12 - HIV disease and AIDS Flashcards
HIV Risk Assessment (Risk Factors)
a. History of sexually transmitted disease(s) (STD’s)
b. History of hepatitis B
c. History of multiple sexual partners or a partner with multiple sexual partners
d. History of IV drug use
e. Woman with IV drug user sex partner
f. Homosexual/bisexual man
What are the three structural genes in HIV and what do they code for?
gag gene: encodes for proteins
env gene: encodes for envelope glycoproteins (gp)
pol gene: encodes for enzymes (polymerase)
p24
“core protein” inner shelf of nucleocapsid; clinically, used as marker for viral replication
p17
outer shelf
p9
structural proteins
p7
structural proteins
gp120
major envelope protein mediates attachment to CD4 receptors and co-receptors
gp41
helps mediate fusion of the virus to the host cell
Reverse transcriptase (RT)
RNA-dependent, DNA polymerase transcribes viral RNA into dsDNA
Integrase
helps integration of viral DNA into the host genome
Protease
aids in maturation of the virion after budding
Which gene encodes for a major envelope protein that mediates attachment to CD4 receptors and co-receptors?
gp120
Which gene encodes for a glycoprotein that helps mediate fusion of the virus to the host cell?
gp41
Which gene encodes for a core protein that makes up the inner shelf of nucleocapsid
p24
What are the steps in the HIV life cycle?
- Attachment – Viral Envelope proteins – gp 120 and gp 41
Cell receptors for HIV:
• CD4 receptor
• Co-receptors – CCR-5 (β-chemokine receptor 5)
– CXCR-4 (Fusin), (α-chemokine receptor 4) - Fusion
- Uncoating
- Transcription – RNA → dsDNA by RT
- Integration of HIV DNA into host genome
- HIV expression – regulatory genes, structural genes
- Assembly of virion
- Budding
- Maturation – by protease enzyme
What clinical tests are used in the diagnosis of HIV infection? What do they test for?
ELISA (enzyme linked immunosorbent assay): detects antibodies.
Reactive/nonreactive.
Nonreactive > negative
Reactive > repeat. Reactive again > Western blot
Western Blot (gel immunoelectrophoresis): detects antibodies for three key bands (gp120/160, gp41, p24) Positive = 2/3 key bands Indeterminate: 1 key band and/or accessory bands found Negative = no key bands Western blot = CONFIRMATORY TEST
CDC guidelines on HIV testing recommends that those at high risk should be tested how often? Who are those at risk?
1) IDU or sex partners of IDU
2) Sex for money or drugs
3) Sexual partner of a known HIV infected patient
4) Men who have sex with men (MSM)
5) Having more than one sexual partner, or have a sexual partner who has more than one sexual partner
6) Beginning a new sexual relationship
CDC Definition of AIDS?
Positive HIV test AND
CD4 count <200 OR AIDS indicator condition
What are the most common methods of transmission of AIDS in the United States?
- Male-to-male sexual contact
- Heterosexual contact
- Male-to-male sexual contact and IDU
- Other
What is the leading mode of HIV transmission worldwide?
Heterosexual contact
What are potentially infectious body fluids?
Blood
Visibly bloody fluid
Semen, vaginal secretions
CSF, synovial, pleural, peritoneal, pericardial and amniotic fluids
What are bodily fluids that are not considered infectious?
Saliva (non-bloody) Tears Sweat Urine (non-bloody) Feces (non-bloody)
What is the standard of care in antiviral treatment for AIDS?
Standard of care is multi-drug combinations = Highly Active Anti-Retroviral Therapy (HAART)
What criteria are used to assess when antiviral therapy should be initiated?
Viral load and CD4 count are used to assess when antiviral therapy should be initiated.
a. Low CD4 count indicates immune deficiency/advanced disease and is a criterion for initiating therapy.
b. High viral loads prognosticate that disease will advance rapidly and therefore can be used as rationale to initiate therapy.
c. Earlier initiation has become the recommended, to decrease general inflammation.
What is a key factor in the success of antiviral therapy?
