, digestive problems, lipodystrophy, peripheral neuropathy, mitochondrial toxicity, and osteoporosis4. Answer 7: Current U.S.guidelines for treatment of HIV: A nonnucleoside reverse transcriptase inhibitor or a protease inhibitor boosted with low-dose ritonavir each combined with 2 nucleoside reverse transcriptase inhibitors is recommended with choice being based on the individual patient profile. Therapy should be changed when toxicity or intolerance mandate it or when treatment failure is documented. The virologic target for patients with treatment failure is now a plasma HIV-1 RNA level below 50 copies/mL. Adherence to antiretroviral therapy in the short-term and in the long-term is crucial for treatment success and must be continually reinforced (International Aids Society 2006 Recommendations). WHO guidelines for prevention of mother-to-child transmission of HIV: Effective prevention of mother-to-child transmission (PMTCT) requires a three-fold strategy: 1) Preventing HIV infection among prospective parents. 2) Avoiding unwanted pregnancies among HIV positive women. 3) Preventing the transmission of HIV from HIV positive mothers to their infants during pregnancy, labour, delivery and breastfeeding.The last of these can be achieved by the use of antiretroviral drugs, safer feeding practices and other methods (WHO Factsheet 2006). Answer 8: According to Fan et al (2004: pp.85-86), the development of the protease inhibitors has led to some extremely effective combination therapies for HIV-infected individuals. Currently the most effective combinations involve the use of two nucleoside analogs and one protease inhibitor. For example, one combination is the nucleoside analogs AZT and 3TC along with the protease inhibitor indinavir. These are sometimes known as triple combination therapies or HAART (highly active antiretroviral therapy). These are more potent than the single drug treatments, and sustained results for several years are obtained. The rationale for the use of HAART is that: the patient became immune to a single drug over a period of time. However, his system could not become immune to a combination of two or more drugs ingested at the same time. Some specific limitations of HAART are: 1) The triple combination therapies are not effective in all infected individuals. 2) There is uncertainty about the duration of effectiveness. 3) Side effects which become progressively more serious. 4) Difficulty in maintaining treatment schedules due to large number of pills to be taken. 5) Prohibitive cost. Due to these problems, HAART cannot be administered on a long-term basis. Answer 9: In the pre-clinical stage, the drug is synthesized and purified. If the review boards’ recommendations are positive, then an application to the FDA occurs and clinical tests begin5. Phase 1: Clinical studies: in this phase represent the first time that an IND is tested on humans either healthy volunteers or sometimes patients. The purpose of these studies is study in a clinical setting the metabolism, structure-reactivity relationships, mechanism of action, any side-effects of the drug in humans. If possible, phase 1 studies are used to determine how effective the drug is. Phase 1 studies are usually conducted on 20 to 80 subjects. The purpose of Phase 2 clinical trials is to determine the efficacy of a drug to treat patients with a specific disease or condition, as well as learn about common short-term side effects or risks. These studies are conducted on a larger scale than phase 1 studies and typically involve several hundred patients. Phase 3 clinical trials provide more information about the effects and safety of the drug and they allow scientists to extrapolate the results of clinical studies to the general population. Phase 3 studies generally involve several hundred to several thousand people. There are several checks and balances in the process of clinical trials; among them is the use of institutional review boards (IRBs) and advisory committees. The sponsor of a drug makes a formal application to the FDA to approve a new drug for use in the United States by submitting a new drug application (NDA). Answer 10: The FDA has recently approved two new drugs that will be used to treat HIV6. Reyataz (atazanavir) This is Bristol Meyer Squibbs entry into the Protease Inhibitor class. Supplied in 200mg capsules, Atazanavir will be taken as two capsules once per day. While the drug is not any more potent than other PIs it does seem that the triglyceride and cholesterol problems associated with other PIs such as Kaletra are not a concern in Atazanavir. The new PI is not without its side effects however. Most notably is the fact that it seems to block the elimination of bilirubin from the blood. As the amount of bilirubin rises in the blood, the skin and other mucous membranes will take on a yellow appearance known as jaundice. The jaundice seemed to go away when the drug was stopped and only 1% of trial cases had to stop therapy because of the increase in bilirubin. Emtriva (emtricitabine) Gilead has received approval for its new nucleoside