Dr. Karatzios -- HIV Flashcards
1
Q
Predominant mode of adult acquisition of HIV
A
Heterosexual intercourse
2
Q
Predominent mode of childhood acquisition of HIV
A
Perinatal exposure
3
Q
6 highly endemic areas for HIV
A
- Sub-Saharan Africa
- Southeast Asia (Thailand)
- India
- Haiti
- China
- Russia
4
Q
How HIV enters cells (3 points)
A
- HIV viral envelope protein (gp120)
- Human T cell receptor
- Human co-receptors (CCR5 or CXCR4 or both)
5
Q
6 cells that HIV infects
A
- CD4+ T lymphocytes
- Dendritic cells (skin, lymph nodes, brain)
- Macrophages
- CD8+ T lymphocytes
- NKC
- Natural killer T cells (viral reservoir)
6
Q
3 systems in which HIV lives
A
- Lymphoid organs
- CNS
- Genitourinary system
7
Q
3 lymphoid organs in which HIV can live
A
- Peripheral lymph nodes
- GI lymph nodes
- Bone marrow
8
Q
Method of transmission of HIV living in GI lymph nodes
A
Neonatal
9
Q
How does HIV enter the CNS?
A
HIV Tat protein disrupts the BBB –> Microglial and dendritic cells
10
Q
2 reservoirs of HIV replication
A
- CNS
- Genitourinary system
11
Q
3 parts of the genitourinary system in which HIV can live
A
- Semen
- Renal epithelium
- Marcophages and lymphocytes in cervix
12
Q
How does HIV infect semen?
A
HIV crosses the blood-testis barrier
13
Q
Why is there a high rate of genomic mutation in HIV?
A
Reverse transcriptase is extremely error-prone
14
Q
2 types of genomic mutations that HIV may undergo?
A
- Spontaneous mutations over time
- Drug-driven mutations
15
Q
2 potential outcomes of spontaneous HIV mutations
A
- Many are silent/no-effect
- Some confer resistance to medications
16
Q
Compare wild type HIV to mutated HIV
A
- Highly mutated = “less fit”
- Wild type = easily transmissible and replicates more efficiently
17
Q
When do mutants overtake wild type HIV?
A
- If medications are failing –> mutants accumulate
- Held in reserve and overtake wild type once medications restarted
18
Q
When does wild type HIV overtake mutants?
A
Once medications are stopped
19
Q
Effect of initial viremia from HIV
A
Infection of lymph nodes
20
Q
Effect of secondary viremia from HIV
A
Mononucleosis-like illness
21
Q
2 events occurring during the window period between initial and secondary viremia
A
- Silent viral replication in lymph nodes
- Little or no HIV antibodies
22
Q
Length of window period between initial and secondary viremia
A
Up to 3 months
23
Q
7 symptoms of acute HIV syndrome
A
Mononucleosis-like illness
- Fever
- Malaise
- Non-exudative pharyngitis
- Maculpapular rash (50%)
- Myalgias
- Headache
- GI distress
24
Q
5 signs of acute HIV syndrome
A
Mononucleosis-like illness
- Generalized lymphadenopathy
- Hepatosplenomegaly
- Oral or vaginal thrush
- Lymphopenia THEN acute lymphocytosis
25
Lab findings of acute HIV syndrome
* HIV antibody negative
* PCR and antigen positive
26
Timeline of acute HIV syndrome
* 1 - 6 weeks after infection
* Lasts up to 3 weeks
* Spontaneous resolution
* --\> Window period
27
Main cell type destroyed by HIV
CD4+ T cells
28
3 ways CD4+ T cells are destroyed
29
Severe immune suppression by age (in No/mm3)
* \<12 months = \<750
* 1 - 5 years = \<500
* \>6 years = \<200
30
Describe the natural history of HIV disease
31
Use of HIV serology
Screening and confirmatory test in humans \>18 months age
32
Use of HIV PCR
Screening and confirmatory test in humans \< 18 months age
33
How to determine viral copy number
* Viral RNA numbers expressed as number of copies/mL blood or log:
* log 2 = 100 copies/mL
* log 3 = 1000 copies/mL
* \< log 1.6 = \<40 copies/mL = undetectable
34
4 infections associated with HIV disease
* Sinopulmonary infections
* Salmonellosis
* Meningitis
* Candidiasis
35
Cardiac problem associated with HIV
Cardiomyopathy
36
3 growth and sexual development issues related to HIV
* Delayed
* Decrease in testosterone/libido
* Osteoporosis
37
3 neurological issues related to HIV
* Cognitive delay
* Encephalopathy
* Dementia
38
Renal problem associated with HIV
HIV nephropathy
39
2 psychiatric issues related to HIV
* Depression
* ADHD
40
Proportion of AIDS patients with esophageal disease
1/3
41
6 typical symptoms of esophageal disease in HIV patients
* Dysphagia
* Odynophagia
* Retrosternal pain
* Nausea
* Anorexia
* Weight loss
NOTE: Usually indolent onset
42
2 causes of dysphagia and odynophagia in AIDS patient
* Esophageal inflammation
* Ulceration
43
Likely cause of HIV-associated idiopathic esophageal ulcers
HIV seen in lymphocytes and lamina propria
44
Biopsy findings of herpes virus esophagitis
Multinucleated giant cells
45
Which other kind of esophagitis does HIV-associated idiopathic esophageal ulcers resemble?
