AIP The HIV/AIDS Epidemic - FULL COURSE NOTES
AIP The HIV/AIDS Epidemic - FULL COURSE NOTES AIP 320
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This 17 page Bundle was uploaded by Jessica Rozycki on Monday October 3, 2016. The Bundle belongs to AIP 320 at Marymount Manhattan College taught by Hanks in Fall 2016. Since its upload, it has received 3 views. For similar materials see The HIV/AIDS Epidemic in AIP at Marymount Manhattan College.
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Date Created: 10/03/16
HIV is a pandemic, not an epidemic HIV destroys your immune system – this disease has been around for a long time, but it was not recognized as the common denominator of people who were getting sick Criminalization transmission, disclosure, issue of proof, intent Transmitted by direct body contact Blood to blood (IV, drug use) Sexually (semen and vaginal secretion) Mother to child (placenta, blood to blood in child birth, breast feeding) 25% of children with mothers who have HIV contract the disease Greatest strides in preventing mother to child transmission – can be given anti retroviral drugs Some people are naturally immune to HIV Not just one type of HIV Difference between a virus and bacteria: Bacteria = living cell Virus = does not show the same signs as a living organism, obligate parasite of the cell, virus uses energy that the cell was using Uses code to make more of itself at a high rate Without the living entity/bacteria, the virus cannot exist First cells – prokaryotes (membrane, DNA code, RNA translator, cytoplasm, ribosomes) Carbohydrates Energy (from glucose) Sugars end in “ose” Hexoses = sugars with six carbons Need to be able to break down things before we put them in our bodies Cannot store glucose, it is used to make energy If it is not used, it can change into a different form and be stored (ex: heat) Monosaccharide – Fructose, glucose C H O6 12 6 Disaccharides – Maltose, sucrose, lactose Polysaccharide – Glycogen (liver, muscle) Enzymes (catalysts) – make the reaction happen quicker Enzymes end in “ase” Glucose and fructose = sucrose (broken down by sucrase) Glucose and galactose = lactose (broken down by lactase) Lipids Can’t transport them, don’t mix with water (hydrophobic) Fatty acids hydrocarbon chains Saturated fat = carbons are all saturated with hydrogen molecules Unsaturated fats = can be transported better (less hydrogen molecules) Triglyceride 3 fatty acids attached to glycerol Phospholipids part phosphate, part fatty acid (half mixes with water, half don’t) Exists on the cell membrane to create a barrier Protein channels let things pass Virus can get into cells through a channel o Imitate something that you need o HIV uses proteins on the cell membrane found on the immune system (not reproductive system, not an STD) Steroids (lipid) can get into a cell because they can mix with the membrane… the membrane is made of fatty acids, which can mix with other lipids Proteins Chains of amino acids (12 can be made by bodies, 8 are in our diet) primary structure The arrangement of the 20 amino acids is what makes different proteins Dictated by your genetic code Fold to form a helix or pleat secondary structure All mixes together and combines into a small structure to give it its function tertiary structure DNA Nucleic acids Sugar (deoxyribose) Sugars are attached in a chain via a phosphate group to make a solid, strong bonds Bases adenine, guanine, cytosine, and thymine (AGCT), weak bonds Bases make up the code, every three make up an amino acid Double helix (A connects with T, G connects with C) If the code changes, the amino acid sequence changes DNA replication copy the DNA based on the bases Uses an enzyme – DNA dependent DNA polymerase Happens in the nucleus Cells are always copying their codes and making new proteins (ex: skin cells) Transcription = copying the code Translation = making it into a protein, an amino acid sequence RNA Sugar (ribose) Connected with phosphate groups Bases adenine, guanine, cytosine, uracil (AGCU) Uracil replaces thymine Copy of the code Keep going back to the original code in order to keep it safe from mutation, get rid of the copy Messenger RNA (mRNA) = RNA has to leave the nucleus and move into the cytoplasm so it can make a protein Code goes through the ribosome (rRNA) Ribosome makes protein o Ribosome reads the code in groups of 3 to determine which amino acids will leave the ribosome, structure is in an amino acid chain to make up a protein o Once the RNA leaves the ribosome it gets destroyed Enzyme = DNA dependent RNA polymerase Frame shift = a base gets added to the DNA and changes the whole code Point mutation = one base is changed in the code, changing the amino acid (not permanent) Code in viruses can be either DNA or RNA (never both) RNA