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Chapter 25: Retroviruses, HIV, and AIDS

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What's a retrovirus?
RNA virus that uses a reverse transcriptase to convert its genome into DNA, which can integrate into the host's own DNA
Describe HIV structure?
Spherical enveloped virion with a central cylindrical nucleocapsid.
Surface glycoproteins 120 and 41
Why is it difficult to make a vaccine for HIV?
Hypervariable regions within the area encoding the gp 120 glycoprotein undergo frequent mutations.
Describe the means of transmission of HIV?
1. Sexual activity (women more likely to get it with vaginal intercourse, anal sex, STDs increases risk)
2. Blood product transfusion
3. IV drug use with needle sharing
4. Transplacental spread
5. NSI in HCWs
To which receptor to HIV glycoproteins bind? Mostly on which cells?
CD4 - on CD4+ T-helper cells
Describe the acute viral illness seen 1 month after HIV exposure?
Acute mono-like viral illness 1 month post-exposure. Lymphadenopathy, viremia, HIV-specific immune response.
Describe the clinical latency stage of HIV?
Clinical latency - median of 8 years, HIV continues to replicate in the lymphoid tissue with a gradual destruction of CD4 T-helper cells. Toward the end of this stage, patients are more susceptible to infections and may develop constitutional symptoms.
List some infections that could occur with a CD4 count of 400-200 (late clinical latency stage)?
Candida infections, herpes zoster, mycobacterium tuberculosis.
What are the serious opportunistic killers that invade at CD4 counts < 200?
PCP, Cryptococcus, and Toxoplasma.
What is a normal CD4 count?
1000 cells/microliter of blood
What does viral load and CD4 count tell you about HIV patients?
Train analogy:
1. CD4 count tells you where the train currently is - current risk of developing particular opportunistic infections.
2. Viral load tells you the speed at which the train is heading for the cliff - risk for future rapid CD4 count decline, infection, and death
Describe the role of gp160 in T cell death in HIV?
The gp160 is integrated into the T cell membrane. It may:
1. Bind to adjacent CD4 receptors, tearing the membrane.
2. Bind to other CD4 T cells, causing cell-cell fusion, and the formation of multinucleated giant cells
3. Mark the cell as non-self, targeting it for autoimmune destruction by CD8 T cells.
Describe the importance of multinucleated giant cells in HIV?
Virus can pass between cells without contacting blood - may protect from circulating antibodies
Describe HIV's effects on B-lymphocytes?
Polyclonal activation, resulting in hypergammaglobulinemia. This diminishes the patient's ability to produce antibodies in response to new antigens or immunization. (Decreases humoral immunity)
What is HIV's effect on monocytes and macs? Why is this important?
Infects but does not destroy them - they serve as reservoirs and can migrate across the BBB, carrying HIV the to the CNS.
What are the two basic processes that occur in AIDS?
1. Direct viral disease
2. Disease secondary to the immunodeficiency state
Describe the neurological disease of AIDS?
Encephalopathy resulting in AIDS dementia complex. Meningeal infection results in aseptic meningitis. Myelopathy and neuropathy can also occur
Which malignancies commonly occur in AIDS?
1. B cell lymphoma (often associated with EBV)
2. Kaposi's sarcoma (particularly in homosexual men)
What are the opportunistic bacterial infections of AIDS?
1. Bacteremia by Staph aureus or epidermidis - from IV lines.
2. Encapsulated bugs - H flu and strep pneumo
3. Mycobacterium tuberculosis (higher chance of reactivation)
4. Mycobacterium avium intracellulare (MAI, MAC)
What are the opportunistic fungal infections of AIDS?
Candida, cryptococcus, histoplasma, and coccidioides.
What does cryptococcus cause in about 10% of AIDS patients? Describe?
Meningitis - without a full immune system, they often don't display meningeal signs or inflammation. Often only fever, nausea, and vomiting.
Describe the opportunistic viral infections seen in AIDS patients?
1. Herpes zoster
2. EBV causing oral hairy leukoplakia
3. HSV outbreaks
4. CMV chorioretinitis and blindness or esophagitis and diarrhea.
What are the opportunistic protozoal infections seen in AIDS?
1. PCP
2. Toxoplasma - mass lesions in the brain
3. Diarrhea from cryptosporidium, microsporidia, and isospora
What is the most common opportunistic infection in AIDS patients with CD4 count < 200?
PCP
How is HIV diagnosed?
1. Within weeks, viral RNA or antigens can be detected in the blood.
2. 6 weeks later, antibodies appear, detectable by ELISA.
3. A western blot of HIV antigens confirms the diagnosis.
What are the four basic areas of attempted control of HIV?
1. Prevention of infection
2. Vaccine development
3. Limiting frowth of HIV once infection has occurred
4. Treating the opportunistic infections that ultimately cause death
How is PCP treated prophylactically in AIDS patients with CD4 < 200?
TMP/Sulfa combo
How are toxoplasmosis brain lesions treated in AIDS patients?
A tetrahydrofolate reductase inhibitor/sulfa combination - pyrimethamine/sulfadiazine.
What is the prophylaxis against future MAI infections in AIDS patients?
Azithromycin or clarithromycin.
How can the progression of visual loss in AIDS patients' CMV infection be prevented?
Ganciclovir or foscarnet
How is Candida thrush and esophagitis treated in AIDS patients?
Oral clotrimazole, nystatin, or fluconazole.

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