CMV esophagitis
* Shallow ulcers
* Inclusion bodies on biopsy
46
3 infectious oral lesions associated with AIDS
* Herpes simplex
* Oral hairy leukoplakia
* EBV-related
* Non-painful
* Oral candidiasis (usually painful)
47
Oral neoplastic lesion associated with HIV/AIDS
Kaposi's sarcoma
48
Effect of HBV in HIV/AIDS (3)
* Spontaneous reactivation seen in AIDS
* 19x more likely to die if HIV/HBV co-infected
* HBV does not influence HIV progression, however
49
3 causes of death in HIV/HBV co-infection
* Cirrhosis
* Live failure
* Carcinoma
50
Effect of HCV in HIV/AIDS
* 94x higher risk of mortality
* HCV may affect progression of HIV
NOTE: All HIV+ patients should be screened for HCV
51
3 pharmacological causes of hepatitis in HIV/AIDS patients
* Protease inhibitors
* NNRTI
* Antimycobacterial drugs
52
Protease inhibitor that can cause hepatitis and steatosis in HIV patients
Ritonavir
53
NNRTI that can cause hepatitis in HIV patients
Nevirapine
54
3 antimycobacterial drugs that can cause hepatitis in HIV patients
* Rifampin
* Rifabutin
* INH
55
3 pharmacological causes of jaundice in HIV patient
* Protease inhibitors (atazanavir)
* Septra
* Macrolides
56
2 pharmacological causes of steatosis in HIV patients
* Mitochondrial toxicity and lactic acidosis (i.e. NRTI such as ZDV, d4T, ddI)
* Protease inhibitors (ritonavir)
57
2 common general causes of diarrhea in HIV/AIDS patients
* Colitis
* Malabsorption
NOTE: There are many causes and this affects 95% of patients in 3rd world with a 72% 10-mo mortality (chronic diarrhea)
58
5 bacterial causes of diarrhea in HIV patients
* SSCYE, *Listeria monocytogenes*
* *Mycobacterium avium *complex
* Obstructive as well
* *Mycobacterium tuberculosis*
* Obstructive as well
* Toxin-mediated (i.e. *C. difficile*)
* Bacterial overgrowth
59
5 viral causes of diarrhea in HIV patients
* CMV
* Adenovirus
* Rotavirus
* HIV
* Other causes of viral gastroenteritis
60
6 parasitic causes of diarrhea in HIV patients
* *Giardia lamblia*
* *Cryptosporidium parvum*
* Microsporida
* *Isospora belli*
* *Cyclospora cayetanensis*
* *Entamoeba histolytica*
61
Fungal cause of diarrhea in HIV patients
*Histoplasma capsulatum*
62
4 risk factors for diarrhea in HIV patients
* Severe immunosuppression
* Environmental conditions
* Travel-related exposures
* MSM
63
2 pharmacological causes of diarrhea in HIV patients
* Most all antiretrovirals
* Antibiotics
64
3 immune-mediated causes of diarrhea in HIV patients
* IBD
* Immune Reconstitution Syndrome
* Celiac disease
65
2 neoplastic causes of diarrhea in HIV patients
* Intestinal lymphoma
* Kaposi's sarcoma
66
3 reasons why HIV-associated enteropathy may be due to HIV itself
* Direct alteration of enterochromaffin cell function
* Enterocyte degeneration
* Microtubular depolymerization
67
2 results of HPV disease in setting of HIV
* Anal condillomatosis
* Cervical/Anal cancer
68
3 bacteria involved in sexually transmitted proctitis
* *Chlamydia trachomatis*
* *Neisseria gonorrhea*
* *Treponema pallidum*
69
7 opporunistic infections in the setting of AIDS
* *Pneumocystosis jiroveci*
* *Toxoplasma gondii*
* Candida esophagitis/moniliasis
* CMV
* Disseminated vericella zoster
* *Mycobacterium avium intercellulare*
* JC virus/Progressive multifocal leukoencephalopathy
70
4 non-opportunistic infections associated with AIDS
* Salmonellosis
* Crypto/microsporidiosis
* *Isospora belli*
* *Giardia lamblia*
71
3 neoplastic transformations in the setting of AIDS
* HHV-8: Kaposi sarcoma
* Castleman disease
* CNS lymphoma
72
