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24 Cards in this Set
- Front
- Back
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Whatis the HIV replication cycle (7 steps)? |
1. Binding and fusion: Free HIV binds to a CD4 Molecule and one of two coreceptors (CCR5 or CXCR4), then the virus fuses with the host cell 2. Infection: Virus penetrates cell. Contents emptied into cell 3. Reverse Transcription: single strands of viral RNA are concerted into dsDNA by the reverse transcriptase enzyme 4. Integration: Viral DNA is combined with the cell's own DNA by the integrase enzyme 5. Transcription: when the infected cell divides, the viral DNA is read and long chain proteins are made 6. Assembly: sets of viral protect chains come together, the protease enzyme starts processing the proteins in the newly formed virus 7. Maturation: the individual proteins combine to make a functioning virus |
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What do B-Cells do? |
They make antibodies that recognize extracellular antigens |
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Whatare the two major functions of antibodies? |
1.Neutralize pathogens 2.Tag pathogens for destruction by theimmune system |
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Whatdo T-cells do? |
Kill pathogen-infected cells, they recognize intracellularantigens that are presented on the surface of cells by Human Leukocyte Antigens(HLA) |
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What are vaccines (how do they work)? |
They contain an agent called "immunogen" that is derived from a disease causing organism or its toxin, these immunogens stimulate pathogen specific immune responses so that the immune system is primed and ready to fight the pathogen if infection occurs |
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What are the 4 challenges to creating an HIV vaccine? |
1. Correlates of immune protection are unknown 2. HIV evolution and immune evasion 3. HIV Evolution and sequence diversity 4. HIV kills immune cells |
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What is "Correlates of immune protection are unknown"? |
our naturally occurring immune response is not sufficient enough to protect from infection of HIV or eliminate HIV from the body, so we need to design a vaccine that stimulates immune response that are more potent and effective than those that occur naturally |
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Describe HIV evolution and immune evasion |
HIV mutates really quickly, which means it remains one step ahead of the immune system and one step ahead of vaccines, immune evasion is where HIV can develop mutations in the envelope proteins that allow it to prevent binding from antibodies therefore are non-neutralizing, or it can mutate so its peptides are not presented by infected cells allowing escape from elimination by T cells |
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What is HIV evolution and Sequence Diversity? |
HIV's ability to mutate rapidly around the globe, which means there is significant sequence diversity in different areas of HIV-1 worldwide |
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How does HIV kill immune cells? |
HIV infects and kills CD4+ Lymphocytes whose purpose is to co-ordinate the immune response |
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What are the 3 current HIV vaccine efforts? |
1. Figure out how to elicit neutralizing antibodies 2. Elucidate role of non-neutralizing antibodies (Elicit HIV-specific antibodies) 3. Design vaccines that stimulate better T-cell responses (immune evasion, animal studies have shown to control infection) |
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Describe the HIV Political agenda starting from 1996, 1998, 2000, 2001, 2002 |
1996 - 11th international AIDS conference (Vancouver) "One world, One hope" 1998 - 12th international AIDS conference (Geneva) "Bridging the Gap" HAART >$10,000/yr 2000 - 13th international AIDS conference (Durban) "Breaking the Silence" HAART >$1,000/yr, G8 Summit Okinawa 3 Billion over 5 years for ID 2001 - UNGASS, Doha Declaration on TRIPS 2002 - The Global Fund to fight AIDS, TB and Malaria |
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What are 3 innovations brought by efforts for universal access to HIV treatment? |
1. Mobilization of diverse actors: strengthening the role of civic society 2. Increasing political attention to Global Health: new funding mechanisms 3. Attention to Public Health Issues in International Trades: DOHA, TRIPS, and public health, new mechanisms to promote access to essential medicines (MPP) |
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What is WTO? |
World Trade Organization: Promotes Trade liberalization: operates a system of trade rules, a forum for government negotiate trade agreements, decisions taken by consensus, to settle trade disputes, WTO agreements are legally binding currently 164 members |
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What is TRIPS? |
Agreement on Trade-related aspectsof intellectual property rightsGlobal minimum standards for theprotection of intellectual property: Came into effect in 1995 for all WTOmembers, 20 year monopoly control over patentable items, TRIPS-plus oftenincluded in bilateral free trade agreements requires >20 years of patentterms, exemptions for least developed countries (Doha Declaration) fromgranting patents for pharmaceuticals until 2033 |
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What is the Pharmacy of theDeveloping World? What does competition among genericmeds produce? |
India, Lower Prices |
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Voluntary vs Compulsory Licensing? |
Voluntary = the pharma companyoffers a license to the generic producer to produce , market and distribute thepatented products (meds)The pharma company can also imposeother restrictions, eg: the price of the generic med, where the generic med canbe sold, etc)The pharma company can request aroyalty on the net sales |
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What happened in Thailand for compulsory licencing? |
In 2006-2007 thailand issues CL forARVS, they got backlash from the US ambassador in Bangkok saying the thaigovernment doesn’t want a trade disputate, a senior official at the thaicommerce ministry said that the CL will only benefit 1 million people while therest 61 million will have to pay the price if US retaliates Thailand declared CL (Jan 2007)because they could save 3.2 billion through 2025, pharma offered them 2200 per,but production cost would only be <$400 |
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What were the costs of Action inThailand for CL? |
Abbott announced to withhold all newmedicines from Thailand, The US trade Representative Office downgraded Thailand’sintellectual property rights protection score to “poor” lobbied by Abbott |
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What challenges do Middle-incomecountries face regarding trade agreements? |
-They are viewed as lucrativemarkets -Trade pressure: must comply withTRIPS or TRIPS plus, backlash against CL -Affordability of newer ARVS, 2ndand 3rd line ARVS |
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What are challenges faced by alllow-and middle-income countries? |
-Long time lag until generic medsbecome available: 5-10 years after FDA approval -Difficult developing new fixed dosecombinations, you cant use 2 drugs in a cocktail if 1 of them is patented -Difficulty promoting generic marketcompetition |
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What is the Medicines Patent Pool? |
All of the patents go into a pool,and these give voluntary licencing to manufacturers to make medicines to PLHIV:benefits are that it’s a large market and accelerates VL negotiations |
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What are challenges with MPP? |
-Relies on voluntary participationof patent holders (pharma) -Financial incentives may not beenough -Pharma have greater bargainingpower: may restrict sales in middle-income countries -Negotiations still slow -Not sufficient consequences forpharma that choose not to participate in MPP |
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What is the Treatment Timebomb? Can MPP Address it? |
the future needs of people with HIV will overwhelm the resources allotted to treat them, threatening to “cripple developing economies, or place unbearable strains on richer countries trying to support them.” The number of people needing medicines is expected to rise dramatically, and the medicines needed are often too expensive MPP can address it if we act early |
