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ARO Training & Consulting Bloodborne Pathogens Module 4: Human Immunodeficiency Virus (HIV) Exposure Page 36 Objectives: 1. 2. 3. Describe the routes of transmission associated with HIV infection. State the prevalence of HIV infection in the population. Describe the incubation period preceding seroconversion in individuals exposed to HIV. 4. Describe the incubation period preceding symptoms of HIV infection. 5. Describe the complications associated with chronic HIV infection. 6. Discuss the risk of developing HIV infection following exposure. 7. Describe safety measures associated with prevention of HIV exposure. 8. Describe safety measures associated with prevention of HIV infection following exposure. 9. Describe the current role of immunization with respect to prevention of HIV infection. 10. Be familiar with the treatment for HIV. 11. Describe the role of prophylactic treatment following exposure to HIV. 12. Be familiar with the differences between HIV screening tests and confirmatory tests, and with the problems associated with false-positive and false-negative results. ARO Training & Consulting Bloodborne Pathogens Module 4: Human Immunodeficiency Virus (HIV) Exposure Page 37 Introduction The human immunodeficiency virus (HIV) was first discovered in 1983. HIV is responsible for causing autoimmune deficiency syndrome (AIDS). HIV attacks the body’s immune system, leaving the host susceptible to opportunistic infections. The incidence of occupationally acquired infection with HIV is relatively low, but needle-stick exposure during phlebotomy procedures presents a serious potential hazard. There is no vaccine to protect against HIV infection, and currently there is no cure. There are two types of HIV: HIV-1 and HIV-2. HIV-2 occurs most commonly in Western Africa, and is uncommon in North America. Retroviruses HIV is a Retrovirus, and like HBV and HCV, relies on the production capabilities of host cells to replicate itself. However, unlike HBV and HCV, which infect liver cells, HIV infects T-cells (specialized lymphocyte), monocytes and macrophages – types of white blood cells that our immune systems produce to help fight infection. During the viral replication process inside the T-cells, genetic material from the virus is integrated in the host’s genetic material, and may remain inactive (latent) for 3-10 years. Once incorporated in the host cell DNA, each time a cell divides, viral genetic material is passed on to the two daughter cells, so that once a cell is infected, all descendents of that cell will also be infected. During the latent phase, the virus remains inactive (dormant). If the cell does not become activated, the virus remains dormant. If the infected cell dies before it divides again, and before it becomes activated (T4-cells live only a few days while monocytes/macrophages live for weeks to months), the virus will be degraded along with the rest of the cell’s DNA, and the number of HIV-infected cells will decrease and could even disappear. However, it is unlikely that T4-cells and monocyte/macrophages will die before becoming activated, as their purpose is to become activated in response to foreign substances entering the body. When the cell is activated or turned-on, the process resulting in virus replication begins. New viral particles are released through the host cell membrane (budding) to infect other host cells. The replication process damages or kills infected helper T-cells; however, infected monocytes usually survive and become reservoirs of infective virus. ARO Training & Consulting Bloodborne Pathogens Module 4: Human Immunodeficiency Virus (HIV) Exposure Page 38 Unless the HIV lifecycle is interrupted by treatment, the virus infection spreads throughout the body and results in the destruction of the immune system. With current anti-viral medications, HIV infection can be contained for a period of time; however, there is currently no cure for HIV infection and sooner or later immune deficiency occurs (AIDS). For more information on HIV pathogenesis. Link to http://www.critpath.org/aric/library/path.htm Epidemiology Global The World Health Organization reported at the end of 2003 that there were approximately 40,000,000 people living with HIV and/or AIDS worldwide. Most cases (95%) occurred in low and middle-income countries. Five million of these were new HIV infections that occurred during 2003 – approximately 14,000 new HIV infections each day. In the same year, a total of 3,000,000 people died of HIV and AIDS related causes. Geographic Distribution Approximately 70% of HIV infections occur in individuals