Median duration of disease prior to HAART
7.8 years
73
Median duration of disease after HAART
\>15 years
74
Most frequent opportunistic pathogen in AIDS patients
*Pneumocystis jiroveci*
75
4 symptoms and signs of *pneumocystis jiroveci* in AIDS patients
* Fever
* Cough
* SOB
* Hypoxia
NOTE: Can involve extra-pulmonary areas as well (liver)
76
4 primary prophylaxis options for *pneumocystic jiroveci*
* Septra po
* Dapsone
* Atovaquone
* Pentamidine
77
Patients to administer *pneumocystic jiroveci *prophylaxis (2)
* All HIV+ children \<1 year regardless of CD4 count
* Older children and adults when CD4 \<200 (or \<15% of total lymphocytic count)
78
3 treatments of *pneumocystic jiroveci*
* Septra (IV or po)
* Systemic corticosteroids
* Supplemental oxygen
79
Secondary prophylaxis for pneumocystic jiroveci
Septra until CD4 \> 200 for 3 months
80
Define *mycobacterium avium *complex
Disseminated disease based in the GIT and reticuloendothelial system
81
3 symptoms of *mycobacterium avium *complex infection
* Pulmonary disease
* Fever
* Weight loss
82
2 primary prophylaxis drugs for *mycobacterium avium* complex
* Azithromycin
* Clarithromycin
83
Patients to give primary prophylaxis for *mycobacterium avium *complex
* Childen \< 5 yo that are severely immunosuppressed
* People \>6 yo with CD4 \< 50 cells
84
Treatment for *mycobacterium avium *complex
* Macrolide + rifabutin
* Other second-line drugs
85
Secondary prophylaxis for *mycobacterium avium *complex
Macrolide + rifabutin until CD4 \>75 for 3 months
86
Effect of HIV on mycobacterium tuberculosis transmission
HIV patients can transmit this to other much more easily than non-HIV patients
87
5 effects of *cryptococcus neoformans *in setting of HIV/AIDS
* Meningitis
* Raised intracranial pressure
* Necrotizing intracranial pressure
* Necrotizing lymphadenitis (mediastinal, cervical)
* Necrotizing pneumonitis
* Skin abscesses
88
Treatment for *cryptococcus neoformans*
* Amphotericin B + Fluconazole IV
* Followed by fluconazole po for weeks to months
89
Length of secondary prophylaxis for *cryptococcus neoformans*
Usually lifelong
90
6 manifestations of CMV in setting of HIV/AIDS
* Retinitis
* Uveitis
* Retinal detachment
* Visual loss
* Pneumonitis
* Disseminated
91
7 opportunistic viruses in setting of AIDS
* CMV
* HSV
* VZV
* HHV-8
* HBC
* HCV
* JCV
92
3 manifestations of toxoplasma gondii in setting of HIV/AIDS
* Encephalitis
* Seizures
* Disseminated CNS lesions (ring enhancing)
93
Treatment for toxoplasmia gondii
Sulfadiazine + pyrimethamine + folinic acid (leucovorin)
94
Secondary prophylaxis for toxoplasma gondii
Sulfadiazine + clindamycin until CD4 \> 200 for 3 - 6 months
95
4 drugs involved in Highly Active AntiRetroviral Therapy (HAART)
Combination therapy with
* NRTI
* NNRTI
* PI (protease inhibitors)
* FI (fusion inhibitors)
96
2 aims of HAART
* Reduction of HIV viral load to undetectable levels
* Elevation of CD4 Th lymphcyte counts
97
8 NRTIs
* ZDV
* 3TC
* d4T
* ddI
* ddC
* Abacavir
* Emtricitabine
* Tenofovir
98
4 combinations of NRTIs
* COmbivir
* Trizivir
* Kivexa
* Truvada
99
5 NNRTIs
* Delaviridine
* Efavirenz
* Nevirpine
* Etravirine
* Rilpivirine
100
2 NNRTI combinations
Atripla
Complera
101
Fusion inhibitor drug
Efurvitide
102
FI mechanism
Inhibition of fusion of HIV with human cells (a salvage mechanism)
103
FI administration
Subcutaneous injection
104
2 newer classes of HAART drugs
* Integrase inhibitors
* Coreceptor antagonists
105
Integrase inhibitor mechanism
Prevent integration of pro-viral DNA into human chromosomal DNA
