HIV Immunology

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HIV Immunology Physiology

• By Raven James

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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

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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

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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

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HIV disease progression

• High-risk behavior transmission
• Primary infection 2-4 weeks
• gt50 experience flu-like symptoms with headaches
• Seroconversion 3-12 weeks
• HIV antibody positive
• Can take up to 6 months

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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

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HIV disease progressionEarly 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

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HIV disease progression Advanced disease - AIDS

• Usually 10-11 years or more
• High viral load
• CD4 count lt200 or 1 of 26 OIs
• Severe infections
• Dementia
• Cancers
• Severe disability
• Death

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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

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Viral dynamics in HIV disease

• 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

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Indications Plasma HIV RNA

• 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

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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

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HIV/AIDSDrug Treatmentand Adherence Issues
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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

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HAART Highly Active Antiretroviral Therapy

• Primary Objective maintenance of viral load at
  undetectable levels
• Preferred therapy
• Use of protease inhibitors, NRTIs and NNRTIs
• And fusion inhibitors as recommended

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HAART

• 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

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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
  NRTIs (this may vary depending on the
  antiretroviral drug history of the client)

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• Alternative Less likely to provide sustained
  viral suppression clinical benefit is
  undetermined
• 1 NNRTI (Nevirapine, Delavirdine, Efavirenz)
• 2 NRTIs

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

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! 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

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• 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

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NNRTIs

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

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NRTIs

• 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

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Protease Inhibitors or PIs

• PIs 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

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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

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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)

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Significance of Adherence

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

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Significance of Adherence

• Research
• Evaluate new treatment
• Monitor side effects
• Determine treatment safety
• Determine treatment acceptability
• Improve study results

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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

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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

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Factors NOT Predictive of Adherence
(Dunbar-Jacob, 1997)

• Age
• Socioeconomic status
• Race/ethnicity

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Clinician Contributing Factors to Adherence
(Frank, 1997)

• 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

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Characteristics of Client-Provider Relationship
Within Shared Decision-making Context

• Trust
• Commonalities
• Accessibility
• Continuity of care
• Extent of collaboration
• Communication
• Client satisfaction

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Client Contributing Factors in Adherence

• 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

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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

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Client Dynamics Influencing Shared Decision-making

• Health beliefs
• Trust in provider
• Cultural factors
• Disease factors
• Social support
• Economic status
• Mental health status
• Substance use

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Client Correlates of Non-Adherence

• Younger age
• Depressed mood
• Perceived stress
• Anxiety
• Pessimism about HIV disease
• Lower levels of coping efficacy

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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

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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

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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

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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

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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