Lecture 8: HIV Infection in the Immunocompromised Flashcards
HIV
transmission (4)
dx (3)
T: 1. blood contaminated needles
- unprotected sexual contact
- mother-fetus
- breast milk
dx: 1. ELISA type antibody screening- test for patient’s anti-HIV antibodies
2. Western blot-test for viral proteins in blood
3. RT-PCR to detect virus RNA in blood
PCR vs. RT-PCR
PCR detecs pathogen’s DNA
RT-PCR can detect pathogen RNA by adding a step to convert the RNA to DNA and then doing PCR
**PCR amplifies DNA nor RNA
HIV epidemic
ardor in the late 19th-early 20th century
- social changes and urbanization
- disruption in tribal values that favored cause; sexual practices with multiple partners - vaccination practices assoc. with colonialism
- increased bushmeat hunting
- forced labor (extreme stress depresses immune system)
HIV structure (5)
- family
- virulence
- structure
- member retroviridae
- lipid-enveloped with viral gp120/gp41 envelope glycoprotein with cylindrical psuedoicosahedral capsid
- gp120-attachment to host cell
- gp41-promotes fusion of viral envelope with host plasma membrane - 2 copies single-stranded RNA
- genome packed with several enzymes
- reverse transcriptase copies single-stranded RNS into double stranded DNA
Reverse transcriptase
enzyme capable of making a DNA copy with RNA template
Replication HIV (4)
- attachment and entry
- gp20, gp41 fusion protein
- *typically infected helper T cells - Reverse transcription and integration
- forms provirus which can remain latent - Biosynthesis
- active provirus transcribed into multiple copies now viral RNA - Assembly and release
- new capsid forms around each viral RNA genome and fever transcriptase
- new nucleocapsids bud off plasma membrane taking up viral envelope spikes as each virion is released from the cell
Stage I: Primary HIV infection` (4)
- may be asymptomatic
- can have flu-like illness
- occurs within 1-2 months exposure
- seroconversion occurs
Stage II: Asymptomatic stage HIV (4)
- viral load rises
- as CD4T cells decline
- skin rashes, night sweats
- Diarrhea, fever, weight loss
Stage III: HIV infection/AIDS (4)
- steep rise in viral load
- CD4 count < 200 cells/mm sqared
- opportunistic infection
- death from opportunistic infection
Opportunistic Infections
- As immune system deteriorates due to HIV, opportunistic infections develop
- CD4T cells count falls bellow 200 cells/mm squared
Viral opportunistic diseases in HIV pts. (5)
- HIV encephalopathy
- progressive multifocal leukoencephalopathy
- shingles
- cytomegalovirus
- recurrent HSV
Bacterial opportunistic disease in HIV pts. (4)
- persisten pneumonia
- tuberculosis
- mycobacterium avian complex
- salmonella septicemia
Fungal opportunistic diseases in HIV pt. (5)
- cryptococcus
- candidiasis
- histoplasmosis
- coccidioidmycosis
- pneumocystis pneumonia
Protozoal Opportunistic Diseases HIV pts. (2)
- toxoplasmosis
2. chronic cryptosporidium diarrhea
Cancers in HIV Pts. (2)
- lymphomas of brain, lympatic tissue
2. Kaposi sarcoma
Misc. conditions affected HIV pts. (5)
- persistent dairrhea
- persistent generalized lymphadenopathy
- wasting syndrome
- night sweats
- persistent fever
HIV tx
- antivirals: Azodiothymidine
- interferes with reverse transcriptase
- chain terminator-inhibiting DNA synthesis
HIV resistance
- many variants become resistant to antivirals
- monotherapy= resistant viruses selected
- resistant variant becomes dominant-dishes progression
HAART
Highly Active Antiretroviral Therapy
HAART tx (4)
- fusion inhibitors
- intefere with virus binding CD4 - reverse transcriptase
- inhibits viral RNA conversion to DNA - DNA Polymerase
- inhibits production of a DNA copy of a virus - Integrase
- inhibits integration of viral DNA into host genome
*can keep disease from progressing indefinitely
Long-term Non-Progressives Def.
- indv. infected with HIV many years, w/o therapy maintain CD4 count > 500, and low viral loads
- eventually can get AIDS if they remain untreated
Elite Controllers
HIV infected individuals with even lower viral loads and LTNP pts.
- HLA allele allows CD8 T cells to efficiently recognize HIV infected cells
- immume response to gag unusually strong
Stem cell transplant
transplant using CCR5 homozygous mutant has achieved “cure” of HIV in 2 patients
CCR5
co-receptor for HIV and crucial for infection in some strains
most common causes fungal lung infections (4)
- Histoplasma capsulatum
- Cryptococcus neoformans
- blastomyces dermatitidis
- coccidioides immitis
2 most important rx factors assoc. w acquiring fungal infection in lung
- immunosuppression
* particularly susceptible to poor outcomes from fungal infection - environmental exposure
Endemic Mycoses Causative agents (3)
- Coccidioides Immitis
- coccidioidomycosis - Histoplasma Capsulatum
- histoplasmosis - Blastomyces dermatitidus
- blastomycosis pulmonary (cough, fever, chest pain, SOB)- skin, bone, CNS involvement