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HIV Disease Transmission Variables How easily a virus can enter the body Encounter rates Influenza and SARS enter by respiratory tract Easy to infect HIV is hard to enter the body. Usually needs sexual contact The number of opportunities that an uninfected person has with an infected person More contacts, the higher the probability of becoming infected. Population density Large populations allow epidemics to occur. Many people die, but some people able to survive pass on their genetics Over time the virus becomes stable in the population but few people die due to immunity Sickle Cell Anemia – Good for Malaria. More Variables Percent of people with the disease in a population or subpopulation. Duration of lifespan before death Population may be bar members, racial groups, select minority group (MSMs) region of the country, nation, etc. More people with HIV, the higher the risk of getting HIV if you have sex with someone. Rapid death, fewer people to pass on the virus Ebola Geographic Isolation If isolated, fewer people can become exposed Difficult with global transportation SARS Risk Behaviors ANY BEHAVIOR THAT RESULTS IN THE TRANSMISSION OF BODY FLUIDS PLACES A PERSON AT HIGH RISK FOR BBPS HIV Hepatitis STD’s ROUTES OF TRANSMISSION Sexual transmission Blood contact during needle sharing Perinatally Blood Transfusions Mother to baby before or during delivery Rare in US today Higher in third world Other Risk Behaviors Anal intercourse with internal ejaculation without a condom Vaginal intercourse with internal ejaculation without a condom or barrier Vaginal intercourse with internal ejaculation without a condom but with spermicidal foam Anal intercourse with a condom and withdrawing prior to ejaculation Vaginal intercourse without spermicidal foam or condom and withdrawing prior to ejaculation Vaginal intercourse using spermicidal foam but without a condom and withdrawing prior to ejaculation Sharing sex toys by more than one partner without a condom Anal Fisting Fisting Anal intercourse with internal ejaculation with a condom and spermicide Vaginal intercourse with internal ejaculation with a condom and no spermicide Vaginal intercourse with internal ejaculation with a condom and spermicide Anal intercourse with a condom, spermicide, and withdrawing prior to ejaculation Vaginal intercourse with a condom, spermicide, and withdrawing prior to ejaculation Fellatio without a condom and ejaculation in the mouth Fellatio without a condom, placing the penis in the mouth, and withdrawing prior to ejaculation Fellatio to orgasm with a condom Fellatio without a condom but not putting the head of the penis inside of the mouth Cunnilingus Use of sex toys with condoms or not shared Mutual masturbation with orgasm on, but not in the partner Intercourse between the thighs Frottage (rubbing a person for sexual pleasure) Mutual masturbation with internal touching using finger cots or condoms Mutual masturbation with only external touching Deep wet kissing Masturbation with another person but not touching one another Hugging/massage/dry kissing Masturbation alone Abstinence Shernoff, 1988 Course of HIV Disease Overview Is a slow virus Mutates rapidly Uses the bodies DNA to hide Uses other processes Does not kill the host for a long period Allows the virus to pass on its genetic codes to many people. Not like Ebola which kills the host in a couple of weeks Result – From a virus standpoint, is an ideal virus HIV Infection Occurs Acute Retroviral Syndrome Occurs Antibodies Develop Asymptomatic Symptomatic HIV Disease AIDS Death Initial Infection Risk depends on the type of activity If know the person was positive, may be able to stop the virus from replicating enough so the immune system can destroy it. Use full battery of HIV drug cocktails Will not be used for general risk populations IDU’s MSM’s May be used for medical exposure or other reasons See MMWR Needle stick Rape Drug cocktails do not work for other STDs or Hepatitis Acute Retroviral Syndrome Usually occurs in 2-4 weeks May occur up to 12 weeks Symptoms Fever, body aches, sore throat, headache malaise Diarrhea, swollen lymph nodes, others May feel like a case of the flu. Treat symptomatically ASA, bed rest, etc. Symptoms usually last 1-2 weeks then go away Inside the Body Virus is being widely disseminated High levels of the virus initially