Transcript Basics of Human Immunodeficiency Virus (HIV)

HIV Medications
&
Adherence Update
Jan Clark, PharmD
April 2008
What we’re going to learn…
 Classes of HIV
medications
 Roles of HIV
medications in viral
suppression
 Important lab tests
 New classes of HIV
medications
 Improving adherence
Lingo update
I knew it…”chicken”
comes first!
•
 CD4 cell
 Viral Load
 ART
 ARV
 HAART
CD4 Cell (CD4+ cell, T-cell)
• This is the cell that HIV attacks
• Ultimately is killed, thereby harming immune system.
• Normal count is about 1000
(range 500 – 1500)
• Considerable variation – significant change between two
tests is defined as ~ 30% change in absolute count and a
3 percentage point change
• Count used to
• Stage HIV illness (< 200 = AIDS)
• Guide differential diagnosis
• Guide therapeutic decisions
Viral Load (VL)
• Measure of viral material in plasma,
reported in copies/mL (aka Viral RNA)
• HIV RNA levels may range from
undetectable to more than one million
• <10,000 = low risk of disease progression
• 10,000 - 100,000 moderate risk of progression
• > 100,000 high risk of disease progression
• VL used in consideration in decision to
initiate or change therapy
Confusing terminology!
 ART = AntiRetroviral Treatment
 ARV = AntiRetroVirals
 HAART = Highly Active AntiRetroviral
Treatment
 Triple Therapy = Three Antiretrovirals
Basically, it all means the same thing.
What are Antiretrovirals?
What are Antiretrovirals?
Medicines that are used to
actually fight the HIV virus.
What are Antiretrovirals?
Medicines that are used to
actually fight the HIV virus.
Versus
What are Antiretrovirals?
Medicines that are used to
actually fight the HIV virus.
Versus
Medicines used to prevent or treat OIs
(opportunistic infections), blood pressure medicines,
diabetes medicines, herbal remedies, mental health
medicines, etc.
What do ARVs do….?
They change HIV from a terminal
(fatal) disease to a “chronic disease”.
What is a Chronic Disease?
An illness which cannot be “cured” but
can be controlled.
•
•
•
•
•
Examples of chronic diseases:
Diabetes
High Blood pressure
Asthma
Schizophrenia
How do ARVs control HIV?
 ARVs reduce the
ability of the HIV
virus to replicate
Virus
Replication
 In turn, this
increases the
ability of the body
to fight disease
Immune
Function
Primary Goal of ARVs
• Decrease or reverse immune system
damage associated with HIV infection
• Improve quality of life
• Reduce HIV-related illness and death
• Reduce HIV transmission
Human Immunodeficiency Virus
How HIV Works
HIV
3. Integration into host cell’s nucleus
4. Reproduction of
viral components
1. Attachment
to host CD4 cell
2. Reverse
transcriptase
makes DNA
from the virus’s
RNA
5. Assembly of new
HIV viruses
6. Release
ARVs at Work…
Remember the enzymes involved in HIV replication….?
Reverse Transcriptase
(essential for copying viral RNA
into DNA in the early stages of replication)
Integrase
(essential for integrating the newly formed viral DNA
into the CD4 cell’s DNA)
Protease
( required for assembly and maturation of fullyinfectious new virus in final stages of replication)
ARVs INHIBIT these enzymes,
thus slowing down the replication cycle.
Classes of Anti-HIV Drugs
• Reverse transcriptase inhibitors
• NRTIs, “nukes”
Truvada, Epzicom, Combivir, AZT, Videx, Zerit
• NNRTIs “non-nukes”
Sustiva, Viramune, Intelence (new!)
Classes of Anti-HIV Drugs
• Protease inhibitors (PIs)
Kaletra, Reyataz, Crixivan,
Lexiva, Prezista, Aptivus, Norvir
Classes of Anti-HIV Drugs
• Integrase inhibitor (IIs)
Isentress (raltegravir)
Classes of Anti-HIV Drugs
• Entry inhibitors (EIs)
• Fusion inhibitors
Fuzeon (T-20)
• CCR5 inhibitors
Selzentry (maraviroc)
How HIV Works
HIV
How EIs Work
HIV
Entry inhibitors (EIs) prevent HIV
from ever entering the CD4 cell and
causing the death of the CD4 cell.
