HIV 2 - pathology, Tx

Question 1

Subtypes of HIV

Answer 1

HIV-1 and HIV-2 (more in Africa, slower response)

Question 2

HIV heterogeneity

Answer 2

Fast replication, high error prone, lack of proof reading. All leads

Question 3

HIV attachment and fusion

Answer 3

Needs CD4 and CCR5 or CCXC4. Attaches to dendritic cells, and Th cells

Question 4

How HIV makes you sick?

Answer 4

Destroys CD4 cells. Drops rapidly in the first few weeks, then rebounds a bit, but slowly drops down. Treatment zone is best before 200. CD4 loss results in low immune memory

Question 5

CD4s in gut lining

Answer 5

HIV depletes these as well. This results in other infections etc diffusing from the gut.

Question 6

Train analogy for HIV

Answer 6

Speed is the viral load, CD4 count is the distance from the cliff; treatment can slow down, stop or back up the train

Question 7

Immune consequences

Answer 7

CD4(+) cell depletion with stimulation of remaining cells (Chronic B cell activation leading to elevated gammaglobulin levels. Chronic cytokine release, resulting in fever, wasting). Opportunistic infections (OI) – low virulence pathogens usually controlled by CTL. Malignancy – specific tumors resulting from chronic viral co-infection

Question 8

Complications with HIV treatment

Answer 8

If you already had some opportunistic infections as a result of low CD4, when you start treatment and CD4 start recovering, it can have an intense inflammatory response and cause problems

Question 9

Common infections (from high CD4 to low)

Answer 9

HSV and pneumonia; shingles; 200: PCP; 100: cryptococcal meningitis; Candida esophagitis; 50: Toxoplasmosis; CMV (retinitis, many other things); PML (white matter disease); mycobacterium avian complex

Question 10

Groups to treat for coexisting conditions

Answer 10

Pregnancy (AI); History of an AIDS-defining illness (AI); HIV-associated nephropathy (AII); HIV/hepatitis B virus coinfection (AII)

Question 11

Opportunistic infections

Answer 11

So many! Specifics: Candida (recurrent thrush, esophygeal, vaginitis); pneumocystis (persists in many, but reactive with weak immune syst.); TB (most important, all HIV+ should be tested for TB and vice versa); cancers (Kaposi’s sarcoma (lesions in mouth, GI, skin), EBV (lymphona), HPV (cervical, anal))

Question 12

ART principles

Answer 12

Goal is to suppress viral replication, use multiple agents, must be dedicated to Tx.

Question 13

ART mechanism

Answer 13

RT inhibitors (nucleotide and non), protease inhibitors, fusion inhibitors, integrase inhibitors, CCR5 antagonists

Question 14

Failure of therapy

Answer 14

Nonadherence, resistance (use genetic sequencing early and follow up), inadequate potency

Question 15

Life span with HIV

Answer 15

if a 20 yo gets diagnosed, he should still reach on average 72 yo