Pathogenesis and Natural History of HIV/AIDS

Question 1

What is meant by the “disproportionate distribution” of HIV transmission?

Answer 1

What region of the world you are in really dictates most frequent infection modes

I.e.
America = gay sex
Eastern Europe = IV drug use
Sub-Saharan Africa = sex work (straight sex)

Question 2

What is the easiest mode of sex to get HIV in?

Answer 2

Receptive anal intercourse (1-2% transfer rate). All other modes are less than 0.1%

Question 3

What is the highest risk of HIV transmission?

Answer 3

Vertical - about 24% chance mother will pass to child

Question 4

What STDs will increase transmission of HIV?

Answer 4

Inflammatory - will result in increase of CD4+ cells near the genitals - transmission is actually more likely to occur to higher CD4 counts

Ulcerative - leads to exposed mucus membranes (i.e. HPV, HSV, Syphilis)

Question 5

What gender has a greater biological susceptibility to infection?

Answer 5

Women - they more soft membranes are exposed during sex - i.e. vaginal canal, where transmission from an infected male is easy. For a male to get the disease, it pretty much has to go up his urethra or find some way to soft membranes.

Question 6

What measure is more closely correlated to risk of all transmission?

Answer 6

plasma HIV RNA level of mother or partner

Question 7

What is the threshold of HIV RNA level for which transmission is at near 0?

Answer 7

400 copies / mL

Question 8

How does HIV initially start and then generate diversity?

Answer 8

One or few founder virions get in, then the virus mutates from there

This is due to an error-prone reverse transcriptase which has one point mutation per 10,000 base pairs (incredibly high mutation rate)

Question 9

How many CD+ T cells can be destroyed and replaced daily, and what is one slow reservoir where the virus still divides?

Answer 9

About 1 billion cells -> 1-10 billion virions produced daily in steady state

Slow reservoir = monocytes and resting CD4+ memory cells (hold all mutations from over the course of infection)

Question 10

How do the CD4+ T cells actually die?

Answer 10

Direct cytopathic effect, or immune-mediated destruction via apoptosis by CD8+ cells

Question 11

What is the serum viral load from?

Answer 11

A spill-over from lymph nodes and other lymphoid aggregates

Question 12

What are the “sanctuary sites” of the immune system which harbor virus?

Answer 12

1. CNS

2. Reproductive tract

Question 13

Other than a loss of cell-mediated immunity, what are two other degradations of the immune system which can occur in HIV?

Answer 13

1. Disordered antibody production and overproduction of non-specific antibodies
2. Bone marrow failure in late AIDS leading to severe neutropenia

Question 14

What is the primary AIDS vaccine target?

Answer 14

gp120, although it mutates too rapidly for a great vaccine. Even early antibodies to gp120 which are used for diagnosis are not effective in stopping the virus

Question 15

Why are certain HLA types associated with a faster progression to AIDS?

Answer 15

Inability to present peptides to CD4 / CD8 cells which allows for CD8+ cell-mediated immunity and virus suppression

Question 16

What is the disease prognosis in CCR5 mutations (heterozygotes and homozygotes)?

Answer 16

Heterozygote - slowly progressing disease

Homozygote - resistance to infection

Question 17

What are CCR5 and CXCR4 normally and how does this relate to SDF-1?

Answer 17

They are chemokine receptors. People with mutations in SDF-1, the natural ligand of CXCR4, have a much slower progression of disease

Question 18

Where is the primary area where HIV replicates in the early stages of infection?

Answer 18

gut-associated lymphoid tissue

Question 19

What are the signs of acute retroviral syndrome? Why should we take it seriously?

Answer 19

Flu-like symptoms: Fever, rash, adenopathy, sore throats

Looks like a cold or flu

Should be taken seriously because the patient is most infectious at this stage

Question 20

What is an “elite-controller”?

Answer 20

A person who’s HIV RNA remains at undetectable levels even without treatment. This is thought to be due to great humoral and cytotoxic T cell response suppressing the virus

Question 21

What is the longterm risk of elite controllers?

Answer 21

Chronic immune activation can produce premature vascular disease (atherosclerosis) as well as non-AIDS cancers

Question 22

What is the limit of detection in current assays?

Answer 22

<48 RNA copies per mL

Question 23

Where does the majority of perinatal transmission occur? How can this be prevented?

Answer 23

During labor in delivery -> much less in utero or postnatally during breastfeeding

Can be prevented by C-section (if viral load is not undetectable)

or

HAART with IV zidovudine to mother at delivery and oral zidovudine to newborn for 6 weeks post delivery

Question 24

What is post-exposure prophylaxis (PEP)?

Answer 24

Use of combination anti-retroviral therapy for 1 month following needlestick exposure or severe mucosal exposure to HIV containing blood or body fluids

Question 25

What is PrEP?

Answer 25

Pre-exposure prophylaxis, a daily combination anti-retroviral therapy for high risk MSM. On demand is thought to be equally effective (knowing you’ll have sex later that night)