coded virus goes to the ribosome (more common) DNA coded virus goes to the nucleus Some viruses can become a permanent part of the cell by attaching their own genes to yours Viral genes are inserted into the chromosomes If that cell replicates, it will have the virus genes in it If RNA wants to do this, it needs to copy itself into DNA, must carry the enzyme RNA dependent DNA polymerase Reverse transcriptase HIV virus is RNA, created the ability to carry the enzyme in order to implement their code into the DNA Anti retroviral drugs only helps slow down the rate of division of the virus so there are no symptoms and it’s not noticeable, but the genes are affected so it cannot be cured ATP – when you break the bonds in glucose, you end up producing a compound called Adenosine triphosphate Base adenine, attached to 3 phosphate groups with negative charges Negatives usually repel, so this is an unstable compound (can’t store it, need to use it quickly) Powers all of the processes inside of the cells Made inside an organelle called mitochondria Capsid = protein house in viruses, non enveloped or capsid only Capsid is made up of individual units called capsomeres Most common shape is highly structure, icosahedral – 20 parts Size of virus is generally 30300 nanometers (nano = billion) o Needs RNA or DNA (one or the other) o Viral attachment proteins, attaches to host cell on cell membrane to get inside o Virus needs to affect multiple hosts in order to survive for a longer period of time After the virus exits the host cell, it coats itself in the host cell membrane (envelope) Enveloped by a phospholipid bilayer Opposite of a capsid virus Does not have an envelope Body recognizes this and the immune system can rid of it faster Lysogenic viruses Once you are a part of the host DNA, you are a part of it forever Does not show physical symptoms that quickly Lytic = actively dividing Peptidoglycan = makes up the cell wall of bacteria (protein sugar) Base analogs Type of drug AGCT/U (bases) Looks like these, but are slightly different Example: Uracil with a fluoride attached If they worked perfectly, you would die (too harsh side effects) If they kind of work, virus would use it and they would divide less quickly, giving your immune system more time to fight it AZT azidothymidine, first used to treat HIV, base analog of thymine Kaposi’s sarcoma – skin cancer, before HIV it was only found in men over the age of 75 Immune system wasn’t working well enough These people also had antibodies to a herpes virus Virus that relates to a cancer The immune system – one of the hardest systems in the human body, based on cell responses Battle 1. Know your enemy 2. Coordinate your attack Nonspecific Fights anything that is foreign using barriers Barriers: Epithelial tissue – skin o Outside of body is keratinized skin o Inside (ex: mouth) mucous membrane o Multiple layers, tight connections Digestive tract o Saliva = lysozyme breaks down the cell wall of bacteria o Hydrochloric acid in the stomach o Digestive enzymes in the small intestines o Bacteria in the large intestine Respiratory tract o Mucous, cilia o No barriers because you need to transport oxygen/CO2 in and out of your blood o Most vulnerable to illness Urinary tract o In males, connected to reproductive system Urinary bladder urethra urine goes out Constantly being flushed, harder for infections to stay and cause damage o In females, they are two different systems More susceptible to infections Eyes o Tears (lysozyme) White blood cells made in red bone marrow Neutrophils = first line defenders Phagocytic = has the ability to engulf (sends material to lysosome) Macrophages o Larger cells, can engulf things multiple times o Start out in bone marrow as monocytes o Move to tissues as macrophages o Can divide themselves Mast cells (tissues) and basophils (blood) ** Bridges gap between specific and nonspecific immune system Endoplasmic reticulum = series of membranes in the cytoplasm Lysosome = recycling center for the cell HIV uses CD4 protein to get into target cells (CD4 = protein receptor) Tricks the cell to let it in CD4 is both in phagocytic cells and macrophages Histamine causes inflammation – 1) Vasodilate – blood vessels get wider 2) Increase capillary permeability T cells Helper T cells – must activate these before B cells can make antibodies, also has CD4 Cytotoxic T cells (CD8) – has the ability to recognize a cell that has been infected with a virus and destroys it Interferons instructs the body to reduce the number of proteins channels that let viruses in Specific: Cells – lymphocytes, macrophages Antigen – foreign agent Antibodies – proteins that are produced by B cells that are partnered with antigens Selfrecognition need to be able to distinguish between self and foreign Major histocompatibility = class proteins specific to your body (MHC) o MHC 1 found on every cell in your body with a nucleus o MHC 2 found on macrophages and B cells (red blood cells) Everyone has different MHC 1s, even identical twins MCHs all have the same structure, found on cell membranes MHC 2 cells bind to CD4 cells (t helper cells) CD8 proteins Recognize self (MHC1) vs. foreign Cell displays itself so the protein doesn’t go inside and destroy if it doesn’t need to Macrophage = antigen presenting cell, shows it to the helper T cell Has a T cell receptor Sends messages to make more white blood cells, calls for B cells o B cells come to cite and make antibodies o When antigens and antibodies bind, they are outwardly noticeable o Helper T cells are a target for HIV because they work for CH4 proteins Lymphocytes = Th, Tc, and B cells Lymphatic system Lymph nodes Lymph nodules Lymphatic vessels Lymph (substance they carry) Spleen Thymus (gland) Most susceptible to cancer cells because they exist throughout the body HIV – RNA lysogenic virus that has to have reverse transcriptase Enveloped by a membrane Gp41 helps the fusion Gp 120 fuses with CD4 on the membrane 9 genes, 2 copies Target cells (Th cells, macrophages) have CD4 plus a co receptor (one or the other) Gp 41 binds to CD4s to get virus into the cell Co receptors = CCR5 (macrophages, first) or CXCR4 (Th cells, second) Reverse transcriptase HIV virus is RNA, created the ability to carry the enzyme in order to implement their code into the DNA This can happen in the nucleus because it is carrying the enzyme Viral RNA is made into viral DNA using RNA dependent DNA polymerase Enzymes in HIV (can all use specific inhibitors) 1) Integrase splices the DNA to get itself into the genome 2) Proteases splits genes into functional protein units 3) RNAase breaks down RNA 9 genes – Structure o pol encodes for RT, I, P, and RNAase o gag encodes for p24 and p17 o env encodes for gp120 and gp41 Other 6 genes are involved with protection, how long it takes for copies to be made o Tat, vif, vpr, nef o rev helps transport messenger RNA to the ribosome o vpu helps virus make an envelope P24 = Capsid of HIV P17 = Connects enzymes and genes to the capsid and envelope HIV replication: https://www.youtube.com/watch?v=RO8MP3wMvqg Step 1 infection of the host cell CD4 positive Tlymphcyte Cell must have certain receptors on the surface (CD4 receptors, and coreceptors such as CCR5 or CXCR4) Receptors interact with proteincomplexes that are embedded in the viral envelope o Gp 120 or gp 41 Step 2 attachment When HIV approaches the target cell, gp120 binds to the CD4receptors This causes further binding to a coreceptor, which results in a change in gp120 o Gp41 unfolds and inserts itself into the cell membrane o When gp41 folds back on itself, the virus is drawn toward the cell and creates fusion Viral nucleocapsid enters the host cell, breaks open, and releases two viral RNAstrands and 3 replication enzymes Replication enzymes = integrase, protease, and reverse transcriptase Step 3 reverse transcriptase begins the reverse transcription of viral RNA Integrase transfers the DNA into the cell nucleus The host cell genome now contains the genetic information of HIV Step 4 Viral RNA migrates into the cytoplasm Building blocks for a new virus are synthesized Two viral RNAstrands and the replication enzymes come together, and core proteins assemble around them forming a capsid This particle leaves the cell to acquire a new envelope of host and viral proteins Step 5 replication When the virus matures, it replicates billions of times a day and infects other cells Destroys the hosts’ immune cells Anti retroviral drugs inhibit certain steps of this process Only helps slow down the rate of division of the virus, there are no symptoms and it’s not noticeable, but the genes are affected so it cannot be cured Fusion inhibitors prevent gp41 because that’s what creates the fusion to let the virus in Integrase inhibitor CCR5 inhibitors prevent the virus from getting in because it needs a co receptor o Can’t make CXCR4 inhibitor because your body needs it, but CCR5 is not as important for the body ** Not used as the first line of treatment Attenuated vaccine weakened, not completely killed (example: small pox, measles, mumps) Recombinant vector vaccine Take a virus, take a gene, and introduce it into another virus When the get inside the cell, they reproduce and make their own proteins Create a foreign antigen gene, and it can make antibodies Introducing another virus into the person, needs to be benign and won’t show any symptoms hasn’t happened yet Attenuated vaccine is better than a killed vaccine because… Has the ability to grow Renders a stronger response With a killed vaccine, once your body uses it, it’s done and won’t be helpful