Adherence/Compliance is a key factor for success of the antiviral therapy.
a. The lack of adherence is the most likely cause of unsuccessful therapy.
b. The lack of adherence is the most likely cause of the development of resistance
What mechanism do nucleoside analogue reverse transcriptase inhibitors employ in treatment of HIV/AIDS?
- Chain terminator (N3 instead of OH)
- Competitive reverse transcriptase inhibitor
What is the mechanism of action for nucleotide analgoues?
- Chain terminator (phosphorylates)
- Same as nucleoside analogues
What is the mechanism of action for non-nucleoside reverse transcriptase inhibitors?
- Attaches to reverse transcriptase
- Inhibits DNA from being made from RNA
What is the mechanism of action for CCR5 inhibitors?
-Blocks co receptor for entry
It is an entry inhibitor, and only useful in patients with R5 virus
What is the mechanism of action for integrase inhibitors?
-Blocks viral integration into host DNA
What is the mechanism of action for protease inhibitors?
-Interrupts modification of viral proteins
Some need to be boosted!
What are factors that can decrease viral resistance to drugs and viral mutation?
- Combination therapy. Reduces replication
- Compliance/adherence to drug dosing protocol is of key importance
- Early therapy = greater duration of antiviral agent efficacy
Pneumocystis (Carinii) Jiroveci Pneumonia (PCP)
- Pneumocystis (carinii) jiroveci is an opportunistic fungus. Does not infect healthy people.
- In HIV infection, PCP is common when CD4 count drops below 200/ml.
- Prophylaxis with Bactrim greatly reduces the incidence of PCP in HIV/AIDS population.
Tuberculosis
Worldwide, TB is the most common opportunistic infection in the HIV population.
- Tuberculosis is caused by infection with Mycobacterium tuberculosis. TB can be pulmonary or disseminated.
- HIV accelerates TB and TB accelerates HIV! Always do PPD for TB testing in HIV patients.
Cytomegalovirus (CMV)
- CMV is an opportunistic herpes family virus.
- Commonly causes retinitis in HIV patients. May cause blindness.
- Can also cause esophagitis, colitis, rarely pneumonia.
Kaposi Sarcoma (KS)
- Presents as multifocal vascular lesions; classified as malignant neoplasm.
- Caused by Human Herpes Virus Type 8 (HHV-8).
- Most commonly affects the skin. Lesions sometimes found in the mouth.
Mycobacterium Avium-intracellulare Complex (MAC)
- Opportunistic acid fast bacillus from soil and water.
- MAC is common in AIDS patients when CD4 count drops below 50.
- Standard of care is prophylaxis for MAC when CD4 count drops below 50 using azithromycin, clarithromycin or Rifabutin.
Cryptococcal Meningitis
- Insidious onset fungal meningitis
2. Headache and fever with minor neck stiffness
Toxoplasmosis
- An opportunistic protozoan; Associated with cats, but usually no history of cat exposure.
- Reactivation of toxoplasmosis due to immunosuppression can result in brain lesions in HIV patients.
Oral Lesions
- Thrush – Candida albicans – may also cause esophagitis, angular cheilitis. In women, it can cause recurrent vaginal candidiasis.
- Oral hairy leukoplakia
- Angular cheilitis (Candida or HIV)
- Dry mouth
- Increased incidence of gingivitis
- Herpes
- Kaposi’s sarcoma
- Oral warts (HPV)
Metabolic Complications – unknown etiology
- Lipodystrophy – Fat accumulation/fat atrophy
- Insulin resistance
- Increased cholesterol, triglycerides
- Mitochondrial toxicity
Cardiovascular Disease (AIDS effect on)
- Increased incidence of myocardial infarction in HIV infected patients
Hepatitis C
- A co-morbid condition
- Increased progression with HIV coinfection
- Higher rates of mortality due to liver disease in HIV patients is largely attributable to hepatitis C
Non-AIDS Related Diseases
Certain non-AIDS related diseases are seen with greater frequency in HIV infected patients
a. Diabetes
b. Cardiovascular Disease
c. Certain Cancers
d. Osteopenia/Osteoporosis
What is AZT? Why is it significant?
It is a nucleoside analogue reverse transcriptase inhibitor.