reverse transcriptase inhibitor. Emtriva. FTC as it is also referred to is going to be dosed as a 200mg capsule once per day. The chemical structure of Emtriva is similar to that of the existing HIV drug, Epivir and because of this probably wont be effective in people already showing resistance to Epivir. In studies conducted prior to its approval, the most common side effects seems to be rash, headache and nausea. Answer 11: The strategic shift on prevention efforts by the CDC from primary to secondary prevention programs: More than three decades ago AIDS and the HIV became a reality globally, which needed to be countered on a war footing. Earlier, the CDC worked to treat AIDS patients with the help of new drugs, and tried to stop the epidemic from spreading by awakening the national consciousness, and introducing barriers to stop the inflow of possibly infected individuals. Since this strategy was not working effectively, they switched to secondary prevention strategy, which also included the previous methods. They found that the most effective preventive methods work at multiple levels simultaneously – at individual, social network and community levels, as well as at the structural level – addressing the sometimes hidden societal barriers to effective prevention. Successful prevention provides support for healthy decision-making. People at risk for HIV infection and those who are already infected, can be helped to avoid spreading the virus to others. This type of strategy would work well in developing countries also, where the spread of the disease has to be prevented among those who are most vulnerable to it. However, specialized testing facilities and highly trained physicians, or treatment with expensive ARV drugs is not yet possible. Answer 12 According to Tan; Wu (2005: p.122), live attenuated vaccines meant for small-pox, poliomyelitis, measles and mumps, though of low cost and having high protective efficiency: have the risk of being infected by the attenuated strains, and possibly resulting in serious disease or death. Due to safety concerns, most candidate HIV and AIDS vaccines belong to the group of non-live-attenuated vaccines. The vaccines are mostly prophylactic (preventive), though currently some vaccines are being developed for treatment purposes. They are meant to prevent or postpone progression to AIDS, with the potential to reduce emergence of drug-resistant HIV strains, and to reduce side-effects on patients. High and prohibitive costs of the vaccine which make it impossible to be used among large numbers of people from the economically lower classes is one of the reasons why the vaccine is not already available. Also, the FDA (Food and Drugs Administration) is working on HIV drugs which will be less likely to have harmful side-effects. Answer 13: Treating AIDS early is always better than late. By nipping the disease in the bud, further spread of the virus can be prevented. Also, earlier intervention will mean that the treatment will be for a shorter duration, and at less cost of drugs. Answer 14: ARVs have proved to be a mixed blessing for AIDS patients. Many of them have severe toxicity and induce strong side effects, sometimes resulting in the patients discontinuing medication. But any deviation from strict adherence to the treatment regimen may result in the development of resistance and the infection tends to rebound with increased virulence. In many cases, the basic triple therapy needs the inclusion of a protease inhibitor, a very expensive ARV. A few years ago, starting HAART as soon as a person was detected to be HIV infected was considered the best course. But, delaying HAART as much as possible is now increasingly being adopted by physicians7. REFERENCES Centers for Disease Control and Prevention (CDC): National HIV Testing Resources. Web site: http://www.hivtest.org/subindex.cfm?fuseaction=faq Douek, Daniel C; Kwong, Peter D; Nabel, Gary J. “The Rational Design of an Aids Vaccine”. Journal: Cell, Vol.124, Feb. 24, 2006. pp. 677-681. George, J. Richard; Schochetman, Gerald. AIDS Testing: A Comprehensive Guide to Technical, Medical, Social, Legal, and Management Issues. New York: Springer, (1994). Fan, Hugh; Conner, Ross F; Villarreal, Luis P. Aids Fourth Edition: Science and Society. Jones and Bartlett Publishers, 2004. Gust, Ian; Koff, Wayne C; Kahn, Patricia. AIDS Vaccine Devlopment: Challenges and Opportunities. Horizon Scientific Press, 2007. International Aids Society – USA Panel: 2006 Recommendations. “Treatment for Adult HIV Infection”. Journal: American Medical Association. Vol.296, No.7, pp.827-844, 2006. Kaufmann, Stefan H.E; Sher, Alan; Ahmed, Rafi. Immunology of Infectious Diseases. ASM Press, 2002. Tan, Wai-Yuan; Wu, Hulin. Deterministic and Stochastic Models of Aids Epidemics and HIV Infections With Interventions. New Jersey: World Scientific Publisher, 2005. WHO Factsheet August 2006. HIV/ AIDS Program: New WHO Guidelines on Antiretroviral Drugs for Treating Pregnant Women and Preventing HIV Infection in Infants. Pp.1-2. 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