anymore HIV drugs: Nucleoside Riv. Transcriptase Inhibitors (NRTI) base analogs, disrupt functions of mitochondria Non Nucleoside Riv. Transcriptase Inhibitors (NNRTI) resemble bases, but they bind to the enzyme and slows it down Protease Inhibitor o Protease inhibitors can interfere with a lot of other drugs Side effects Liver problems, lactic acidosis (lowers ph of blood), diabetes, heart disease, kidney damage HIV 2: Found mostly in Africa Causes less serious symptoms HIV 1: 4 major types M (main), O (outlier, found in discrete geographic areas), N (new), x In MAIN Subtypes A, B, C, D, E, F, G, H, I, J, K (genetic nuances of the 9 genes) Need to sequence DNA to detect which subtype it is Need money to do this, only being done by western countries Circulating recombinant forms (CRCs) = different forms that are combined Testing for HIV: Anonymous vs. confidential (Opt in & opt out) Based on negative stigma Used numbers instead of names Testing – antibody test Introduce blood sample into something that has HIV antigen Look to see if it changes color 1) Eliza test 2) If you get positive results, you will be tested again with western blot 3) PCR (polymerase chain reaction) = if you have the economic infrastructure, the next test will amplify genes to be able to count DNA, know viral load 4) Another test for number of CD4 t cells (1,000 is the average number of t cell counts) Staging CD4 < 200 cells per mL of blood = AIDS CDC = Center for Disease Control Bacteria = prokaryotic cells Can be given antibiotic, treatable Repetitive occurrences garner more attention Sal manila Related to food Need to ingest a lot if you have a good immune system in order to get it People who have HIV are more likely to get it Pneumonia Lower immune system will have a better chance of contracting They have vaccines now, gives strong immunity, subunit = dead People who get these vaccines have respiratory problems People with low immune systems might not have the ability to build up resistance with the vaccine Bacterial STDs Chlamydia o Easily transmitted o Women are more symptomatic o If not treated, can lead to pelvic inflammatory disease for women o Cannot cross placenta Gonorrhea o Stays in the reproductive tract o Equally affects males and females o Can cause infertility in both o Males have symptoms earlier than females o Cannot cross placenta, but infant could pick up bacteria during birth from outside of the body Syphilis o 3 stages o Sore develops at sight of contact o Sore heals and organisms move to other parts of the body o Slowly affects other organs of the body o Can eventually lead to the brain and cause damage o Tested with Waserman test o Can cross placenta ** Can all be treated with antibiotics HIV is not an STD because it does not affect the reproductive tract Viruses HPV – likely to be found in people who have HIV, can be associated with cancer Hepatitis B and C o B blood to blood or sexually, has a vaccine o C organ transplants, faulty health safety Herpes – Simplex I and II, Epstein Barr, chicken pox and shingles, CMV (cytomegalovirus) Epstein Barr Causes mono, attacks lymphocytes, lymph nodes get swollen and low grade fever Kaposi’s sarcoma – skin cancer, before HIV it was only found in men over the age of 75 Immune system wasn’t working well enough These people also had antibodies to a herpes virus o KS is also known as herpes 8 Virus that relates to a cancer Directly related to HIV in younger people CMV (cytomegalovirus) May have antibodies, might never show symptoms Can cross placenta Can causes illness in nervous system, poor development of other organs Wasn’t widely known until HIV Drugs are called acyclovins (ex: Valtrex) Top 3 causes of deaths: HIV, malaria = parasite, TB = bacteria Fungi – 1) Candida = yeast present in the mouth Don’t compete well with immune system and bacteria Antifungal drug azoles HIV – can’t keep the candida low in numbers so they will get repetitive candida thrush infections, eventually travels down to esophagus, lungs, leading to AIDS 2) PCP pneumonia Fatal to a person with HIV Can be repetitive 3) Toxoplasma – indicative of someone with AIDS, originally thought to be a parasite Can’t give an immunosuppressed person an attenuated vaccine When people first started going to the doctor’s for HIV, they had Toxoplasma, KS, or PCP pneumonia TB – Affects 1/3 of the world, 1 million deaths a year associated with it (appox.) Contract it by inhaling respiratory droplets Bacteria – genus is called mycobacteria, species is tuberculosis In the cell wall, mycolic acid immune system has a hard time phagocytizing it and getting rid of it o Can stay in the body for a long time o Most people who come in contact with it don’t get TB o People in confined areas are more likely When it is contracted: Bacteria in your