How NRTIs Work
HIV
Nucleoside reverse transcriptase inhibitors
(NRTIs) latch onto the new strand of DNA
that reverse transcriptase is trying to build.
How NNRTIs Work
HIV
Non-nucleoside reverse transcriptase
inhibitors (NNRTIs) hook onto reverse
transcriptase and stop it from working
How IIs Work
HIV
Integrase inhibitors (IIs) prevent the
new DNA from being inserted into
the CD4 cell’s DNA
How PIs Work
HIV
Protease inhibitors (PIs) prevent final
assembly and completion of new HIV
viruses within the cell
Does everyone with HIV need ARVs ?
NO
Treatment depends on…
• Immunological markers (CD4 count)
• Clinical symptoms (opportunistic
infections)
• It also depends on whether the
patient is READY to start!
Initial Treatment: Preferred Components
NNRTI Option
NRTI Options¹
Sustiva*
OR
PI Options
Epzicom
+
Truvada
Reyataz + Norivr
Lexiva + Norvir (twice a day)
Kaletra (twice a day)
* Avoid in pregnant women and women with significant pregnancy potential
¹ Emtricitabine can be used in place of lamivudine and vice versa
² For patients who have tested negative for HLA-B*5701
³ Tenofovir + emtricitabine or lamivudine is preferred in patients with HIV/HBV coinfection
Initial Treatment: Alternative Components
NNRTI Option
Nevirapine*
PI Options
Reyataz¹
Lexiva
Lexiva + Norvir (1x/day)
NRTI Options¹
+
Combivir
Videx + Epivir
or Emtriva
Kaletra (1x/day)²
Invirase + Norvir
* Nevirapine should not be initiated in women with CD4 counts >250 or men with
CD4 counts >400
¹ Atazanavir must be boosted with ritonavir if used with tenofovir
² May be insufficient if HIV RNA >100,000 copies/mL
Antiretroviral Drugs 2008
RT Inhibitors
Nucleoside/tide analogues (NRTI)
abacavir (Ziagen®)
didanosine (Videx®)
emtricitabine (Emtriva®)
lamivudine (Epivir®)
stavudine (Zerit®)
tenofovir (Viread®)
zidovudine (Retrovir®)
Nonnucleoside analogues (NNRTI)
efavirenz (Sustiva®)
nevirapine (Viramune®)
delavirdine (Rescriptor®)
etravirine (Intelense® ) NEW
Dual and triple combinations
Combivir®, Epizicom®,
Trizivir®, Truvada®, Atripla®*
* NNRTI and NRTI combo
Protease Inhibitors
amprenavir (Agenerase®)
atazanavir (Reyataz®)
darunavir (Prezista®)
fosamprenavir (Lexiva®)
indinavir (Crixivan®)
lopinavir/ritonavir (Kaletra®)
nelfinavir (Viracept®)
ritonavir (Norvir®)
saquinavir (Invirase®)
tipranavir (Aptivus®)
Entry Inhibitors
enfuvirtide – T 20 (Fuzeon®)
maraviroc (Selzentry®) NEW
Integrase Inhibitors
raltegravir (Isentress®) NEW
New Tests
• HLA-B*5701 screening
• Recommended before starting abacavir
(Ziagen or Epzicom), to reduce risk of
hypersensitivity reaction (HSR)
• Co-receptor tropism assay
• Should be performed when CCR5
antagonist (maraviroc [Selzentry]) is
being considered
New Agents
• Non-Nucleoside RT Inhibitor
• etravirine (Intelense®)
• Oral agent 2 x 100mg 2x/day following a meal
• Role
• Treatment experienced individuals who’ve failed
current NNRTIs (evidence of resistance)
• Side effects
• Rash
• Nausea
New Agents
• CCR5 Entry Inhibitor
• maraviroc (Selzentry®)
• Oral agent 150 to 600mg 2x/day
• Depends on other drugs in the regimen
• Role
• Treatment experienced individuals
w/CCR5-tropic virus
• Side effects
 Cough
 Rash
 Fever
 URIs
 Musculoskeletal symptoms
 Abdominal pain
New Agents
• Integrase Inhibitor
• raltegravir (Isentress®)
• 400mg 2x/day
• Role
• Treatment experienced patients
• Side effects
•
•
•
•
Nausea
Headache
Diarrhea
Fever
Adherence
Adherence – Why Do We Care?