106
2 integrase inhibitors
Raltegravir (Isentress)
Elvitegravir
107
Coreceptor antagonist mechanism
Prevent binding of HIV onto human cells
108
Coreceptor antagonist drug
Maraviroc
109
How to boost antiretrovirals
Inhibition of liver cytochrome p450 enzymes that metabolize some antiretrovirals (PIs, elvitegravir)
110
Aim of cytochrome p450 inhibition in antiretroviral therapy
Increase levels of antiretrovirals in the blood and tissues for max efficiency
111
2 boosting agents for antiretrovirals
Low doses of ritonavir
Newer = cobicistat
112
2 problems with ritonavir (a PI)
GI side fx and hyperlipidemia
May drug-drug interaction because of p450 inhibition
113
Advantage of using cobicistat
Less side fx than ritonavir
114
CD4 count when HIV treatment is mandatory
\<300 cells/mL
115
Viral load log when HIV treatment is mandatory
\>5.0
116
4 obstacles to HIV treatment
* Adherence to medication
* Intolreance and toxicity due to medications
* Metabolic complications due to medications
* HIV resistance to antiretrovirals
117
Compare the viral load of neonates to adults
Initial higher viral load --\> may take longer to become undetectable
118
Describe the progression of rapidly progressing HIV in children
* Rapid destruction of immune system
* AIDS before 5 years of age (\<5 months)
* 50% 5 year survival
119
5 manifestations of AIDS in children
* Opportunistic infections
* Failure to thrive
* Hepatitis
* Diarrhea
* Neurocognitive deterioration
120
Describe the disease progression of slowly progressing HIV in children
* Effective immune activity and viral suppression
* Asymptomatic or lymphadenopathy/parotitis
* 68% 5-y survival; 71% 6.5-y survival
121
3 main aspects of disease presentation of HIV in children
* Growth failure
* Decline in weight-growth velocity despite adequate nutrition
* Progressive neurodevelopmental deterioration
* LIP (lymphoid interstitial pneumonitis)
122
3 manifestations of LIP in children with HIV
* Immune0mediated lymphocytic infiltration of lungs
* Respiratory distress; hypoxia
* Reticulonodular infiltrates
123
Treatment for LIP in HIV children
Corticosteroids
124
Opportunistic infection for children with HIV
*Pneumocystis jiroveci *pneumonia
125
6 live vaccines
* MMR
* Varivax
* Yellow fever
* Oral typhoid
* Oral polio
* Intranasal influenza
126
Vaccine recommendations for children with HIV (3)
In severely immunosuppressed:
* Vaccines not effective (defer or re-immunize once reconstituted)
* Live vaccines contraindicated until CD4 rises to normal levels
* BCG absolute contraindication
127
5 methods of acquisition of HIV in children
* Perinatal exposure
* Blood product transfusion
* Sexual abuse
Adolescent years:
* Sexual intercourse
* IV drugs
128
3 perinatal exposures that may cause children to contract HIV
* Intrapartum especially
* Postpartum (i.e. breastmilk)
* Rarely *in utero*
129
4 measures to reduce mother-child transmission of HIV
* Implementation of universal prenatal HIV counseling and testing
* Antiretroviral treatment and prophylaxis
* Scheduled C-section (in some cases)
* Avoidance of breastfeeding
130
Main tool for reducing perinatal exposure HIV transmission
Universal informed opt-out screening for HIV infection in all pregnant women
131
3 highest risk infectious materials for HIV transmission
* Concentrated lab HIV
* Blood
* Any fluid contaminated with blood
132
6 infectious materials of intermediate risk for HIV transmission
* Semen
* Vaginal secretions
* CSF
* Amniotic fluid
* Pleural/pericardial/peritonial/synovial fluids
* Human milk
