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48 Cards in this Set
- Front
- Back
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What are four reasons why there is not an HIV/AIDs vaccine?
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1) T-cell mediated response required
2) High mutation rate of HIV 3) Hard to vaccinate agains STDs (vaccination needs to cross mucosal barriers) 4) Lack of knowledge |
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Why does a high mutation rate result in a difficulty in developing an HIV/AIDs vaccine?
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Results in:
1) instability of epitopes 2) drug resistance |
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What was the first type of HIV drug?
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Zidovudine (ZDV)/azidothymidine (AZT) - nucleoside analog
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What is Indinavir?
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protease inhibitor
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What is 3TC?
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Nucleoside analog
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What are some problems with HIV drugs?
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1) drug resistance
2) drug toxicities 3) long-term consequences of HIV itself or ARV drugs |
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What is a PHI (primary HIV-1 infection cohort)?
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People that are newly infected with HIV
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What is are the viral genomes like in newly infected patients/
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Homogeneous
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What happens to the homogeneity of the HIV genomes after a year post-infection?
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Become heterogenous
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What accounts for this high heterogeneity of the HIV genomes in patients in a year post-infection?
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High mutation rate of HIV- largely due to reverse transcriptase enzyme that always makes mistakes
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How long can a homogeneous HIV population be found in an infectedi ndividuaL?
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Homogeneity is only found to about 6 months post-infection
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What does the comparison of PHI clusters vs. non clusters tell us?
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About half of ALL new infections must, by definition, be coming from people who are themselves newly infected
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What is so special about the time period (1-2 months) post infection that makes viral transmission so likely?
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1) This is the highest point of viral load (especially in the genital fluids)
2) Individual does not know they are infected - antibody test shows negative results, more sensitive tests (PCR etc) are too expensive |
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Where is subtype B mostly found?
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Canada, North America, and Western Europe
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Where is subtype C mostly found?
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South Africa, Botswanna and India, etc
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In which subtype is the K65R mutation typically found?
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Subtype C
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What type of mutation is K65R?
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Lysine to arginine mutation
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Where is the K65R mutation found?
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In the HIV reverse transcriptase enzyme
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What drug does K65R confer resistance to?
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Tenofovir - an NRTI (nucleotide analogue reverse transcripase inhibitor)
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What type of drugs are ddl/d4t?
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Nucleosides
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What type of drug is NVP (nevirapine?
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Non-nucleoside reverse transcriptase inhibitor
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Why does HIV develop resistance if a patient stops taking a drug?
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When an individual takes a drug, there is small amounts of Residual drug- these subadequate concentrations create a eselection pressure, and there is the emergence of drug-resistant viruses
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What is a microbicide approach?
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Treating people with drugs in a prophylactic manner so that they will kill any HIV at initial infection
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What is FTC?
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Nucleoside analog
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What is Tenofovir?
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nucleotide analog
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What are some important differences in how people are treated in developed vs. developing countries?
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Quality of drugs, and how drug treatment is carried out
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How are people monitored in rich countries?
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Viral load tests
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What is the detectable level of HIV to indicate someone is HIV positive/
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>50 copies of viral DNA/mL
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How are people monitored in poor countries?
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By measuring CD4+ T cell counts
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Why does leaving somebody on a drug treatment that they are resistant to for longer periods of time such a bad idea?
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Creates a selection pressure- the virus wants to be even more resistant. Possibilty to get new mutations to other drugs and become MULTIPLY resistant
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What is Etravirine?
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A second generation drug (NNRTI) that can be used to treat patients with a K103N mutation
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What is Efavirenz?
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A second generation NNRTI
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What is T20?
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An entry inhibitor - taken via injection. Worksby blocking fusion process between the viral envelope and cell membrane
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Mutations in what cause resistance to T20?
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Gp41 viral protein
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What is Maraviroc?
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Blocks HIV CCR5 mediated entry
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Why doesnt Maraviroc work "forever"?
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-Strains may be CXCR4 -tropic
-Even in CCR5 tropic strains, theyre is a switch intropism over time due to the mutations accumulated |
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What are three examples that prove that you can treat HIV by preventing it?
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1) Discordant couples
2) Pregnant mothers 3) Circumcision |
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Why does circumcision exert a protective effect against HIV infection?
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The foreskin contains cells that are very susceptible to HIV as a portal of entry into the body. These cells act as a carrier of HIV to the internal tissues, where HIV can then replicate. Getting rid of these portals (Langerhans cells) may cause the protective effect
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What percentage of HIV-infected indivudals have AT least one drug-resistance mutation?
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5-10%
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What are thymidine analog mutations (TAMS) associated with?
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Mutations to NNRTIs
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What are M184V mutations associated with?
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Protease inhibitors
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What is the most common mutation in NEWLY infected individuals?
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NNRTI mutation
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What is the least common mutation in NEWLY infected individuals?
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M184V
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Why is it that the M184V mutation is very common in people that are treated for long periods, but is the least frequent in NEWLY infected people?
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Viral fitness: some mutations have little effect on viral fitness (like K103N) and therefore willb e found MORE frequently in new HIV transmissions
-The virus that can grow out the most is the one that will be the most detected |
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What happens to the M184V mutations in newly infected individuals?
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There is some eversion (spontaneous back mutation) - this WT will outcompete the M184V and grow out (more fit) and therefore when genotyping it would appear that there is no M184V virus since it is present at low levels and thus not easily detectable
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Therefore, what is the major difference between the K103N and M184V mutations?
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K103N leads to a more fit HIV virus - grows out
M184V leads to a less fit HIV strain- does not grow out |
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What percentage of HIV strains can classic genotyping detect?
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20%
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What techniques can be used to circumvent this?
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Allele-specific PCR assay
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