in Sub-Saharan Africa, followed by 15% in South and South-East Asia. Only 2.5% of HIV infections occur in North American individuals. Globally, nearly 2% of all new HIV infections are caused by unsafe injections with a total of 96,000 people infected annually. In South Asia up to 9% of new cases may be caused by unsafe injections. As was mentioned in Module 1, reuse of unsterilized or improperly sterilized syringes and needles exposes millions of people to infection. United States The CDC estimated that currently there are approximately 200,000 persons in the U.S. living with HIV infection, and another 800,000 persons with HIV infection that has progressed to AIDS. Of these, the majority of cases are seen in men (~80%); however, the occurrence is increasing in women, especially among IDU. http://www.cdc.gov/hiv/stats.htm#data ARO Training & Consulting Bloodborne Pathogens Module 4: Human Immunodeficiency Virus (HIV) Exposure Page 39 Approximately 48% of all HIV/AIDS infected individuals in the U.S. live in the following States (listed in order of prevalence): - New York California Florida Texas Race/Ethnicity distribution HIV/AIDS infection is increasing most rapidly among minority populations and is a leading killer of African-American males aged 25-44 years. AIDS affects ~ 7 times more African Americans and 3 times more Hispanics than whites. Exposure category distribution Approximate distribution of individuals with HIV/AIDS in the U.S. by exposure category: - men who have sex with men (MSM) – 40% IDU – 24% MSM/IDU – 5% Heterosexual contact – 30% Not identified – 2% For further information on HIV infection in the U.S. Link to – http://www.cdc.gov/hiv/pubs/facts.htm Canada Health Canada estimated that 56,000 Canadians were living with HIV infection and/or AIDS in 2002, and that approximately 30% of those infected did not yet know they are infected. The undiagnosed group is important, because they may unknowingly spread the HIV virus, and until diagnosed, cannot receive treatment and counselling. In Canada, risk groups for HIV and AIDS are: - Aboriginal people Injection drug users (16 - 23.9% of HIV infections) Men who have sex with men (up to 70%) Women (~ 8 %) Youth (~ 3 %) Although Aboriginal groups represent only 3.3% of the Canadian population, they are at high-risk for HIV infection (due to poverty, substance abuse, sexually transmitted diseases, and limited health-care access). ARO Training & Consulting Bloodborne Pathogens Module 4: Human Immunodeficiency Virus (HIV) Exposure Page 40 In addition, HIV infection among women is also increasing, due largely to substance abuse. For further information on HIV infection in Canada, Link to Health Canada Website - http://www.hc-sc.gc.ca/english/diseases/aids.html Discrimination and stigma A survey performed by Health Canada indicates that stigma and discrimination associated with HIV/AIDS still persist in Canada: - 30% of adult Canadians would be uncomfortable working in an office with a person with HIV 40% would be uncomfortable if their child was attending a school where one of the students had HIV/AIDS > 50% would be uncomfortable if a close friend or relative were dating someone with HIV/AIDS ~ 50% of Canadians believe that people living with HIV/AIDS should not be allowed to serve the public in positions such as cooks and dentists A survey of 50 people with HIV/AIDS in New Brunswick found that ~ 30% of those surveyed reported being rejected by family and friends in 2000. A recent survey of 34 people with HIV/AIDS in Alberta indicated that ~ 30% reported being treated unfairly by employers or co-workers as a result of their HIV status. ARO Training & Consulting Bloodborne Pathogens Module 4: Human Immunodeficiency Virus (HIV) Exposure Page 41 Transmission Human immunodeficiency virus (HIV), the virus that causes acquired immunodeficiency syndrome (AIDS), is transmitted through sexual contact, exposure to infected blood or blood components, and perinatally from mother to newborn. Risk factors are: - - unprotected sexual intercourse – entry through the lining of the vagina, vulva, penis, rectum or mouth during sex sharing of needles and IV drug equipment infected mother to infant o during pregnancy o during delivery o during breast feeding treatment with blood and blood products prior to national screening initiatives occupational exposure o health care workers o emergency responders (fire, ambulance, etc.) o law officers o prison guards HIV has been recovered from the following body fluids: - blood - semen - vaginal secretions - saliva - tears - breast milk - cerebrospinal fluid - amniotic fluid - urine Despite the range of body fluids