1. Microbiology, Chapter 20, HIV Pull up HIV separate handout from Unit 4 notes. You are responsible for that material. The following slides from your text help explain some of those concepts.

2. Aids: Acquired Immune Deficiency Syndrome (Rev. 10/06) 1. Caused by the HIV virus (human immunodeficiency virus – a retro virus) 2. Rna virus, with reverse transcriptase for a copy of viral DNA, which is then transcribed into viral RNA. 3. Some retroviruses can become incorporated into host DNA genome. This may occur with HIV – an example of viral latency. A second enzyme, integrase, helps to splice the viral DNA into host DNA genome. Another enzyme, a protease, helps cut the new viral proteins coded for by the viral nucleic acid, into viral capsid subuinits. These bud from the cells, acquiring their envelope as virus leaves host cells. See pg 640.

3. Fig. 20.22

4. Fig. 20.24

5. HIV 4. Origin HIV: most researchers feel the virus originated in west Africa, somewhere between 40 and 100 years ago. This infection was contained in a small area, probably remote, until the 1950’s and 1960’s. Both social and political upheaval in Africa as well as the development of rapid and wide spread travel contributed to its spread. (this is theoretical – an emerging disease – contained for long time and then spread)

6. Origin of aids; controversial, similar to SIV

8. HIV transmission 5. Transmission of HIV –a. HIV is extremely labile in a free state and cannot readily enter through intact body –surfaces. –b. HIV has been detected in a number of body fluids including blood, semen, cervical secretions, breast milk, urine, CSF, saliva, and tears. According to most sources, the last four are not likely a mode of transmission. –c. The most common routes of transmission in the US are sexual contact, IV drug use, and vertical passage from infected mothers to offspring. –d. Since 1985, transmission by blood transfusion has been rare due to good testing of blood supply and heat treatment of plasma products.

9. Fig. 20.24

10. HIV e. Although in the US, the HIV infection and resulting aids cases have been predominately spread through the gay community, the percentage of heterosexual transmission has been increasing. This is due, according to epidemiologists, to the spread of HIV through use of contaminated needles by IV drug users. There is also and increase in the spread of HIV from infected mothers to fetuses. f. There is ample evidence that the spread of HIV infection in less developed countries is overwhelmingly heterosexual. CDC.gov 2005

11. HIV 6. Damage to the host: a.HIV specifically damages T helper lymphocytes, called T4 because they have an antigen CD4 on the surface of the cell. The CD4 receptors, plus a co-receptor, are the site of attachment for HIV. The viral envelope fuses with the cell membrane and releases the viral enzymes and two strands of RNA of the HIV genome. Pg639 b. Many cells are killed as the virus replicates. The acute stage of the infection, lasting some where around 6 weeks or so, is marked by rapid viral replication and killing CD4 cells. Many people will have symptoms similar to other viral infections, such as fever, enlarged lymph nodes, rash, muscles aches, and headaches. c. The immune response to such and infection holds the viral replication in check, but does not eliminate the virus. A steady state of viral replication is then reached, which is the chronic phase. CD4 cell levels remain high enough to hold secondary infections in check.

12. HIV d. Eventually, the continued assault on the T4 cells leads to an imbalance in the ratio of (helper / suppressor / cytotoxic) lymphocytes. This leads to an even further suppression of the immune response. The course of the disease can vary tremendously from one individual to another. e. Since the T helper cells also help regulate the B cells, as well as macrophages, these immune functions are also damaged. Graph pg. 637

13. HIV 7. Diagnosis a. Symptoms, or clinical findings – will be discussed more in aids section –b. Serology: i. EIA tests for antibodies against the HIV virus –1. Enzyme linked immuno assay. The body may produce antibodies »in 6 to 12 weeks, it is currently recommended that a person be tested 3 months after engaging in risky behavior, to allow the body time to produce detectable antibody levels (titer). If this test is negative a follow up test is recommended in 3 months. –2. The first positive EIA test is followed by a second test, and then confirmed by another test called the western blot test. »This is a method to measure antibodies against individual viral polypeptides.

