Академический Документы
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Культура Документы
Ariberto Fassati
What is AIDS?
Acquired ImmunoDeficiency Syndrome
First reported in 1981 in 5 North American gay men
www.cdc.gov/mmwr/PDF/wk/mm5021.pdf
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HIV/AIDS: how?
Chimpanzee
Gorilla
Sooty mangabey
SIVcpz
SIVgor
SIVsm
HIV-1 M
HIV-1 O
HIV-2
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/AIDS
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Consequences for
1) Vaccine design
2) Diagnosis
3) Pathogenesis
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HIV/AIDS: when?
Date of origin of HIV-1: around 1920
First virus isolate available to date: 1952 from Kinshasa (DR Congo)
First retrospective case of HIV-1 seroconversion (infection): 1959
in Kinshasa.
First 5 cases reported in 1981 in USA
(Gottlieb et al. 1981 N. Engl. J. Med 305: 1425)
Number of deaths directly due to AIDS to 2007: >24 million
Number of people infected with HIV-1 at 2008: ~32 million
HIV/AIDS: where?
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Samples (from 1960) recovered from hospital in Congo showed that the epidemic probably started
around 1908
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Major co-receptors: chemokine receptor CCR5 and CXCR4. CCR5 is essential for virus
transmission in vivo, present on T-helper lymphocytes, macrophages, microglial cells.
CXCR4 used in the late phase of the infection.
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Reverse transcription:
Reverse Transcription
5 R U5 PBS
tRNA
PPT
U3 R
AAA 3
DNA synthesis
R U5 PBS
PPT
U3 R
PPT
U3 R AAA
AAA
RNase H
PBS
R U5
PPT
DNA synthesis
RNase H
PBS
PPT
PBS
DNA synthesis
RNase H
PPT
U3 R AAA
R U5
U3 R U5
U3 R U5
U3 R U5
U3 R U5
Second strand transfer
DNA synthesis
U3 R U5
U3 R U5
U3 R U5
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Visualisation of HIV-1 inside an infected cell. The RTC/PIC travels along microtubules and is
a large structure composed of viral and cellular factors. Reverse transcription takes place within
this structure.
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Protease
MLV
Changes in virion
morphology during maturation
MPMV
HTLV
HIV
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R5X4
X4
CD4+ T
Dendritic,
Langerhans
Macrophage
Activated/
effector memory
?
Microglia
naive
CD4
CCR5
CXCR4
Astrocyte
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Primary
Infection
(months)
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AIDS
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V. Antiretrovirals
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Approved Antiretrovirals
Brand name
Generic name
Nucleoside reverse transcriptase inhibitors (NRTIs)
Retrovir
Zidovudine (AZT
Videx
Didanosine (ddI)
Hivid
Zalcitabine (ddC)
Zerit
Stavudine (d4T)
Epivir
Lamivudine (3TC)
Combivir
Lamivudine+Zidovudine
Ziagen
Abacavir
Trizivir
Abacavir+lamivudine+zidovudine
Videx EC
Didanosine (ddI)
Viread
Tenofovir disoproxil
Emtriva
Emtricitabine (FTC)
Epzicom
Abacavir+Lamivudine
Truvada
Emtricitabine+Tenofovir
Non-nucleoside reverse transcriptase inhibitors (NNRTIs)
Viramune
Nevirapine
Rescriptor
Delavirdine (DLV)
Sustiva
Efavirenz
Intelence
etravirine
Protese Inhibitors (PIs)
Aptivus
Tipranavir (TPV)
Invirase
Saquinavir
Norvir
Ritonavir
Crixivan
Indinavir (IDV)
Viracept
Nalfinavir
Fortovase
Sequinavir Mesylate
Agenerase
Amprenavir
Kaletra
Lopinavir+Ritonavir
Reyataz
Azatavir
Lexiva
Fosemprenavir
Fusion Inhibitors
Fuzeon
Enfuvirtide (T20)
Entry inhibitors
Selzentry
Maraviroc
HIV integrase strand transfer inhibitor
Isentress
Raltagrevir
Multi-class Combination Product
Atripla
Efavirenz,emtricitabine and tenofovir
manufacturer
GlaxoSmithKline
Bristol-Meyers Squibb
Roche Pharmaceuticals
Bristol-Meyers Squibb
GlaxoSmithKline
GlaxoSmithKline
GlaxoSmithKline
GlaxoSmithKline
Bristol-Meyers Squibb
Gilead Sciences
Gilead Sciences
GlaxoSmithKline
Gilead Sciences
Boehringer Ingelheim
Pfizer
Bristol-Meyers Squibb
Tibotec Therapeutics
Boehringer Ingelheim
Roche Pharmaceuticals
Abbott Laboratories
Merck
Pfizer
Roche Pharmaceuticals
GlaxoSmithKline
Abbott Laboratories
Bristol-Meyers Squibb
GlaxoSmithKline
Hoffman-La Roche
Pfizer
Merck & Co
Brtistol MS and Gilead Sciences
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Side Effects
Lipodystrophy
Myopathy
Hepatotoxicity
Immunorestoration
Disease
Rashes
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Is a cure possible?
One case of cure known (Berlin patient)
The cured baby was not cured
Several cases of long term remission known
May depend on size of reservoir (the smaller the better)
and time of therapy. May need novel approaches.
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