that HIV has been recovered from, only blood, semen, and vaginal secretions have been implicated in the transmission of HIV. The risk of HIV transmission through breast milk, CSF, synovial fluid, pleural fluid, peritoneal fluid, pericardial fluid, and amniotic fluid has not yet been determined. ARO Training & Consulting Bloodborne Pathogens Module 4: Human Immunodeficiency Virus (HIV) Exposure Page 42 Occupational Exposure A significant occupational exposure that may place a worker at risk of HIV infection is defined as a percutaneous injury, contact of mucous membranes, or contact of skin (especially when the exposed skin is chapped, abraded, afflicted with dermatitis, or the contact is prolonged or involves an extensive area) with blood, tissues, or other body fluids (semen, vaginal secretions, other body fluids contaminated with visible blood, CSF, synovial fluid, pleural fluid, peritoneal fluid, pericardial fluid, and amniotic fluid, and laboratory specimens and preparations (e.g., suspensions of concentrated virus) that contain HIV. Occupational HIV Transmission Risk to Health-Care Workers Transmission of HIV following occupational exposure appears to be related to a number of factors. Morbidity Mortality Weekly Report (MMWR), a publication of the Centers for Disease Control and Prevention (CDC), reported three factors associated with seroconversion among workers who received occupational exposures to HIV: - - volume of blood injected (deep injury, procedure involving needle placed directly into source patient's vein or artery, visible contamination of sharp with patient's blood) terminal HIV illness in source patient due to high levels of circulating virus lack of post-exposure prophylaxis Reference: Case-Control Study of HIV Seroconversion in Health-Care Workers After Percutaneous Exposure to HIV-Infected Blood -- France, United Kingdom, and United States, January 1988-August 1994. Retrieved from http://www.cdc.gov/mmwr/preview/mmwrhtml/00039830.htm on August 14, 2004. Evidence also suggests that host defences of an individual influence the risk for HIV infection following exposure to HIV infected blood. Under the same circumstances involving exposure to two individuals, one may develop infection while the other does not. It is likely that differences in individual immune response affect the risk of whether an individual who is exposed to the HIV virus actually becomes infected. ARO Training & Consulting Bloodborne Pathogens Module 4: Human Immunodeficiency Virus (HIV) Exposure Page 43 Percutaneous injury (sharps) Although the risk of seroconversion following needle-stick injury involving HIVpositive body fluids is low, the potential is real, with about one seroconversion for every 200 - 300 needle-sticks. The rate of transmission of HIV is considerably lower than that for HBV, possibly due to the lower concentrations of virus in the blood of HIV-infected patients. Reference: Centers for Disease Control and Prevention (CDC). (1989). Guidelines for Prevention of Transmission of Human Immunodeficiency Virus and Hepatitis B Virus to Health-Care and Public-Safety Workers A Response to P.L. 100-607 The Health Omnibus Programs Extension Act of 1988. MMWR; 38(S-6);3-37. Retrieved from http://www.cdc.gov/mmwr/preview/mmwrhtml/00001450.htm on August 14, 2004. Mucous membrane exposure The risk of seroconversion approximately 0.09%. following mucous membrane exposure is Non-intact skin exposure HIV transmissions following exposure of non-intact skin to blood have been documented, but the average risk of seroconversion has not been determined. It is expected that the risk of infection following exposure of non-intact skin to body fluids from patients infected with HIV is less than the risk following mucous membrane exposure. Exposure to body fluids and tissues The risk of transmission after exposure to fluids or tissues other than HIVinfected blood has not been quantified, but is likely even lower than the probability associated with exposure to blood. HIV infection in healthcare workers (HCWs) has been attributed to needle-stick exposures to blood from HIV infected patients, extensive contact with blood or other body fluids in the absence of barrier precautions, and direct contact of skin with blood from infected patients (skin lesions present), and mucous-membrane exposure. The risk of exposure of non-intact skin or mucous membranes is likely to be much less than that from percutaneous exposure. As of June 2000, the CDC had received 56 voluntary reports of HCW with documented seroconversion associated with occupational exposure to HIV in the U.S. An additional 138 HIV transmissions in HCW were