occurred then drop off. Antibody production begins No immune response yet to combat it Destroys lots of the virus but not all Virus infects Thelper Lymphocytes Virus continues to replicate in lymph tissue Antibody Development Begins about 2-3 weeks Can be detected in about 12 days with specialized testing which is expensive Usually detectable within 3 months If exposed, 99.9% of the people will be detectable with 6 months Several tests Viral culturing PCR Polymerase Chain Reaction Reverse Transcriptase Others Asymptomatic Stage Median time 10 years in most people Virus proliferates in lymphatic system Virus also continues to replicate and destroy immune system cells Initially does not cause life-threatening diseases May experience a variety of symptoms during this period Symptoms can be brief or chronic Some Symptoms Recurrent swollen lymph glands Diarrhea Fever Weight loss Oral and Vaginal Yeast infections Others Symptoms can also result from other diseases Bacteria Fungus Parasites Behaviors Person may not know they have HIV Person may suspect they have HIV but will not get tested so they can say, “I do not know if I have the disease.” Sexual activity may continue, increase, or decrease Chronic Symptomatic HIV Disease Immune system is being further deteriorated Symptoms become more frequent Symptoms last longer Ultimately overwhelms lymphatic system T4 or CD4+ cells decrease Large increase of virus in the bloodstream Seems to be a marker against stopping the disease 30% of people who do not take medications develop AIDS-Related infections in 5 years. AIDS Diagnosed when the following occurs CD4 + T lymphocyte counts <200 cells/microliter CD4 + T lymphocyte count <14% of total lymphocytes Experiences opportunistic infections Generally, the immune system is unable to control HIV replication. Some Opportunistic Infections Pneumocystis Carinii Pneumonia Kaposi’s sarcoma Recurrent Pneumonia Candidiasis Toxoplasmosis of the Brain Many Other Disorders as Well Wasting Syndrome Candidiasis of bronchi, trachea, lungs, esophagus Cytomegalovirus Encephalopathy Histoplasmosis Lymphoma’s Many others With Aids Immune system continues to deteriorate Other diseases occur (TB) Drugs may prolong lifespan Degree of impairment varies from day to day and week to week. Person experiences many personal and societal issues Physical Issues Persons become debilitated by symptoms Commonplace behaviors become difficult Hard to have steady employment May have difficulty shopping for food Hard to do chores at home Psychological/Neurological Issues Progressive dementia occurs in 55%-65% of cases Some estimates - 90% have dementia Pathological CNS changes found in 80% of HIV cases AIDS-Related Dementia Solely associated with AIDS Early symptoms Forgetfulness Recent memory loss Loss of concentration Loss of thought Movement problems - balance Late Symptoms Loss of speech Fatigue Bladder and bowel incontinence Seizures Coma Death Some Neurological Problems Associated with HIV Infection Asymptomatic infection – no mental impairment AIDS Dementia Complex (ADC) Acute Encephalitis Aseptic Meningitis Distal sensory neuropathy Treatment PREVENTION IS THE BEST TREATMENT After becoming infected Keep the immune system from becoming taxed Your genetics is important Good nutrition Exercise Counseling if necessary Peer support network Social Services Support Drugs Drugs Are designed to target virus replication at different points HIV VIRUS Reverse Transcriptase ssRNA CD4 Receptor Reverse Transcriptase HIV VIUS CXCKR-4 (fusin) CC-CKR-5 ss DNA Genome RNA ds DNA RT Viral RNA Mature HIV MRNA Protease HIV Bud Viral Proteins CD4 Receptor VIRUS ss DNA ds DNA Genome RNA RT 1 Viral RNA Mature HIV MRNA Add Protease 2 Viral Proteins HIV Bud Reverse Transcriptase Inhibitors Two groups Nucleoside Analogs Non-Nucleoside Analogs Generally are designed to interfere with the viruses ability to replicate itself Nucleoside Analogs’ Called Nukes Interferes with the virus’s ability to replicate itself Stops the synthesis of the DNA strand Incorporate into the elongating strand of viral DNA Generally stops RT replication of HIV-DNA Names by Year of Introduction Zidovudine ZDV/Retrovir 1987 AZT Retrovir 1987 Didanosine ddI, Videx 1991 Zalcitabine ddC, Hivid 1994 Stavudine d4T, Zerit 1994 Lamivudine 3TC, Epivir 1995 Abacavir Ziagen 1998 Non Nucleoside Compounds Called non-Nukes Are not structurally