14. Tests for HIV

16. HIV 3. There is some difficulty in false positives – especially in comparing low risk and high risk groups. So several tests are done to make sure there are no false positives or missed positives. 4. It is also important to clarify that a positive HIV antibody test signifies current infection. It is extremely important, therefore that such individuals be counseled on the issues involved in HIV transmission so that further spread can be minimized.

17. HIV c. One measure of this progression is the number of cd4 lymphocytes present in the blood. Since these are the main target cells for infection, a low number would indicate that the infection is becoming more serious. Measures of viral load (the number of viral RNA per milliliter of blood plasma) can help monitor the infections progress and have aided in the understanding of both the disease process and the means of therapies to hold viral replication in check. d. The designation of aids related complex, ARC, has been used in the past to type the beginning of the aids disease. This is an artificial separation that is not being used much today.

18. Fig. 20.21

19. HIV 8. Aids: Aids is a constellation of clinical illnesses, primarily opportunistic infections, and malignancies that are the consequences of the destruction of the immune system by the HIV virus. a. HIV infections and aids are not synonyms. HIV infection can initially resemble many viral infections, with symptoms such as a low grade fever, swollen lymph nodes, and a rash. This is followed by a period of time referred to as “clinical latency”, where symptoms do not occur for a period of months to years. b. At the present time, a person who has been diagnosed with a positive HIV test will eventually develop aids. There is still quite a bit to learn about the progression of the disease. There is a lot variability among individual HIV and aids patients.

20. HIV c. One measure of this progression is the number of cd4 lymphocytes present in the blood. Since these are the main target cells for infection, a low number would indicate that the infection is becoming more serious. Measures of viral load (the number of viral RNA per milliliter of blood plasma) can help monitor the infections progress and have aided in the understanding of both the disease process and the means of therapies to hold viral replication in check. d. The designation of aids related complex, ARC, has been used in the past to type the beginning of the aids disease. This is an artificial separation that is not being used much today.

21. Fig. 20.21

23. HIV e. Early signs, in addition to viral load and the lower T4 cell levels are: i. Weight loss ii. Fever that persists for longer than a month iii. Persisting diarrhea iv. Recurrent oral or vaginal Candidiasis in females v. Herpes zoster vi. Fatigue

24. HIV f. Later symptoms fall into two categories: i. Infectious diseases: 1. Opportunistic infections such as Cryptosporidium, Toxoplasmosis, Pneumocystis, Candida, Cryptococcus 2. Mycobacterial infections such as Tb or M. avium 3. Viral infections such as CMV, or Herpes simplex ii. Oncological manifestations such as Kaposi’s sarcoma, lymphoma, and Scervical cancer

25. HIV 9. Treatment: pg 644 A. All approved anti-HIV drugs attempt to block viral replication within cells by inhibiting either reverse transcriptase or the hiv proteases. 1. Reverse transcriptase inhibitors: nucleoside analogues (“look alikes” for HIV DNA - azt, idanosine, lamivudine, stavudine, and zalcitabine 2. Non-nucleoside analogues targeting reverse transcriptase: delavirdine and nevirapine 3. Protease inhibitors: indinavir, nelfinavir, ritonavir

26. Fig. 20.23

27. Fig. 20.25

28. HIV B. Recommended therapy: current recommended therapy is called HARRT: highly active antiretroviral therapy. This consists of triple therapy, including two nucleoside analogues and a protease inhibitor. This means between 8 and 16 or even more pills a day at a cost of 10,000 – 12,000 dollars per year. C. Prevention: 1. No vaccine 2. Education is the best and most effective tool. The target would be general but a significant strategy is need for high risk populations – homosexual community and IV drug abusers?? Well planned, continuing, good follow up studies?? $$$$$$$$$$$$$$$$$$

30. Fig. 20.24