considered possible occupational HIV transmissions. Although there was a history of occupational exposure to blood, other body fluids or laboratory solutions containing HIV, and no other identified risk for HIV infection in these 138 possible occupational transmissions, a single specific exposure was not associated with HIV seroconversion. ARO Training & Consulting Bloodborne Pathogens Module 4: Human Immunodeficiency Virus (HIV) Exposure Page 44 In 1996, the first documented occupational transmission of HIV in Canada clearly linked to a specific incident occurred in a HCW in British Columbia. The HCW, who was not wearing gloves at the time, received a puncture wound while caring for a person with advanced HIV disease. Two other cases of possible occupational transmission of HIV have also been reported in Canada. Both involved laboratory workers. For further information Link to Health Canada - http://www.hc-sc.gc.ca/pphbdgspsp/publicat/ccdr-rmtc/96vol22/dr2207ec.html Risk to Emergency Responders and Public Safety Workers Acquiring HIV in Health-Care Settings Emergency medical technicians (EMTs) In the U.S., one study documented 115 occupational exposures among firstresponder subgroups with 84% occurring in emergency medical technicians (EMTs). In another study of a city-wide EMT work-force, 472 body fluid exposures were documented in 1400 patient encounters. Personal protective equipment prevented skin or face contact in 87% of these exposures. Police officers A study involving police officers found that 33 of 111 exposures were significant. Of the 29 sources, 3 individuals were documented HIV antibody positive. Although no seroconversions in exposed officers occurred, the potential for transmission exists. Correctional facility workers Another survey of 2215 correctional facility workers found that 88 of 149 exposures occurred in the medical/dental units. Reference: Int Conf AIDS 1991 Jun 16-21; 7:425 (abstract no. W.D.4150) Strine PW, Martin LS, Mullan RJ; Centers for Disease Control, National Institute for Occupational Safety and Health, HIV Activity, Atlanta, GA Future trends The increasing prevalence of HIV increases the risk that HCWs will be exposed to blood from patients infected with HIV, especially when standard precautions are not followed for all patients. HCWs must consider ALL patients as potentially infected with HIV and/or other blood-borne pathogens and adhere to infection-control precautions for minimizing the risk of exposure to blood and body fluids of all patients. ARO Training & Consulting Bloodborne Pathogens Module 4: Human Immunodeficiency Virus (HIV) Exposure Page 45 HIV disease progression Infection with HIV-1 results in a progressive loss of immune function, which ultimately leads to opportunistic infections and malignancies associated with acquired immunodeficiency (AIDS). Currently, 5 stages of illness are recognized: Acute infection (seroconversion) Early disease Middle stage disease Late disease Advanced disease Acute HIV infection (Seroconversion) Acute HIV infection may also be referred to as acute retroviral seroconversion syndrome. The acute phase of HIV infection refers to the period from initial infection until the immune response demonstrates some control over viral replication, lasting from a few weeks to a few months. Symptoms usually occur within 2 – 6 weeks following exposure and usually disappear within one week to one month. Many individuals do not have symptoms or may have mild flu-like symptoms when they are first infected with HIV and initial infection is often not recognized. Only 20 – 30% of symptomatic individuals seek medical attention, and when they do symptoms are often mistaken for other viral infections. If present, symptoms are nonspecific and temporary - fever, malaise, rash, lymphadenopathy, pharyngitis, headache, and diarrhea. Acute infection is characterized by active viral replication and extremely high levels of circulating virus in the blood. At this point, people are very infectious and HIV is present in large quantities in genital fluids. During the acute phase, the virus spreads throughout the body and seeds lymphoid tissues, where replication is partially suppressed. Seroconversion generally occurs 2-3 months following HIV exposure. ARO Training & Consulting Bloodborne Pathogens Module 4: Human Immunodeficiency Virus (HIV) Exposure Page 46 Early disease (Asymptomatic) With the exception of mild to moderate lymphadenopathy and skin conditions (dermatitis, psoriasis, dry skin, fungal infection, etc.), there are generally no symptoms related to HIV infection. This asymptomatic phase of the disease is referred to as the clinically