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HIV Immunology & Physiology

HIV Immunology & Physiology. By Raven James. Characteristics of HIV. Retrovirus family RNA virus Mostly infects T Helper Cells (CD4) Also infects some other white cells and nerve cells Rapid reproducer Very error prone, mutates easily. Pathogenesis of HIV Disease.

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HIV Immunology & Physiology

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  1. HIV Immunology & Physiology By Raven James

  2. Characteristics of HIV • Retrovirus family • RNA virus • Mostly infects T Helper Cells (CD4) • Also infects some other white cells and nerve cells • Rapid reproducer • Very error prone, mutates easily

  3. Pathogenesis of HIV Disease • Exposure to infected body fluid • Attachment of HIV to T helper cell • RNA inserted into cell • RNA changed to DNA • Viral DNA takes over T cell DNA • Virus reproduces new parts • New viruses are assembled • Viruses are released and T cell dies

  4. T Helper cell or CD4 Lymphocyte • One of many types of white blood cells • Primary role is to identify infection and assist other cells in producing an immune response • Loss of T cells from HIV infection causes a collapse of the immune system • Normal T helper cell count 500 to 1500 per milliliter of blood

  5. HIV disease progression • High-risk behavior: transmission • Primary infection: 2-4 weeks >50% experience flu-like symptoms with headaches Seroconversion: 3-12 weeks HIV antibody positive Can take up to 6 months

  6. HIV disease progression: Asymptomatic Infection • 12 weeks to eight or more years • Initially high viral load • Low viral load after immune response • High levels of viral activity • No apparent symptoms • Early intervention important

  7. HIV disease progression:Early symptomatic period • Usually 8 to 10 years • Immune system begins to weaken • Candida, Herpes, lymphadenopathy, weight loss and fatigue • CD4 count: some variability • Increased viral load

  8. HIV disease progression: Advanced disease - AIDS • Usually 10-11 years or more • High viral load • CD4 count <200 or 1 of 26 OI’s • Severe infections • Dementia • Cancers • Severe disability • Death

  9. Viral Load • Measures # of virus copies in blood • Does not measure virus in other parts of the body (lymph system, brain) • Predicts disease progression • Low viral load is treatment goal • High viral load leads to progressive failure of the immune system

  10. Rapid increase in viral load after infection Immune system kicks in and viral load drops No latency period exists Asymptomatic period is a time of intense battle by the immune system Eventual burn out of the immune system 10 billion new viruses per day 2 billion CD4 cells lost per day Numerous viral mutations occur per day Drug resistance occurs easily Combination therapy helps to prevent mutation Viral dynamics in HIV disease

  11. Acute HIV infection Initial evaluation Every 3-4 months for patient not on antiviral treatment 4 weeks after treatment begins Every 3-4 months for patient on treatment Clinical event or decline in CD4 Establish diagnosis Baseline, set point Change in viral load Assess drug efficacy Durability of treatment effect Viral load stable or changing Indications: Plasma HIV RNA

  12. Clinical use of viral load • Rapid testing of new drugs • Monitor effects of antiviral treatment for individuals • Determine development of viral drug resistance • Determination of need for change in treatment regime if viral load increases

  13. HIV/AIDSDrug Treatmentand Adherence Issues

  14. Treatment of HIV Disease: Combination Therapy • Use of several different classes of drugs that attack at different points in viral reproduction • Better, faster reduction in viral load • Increased time to resistant strains developing

  15. HAART: Highly Active Antiretroviral Therapy • Primary Objective: maintenance of viral load at undetectable levels • Preferred therapy: • Use of protease inhibitors, NRTIs and NNRTI’s • And fusion inhibitors as recommended

  16. Pros Minimize chance of emergence of resistant virus May play a role in reduction of HIV transmission Slows disease progression Improves quality of life Cons Negative impact on immune system Drugs can be toxic Frequent side effects Complexity of dosing regimens Impact of adherence on failure Consequences of failure Expensive HAART

  17. Recommended Antiretroviral Agents of Treatment of Established HIV Infection Preferred: Strong evidence of clinical benefit and sustained suppression of plasma viral load with 1 highly active protease inhibitor + 2 NRTI’s (this may vary depending on the antiretroviral drug history of the client)

  18. Alternative: Less likely to provide sustained viral suppression; clinical benefit is undetermined 1 NNRTI (Nevirapine, Delavirdine, Efavirenz) + 2 NRTI’s

  19. Not generally recommended: Clinical benefit demonstrated but initial viral suppression is not sustained • 2 NNRTI’s, as listed in previous slide Not Recommended: Evidence against use, virologically undesireable • All Monotherapies

  20. ! New Arrival ! • Once a day dosing medication • Combines three drugs in one pill, Sustiva and Truvada (Viread and Emtriva) • The drugs in the new pill constitute the most widely prescribed regimen in the US and also the most effective

