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Premium member Presentation Transcript History of the HIV Epidemic: History of the HIV EpidemicHistory of the HIV Epidemic: 2 History of the HIV Epidemic Before 1980 Sporadic case reports of AIDS and sero-archaeological studies have documented human infections with HIV prior to 1970. available data suggest that the current pandemic started in the mid- to late 1970s. By 1980, HIV had spread to at least five continents (North America, South America, Europe, Africa and Australia).PowerPoint Presentation: 3 1981 History Kaposi's Sarcoma (KS) was a rare form of relatively benign cancer that tended to occur in older people. But by March 1981 at least eight cases of a more aggressive form of KS had occurred amongst young gay men in New York. At about the same time there was an increase, in both California and New York, in the number of cases of a rare lung infection Pneumocystis carinii pneumonia (PCP)3. In April this increase in PCP was noticed at the Centers for Disease Control (CDC) in Atlanta.Initial Reports: 4 Initial Reports June 5, 1981: 5 cases of PCP in gay men from UCLA (MMWR) July 3, 1981: 26 additional cases Dec 10, 1981: 3 NEJM papers describe cases Gottlieb MS NEJM 2001;344:1788-91PowerPoint Presentation: 5 Just five months later, in December 1981, it was clear that the disease affected other population groups, when the first cases of PCP were reported in injecting drug users . At the same time the first case of AIDS was documented in the UK. 1982 History The disease still did not have a name, with different groups referring to it in different ways. The CDC generally referred to it by reference to the diseases that were occurring, for example lymphadenopathy (swollen glands), although on some occasions they referred to it as KSOI, the name already given to the CDC task force.14PowerPoint Presentation: 6 In contrast some still linked the disease to its initial occurrence in gay men, with a letter in The Lancet calling it "gay compromise syndrome".16 Others called it GRID (gay-related immune deficiency), AID (acquired immunodeficiency disease), "gay cancer" or "community-acquired immune dysfunction". In June a report of a group of cases amongst gay men in Southern California suggested that the disease might be caused by an infectious agent that was sexually transmitted.PowerPoint Presentation: 7 The acronym AIDS was suggested at a meeting in Washington, D.C., in July.24 By August this name was being used in newspapers and scientific journals.25 26 27 AIDS (Acquired Immune Deficiency Syndrome) was first properly defined by the CDC in September . In December a 20-month old child who had received multiple transfusions of blood and blood products died from infections related to AIDS. This case provided clearer evidence that AIDS was caused by an infectious agent, and it also caused additional concerns about the safety of the blood supply. Also in December, the CDC reported the first cases of possible mother to child transmission of AIDS. Meanwhile in Uganda, doctors were seeing the first cases of a new, fatal wasting disease. This illness soon became known locally as 'slim'.PowerPoint Presentation: 8 In May 1983, doctors at the Institute Pasteur in France reported that they had isolated a new virus, which they suggested might be the cause of AIDS In May 1983, doctors at the Institute Pasteur in France reported that they had isolated a new virus, which they suggested might be the cause of AIDS. Little notice was taken of this announcement at the time, but a sample of the virus was sent to the CDC. A few months later the virus was named lymphadenopathy-associated virus or LAV, patents were applied for, and a sample of LAV was sent to the National Cancer Institute.PowerPoint Presentation: 9 Reports from Europe suggested that two rather separate AIDS epidemics were occurring. In the UK, West Germany and Denmark, the majority of people with AIDS were homosexual, and many had a history of sex with American nationals. However in France and Belgium AIDS was occurring mainly in people from Central Africa or those with links to the area. In September 1983, the CDC published their first set of recommended precautions for health-care workers and allied professionals designed to prevent "AIDS transmission".In the UK, people who might be particularly susceptible to AIDS were asked not to donate blood.PowerPoint Presentation: 10 April 23rd, 1984 the United States Health and Human Services Secretary Margaret Heckler announced that Dr. Robert Gallo of the National Cancer Institute had isolated the virus which caused AIDS, that it