lungs Can live on mucous Ingested by macrophages, but macrophages can’t destroy them bc of the mycolic acid, so they stay alive in the macrophages o Lung responds by trying to wall them off (in structures called tubercles) = primary TB o Don’t show a lot of symptoms o When the body walls in off, it’s almost dormant Testing tuberculin test, also called PPD Not that specific Second step is a chest xray o Over time, calcium is deposited around the tubercles, which shows up in an xray Sometimes TB could stay dormant, but other times bacteria in tubercles start to grow and divide, causing a serious lung infection = secondary or reactivated TB Tertiary or disseminated TB leaves the lungs and starts to affect other parts of the body, one of which is bone (which is called Pott’s disease) Blood tissue and vessels are used, bone gets deformed Often diagnosed after death by looking at their skeleton Antibiotics are given to break down mycolic acid Another drug for people who also have HIV Becomes an overwhelming amount of drugs to take every day BCG vaccine attenuated, been around for over 70 years Weakened form of TB that occurs in cows (myco. Bovis) A lot of places do not vaccinate because they have the surveillance and treatment Other countries vaccinate, success is anywhere from 4060% Doing a PPD test means you will always test positive Better to not vaccinate so you can be tested, but some places don’t have the supplies to do chest xrays Vaccine is beneficial for people with HIV A new vaccine is in trials because you can’t give someone with HIV an attenuated vaccine Introduced a gene into the mycobacteria bovis that prevented the bacteria from multiplying more than 10 times – gave attenuated bacteria a kill gene o Stays in the body long enough to build up immunity and then it died, so there is a better chance they will not get TB There are now drug resistant strains of TB 1) Drug resistant TB 2) Multi drug resistant TB Must be quarantined, bc there is nothing to treat it Mostly affecting the HIV population Certain tests now can get results in 2 hours Detects both TB and drug resistant TB You will know how to treat it and if you have to confine people When someone goes on drugs for it, they will pretty much not transmit TB Directly observable treatment (DOT) People are paid to visit people with TB and give them their monthly drugs, check them, and see if they’re taking their medication Very successful for keeping people on TB drugs and making them transmissible TB in females Associated with more than 6x prenatal deaths Person with TB and HIV usually delivers premature low birth weight babies Increased risk of mortality in infants (300%) TB doubles the rate of transmission of HIV from mother to infant (based on study in India) Mycobacteria has a sister species that causes leprosy myco. leprae Most common in Brazil and India, some parts of Africa “Media” attention in biblical times Affects ears, nose, and nerves (not lungs) o Lose feeling in places in their body o Can get deformities Difficult to contract from another person Causes appearance marginalization, society didn’t want to deal with it Organized into places where the caretakers devoted their lives to taking care of time, patients were isolated from society People with HIV were showing up with leprosy Reactivation of leprosy bacteria that was dormant in their macrophages When people were on antiretroviral drugs, macrophages are surviving again, they come alive and had a viable cell to infect Malaria Caused by parasite, targets red blood cells The mosquito that transmits malaria is prevalent in areas where there is a lot of rainfall, tropical areas o Not in US because historically, they were killed with DDT o Can still contract Malaria in places in the south but because there aren’t many mosquitos carrying it, it is not a big issue Red blood cells carry oxygen, when they die you get anemia (could be fatal for young children) Malaria can appear like it is gone or in remission, but it can come back Parasite, eukaryotic cell Not a lot of drugs for this because humans have eukaryotic cells Not easy to find a drug that doesn’t also harm the person Has a big history of it mutating (because it has been around for so long) Severe symptoms Organism = plasmodium (genus) Small, single celled parasite o Parasite Symbiotic relationship where one benefits one deteriorates Vivax, ovale, and falciparium (most common) When these parasites infect someone with HIV Mosquito’s needle is connected to salivary glands o Similar to cleaning it o When it takes your blood, it goes into the digestive tract o Breaks the blood down and they use the nutrients West Nile vs. HIV Viruses have to get inside a cell to duplicate and infect someone West Nile is the only virus that can be transmitted by a mosquito HIV