or chemically similar to nucleosides Are often used in triple-therapy regimes Prevent the conversion of HIV RNA into HIV DNA Unlike Nucleoside compounds do not incorporate into the DNA Instead, binds directly to the RT Names by Year Nevirapine Viramune 1996 Delavirdine Rescriptor 1997 Efavirenz Sustiva 1998 Others Under Development Problem Initially worked HIV resistant strains developed in weeks Better results when used in combination Did not increase survival rates Do extend the asymptomatic period Allows you to delay the onset of Protease Inhibitors May interfere with oral contraceptives Examples of Side effects Liver Toxicity Rash Nevirapine (Viramune) Other Problems 15% of HIV infected people cannot tolerate nucleoside or non-nucleoside compounds. Both groups are time limited for effectiveness. Protease Inhibitors Newest line of defense HIV protease generally cuts viral strands Is essential for viral replication PI basically stop the virus from maturing Blocks the binding and cutting sites for viral protease Result- Virus not cut – cannot replicate Also indirectly decrease the production of RT Names by Year Saquinavir Mesylate Ritonavir Indinavir Nelfinavir Saquinavir Amprenavir ABT-378 Others Invirase 1995 Norvir Crixivan Viracept Fortovase Agenerase Kaletra Under 1996 1996 1997 1997 1999 2000 Testing Protease Cutting Sites Protease Cutting Proteins Result Different Lengths of Protein that Perform Different Tasks Protease Inhibitors Prevent Protease from Entering Cleavage Sites Result, No Cleavage HIV Remains Immature and Cannot Replicate Drug Resistance Drug-Resistant Nucleoside Analog Mutations RT is unable to edit or eliminate all nucleic acid replication Result 1-5 mutations in each new replication cycle Result – Each new virus is different from the others New virus is being reproduced 1-10 BILLION times per day Thus, 1-10 BILLION mutations being produced DAILY Protease Inhibitor Resistance HIV continues to mutate Also getting cross resistance Darwinian models are very applicable with HIV Weak strains die out, stronger strains survive and replicate. Many mutations probably exist before a drug is taken Therapy Must Address Resistance Issues Maximize the suppression of viral replication. Use combination therapies requiring HIV to create multiple drug mutations for resistance Force the emergence of strains with slower replication or decreased virulence New Therapies Entry inhibitors Designed to block the virus from entering the cell Fusion Inhibitors Pentafuside (T-20) Integrase Inhibitors Prevents HIV DNA from entering human DNA Zintevir (AR-177) Zinc Finger Inhibitors Disrupts polyprotein formation essential for HIV replication. Benzamide-Disulfide Final Issues Demise of Monotherapy Use of single drugs leads to drug resistance Today, combinations usually include Two reverse transcriptase inhibitors One Protease Inhibitor Combination of three or more drugs called HAART - Highly Active Anti-retroviral Therapy Result of HAART Only one RNA strand out of 1 trillion strands caries resistance to all three drugs at the same time. Problem 1-10 billion genetically different strands are produced each day Strands can exchange nucleotides (recombination) Result- Resistance to HAART cocktails Results of Resistance 30% of newly infected individual are carrying forms of HIV that are resistant to at least one drug. 10% are resistant to 2 drugs used in combination. 60% of patients experience HIV suppression failure during first line antiviral drug treatment Salvage Therapy Is the use of drugs to suppress viral replication when standard therapy fails. Some patients are taking 10 of the 15 drugs at one time to SUPPRESS HIV replication. In USA 30-50% of individuals are in Salvage therapy (Stein) Problem- is not proving effective. 70-80% experience salvage or second line drug treatment failure. Final Issues New strains from people in high risk having sex together. Behaviors that rapidly increased HIV have returned Individuals in minority communities that do not identify themselves as Gay have high-risk behavior and transmit HIV to their heterosexual partners Bathhouses Sex Clubs Barebacking Individuals engaging in the “Down Low” Bug Catchers Glorification of being “Positive No realization of problems with being Positive Future More people will get the disease Costs to society will increase – Who pays? Africa, Eastern Europe, Asia, IDU’s