Transcript Overview of ARV Drug Classes and Individual Drugs

Ardis Ann Moe, M.D.
[email protected]
UCLA CARE clinic/NEVHC Van Nuys HIV Clinic
29 August 2014
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1)to understand the differences between the
four major drug classes of HIV medications
2)Issues on how to obtain medications
3)Issues on different formulations of HIV
meds (liquid, injection, tablet, gel, etc)
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Two major forms:
◦ Maraviroc (Selzentry), a twice daily oral medication
◦ Envirfiratide (Fuzeon), a twice daily injected
medication
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Maraviroc (Selzentry)
◦ Twice daily oral medication
◦ Acts as a “condom for the CD4 cell”
◦ Blocks the attachment of the HIV virus to one of the
proteins on the surface of the CD4 cell—the CCR5
attachment receptor protein
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Maraviroc (Selzentry) requires an expensive
blood test “Trofile” in order to determine if
the medication will work.
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Some patients have strains of HIV virus that
do NOT attach to the CCR5 protein, and so
are resistant to Maraviroc.
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The blood test costs $2,000 or more, often
requires prior authorization, and is available
from ADAP with a rationed system of coupons
In addition, the patient has to have a viral
load of >1,000 in order for the usual “trofile”
test to be valid.
A specialized form of the “trofile”can be used
in patients with <1,000 copies
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The drug itself is quite well tolerated; the
only real problem is the trofile test
Most insurance companies or ADAP will not
pay for maraviroc unless a trofile is done and
it indicates that maraviroc will work.
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Enfuvirtide (T-20) or Fuzeon
◦ Injectable drug, twice daily.
◦ Essentially doubles the cost of HIV treatment
◦ Rarely used; less potent than most other available
HIV medications
◦ “condom for the HIV virus”
 Prevents the HIV virus from attaching to the CD4 cell
by blocking the attachment of the gp41 protein of the
HIV virus to the CD4 cell.
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Major value of Fuzeon is that it has
essentially no drug interactions, and can be
given as an injection.
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AZT (zidovudine). The first HIV drug. Licensed
in 1987
◦ As monotherapy, AZT drops HIV viral load approx
50% for a few months
◦ Available as pills, IV, and liquid forms. generic
◦ Transformed the future for pregnant women with
HIV. AZT monotherapy dropped transmission from
25% to 8% in PAETC 076
◦ Excellent brain tissue penetration
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CONCORD study (1994) indicated that AZT
monotherapy did not improve survival
beyond the first year of therapy.
Initial doses of AZT were 3x what are used
now.
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DDI (Videx) didanosine
Second drug approved to treat HIV
Most dangerous drug in the whole
armamentarium because of side effects
Cheap, available on PEPFAR formularies
Powder forms; tablet. Once daily. generic
Has to be taken on an empty stomach
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Tenofovir (Viread) Part of Truvada
◦ Nucleotide RT
◦ One of the most common HIV meds used worldwide
◦ Once daily pill or pediatric powder; also treats
hepatitis B
◦ As part of PREP, also has some prevention of HSV-2
◦ Poor brain tissue penetration
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Lamivudine/emtricitabine
Epivir /emtriva
Available in pill, liquid forms. Lamivudine
generic
Both treat hepatitis B
Emtriva is a part of Truvada
Lamivudine is part of Epzicom
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Abacavir (Ziagen) part of Epzicom
Available in pill and liquid forms; generic
Can cause a severe allergic reaction in
persons who have genetic predisposition
Needs HLAB5701 blood test before use of
medication
Good brain tissue penetration
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Stavudine (Zerit)
Rarely used because of long term side effects
“bridge” drug for short term use;
fair/poor brain tissue penetration
Pill and liquid forms; generic available.
Can not be given in combination with AZT
because of intracellular antagonism, and
cannot be combined with Videx because of
synergistic toxicity
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Combination drugs:
Trizivir (AZT/Epivir/Ziagen)
Epzicom (Epivir/Ziagen)
Truvada (Viread/Emtriva)
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In general, Trizivir not adequate treatment for
HIV infection for newly diagnosed HIV+
persons.
Triple therapy with all-nuceloside cocktails
have suboptimal potency
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As a class the non-nucs have multiple drug
interactions, esp with seizure medications,
cardiac medications, methadone, etc.
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Non-nucleoside RT inhibitors act on the RT
enzyme directly; nucleoside RT inhibitors act
on the growing DNA chain, inserting
themselves as false pieces into the growing
DNA chain.