Generic name: Zidovudine
Brand name: Retrovir
Side effects: Bone marrow suppression, GI intolerance
Reduced risk of infection by 80% in occupational exposure to HIV.
HIV transmission rate between mother and fetus =8% vs control = 24%. With combination drugs, HIV transmission = 0-2%
What antiviral drug is also able to boost other antiviral drugs?
Ritonavir
What is ritonavir?
Boosting effect of ritonavir It is a protease inhibitor Generic name: Ritonavir Brand name: Norvir Side effects Nausea, vomiting, diarrhea, abnormal liver function
What are symptoms of primary HIV infection?
Fever Fatigue Pharyngitis Weight loss Myalgias Headache Nausea Cervical LN Night sweats Diarrhea Vomiting Rash
What is HAART?
Highly Active AntiRetroviral Therapy
Combination therapy
Usually 3 or more agents
Not all combinations are highly active
- Chain terminator (N3 instead of OH)
- Competitive reverse transcriptase inhibitor
nucleoside analogue reverse transcriptase inhibitors
-Chain terminator (phosphorylates)
nucleotide analgoues
- Attaches to reverse transcriptase
- Inhibits DNA from being made from RNA
non-nucleoside reverse transcriptase inhibitors
-Interrupts modification of viral proteins
protease inhibitors
What are the AIDS indicator conditions?
Candidiasis of bronchi, trachea, or lungs
Candidiasis, esophageal
Cervical cancer, invasive*
Coccidioidomycosis, disseminated or extrapulmonary
Cryptococcosis, extrapulmonary
Cryptosporidiosis, chronic intestinal for >1 month
Cytomegalovirus disease (other than liver, spleen, or nodes)
Cytomegalovirus retinitis (with loss of vision)
Encephalopathy, HIV-related
Herpes simplex: chronic ulcer(s) for >1 month; or bronchitis, pneumonitis, or esophagitis
Histoplasmosis, disseminated or extrapulmonary
Isosporiasis, chronic intestinal for >1 month
Kaposi’s sarcoma
Lymphoma, Burkitt (or equivalent term)
Lymphoma, immunoblastic (or equivalent term)
Lymphoma, primary, of brain
Mycobacterium avium complex or M. kansasii, disseminated or extrapulmonary
Mycobacterium tuberculosis, any site (pulmonary* or disseminated)
Mycobacterium, other species or unidentified species, disseminated or extrapulmonary
Pneumocystis carinii pneumonia
Pneumonia, recurrent*
Progressive multifocal leukoencephalopathy
Salmonella septicemia, recurrent
Toxoplasmosis of brain
Wasting syndrome due to HIV
AIDS-Indicator Conditions
APPENDIX B. Conditions included in the 1993 AIDS surveillance case definition
Candidiasis of bronchi, trachea, or lungs
Candidiasis, esophageal
Cervical cancer, invasive*
Coccidioidomycosis, disseminated or extrapulmonary
Cryptococcosis, extrapulmonary
Cryptosporidiosis, chronic intestinal for >1 month
Cytomegalovirus disease (other than liver, spleen, or nodes)
Cytomegalovirus retinitis (with loss of vision)
Encephalopathy, HIV-related
Herpes simplex: chronic ulcer(s) for >1 month; or bronchitis, pneumonitis, or esophagitis
Histoplasmosis, disseminated or extrapulmonary
Isosporiasis, chronic intestinal for >1 month Kaposi’s sarcoma
Lymphoma, Burkitt (or equivalent term)
Lymphoma, immunoblastic (or equivalent term)
Lymphoma, primary, of brain
Mycobacterium avium complex or M. kansasii, disseminated or extrapulmonary
Mycobacterium tuberculosis, any site (pulmonary* or disseminated)
Mycobacterium, other species or unidentified species, disseminated or extrapulmonary
Pneumocystis carinii pneumonia
Pneumonia, recurrent*
Progressive multifocal leukoencephalopathy
Salmonella septicemia, recurrent
Toxoplasmosis of brain
Wasting syndrome due to HIV
* Added in the 1993 expansion of the AIDS surveillance case definition.