was named HTLV-III, and that there would soon be a commercially available test able to detect the virus with "essentially 100 percent certainty".PowerPoint Presentation: 11 The same day patent applications were filed covering Gallo's work, but there was clearly a possibility that LAV and HTLV-III were the same virus The scientific papers regarding Gallo's discovery of HTLV-III were published on 4th May.PowerPoint Presentation: 12 Human immunodeficiency virus Scanning electron micrograph of HIV-1 (in green) budding from cultured lymphocyte. Multiple round bumps on cell surface represent sites of assembly and budding of virions.PowerPoint Presentation: 13 In 1985, at 13, Ryan White became a symbol of the intolerance that is inflicted on AIDS victims. Once it became known that White, a haemophiliac, had contracted the disease from a tainted blood transfusion, school officials banned him from classes." The actor Rock Hudson died of AIDS on October 3rd 1985. He was the first major public figure known to have died of AIDS. All UK blood transfusion centres began routine testing of all blood donations for HTLV-III/LAV in October. In December 1985, the Pasteur Institute filed a lawsuit against the National Cancer Institute to claim a share of the royalties from the NCI's patented AIDS test.PowerPoint Presentation: 14 1986 History "The name of the virus had itself become a political football as the French insisted on LAV (lymphadenopathy-associated virus), while Gallo's group used HTLV-3 (human T-cell lymphotropic virus, type 3)." - Time Magazine In May 1986, the International Committee on the Taxonomy of Viruses ruled that both names should be dropped and the dispute solved by a new name, HIV (Human Immunodeficiency Virus).121PowerPoint Presentation: 15 In September there was dramatic progress in the provision of medical treatment for AIDS, when early results of clinical tests showed that a drug called azidothymidine (AZT) slowed down the attack of HIV. AZT was first synthesised in 1964 as a possible anticancer drug but it proved ineffective. The AZT clinical trial divided patients into two groups: one received AZT and the other received placebo, or dummy drugs. At the end of six months, only one patient in the AZT group was dead, whilst there were 19 deaths among the placebo group. The clinical trial was stopped early, because it was thought to be unethical to deny the patients of the placebo groups a better chance of survival.PowerPoint Presentation: 16 By this time, scientists had accumulated enough evidence to form an overview of AIDS in Africa. Studies of medical records showed there had been marked increases in a number of AIDS-related conditions during the late 1970s and early 1980s. In particular: Slim disease in Kinshasa, Zaire (late 1970s) Slim disease in Uganda and Tanzania (early 1980s) Esophagel candidiasis in Rwanda (from 1983) and Haiti."PowerPoint Presentation: 17 Aggressive Kaposi's sarcoma in Kinshasa, Zaire (early 1980s) Aggressive Kaposi's sarcoma in Zambia and Uganda (from 1982 and 1983) Crypotococcal meningitis in Kinshasa, Zaire (late 1970s to early 1980s). In conclusion: "These studies suggested that while isolated cases of AIDS may have occurred in Africa earlier, it was probably rare until the late 1970's and early 1980's, a pattern similar to that in the United StatesPowerPoint Presentation: 18 L entivirus (a member of the retrovirus family) Lead to acquired immunodeficiency syndrome (AIDS), a condition in humans in which the immune system begins to fail, leading to life-threatening opportunistic infections . Previous Names Human T-lymphotropic virus-III (HTLV-III), Lymphadenopathy-associated virus (LAV), AIDS-associated retrovirus (ARV). [PowerPoint Presentation: 19 Infection with HIV transfer of blood , semen , vaginal fluid , pre-ejaculate , or breast milk . Within these bodily fluids , HIV is present as both free virus particles and virus within infected immune cells . The four major routes of transmission are unprotected sexual intercourse , contaminated needles, breast milk, and transmission from an infected mother to her baby at birth ( Vertical transmission ). Screening of blood products for HIV has largely eliminated transmission through blood transfusions or infected blood products in the developed world .PowerPoint Presentation: 20 Eventually most HIV-infected individuals develop AIDS . These individuals mostly die from opportunistic infections or malignancies associated with the progressive failure of the immune system. Without treatment, about 9 out of every 10 persons with HIV will progress to AIDS after 10–15 years.PowerPoint Presentation: 