13_HIV/AIDs

Question 1

What is underlying pathological cause of immunosuppression?

Answer 1

• depletion of CD4 T cells
• isolation of HIV retrovirus occurred in 1984 –> shown to be CD4 T tropic key link

Question 2

when did symptoms develop for HIV in the US?

Answer 2

• there’s a delay between HIV-1 infection and development of sxs (clinical latency), such as secondary infections –> indicates HIV-1 infections in US begain in early to mid-1970S

Question 3

epidemiology of HIV in US

Answer 3

• 1.2M people w/ HIV in the US, at diff’t stages

Question 4

HIV virion:

• structure
• prevalence
• origin for HIV-1

Answer 4

• structure: mature HIV type 1 –> elongated internal cores
• most prevalent in Africa, but still a global concern
  
  • sub-saharan Africa
  • 40M worldwide
• primate origin for HIV-1

Question 5

Describe the origin of HIV virus

Answer 5

• Lentivirus from primates made the adaptation to humans in mid-1900s –>
• gave rise to HIV-1 and HIV-2
• how?
  
  • monkeys destined for local market place or export
  • some pet monkeys
  • monkeys as food source

Question 6

how is HIV transmitted?

Answer 6

• unprotected sexual intercourse w/ infected partner
• vertical transmission (mother to child)
• injection drug use (rare)

Question 7

describe the replication cycle for HIV-1

Answer 7

Question 8

how is the HIV-1 genome organized?

Answer 8

• structural proteins
• enzymes
• coat proteins

Includes Gag, Pol, and envelope genes

Question 9

two different tropic strains of HIV-1

fuction of each?

Answer 9

• M-tropic = “macrophage-tropic strain of HIV-1”
• T-tropic = “T-cell-line-tropic strain of HIV-1”

M tropic infxn is followed by switch to T tropic –> depletes CD4 T cells –> resulting in AIDS

Question 10

At what point can HIV-1 lead to T cell depletion?

Answer 10

after HIV-1 infects monocytes –> can genetically change to tropic T cells –> leading to T-cell depletion

Question 11

what is the suggested meghanisms for depletion of CD4 cells?

Answer 11

Question 12

what are the functions of T helper cells?

Answer 12

Question 13

what confers genetic plasticity to HIV-1?

Answer 13

1. Reverse Transcription (RT) error prone lacks proof-reading 1 in 10,000
2. Stand switching from one genome to another during replication, co-infection, or following super-infection (HIV-1 is diploid)
3. recombination following co-infection and superinfection
4. transcription of integrated proviral DNA by host RNA polymerase II error prone

Question 14

what are the consequences of HIV-1’s genetic plasticity?

Answer 14

Question 15

disease course of HIV/AIDS

relationship b/w CD4+ lymphocyte count and HIV RNA copies?

Answer 15

• as HIV RNA copies increase, the CD4 T cell cound decreases
• Once CD4 count is below 200/mL, considered AIDS

Question 16

what is the acute phase of HIV syndrome?

Timing and sxs?

Answer 16

• T cells appear to be targets of infxn even early on; high levels of circulating virus (10^8 viral particles/mL)
  
  • viral population may double every 6-10 hours
  • each infected cell can resul tin infxn of about 20 cells;
  • seeding of lymphoid organs and CNS
• Sxs occur days-wks after infxn w/ HIV
  
  • sxs: fever, fatigue/lack of energy and motivation
  • rash (maculopapular)
  • lymphadenopathy
  • pharyngitis
  • thrush (candida)

Question 17

disease progression of HIV

(acute vs. long)

Answer 17

Question 18

How does AIDS affect the clinical presentation of diseases?

Answer 18

clinical presentation of any of these conditions is much worse (due to fever CD4 T cell count)

Question 19

What are the early sxs in secondary infections?

last symptom of secondary HIV infxn?

Answer 19

• Early sxs:
  
  • Thrush, and
  • Oral Hairy Leukoplakia
• Late sxs: Mycobacterium avium complex disease

Question 20

Oral hairy leukoplakia (OHL):

what is it a sign of?

Answer 20

sign of EBV replication in epithelial cells

if not already diagnosed w/ HIV, this is an indiction for testing

Question 21

Mycobacterium avium complex:

prevalence

when does it develop?

Answer 21

• organisms are ubiquitous; but commonly found in water/soil
• develops when CD4 count is lower than 75
  
  • usually, organism is ingested –> disseminates to rest of the body

Question 22

What virus is associated w/ the following malignancies?

Answer 22

Question 23

what is the following skin lesion?

Answer 23

Question 24

progressive multifocal leukoencephalopathy (PML)

define

Answer 24

caused by Human polyomavirus JC

Question 25

HIV-1 Associated Neurological DIsease (HAND)

define

Answer 25

HIV-1 Infxn can often lead to neurological sxs directly or by inducing the reactivation and infection of the brain by other agents –

common to develop neuro conditions

Question 26

How to diagnose AIDS?

How to diagnose HIV-1?

Answer 26

• AIDS: dx by depleted immune system (<200 CD4 cells/mL)
• HIV-1
  
  • Primary infxn:
    
    • infectious mono-like illness, viral syndrome, flu-like sxs
    • enzyme-linked immune sorbent assay (ELISA) TO P24
    • western blotting gp120, gp160, gp41, p24
  • Late onset –> beginning of AIDS: Oral hairy leukoplakia & lymphadenopathy
    
    1. CD4+ T cell numbers and HIV RNA load in plasma
    2. Sequencing of HIV-1 pol gene, or phenotyping to determine sensitivity to HAART is cost effective

Question 27

what is the optimal management of HIV-1 positive patients?

Question 28

how to prevent HIV-1 infection?

Answer 28

• HAART Therapy: highly active anti-retroviral therapy
  
  • only therapy available for HIV-1/AIDS pts;
  • consists of reverse transcriptase, fusion/entry, and proteast inhibitors
• AND CONDOM USE
• (combined, the 2 can reduce transmission risk to near 0% risk)

Question 29

when to start tx after HIV infxn?

what effect does it have on breastfeeding?

Answer 29

• w/in a year of seroconversion – w/in a few weeks of HIV infxn when Abs to the virus are first produced and their concentration reaches a detectable level (tx should be as soon as possible)
• 10-15% of HIV-negative babies will become infected by breastfeeding mother; can be prevented by ART of newborn