latent period of HIV infection due to the absence of symptoms suggesting that, although the virus is present, it is inactive at this point. This is the longest stage of HIV infection, responsible for approximately 80% of the total disease course. Middle Stage Disease Most individuals remain asymptomatic or mildly symptomatic during this period. Skin conditions persist and may worsen, and mouth ulcers and lesions may appear or worsen. Other disorders begin to appear during the middle stage of disease – herpes simplex, varicella-zoster virus (shingles), oral or vaginal candidiasis, oral hairy leukoplakia, recurrent seborrhea and other skin disorders, recurrent diarrhea, intermittent fever, and unexplained weight loss (> 10 pounds in 6 – 8 week period). Other symptoms including muscle and joint pain, headache and fatigue may also be present during this stage. Routine bacterial infections such as sinusitis, bronchitis and pneumonia are more common, as well as tuberculosis, syphilis, herpes infection and lymphoma. Late Disease – AIDS The early presentations of AIDS include generalized enlargement of lymph nodes, fever, chronic fatigue, weight loss, and in some cases thrombocytopenia. The disease gradually progresses and late presentations include increased susceptibility to opportunistic infections, predisposition to malignant tumors, central nervous system damage, and general weakening of the body. During this state of infection, large numbers of viral particles are present in blood and body fluids. As the disease progresses, the rate of loss of T-cells increases. HIV over time will usually succeed in reducing the available number of T-cells to very low levels, increasing the risk of opportunistic infections and malignancies that may be life threatening. ARO Training & Consulting Bloodborne Pathogens Module 4: Human Immunodeficiency Virus (HIV) Exposure Page 47 During the late stage of disease, lymphoid tissue is destroyed, resulting in the loss of virus-trapping capability and contributing to severe immune deficiency. Infected individuals are at high risk for developing life-threatening opportunistic infections and malignancies. Approximately 6% of HIV-infected individuals show rapid disease progression, experiencing a rapid decline in T-cell counts within 2 to 3 years, and developing full-blown AIDS within 3 years of acute HIV infection. Advanced HIV Disease Prior to current treatment programs, individuals with advanced HIV disease were likely to develop a new AIDS-defining illness and/or die within 2 years of progressing to AIDS. Certain opportunistic infections are associated with advanced stages of immunosuppression – Mycobacterium avium complex infection, meningitis caused by Cryptococcus, invasive fungal infections (i.e. aspergillosis and histoplasmosis), and wasting (loss of > 10 lb. of usual body weight). Typically, multiple disease conditions coexist. Retinitis caused by the cytomegalovirus (CMV) is the leading cause of blindness in advanced HIV disease. Individuals with advanced disease are living much longer than in the early years of the AIDS epidemic due to aggressive antiretroviral therapy and earlier identification and treatment of opportunistic infections. Recent statistics indicate that AIDS-related deaths among all AIDS cases have decreased. ARO Training & Consulting Bloodborne Pathogens Module 4: Human Immunodeficiency Virus (HIV) Exposure Page 48 Complications of AIDS - Infections Malignant tumors Damage to nerves, muscles, spinal cord AIDS dementia - cognitive and memory impairment, and impaired ability to concentrate and perform complex tasks Wasting syndrome (general weakening and degeneration of the body) Laboratory Testing Diagnosis HIV is diagnosed by screening blood for antibodies to the virus. If the body is making antibodies to HIV, then the body has been exposed and probably is infected with the virus. Antibodies to the HIV virus are usually detectable within 23 months following infection, but may take longer (up to 14 months). False-positive and false-negative HIV-antibody reactions have been reported. False positive results occur when HIV antigens used in testing cross-react with antibodies in the patient’s serum produced against antigens unrelated to HIV. Initial positive test results are confirmed by additional testing. Presence of antibodies to the HIV virus indicates that a person has been exposed to the virus and has mounted an immunologic response (serum antibodies). However, antibody testing does not indicate whether the individual currently harbours the virus, although current evidence related to retroviruses suggests that most, if not all, HIV-antibody