HIV Disease

1. HIV Disease

2. Transmission Variables • How easily a virus can enter the body • Influenza and SARS enter by respiratory tract • Easy to infect • HIV is hard to enter the body. Usually needs sexual contact • Encounter rates • 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.

3. More Variables • Percent of people with the disease in a population or subpopulation. • 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. • Duration of lifespan before death • Rapid death, fewer people to pass on the virus • Ebola • Geographic Isolation • If isolated, fewer people can become exposed • Difficult with global transportation SARS

4. Risk Behaviors • ANY BEHAVIOR THAT RESULTS IN THE TRANSMISSION OF BODY FLUIDS PLACES A PERSON AT HIGH RISK FOR BBPS • HIV • Hepatitis • STD’s

5. ROUTES OF TRANSMISSION • Sexual transmission • Blood contact during needle sharing • Perinatally • Mother to baby before or during delivery • Blood Transfusions • Rare in US today • Higher in third world • Other

6. Risk Behaviors

7. 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

8. Course of HIV Disease

9. Overview • Is a slow virus • Allows the virus to pass on its genetic codes to many people. • Mutates rapidly • Uses the bodies DNA to hide • Uses other processes • Does not kill the host for a long period • Not like Ebola which kills the host in a couple of weeks • Result – From a virus standpoint, is an ideal virus

10. HIV Infection Occurs Acute Retroviral Syndrome Occurs Antibodies Develop Asymptomatic Symptomatic HIV Disease AIDS Death

11. 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 • See MMWR • Will not be used for general risk populations • IDU’s • MSM’s • May be used for medical exposure or other reasons • Needle stick • Rape • Drug cocktails do not work for other STDs or Hepatitis

12. 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

13. Inside the Body • Virus is being widely disseminated • High levels of the virus initially occurred then drop off. • No immune response yet to combat it • Antibody production begins • Destroys lots of the virus but not all • Virus infects Thelper Lymphocytes • Virus continues to replicate in lymph tissue

14. 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

15. 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

16. 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

17. 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

18. Chronic Symptomatic HIV Disease • Immune system is being further deteriorated • T4 or CD4+ cells decrease • Symptoms become more frequent • Symptoms last longer • Ultimately overwhelms lymphatic system • 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.

19. 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.

20. Some Opportunistic Infections • Pneumocystis Carinii Pneumonia • Kaposi’s sarcoma • Recurrent Pneumonia • Candidiasis • Toxoplasmosis of the Brain

21. Many Other Disorders as Well • Wasting Syndrome • Candidiasis of bronchi, trachea, lungs, esophagus • Cytomegalovirus • Encephalopathy • Histoplasmosis • Lymphoma’s • Many others

22. 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

23. 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

24. 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

25. AIDS-Related Dementia • Solely associated with AIDS • Early symptoms • Forgetfulness • Recent memory loss • Loss of concentration • Loss of thought • Movement problems - balance

26. Late Symptoms • Loss of speech • Fatigue • Bladder and bowel incontinence • Seizures • Coma • Death

27. Some Neurological Problems Associated with HIV Infection • Asymptomatic infection – no mental impairment • AIDS Dementia Complex (ADC) • Acute Encephalitis • Aseptic Meningitis • Distal sensory neuropathy

28. 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

29. Drugs • Are designed to target virus replication at different points

30. HIV VIRUS • Reverse Transcriptase ssRNA

31. CD4 Receptor HIV VIUS Reverse Transcriptase CC-CKR-5 CXCKR-4 (fusin) ss DNA Genome RNA ds DNA RT Viral RNA Mature HIV MRNA Protease HIV Bud Viral Proteins

32. CD4 Receptor VIRUS ss DNA ds DNA Genome RNA 1 RT Viral RNA Mature HIV MRNA 2 Add Protease HIV Bud Viral Proteins

33. Reverse Transcriptase Inhibitors • Two groups • Nucleoside Analogs • Non-Nucleoside Analogs • Generally are designed to interfere with the viruses ability to replicate itself

34. 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

35. Names by Year of Introduction

36. 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

37. Names by Year

38. 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

39. Examples of Side effects • Liver Toxicity Nevirapine (Viramune) • Rash

40. Other Problems • 15% of HIV infected people cannot tolerate nucleoside or non-nucleoside compounds. • Both groups are time limited for effectiveness.

41. 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

42. Names by Year

43. Protease Cutting Sites

44. Protease Cutting Proteins

45. ResultDifferent Lengths of Protein that Perform Different Tasks

46. Protease Inhibitors Prevent Protease from Entering Cleavage Sites

47. Result, No Cleavage HIV Remains Immature and Cannot Replicate

48. Drug Resistance

49. 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

50. 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