could only be viable in the mosquito if it could get into the mosquito’s cells of their digestive tract and divide o If it stayed in the blood it would just be killed, which is why it is not transmitted Mosquito/malaria life cycle 1) In the salivary glands, there is a form of malaria called sporozoite 2) Injects some of the saliva into the blood of the human, so there are sporozoites in the blood 3) Sporozoites travel to the liver, where they have target receptors on the cell membrane, so they can get inside the liver cells 4) Cell division to make more 5) Sporozoites need an attachment protein for blood cells, so they change their form a. Merazoite, attacks red blood cells b. Divide until they can attack more blood cells c. Develop anemia d. Past this stage, the mosquitos might not transmit malaria to anyone else e. Drug that disrupts this life cycle doesn’t help the person affected with malaria 6) Eventually, some of the merazoites become male and female gametes in the blood a. Gametes unite and form a fertilized egg b. Cell division becomes sporozoites Treatment No vaccine yet They have drugs but they are only helpful in certain stages o Cinchona trees, bark is made into tea and has a chemical called quinine o Have certain drugs that are given prophylactically (eg. When you travel) Duffy antigen mutation – you don’t contract plasmotium vivax, you have a greater chance of contracting HIV o Susceptibility to HIV is increased by 50% HIV and malaria Severity of the anemia is worse because they can’t fight it off Acute malarial infection increases the viral load in semen Woman with malaria has a greater chance of transmitting HIV to child Protease inhibitors can interfere with malarial drugs Someone who has both has a quicker decline in helper T cells RTSS recombinant vaccine – piece of sporozoite is fused to one of the antigens associated with hep. B and inducing antibodies to the sporozoites Trials are only occur in infants Dramatic decline in the transmission of malaria Groups affected by HIV – 1) Women: http://www.avert.org/professionals/hivsocialissues/keyaffected populations/women Sometimes due to genderbased violence, lack of access to healthcare services, education, and recognition under the law Constitute more than half of the population of people with HIV worldwide ¼ of people living with HIV are women o 84% of new HIV infections in women are the result of heterosexual sex o 88% of women who are living with HIV are diagnosed, but only 32% have the virus under control Timeline of the disease: http://www.avert.org/professionals/historyhivaids/overview President’s Emergency Plan For AIDS Relief (PEPFAR) Ryan White = Teenage boy who got AIDS and was banned from school San Francisco coordinated with the physicians New York enacted social programs Mental Health and HIV – Depression, 2x more likely to develop o Can be a side affect of HIV drugs o Usually comes about from first result Anxiety, related to OCD, PTSD, panic attacks o 15.8% of HIV positive people, as opposed to 2.1% of the general population o Need to be careful with anxiety medications interacting with HIV drugs o Can be brought about from people seeing you continuously take the drug cocktail Substance use o Could affect effectiveness of HIV drugs o If they already have HIV, using drugs could cause them to come in contact with another strand, making it even more dangerous Counseling techniques o Important to also use nonpharmaceutical treatments in addition to HIV drugs HIV in the workplace Types of insurance available: Medicaid, Social Security Disability Insurance, Supplemental Security Income, Ryan White Care Act Disclosing your HIV status in the workplace is optional (unless you are a sex worker or a physician) There are a number of laws of protection against discrimination ADA, WIA, FMLA, Rehabilitation Act of 1973 Pharmacies: The first generic HIV medication was approved by the FDA in 2001 – took over 20 years AZT was not that affective, too expensive Main concern is money, not offering effective drugs Sex workers Better to be called prostitution because sex work implies that it’s a choice If it were legal in the United States, the rates of HIV and STIs would decrease o Example: Nevada has never had a case of HIV from sex workers o There needs to be certain criteria o Pros and cons Pro monitor STIs, HIV, enforce condom use, could potentially limit abuse/violence Con could increase trafficking, rape, other dangerous situations, there will be a law backing a man’s “entitlement” to buy sex o Minority of these people are doing it with consent (white middle class women) Nordic model = selling sex is legal, and buying sex is illegal o Seems to be helping, but there is no data about if they have gone underground
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