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Neviripine (Viramune)
Available as pill and liquid forms
Safe in pregnancy, penetrates brain tissue
well
Twice or once daily
Viramune XR more expensive; many
insurance companies will only pay for generic
neviripine
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Delavirdine (Rescriptor)
Rarely used because of large pill counts
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Efavirenz (Sustiva) part of Atripla
Once daily; tabs or caps, taken on an empty
stomach
Capsules can be opened up and sprinkled as
a powder
Good penetration into brain tissue BUT can
reduce memory because of more depression
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Rilpivirine (Edurant) Part of Complera
“Sustiva” jr.
◦ Less potent, less side effects
◦ Is taken with food.
◦ Tablet only (small tablet—25 mg)
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Etravirine (Intelence)
Twice daily, useful as salvage if a patient has
resistance to Sustiva or Edurant or Viramune.
Tablet form only; but does dissolve in water
Good penetration into brain tissue
Gritty taste
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Raltegravir (Isentress)
Twice daily tablet. Has the advantage of
relatively few drug interactions.
Once daily dosing is less effective.
Good penetration into brain tissue
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Elvitregravir. Available currently only as part
of Stribild
Needs boosting agent to work: cobisistat
(part of Stribild)
Drug interactions
Once daily tablet form
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Dolutegravir (Tivicay) Part of Triumeq
Once daily for HIV treatment naïve; twice daily
as salvage treatment.
Small tablets
Drug interactions
Good penetration into brain tissue
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As a class, protease inhibitors were the
linchpin of HIV cocktails. When the first PI’s
were approved in 1996 and were used in
combination with the older nucelosides, there
was a revolution in the treatment of HIV
PI’s still have the best data on treating
severely ill AIDS patients with AIDS cancers
and OI’s.
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In general, PI’s have many drug interactions,
esp with cardiac medications, methadone,
seizure medications, and coumadin (warfarin)
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Ritonavir (Norvir).
One of the first PI’s
Now used as boosting agent; ritonavir
combined with other PI drugs to make them
more effective by raising blood levels of the
other PI drugs.
Capsule, liquid (vile), and tablet form
Usually dosed as 1 or 2 tablets once daily
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Ritonavir blocks first pass effect, so less
drugs are needed less often.
Once-daily dosing possible with PI’s
Also sold on streets to make heroin, meth,
and viagra more effective
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Indinavir (Crixivan)
One of earliest PI’s; now rarely used because
of side effects
Best taken with ritonavir for boosting effect
Tablet form only
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Saquinavir (Invirase)
Tablet and capsule form
Best used with ritonavir for boosting effect
Now rarely used because of side effects
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Nelfinavir (Viracept)
Tablet and powder form
Only PI currently in use that does NOT use
ritonavir
Less effective than other boosted PI’s
Safe in pregnancy
Poor penetration into brain tissue
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Lopinavir/ritonavir (Kaletra)
Combination drug of 2 PI’s; ritonavir used
only for boosting.
Liquid (vile) and tablet form.
Better tolerated as 2 tabs twice daily with
food. Good penetration to brain tissue
Best safety data in pregnancy. Used in
combination with AZT/lamivudine
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Atazanavir (Reyataz)
Once daily dosing, taken with ritonavir 1 a
day
Tablet and oral powder form
Drug interaction with heartburn meds
Penetrates brain tissue poorly
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Fos-amprenavir (Lexiva)
2 tabs once a day, used with ritonavir.
Liquid, tablet forms available
Can be taken with heartburn medications
Good penetration to brain tissue
Tipranavir (Aptivus)
Rarely used because of high pill count (2 pills
twice daily + 1 ritonavir twice daily)
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Darunavir (Prezista)
Tablet and liquid forms
Once daily with 1 ritonavir for initial therapy;
twice daily with 1 ritonavir twice daily for
salvage therapy
Can be used as initial or salvage therapy
Can be taken with heartburn meds
Good penetration to brain tissue
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59 yo male
HIV RNA PCR <20 copies, CD4 count 400’s
on Reyataz, Norvir, truvada.
Worsening memory loss
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42 yo male
New diagnosis of AIDS and lymphoma of
esophagus (AIDS cancer). Needs large doses
of heartburn medications
Cannot swallow pills.
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35 yo male with HIV
Has been on Viramune XR and truvada for
several years while on ADAP; now had
insurance through Covered California and
discovers he has to pay 50% of the actual
drug cost since his current meds are nongeneric.
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Multiple HIV medications, and multiple
different combinations.
Drug interactions, generic vs brand drugs,
formulations are issues in what drug is used.