  21. Pros May improve adherence Less pills to remember to take Convenience Reduced co-pays Important for developing countries where people have less access to medical care, and may be illiterate or uneducated Cons Persons already resistant not eligible for protocol 1,500 milligrams, very large and difficult to swallow Side effects of Sustiva cannot be tolerated by certain individuals Concern about complacency over becoming infected

  22. NNRTI’s • Nonnucleoside Reverse Transcriptase Inhibitors • NNRTI’s bind to and disable reverse transcriptase, a protein that HIV needs to make more copies of itself • They work at the same stage as NRTI’s, but act in a completely different way • Prevents the conversion of RNA to DNA

  23. NRTI’s • Nucleoside Reverse Transcriptase Inhibitors (aka nucleoside analogs) • Faulty versions of building blocks that HIV needs to make more copies of itself • When HIV uses an NRTI instead of a normal building block, reproduction of the virus is stalled • They act by incorporating themselves into the DNA of the virus, stop the building process and the DNA is incomplete and unable to replicate

  24. Protease Inhibitors or PI’s • PI’s disable protease, a protein that HIV needs to make more of itself • Work at the last stage of the virus reproduction cycle • They prevent HIV from being successfully reassembled and released from the infected CD4 cell

  25. Fusion Inhibitors • Newest class of drugs • Enfuvirtide (generic name), Fuzeon, T-20 (Brand and other names) • FDA approved in March 2003 • This drug works by blocking HIV entry into CD4 cells

  26. Definition of Adherence The extent to which a clients behavior coincides with the prescribed health care regimen determined through a shared decision making process between the client and the health care provider (Frank, Miramontes, 1997)

  27. Significance of Adherence • Clinical • Determine treatment efficacy • Assess treatment acceptability • Assess clinical effects on disease progression • Enhance quality of life • Increase cost savings

  28. Significance of Adherence • Research • Evaluate new treatment • Monitor side effects • Determine treatment safety • Determine treatment acceptability • Improve study results

  29. Characteristics of HIV Treatment That Influence Adherence • Lifelong, expensive treatment • Treatment may involve disclosure • Skepticism about treatment • Treatment constant reminder of infection and illness • HIV-related conditions may interfere • Treatment failure due to resistance or inadequate dosing

  30. Factors Influencing Adherence Regimen • Regimen complexity • Duration of therapy • Extent of behavior change required • Amount of resulting life disruption • Side effects and complications • Cost of regimen

  31. Factors NOT Predictive of Adherence (Dunbar-Jacob, 1997) • Age • Socioeconomic status • Race/ethnicity

  32. Consistent provider Satisfaction with relationship Knowledge of adherence regimen Treatment experience Time for client teaching Style matched to client Belief in client Belief in treatment Knowledge of adherence Enthusiasm Cultural competence Clinician Contributing Factors to Adherence (Frank, 1997)

  33. Characteristics of Client-Provider Relationship Within Shared Decision-making Context • Trust • Commonalities • Accessibility • Continuity of care • Extent of collaboration • Communication • Client satisfaction

  34. Understand treatment regimen Fits with routine Skills to carry out regimen Stage of disease, level of wellness Remembers meds Family/caregiver support View of health Belief ineffectiveness Cultural relevancy Fear of side effects Ability to control side effects Mental health Interaction with street drugs Client Contributing Factors in Adherence

  35. Client Contributing Factors to Non-Adherence • Failure to take meds • Taking meds in unprescribed amounts • Taking meds off prescribed schedule • Failure to match dose with food as directed • Sharing or selling meds • Hoarding meds for future use

  36. Client Dynamics Influencing Shared Decision-making • Health beliefs • Trust in provider • Cultural factors • Disease factors • Social support • Economic status • Mental health status • Substance use

  37. Client Correlates of Non-Adherence • Younger age • Depressed mood • Perceived stress • Anxiety • Pessimism about HIV disease • Lower levels of coping efficacy

  38. Adherence Issues in Antiretroviral Therapy Health care providers should assess readiness for treatment on an individual basis and not consider any specific group unable to adhere

  39. Adherence is a skill to be learned Client must be able to: • Understand the regimen • Believe they can adhere • Remember to take meds • Integrate regimen into lifestyle • Problem solve changes into schedule and routines

  40. Adherence acquisition is a gradual process • Assessment of readiness for treatment is a major first step • Client involvement in process • Develop programs that teach problem-solving skills • Teach the behavioral skills and approaches to maintain regimen • Use direct experience to reinforce regimen, such as guided practice

  41. Adherence requires client and provider relationships • Assessment for readiness must be done on a case-by-case basis • Access is not based on any specific client characteristic • Client involvement in decisions • Relationship between client and provider is critical • Increased client control and success are reinforcing • Direct incentives and rewards increase behavior change

  42. Strategies to Establish and Maintain Optimal Adherence • Clarify the regimen • Tailor the regimen to lifestyle • Demonstrate use of medication diary • Establish time to set out pills • Establish set places for pill-taking • Plan changes in routine in advance • Make plans for holidays, weekends • Lower barriers to care • Refer to social services • Follow-up

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