Adherence to ARV Therapy
High rates of adherence correlate to:
• HIV viral suppression
• Reduced rates of resistance
• Improved survival
Commitment to lifelong therapy requires
a commitment of both the patient
and the health care team.
Relationship Between Adherence
and HIV Suppression
*Series of 886 treatment-naive HIV patients;
CD4 cell count <500 x 106 cells/L or plasma
viral load >5000 copies/mL.
†Prospective,
observational study of
81 HIV patients.
‡MEMS, Medication Events Monitoring System.
1. Low-Beer S et al. JAIDS. 2000;23:360-361. Letter.
2. Paterson DL et al. Ann Intern Med. 2000;133:21-30.
Relationship Between Adherence
and CD4 Count
*Observational
and research study of 1522 ART-naive patients initiated on
HAART; adherence was measured as prescriptions refilled.
1. Wood et al. JAIDS. 2004;35:261-268.
Adherence Impacts HIV-Related
Mortality and AIDS Progression*1
For every 10%
decrease in
adherence
16% increase in
HIV-related mortality
1.17 times higher likelihood
of progression
to AIDS
and/or death
*Prospective, observational study of 950 ART-naive patients treated with triplecombination therapy; adherence was estimated by prescriptions dispensed.
1. Hogg et al. 7th CROI 2000. Abstract 73.
5
Consequences of
Non-adherence
• Resistance
• Decrease CD4
• New Regimen
• Possible O.I.’s
• New Side Effects
• Hospitalizations
• Detectable Viral
Load
• Death
Meta Analysis on Adherence
• “There does not seem to be any one
intervention that robustly enhances
adherence, perhaps because so many
variables affect a patient’s decision to
take a drug. A combined approach
intuitively may best address a patient’s
needs…” (Peterson et al. AJHP, 60: 663)
Conditions Necessary for Adherence
• Patients Must:
• Understand and believe the diagnosis
• Be interested in their health
• Correctly assess the impact of the diagnosis
• Believe in the efficacy of the prescribed
treatment medication
• Know the onset of action and how will they know
when med is working
Conditions Necessary for Adherence
(cont’d)
• Patients Must:
• Find ways of using the medication that are not
more trouble than the disease
• Value the outcome of the treatment more than
the costs
• Believe the provider cares about them
• Be ready to use the medication
• Be involved
Approaches to Improved
Adherence
• Simplify and explain treatment regimen
• Discuss side effects – put into perspective
• Open communication (e.g. importance of doctor-patient
relationship)
• Social support (e.g. family, friends, role models, case
manager, nurses, pharmacists
• Treat depression
• Promote patient organizational skills
• Medication tracking aids
• Set up weekly pill boxes
• Negotiate with pharmacy to call regarding refills
Techniques to Improve
Patient Understanding
• Examine own attitude toward patient counseling.
• Emphasize key points.
• Give reasons why something is important (OI
prophylaxis).
• Give concrete instructions.
• Present key information at the beginning and the
end of your discussions.
• Written information to back up verbal counseling.
• Verify what patients have learned.
Techniques to Improve
Patient Behavior
• Integrate new behaviors with current behaviors.
• Provide good aids when you can, like pill organizers,
counter caps, alarms etc.
• Help patients with self monitoring options, log
books, calendars, etc.
• Monitor medication use on your end –refill records
– and encourage patients where appropriate.
• Refer patients with extreme or special needs to
appropriate help – Medicaid, various medication
assistance programs, reading comprehension
services, and so on.
"Medicines don’t work if
you don’t take them".
Principles of Success
1. Negotiate and understandable
treatment plan to which the patient
can commit
•
•
Establishing a trusting relationship is
critical
Often requires several office visits before
therapy can be initiated
Principles of Success
2. Assess patient’s readiness to take
medication
•
•
•
Assess emotional stability
Acceptance of disease
Accessibility to health care
Principles of Success
3. Patients need to understand that
the first regimen is the best chance
for long-term success.
Principles of Success
4. Adherence counseling and
assessment should be done at each
clinical encounter.
•
Never assume someone else is talking
about adherence