21 Many progress much sooner. Treatment with anti-retrovirals increases the life expectancy of people infected with HIV. Even after HIV has progressed to diagnosable AIDS, the average survival time with antiretroviral therapy (as of 2005) is estimated to be more than 5 years. Without antiretroviral therapy, death normally occurs within a year.PowerPoint Presentation: 22 HIV primarily infects vital cells in the human immune system such as helper T cells (specifically CD4+ T cells ), macrophages , and dendritic cells . HIV infection leads to low levels of CD4 cells through three main mechanisms: Firstly, direct viral killing of infected cells Secondly, increased rates of apoptosis in infected cells Thirdly, killing of infected CD4+ T cells by CD8 cytotoxic lymphocytes that recognize infected cells.PowerPoint Presentation: 23 When CD4+ T cell numbers decline below a critical level, cell-mediated immunity is lost, and the body becomes progressively more susceptible to opportunistic infections .Other Early Developments 1: 24 Other Early Developments 1 1982: Term “AIDS” coined First cases in women reported First transfusion and vertically transmitted cases reported 1983: Isolation of a retrovirus from a patient with AIDS by Montagnier’s group 1984: Detection of HTLV-III in pts with and at risk for AIDS (Gallo) Sepkowitz K NEJM 2001;344:1764-72Other Early Developments 2: 25 Source : National AIDS case surveillance data, CDC Months after OI diagnosis 0.2 0.4 0.6 0.8 1.0 0 1981-1987 Proportion surviving 10 30 40 50 60 20 0 Other Early Developments 2 1985: FDA approves first commercial HIV antibody test 1986: NIH establishes the AIDS Clinical Trials Group 1987: AZT = first antiretroviral approved by FDAEarly Antiretroviral Therapy 1: 26 Early Antiretroviral Therapy 1 1991-92: ddI, ddC approved Sequential monotherapy Ryan White Care Act passed 1993: Concorde: no difference in clinical endpoints over 3 yrs with early vs. deferred AZTEarly Antiretroviral Therapy 2: 27 Early Antiretroviral Therapy 2 1994: ACTG 076: AZT reduces mother-to-child transmission of HIV Dual nucleoside therapy better than monotherapy (Delta, ACTG 175, ZDV/3TC) 1994–95: era of dual combination therapyThe New Treatment Era: 28 The New Treatment Era 1995-96: HIV viral load testing became available Clinicians could directly assess the effect of antiretrovirals on viral replication (HIV RNA) First protease inhibitors approved by FDAThe Era of HAART: 29 The Era of HAART Paradigm: Aim to achieve durable suppression of HIV viremia Striking reductions in HIV-related morbidity and mortality Aggressive treatment guidelines: “Hit hard, Hit early!” Mathematical models suggested that 3 years of viral suppression would result in eradicationAIDS Mortality Rates: 1996-2001: 30 Percentage of Patient-days on HAART Deaths per 100 Person-Years 0 5 10 15 20 25 30 35 40 1995 1996 1997 1998 1999 2000 2001 Deaths per 100 person-years 0 25 50 75 100 Percentage of patient-days on ART DEATHS USE OF ART Mortality vs. ART utilization Palella F et al . 8th CROI 2001; abstract 268b. AIDS Mortality Rates: 1996-20011998 - 2000 Realism: 31 1998 - 2000 Realism HIV eradication is not possible with current therapy viral “reservoir” in resting T-memory lymphocytes viral replication continues in lymph nodes even when HIV RNA in plasma is <50 copies/mL Awareness that HIV is a chronic disease Recognition of long-term toxicities: fat redistribution (lipodystrophy) metabolic abnormalities (insulin resistance, diabetes, increased lipids) 2000: Durban AIDS conference – momentum builds to bring antiretrovirals to the developing world2001- 2006: 32 2001- 2006 Interest in PI-sparing regimens Emergence of NNRTI-based regimens Deferred initiation of antiretroviral therapy Interest in treatment interruption strategies Ultimately not supported by clinical trials Simpler, once daily regimens with fewer pills Optimism about new classes of drugsPowerPoint Presentation: 33 HIV enters the bloodstream through: Open Cuts Breaks in the skin Mucous membranes Direct injectionPowerPoint Presentation: 34 HIV Transmission Common fluids that are a means of transmission: Blood Semen Vaginal Secretions Breast MilkPowerPoint Presentation: 35 HIV in Body Fluids Semen 11,000 Vaginal Fluid 7,000 Blood 18,000 Amniotic Fluid 4,000 Saliva 1 Average number of HIV particles in 1 ml of these body fluidsPowerPoint Presentation: 36 Routes of Transmission of HIV Sexual Contact: Male-to-male Male-to-female or vice versa Female-to-female Blood Exposure: Injecting drug use/needle sharing Occupational exposure Transfusion of blood products Perinatal: Transmission from mom to baby