positive individuals will remain indefinitely infected. HIV Vaccine Currently, no HIV/AIDS vaccines are approved for use; however, many are in clinical trial studies. For information on vaccine clinical http://www.aidsinfo.nih.gov/vaccines/ trial studies in progress - ARO Training & Consulting Bloodborne Pathogens Module 4: Human Immunodeficiency Virus (HIV) Exposure Page 49 Treatment The Canadian Youth, Sexual Health and HIV/AIDS Study demonstrated that approximately 67% of Grade 7 students and 50% of Grade 9 students in Canada do not know that there is no cure for HIV/AIDS. Although most Canadian adults recognize that HIV/AIDS is a serious problem, close to 20% believe that it can be cured if treated early, and they perceive their own personal risk of HIV infection to be low. Reference: Link to HIV/AIDS: Responding to a changing epidemic. - http://www.hcsc.gc.ca/hppb/hiv_aids/report03/wad2.html There is still no cure for AIDS — prevention is the only protection against AIDS at this time, and for people living with HIV/AIDS, treatment failures are becoming more common as new strains of the virus appear and the human body develops resistance to HIV/AIDS drugs. Guidelines for the treatment of HIV infection include recommendations for the use of three drugs. Because of the ability of HIV to remain in some latently infected cells and the lack of therapeutic agents that target latently infected cells, patients must remain on anti-viral therapy for life. The current goal of HIV treatment is to completely suppress viral replication for as long as possible with periodic determination of the number of virus particles in the blood to measure response to therapy. Treatment most commonly involves combination antiretroviral therapy for patients in the early or middle stage of disease. Future directions One immediate goal in HIV treatment is to design new, more potent medications that are easier to take and have fewer side effects. As our understanding of the HIV lifecycle improves, the ability to develop medications to cure HIV infection and create a vaccine that will prevent infections from occurring is the hope for the future. Side effects of anti-HIV medications Side effects related to the drugs used for treatment are common and may be severe. In addition, drug resistance may occur especially if drugs are not taken as prescribed. ARO Training & Consulting Bloodborne Pathogens Module 4: Human Immunodeficiency Virus (HIV) Exposure Page 50 Post Exposure Prophylaxis (PEP) Post exposure prophylaxis is short-term antiretroviral treatment to reduce the likelihood of HIV infection after potential exposure, either occupationally or through sexual intercourse. Although the risk of seroconversion following needle-stick injury involving HIVpositive body fluids is low, the risk is real (1 seroconversion in every 200 to 300 needle-stick injuries). Occupational exposure to an HIV-infected individual should be considered an urgent medical concern. Information about primary HIV infection suggest that systemic infection does not occur immediately, leaving a brief window of opportunity during which post-exposure antiretroviral treatment might reduce or prevent viral replication. Theoretically, initiation of antiretroviral PEP soon after exposure might prevent or inhibit systemic infection by limiting the replication of virus in the initial target cells or lymph nodes. Post-exposure treatment guidelines (CDC, 2001) Recommendations for treatment following exposure to HIV include a 4-week regimen of two different classes of drugs. An expanded treatment regimen includes the addition of a third drug for HIV exposures that pose an increased risk for transmission. When the source virus is known or suspected to be resistant to one or more of the drugs considered for the PEP regimen, the selection of drugs to which the source person’s virus is unlikely to be resistant is recommended. Reference: U.S. Department of Health and Human Services. 2001. Updated U.S. Public Health Service Guidelines for the Management of Occupational Exposures to HBV, HCV, and HIV and Recommendations for Postexposure Prophylaxis. MMWR;50(RR-11) http://www.aidsinfo.nih.gov/guidelines/health-care/HC_062901.pdf Toxicity Associated with PEP has been reported - nearly 50% of HCW experience adverse symptoms that include symptoms of nausea, malaise, headache, anorexia and headache while taking PEP. Approximately 33% of HCW stop taking PEP because of adverse signs and symptoms. Serious side effects, including hepatotoxicity, kidney stones, hepatitis, pancytopenia and serious skin disorders have also been reported with the use of combination drugs for PEP.