VII- Viral STI HIV Flashcards
basic HIV disease states
- acute HIV syndrome - like mono + faint rash + burst of viremia > immune resp curtails
- chronic phase - low viremia, asymp
- AIDS - dec CD4 and ability to fight other microbial agents
pathologic basis of immunodef from HIV
CD4 T cell count less than 200 so inc susceptibility to opportunistic infections
possible ways T cells are killed by HIV
- copious budding
- interference with cellular processes
- other mechanisms
diagnosing HIV
-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
HIV-1/2 Ag/Ab immunoassay detects
HIV-1 and 2 antibodies + HIV p24 antigen
screening function but can’t differentiate b/t serovars
HIV-1/2 Ab differentiation immunoassay
HIV-1 and 2 antibodies
-differentiates b/t 1 and 2
HIV nucleic acid tests for
NAT
HIV RNA genomes - detectable earlier than antibodies (indicates acute)
-do if neg or indeterminate antibody tests for both 1 and 2
virology of acute HIV
viremia burst followed by immune resp
-may not have detectable anti-HIV in acute phase
virology of chronic HIV
-low levels viremia bc viral replication
-inc antibody levels
-dec CD4 T cells
retrovirus life cycle
- attachment by gp120 to CD4
- fusion of membranes by gp41
- reverse transcription by enzyme in virion
- integration into host DNA by viral integrase = provirus
- genome rep and transcription
- budding aka egress on lipid rafts
- maturation by viral protease cleaving gag and gag-pol proteins
how retrovirus differs from other +ssRNA
-most error prone so rapid evolution
-provirus stays in cell for as long as survives
HIV transmission
- sexual- esp male to female (heterosex)
- perinatal- esp at birth
- contaminated blood or body fluids
NO casual contact or insect vectors
preventing HIV
- public edu
- prophylactic antivirals for health care exposure
- mother-infant antivirals, no breast feeding, C sections
- screen blood donations
no vaccine
coreceptor antagonists
Maraviroc
-CCR5 only antagonists so prevent interaction with gp120
fusion inhibitors
Enfuvirtide
-bind gp41 to prevent conform change needed for fusion
-limited by injection instead of oral
gp120 attachment inhibitors
Fostemsavir
-binds gp120 near CD4 binding site
class combos for initial HIV
preferred combo is 1 integrase inhibitor + 1 or 2 NRTIs
at least two ARV drugs from different classes
commonly associated infections early HIV
- oral hairy leukoplakia from EBV
- pneumonia from pneumocystis carinii or mycobacterium tuberculosis
- thrush from candida albicans
- CMV retinitis
- neoplasms like kaposi’s sarcoma or B cell lymphomas
- diarrhea from cryptosporidium or isospora belli
HIV coreceptors
- R5 tropic = CCR5, transmitted person to person, predoms early dz, efficiently infects macrophages
- X4 tropic = CXCR4, rapid progression to AIDS, conversion from R5 possible
CD4 post attachment inhibitor
Ibalizumab
-binds CD4 extracellular domain 2 so steric hinderance of conform change for fusion
-gp120 can still bind CD4
-humanized monoclonal Ab
reverse transcriptase inhibitors
- nucleoside inhibitors NRTIs - azidothymidine (AZT) incorporated into DNA chain during provirus syn = chain terminate
- nonnucleoside inhibitors NNRTIs - Nevirapine, binds reverse transcriptase to inhibit
integrase inhibitors
Raltegravir
-blocks integration of DNA copy of viral genome into cellular genome so stops permanent infection
Protease inhibitors
Saquinavir
-peptidomimetric inhibitor so produce immature defective HIV particles
