VII- Viral STI HIV

Question 1

basic HIV disease states

Answer 1

1. acute HIV syndrome - like mono + faint rash + burst of viremia > immune resp curtails
2. chronic phase - low viremia, asymp
3. AIDS - dec CD4 and ability to fight other microbial agents

Question 2

pathologic basis of immunodef from HIV

Answer 2

CD4 T cell count less than 200 so inc susceptibility to opportunistic infections

Question 3

possible ways T cells are killed by HIV

Answer 3

1. copious budding
2. interference with cellular processes
3. other mechanisms

Question 4

diagnosing HIV

Answer 4

-set point to measure virus load after 1 yr for predicting progression rate
-immunoassay for p24 antigen or antibodies to HIV gp120
-NAT
-PCR for provirus in infected cells

Question 5

HIV-1/2 Ag/Ab immunoassay detects

Answer 5

HIV-1 and 2 antibodies + HIV p24 antigen

screening function but can’t differentiate b/t serovars

Question 6

HIV-1/2 Ab differentiation immunoassay

Answer 6

HIV-1 and 2 antibodies
-differentiates b/t 1 and 2

Question 7

HIV nucleic acid tests for

NAT

Answer 7

HIV RNA genomes - detectable earlier than antibodies (indicates acute)
-do if neg or indeterminate antibody tests for both 1 and 2

Question 8

virology of acute HIV

Answer 8

viremia burst followed by immune resp
-may not have detectable anti-HIV in acute phase

Question 9

virology of chronic HIV

Answer 9

-low levels viremia bc viral replication
-inc antibody levels
-dec CD4 T cells

Question 10

retrovirus life cycle

Answer 10

1. attachment by gp120 to CD4
2. fusion of membranes by gp41
3. reverse transcription by enzyme in virion
4. integration into host DNA by viral integrase = provirus
5. genome rep and transcription
6. budding aka egress on lipid rafts
7. maturation by viral protease cleaving gag and gag-pol proteins

Question 11

how retrovirus differs from other +ssRNA

Answer 11

-most error prone so rapid evolution
-provirus stays in cell for as long as survives

Question 12

HIV transmission

Answer 12

1. sexual- esp male to female (heterosex)
2. perinatal- esp at birth
3. contaminated blood or body fluids

NO casual contact or insect vectors

Question 13

preventing HIV

Answer 13

1. public edu
2. prophylactic antivirals for health care exposure
3. mother-infant antivirals, no breast feeding, C sections
4. screen blood donations

no vaccine

Question 14

coreceptor antagonists

Answer 14

Maraviroc
-CCR5 only antagonists so prevent interaction with gp120

Question 15

fusion inhibitors

Answer 15

Enfuvirtide
-bind gp41 to prevent conform change needed for fusion
-limited by injection instead of oral

Question 16

gp120 attachment inhibitors

Answer 16

Fostemsavir
-binds gp120 near CD4 binding site

Question 17

class combos for initial HIV

Answer 17

preferred combo is 1 integrase inhibitor + 1 or 2 NRTIs

at least two ARV drugs from different classes

Question 18

commonly associated infections early HIV

Answer 18

1. oral hairy leukoplakia from EBV
2. pneumonia from pneumocystis carinii or mycobacterium tuberculosis
3. thrush from candida albicans
4. CMV retinitis
5. neoplasms like kaposi’s sarcoma or B cell lymphomas
6. diarrhea from cryptosporidium or isospora belli

Question 19

HIV coreceptors

Answer 19

1. R5 tropic = CCR5, transmitted person to person, predoms early dz, efficiently infects macrophages
2. X4 tropic = CXCR4, rapid progression to AIDS, conversion from R5 possible

Question 20

CD4 post attachment inhibitor

Answer 20

Ibalizumab
-binds CD4 extracellular domain 2 so steric hinderance of conform change for fusion
-gp120 can still bind CD4
-humanized monoclonal Ab

Question 21

reverse transcriptase inhibitors

Answer 21

1. nucleoside inhibitors NRTIs - azidothymidine (AZT) incorporated into DNA chain during provirus syn = chain terminate
2. nonnucleoside inhibitors NNRTIs - Nevirapine, binds reverse transcriptase to inhibit

Question 22

integrase inhibitors

Answer 22

Raltegravir
-blocks integration of DNA copy of viral genome into cellular genome so stops permanent infection

Question 23

Protease inhibitors

Answer 23

Saquinavir
-peptidomimetric inhibitor so produce immature defective HIV particles