Flashcards in HIV Deck (28)
Epidemiology of HIV
RNA retrovirus which targets CD4+ T helper cells as hosts (also CD4+ monocytes and dendritic cells)
CD4 molecule is receptor for HIV. the virus binds via gp120 (initial) and gp41 (conformational change)
Most strains also use CCR5 and CXCR4 chemokine co-receptors
How is HIV transmitted?
Sexual, infected blood, Mother-to-child (vertical- Breastfeeding, in utero, intra partum)
what type of CD is involved in HIV?
What glycoproteins does the virus bind to?
41 (conformational change)
Pathogenesis of HIV - The Innate Response
Non specific activation of macrophages, NK cells and complement
Stimulation of dendritic cells via Toll Like Receptors
Release of cytokines and chemokines
Pathogenesis of HIV - The Adaptive Response
Neutralising antibodies - anti gp120 and anti gp41
Non-neutralising antibodies - anti p24 gag IgG
CD8+ T cells can precent HIV entry by producing chemokines MIP-1a, MIP-1b and RANTES which block co-receptors
HIV damages the immune response
(long card with loads of info on, if anyone can think how to split this into more cards please feel free)
HIV remains infectious even when Ab coated
Activated infected CD4 helper T cells are killed by CD8 T cells
Activated infected CD4 helper T cells are energised (disabled)
CD4 T cell memory lost & failure to activate memory CTL
Monocytes and dendritic cells are therefore not activated by the CD4 T cells and cannot prime naive CD8 CTL (due to impaired antigen presenting functions)
Infected monocytes and dendritic cells are killed by virus or CTL
Quasispecies are produced due to error-rpone reverse transcriptase= these escape from immune response
7 stages of the life cycle of the HIV virus
2) Reverse transcription & DNA synthesis
4) Viral transcription
5) Viral protein synthesis
6) Assembly of virus & release of virus
What is the median time from infection with HIV to AIDS
How many years is classed as rapid HIV->AIDS progressions?
2-3 years and happens in 10%
What is Long Term no progression HIV and roughly what percentage of HIV pts have it?
stable CD4 counts and no symptoms after 10 years, occurs in less than 5% of pts
What is a good predictor of disease progression?
Initial viral burden (set point)
Screening test for HIV- what does it detect and what method is used?
Detects andi-HIV Ab via ELISA
Confirmation test - what does it detect and what method is used?
Detects Abs via Western Blot. A positive test requires a pt to have seroconverted (started to produce Ab)
How long after becoming infected will the pt have seroconverted?
after ~10 weeks incubation period
After Diagnosis, what tests are carried out? what doe they detect and how are they done?
Viral Load - PCR is used to detect viral RNA
CD4 Count - via FACS (flow cytometry), used to assess course of disease, onset go AIDS correlates with diminution in number of CD4 T cells.
Starting treatment and what guidelines are followed?
if CD4 count
What is HAART?
Highly Active Anti Retroviral Therapy = 2NRTIs + PI or NNRTI
example regiment - Emtricitabine + Tenofovir + Efavirenz - available as one pill Atripla
HIV treatment during Pregnancy
given Orally but switched to IV for delivery.
given to newborn for 6/52
what are the limitations of HAART?
It doesnt eradicate latent HIV-1; fails to restore HIV-specific T-cell responses; toxicities; high pill burden;adherence; threat of drug resistance; QoL; cost
HIV Treatment - what are the sites of action of the major drug classes?
1) Prevention of protein cleavage
2) block integration of the virus into DNA
3) block reverse transcriptase mediated trascription
4) block the docking process
HIV Treatment - Protease Inhibitors - drug names? side effects?
Indinavir, Nelfinavir, Ritonavir, Amprenavir, Fosamprenavir, Lopinavir, Atazanavir, Saquinavir
Side effects - Hyperlipidemias, Fat redistribution and Type 2 Diabetes
HIV Treatment - Integration inhibitors - drug names? side effects?
Side effects - Unknown
HIV Treatment - 3 classes of Reverse Transcriptase mediated Transcription inhibitors
1)Non-nucleoside Reverese Transcriptase Inhibitors (non-NRTIs)
HIV Treatment - 3 drug examples of Non-NRTIs and their side effects
Nevirapine - can cause Hepatitis and Rash
Delavirdine - can cause a Rash
Efavirenz - can have CNS effects
HIV Treatment - Nucleotide RTI - drug name example and side effects?
Tenofovir - can cause bone and renal toxicity
HIV Treatment - NRTI - drug name examples and side effects
Zidovudine, Didanosine, Stavudine, Lamivudine, Zalcitabine, Avacavir, Emtricitabine, Epzicom, Combivir, Trizivir
Side effects - Generally rare; feverm headachem GI distrubance, BMS (zudovudine), Peripheral Neuropathy (Zalcitabine, Stavudine), Mitochondrial Toxicity (Stavudine), Hypersensitivity (Abacavir)