a virology 14 hiv
Terms
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- HIV Sturcture
- - retrovirus – enveloped, RNA - uses reverse transcriptase, RNase H, integrase, protease
- HIV Replication strategy
- - Attach via CD4 protein receptor (chemokine as a co-receptor to fuse) - RT and RNase H copy in DNA, then that’s transported to the nucleus where integrase inserts viral DNA into host chromosome - large precursor proteins assemble then protease cleaves - RT and protease are current drug targets
- HIV Clinical Features and Pathogenesis
- - progressive loss of CD4+ helper Ts -> immunodef - Acute Infection - levels of virus present w/in 6 months - some immune insult that can’t be repaired by controlling viral replication later on - Chronic infection - high rates of replication and immune clearance – sometimes and aggressive form uses a different co-receptor -> more rapid disease - CD4+ T cell count drops below 200
- HIV Opportunistic infections – Fungal
- - Candida (oral -> esophagus) - Pneumocystis carinii (pneumonia - PCP) - Cryptococcus neoformans (meningitis) - Histoplasma capsulatum (pneumonia or disseminated)
- HIV Opportunistic infections – Protozoan
- - Cryptosporidium (gastroenteritis) - Toxoplasma gondii (encephalitis)
- HIV Opportunistic infections - Bacterial
- - Mycobacterium tuberculosis (pneumonia and/or disseminated) - Mycobacterium avium complex (MAC, disseminated infection, fever) - higher susceptibility to common infections
- HIV Opportunistic infections – Viral
- - cytomegalovirus (retinitis) - herpes simplex virus (mucocutaneous lesions) - Epstein-Barr virus (oral hairy leukoplakia, lymphomas) - varicella-zoster virus (shingles)
- HIV Diagnosis
- - AIDS-defining illness in healthy person - then do western blot - test positive for anti-HIV-1 Abs - then count CD4+ T and level of viral RNA - flu-like symptoms from acute HIV-1 - common symptoms so consider risk factors – no Abs but plasma RNA - After a known exposure – - After birth of a baby to an HIV infected mother - monitor for Abs or plasma RNA for 6 months - some starts administering therapy anyway
- HIV Treatment
- - inhibitors include Nucleoside analogs (AZT, 3TC, ddI, ddC) are chain terminatorys - Non-nucleoside RT inhibitors (NNRT) bind RT to inactivate - Protease inhibitors - make sure its strong, wont develop resistance (use combos), and is tolerated - if 50 copies/ml of plasma, probably no progress or resistance - AZT, 3TC and the protease inhibitor indinavir usually will do this - if suppression is incomplete, resistance more probable - for NNRTIs, a single mutation can do resistace – more mutations needed for protease inhibitors - treat opportunistics normally, except Pneumocystis pneumonia, Toxoplasma encephalitis and Mycobacterium avium - give prophylactics if CD4+ below 200 - most pts survive until T is at 50 - promising alternative therapy is CD4+ T cell production with IL2 – also maybe bone marrow transplants
- HIV Epidemiology
- - 750,000 and one million in US, 36 million in the world – 3rd world bad - Worldwide spread sustained by heterosexual transmission - in US, main spread is from homosexuals and IV drugs - esp bad in coastal cities – migration to rural - leading cause of death in the US among 25 to 44 year-olds - two related variants (HIV-1 and HIV-2) - 1 is more widespread and pathogenic, 2 is mainly in western Africa - virus load is high early and late, low in between - concurrent STD infections increase risk - 15 30% vertical transmission (in utero and at birth) - AZT decreases chance - 1 in 300 in sharing needles, 90% in blood transfusions
- HIV Prevention Strategy/Vaccine
- - probability of STD spread determined by # of partners, likelihood that partner is infected, transmission conditions - not all virus-containing blood has antibodies (during acute infection but prior to seroconversion) - Factor VIII and IX clotting factors are now heat treated to inactivate virus - immediate AZT treatment after exposure - No vaccine due to extreme sequence variability - must try to attain sufficiently high levels of protection to block an initial infection (since body cant rid itself of it) - most vaccines increase immunity for a subsequent infection