BreastfeedingWindow Period: 37 Window Period This is the period of time after becoming infected when an HIV test is negative 90 percent of cases test positive within three months of exposure 10 percent of cases test positive within three to six months of exposurePowerPoint Presentation: 38 Requirement for HIV testing Requires informed consent No premarital testing requirement Prenatal testing not required but recommended School notification not required for positive staff or students (universal precautions)PowerPoint Presentation: 39 HIV Risk Reduction Avoid unprotected sexual contact Use barriers such as condoms and dental dams Limit multiple partners by maintaining a long-term relationship with one person Talk to your partner about being tested before you begin a sexual relationshipPowerPoint Presentation: 40 HIV Risk Reduction Avoid drug and alcohol use to maintain good judgment Don’t share needles used by others for: Drugs Tattoos Body piercing Avoid exposure to blood productsPowerPoint Presentation: 41 Condoms Using condoms is not 100 percent effective in preventing transmission of sexually transmitted infections including HIV Condoms = Safer sex Condoms ≠ Safe sexPowerPoint Presentation: 42 Condom Use Should be used consistently and correctly Should be either latex or polyurethane Should be discussed with your partner before the sexual act begins Should be the responsibility of both partners for the protection of both partners Male and female condoms are availablePowerPoint Presentation: 43 People Infected with HIV Can look healthy Can be unaware of their infection Can live long productive lives when their HIV infection is managed Can infect people when they engage in high-risk behaviorPowerPoint Presentation: 44 HIV xposure and Infection Some people have had multiple exposures without becoming infected Some people have been exposed one time and become infectedPowerPoint Presentation: 45 “When you have sex with someone, you are having sex with everyone they have had sex with for the last ten years.” Former Surgeon General C. Everett KoopPowerPoint Presentation: 46 HIV and other Sexually Transmitted Diseases STDs increase infectivity of HIV A person co-infected with an STD and HIV may be more likely to transmit HIV due to an increase in HIV viral shedding More white blood cells, some carrying HIV, may be present in the mucosa of the genital area due to a sexually transmitted infectionPowerPoint Presentation: 47 HIV and Other Sexually Transmitted Diseases STDs increase the susceptibility to HIV Ulcerative and inflammatory STDs compromise the mucosal or cutaneous surfaces of the genital tract that normally act as a barrier against HIV Ulcerative STDs include: syphilis, chancroid, and genital herpes Inflammatory STDs include: chlamydia, gonorrhea, and trichomoniasisPowerPoint Presentation: 48 HIV and Other Sexually Transmitted Diseases The effect of HIV infection on the immune system increases the the risk of STDs A suppressed immune response due to HIV can: I ncrease the reactivation of genital ulcers Increase the rate of abnormal cell growth Increase the difficulty in curing reactivated or newly acquired genital ulcers Increase the risk of becoming infected with additional STDsPowerPoint Presentation: 49 HIV Occupational Exposure Review facility policy and report the incident Medical follow-up is necessary to determine the exposure risk and course of treatment Baseline and follow-up HIV testing Four week course of medication initiated one to two hours after exposure Liver function tests to monitor medication tolerance Exposure precautions practicedPowerPoint Presentation: 50 HIV Post Exposure ProphylaxisPowerPoint Presentation: 51 HIV Non-Occupational Exposure No data exists on the efficacy of antiretroviral medication after non-occupational exposures The health care provider and patient may decide to use antiretroviral therapy after weighing the risks and benefits Antiretrovirals should not be used for those with low-risk transmissions or exposures occurring more than 72 hours after exposure PREVENTION --- FIRSTPowerPoint Presentation: 52 HIV Non-Occupational Exposure Provider Considerations: Evaluate HIV status of patient and risk history of source patient Provide necessary medical care and counseling Evaluate risk event and factors for exposure Determine elapsed time from exposure Evaluate potential for continuous HIV exposure Obtain informed consent for testing and treatment Evaluate pregnancy status of females Monitor for drug toxicity and acute infection You do not have the permission to view this presentation. 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