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Editor's Notes

1. The establishment that the disease is caused by a virus and therefore the ability to produce antibodies against viral antigens led to the first tests for HIV, the ELIZA and Western blot tests. However, there is a 1 to 2 month time lag before antibodies are produced. This can be overcome by using a test that identifies viral RNA rather than antibodies produced against viral protein e.g PCR. The very fact that we can use an antibody test shows us that there is a good immune response and it is neutralizing antibody which gives hope for a vaccine. But the virus is not completely neutralized which argues that a vaccine may be difficult to develop. The virus goes underground within the cells and because it is a retrovirus, is prone to genetic drift. As it changes it overcomes the immune system. As we shall see retroviral vaccines pose special problems and HIV is more complicated than other retroviruses
2. Because HIV is transmitted by sex or contaminant blood, the groups that are at increased risk of contracting the disease are listed in this slide. Men, practicing unsafe sex are at high risk if they are homosexual or bisexual. If a patient uses IV drugs and shares needles with another that is HIV positive, this is another means of contracting the disease. The other groups are self-evident. Certain patient may have had a blood transfusion between 1987 and 1992 and became infected by that route also.
3. This slide details some of the steps that are necessary for HIV pathogenesisity. After HIV entry into the body by the different routes, within 2-4 weeks, the patient will have the peak viremia. However, the patient will be negative by HIV serology. This means that a patient can be infected with HIV and if tested too soon, the patient will have a negative HIV test however, the patient may still be HIV-positive. HIV will enter lymph tissue after infecting CD4 cells as early as 5 days after acute infection. After the initial peak plasma viremia, virus-specific immune responses can be detected and may contribute to both the control of the initial peak of virus replication and the reduction in plasma viremia. The immune response lack the ability to control HIV and block progression of the disease. This is different than other viruses such as Epstein-Barr virus where the immune response will stop progression of the disease. Soon after the acute infection, a pool of latently infected CD4 cell contain the virus and is capable of replicating. This is the key to the immunopathogenesis of HIV. This stable reservoir remains sheltered from the effects of host response and drug therapy.
4. Certainly with these mechanisms in place, HIV can then destroy lymph tissue and directly kill CD4 cells leading to immune suppression and opportunistic infections and neoplastic diseases.
5. This slide indicates the laundry list of opportunistic infections that patients can experience with a reduction in the numbers of CD4 cells. Most occur with CD4 cells < 200/mm3.
6. time has increased with new protease inhibitors must be used in combination with other drugs
7. This slide details the classic 6 symptoms of patients in the primary HIV infection period. These symptoms can continue and may be the reason why patients seek medical attention. Therefore, physicians and other health care practitioners must be aware of these symptoms for adequate identification of the high risk patient. Certain questions should be asked of all patients between 17 and 30 regarding sexual preferences and activity when patients present to outpatient clinics with these symptoms.
8. Additionally, patients can develop HIV associated cancers as this slide indicates.
9. This slide indicates the patients that therapy is recommended. Therapy should be highly recommended to patients with RNA levels > 30,000 copies/ml regardless of their CD4 cell counts. Additionally, therapy should be highly recommended for patients with CD4 cell counts < 350/l irrespective of viral RNA level. Therapy should be encouraged in patients with viral RNA levels between 5,000-30,000 copies/ml or with CD4 cell counts between 350 and 500/l.
10. Dual NRTIs are used in most 3 to 4-drug regimens. There are no current data regarding preferred sequencing of NRTI however, AZT and D4T should not be used together because of drug-drug antagonism. ddC plus ddI or D4T is not recommended due to overlapping toxicities. Lamivudine should be reserved for regimens that maximally suppress replication as M184V mutation results in loss of lamivudine activity. AZT + 3TC use results in loss of abacavir effectiveness. Abacavir is useful in initial regiments but its effectiveness with NRTI combinations other than AZT + 3TC is not well characterized. Efavirenz+3TC+AZT produced HIV suppression and CD4 cell count elevation is at least comparable to that with indinavir+3TC+AZT. Remember it is contraindicated in the 1st trimester of pregnancy. Potential for high-level resistance as a result of a single reverse transcriptase mutation suggests that NNRTI should be used only in regimens designed to maximally suppress HIV. Dual protease inhibitors (PI) are increasingly being used because of pharmacokinetic advantages of low-dose ritonavir inhibiting P4503A metabolism of the other PI improving the plasma concentrations of these drugs. May offer increased potency and reduced pill counts.
11. This slide details the goal of therapy. If for whatever reason, this goal can not be reached, some investigators admit that withholding therapy until the patient can meet these expectations may be necessary for some patients.