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What is Viread?
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Viread is an anti-HIV medication. It is in a
category of HIV medicines called nucleotide
reverse transcriptase inhibitors. Viread prevents
HIV from altering the genetic material of healthy
T-cells. This prevents the cells from producing
new virus and decreases the amount of virus
in the body.
•
Nucleotide analogues, such as Viread, are very
similar to nucleoside analogues (e.g., Retrovir
(AZT), Zerit (d4T),
and Epivir (3TC)).
The only difference is that nucleotide analogues,
unlike nucleoside analogues, are chemically
preactivated and thus require less processing
in the body for them to become active.
•
Viread, manufactured by Gilead Sciences, was
approved by the U.S. Food and Drug Administration
for the treatment of HIV in 2001.
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Viread is available in pharmacies as a single
drug, which is always combined with other anti-HIV
drugs, or in the combination capsules Truvada
(Viread and Emtriva) and Atripla
(Viread, Emtriva, and Sustiva [efavirenz]).
•
Viread is also active against the hepatitis
B virus (HBV), the virus responsible for
hepatitis B. Although it has not been approved
by the FDA for the treatment of hepatitis B,
some doctors prescribe it to treat both hepatitis
B and HIV. See What is known about side effects?
below for more important information regarding
Viread and hepatitis B.
What is known about Viread?
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The dose is one 300mg pill, taken once a day.
Truvada, which contains Viread and Emtriva,
needs to be taken once a day.
•
Viread can be taken either with or without food.
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Viread is not approved for children younger
than 18 years of age.
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Studies have demonstrated that Viread is effective
for the treatment of HIV when combined with
other anti-HIV drugs, usually at least one other
nucleoside reverse transcriptase inhibitor (NRTI)
and either a protease inhibitor or non-nucleoside
reverse transcriptase inhibitor (NNRTI). Viread
should not be taken alone (as monotherapy) or
with just one other anti-HIV drug.
•
For HIV-positive adults beginning anti-HIV drug
therapy for the first time, Viread is listed
as a "preferred" NRTI option—used
in combination with Sustiva
(efavirenz) and either Epivir
(3TC) or Emtriva
(emtricitabine)—by the United States Department
of Health and Human Services in its treatment
guidelines. Alternative ways to use Viread,
in a first-time drug regimen, are also listed.
•
Viread is active against many strains of HIV
resistant to Retrovir (AZT), Zerit
(d4T), Videx/Videx EC
(ddI), Hivid (ddC), and Ziagen
(abacavir). There is also some data from studies
indicating that HIV that has become resistant
to Epivir (3TC)
may be even more sensitive to Viread. The drug
is also active against virus containing the
Q151M mutation—a single mutation that results
in high-level resistance to multiple nucleoside
analogues.
What about drug interactions?
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HIV-positive people must be very careful about
using Viread in combination with Videx®/Videx
EC® (ddI). There are two important warnings
to know about:
• Drug regimens
consisting of Sustiva®
(efavirenz) or Viramune®
(nevirapine) plus Viread and Videx/Videx
EC have been associated with premature
drug failure. If you are receiving Viread
and Videx EC with either Sustiva or Viramune,
you may want to discuss alternative options
with your doctor.
• Viread
increases the amount of Videx/Videx EC in
the body. This can increase the risk of Videx-related
side effects. In turn, if Viread and Videx/Videx
EC are used together, Videx EC should be taken
at a dose of 250mg once a day (reduced from
the usual daily dose of 400mg a day).
Because there are now a number of concerns
regarding the use of Viread in combination with
Videx/Videx EC, many experts recommend avoiding
this combination altogether.
• HIV-positive
people should be careful if they use Viread
in combination with Reyataz®
(atazanavir), a protease inhibitor used to treat
HIV. Viread can decrease Reyataz levels in the
bloodstream and Reyataz can increase Viread
levels in the bloodstream. Thus, if you are
using Reyataz in combination with Viread, your
doctor should also prescribe low doses of Norvir®
(ritonavir), another protease inhibitor that
can significant boost the amount of Reyataz
in the bloodstream. The correct dose is 300mg
Reyataz plus 100mg Norvir, combined with the
standard daily dose of Viread. To make sure
that the increased Viread levels do not cause
kidney damage (a possible side effect of Viread),
blood tests to monitor kidney function should
be performed regularly.
• Levels of
lopinavir, one of the two protease inhibitors
in Kaletra®
(lopinavir/ritonavir), can decrease when the
drug is combined with Viread. Kaletra can also
increase Viread levels in the bloodstream. If
Kaletra and Viread are used together, it is
important to watch out for potential side effects
of Viread (e.g., kidney problems).
Resistance and Cross-Resistance
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Viread drug resistance means that HIV is still
able to reproduce in a person who is taking
the drug. Most of the data that are indicative
of Viread resistance and cross-resistance are
derived from in vitro studies or from
studies involving antiretroviral experienced
patients. At this time, very limited data are
available regarding the nature and extent of
Viread-associated resistance mutations that
develop in antiretroviral naïve patients.
•
HIV resistance to Viread in vitro is associated
with the K65R mutation. HIV with this mutation
shows a 3-4 fold reduction in susceptibility
to Viread. Two studies evaluating the occurrence
of this mutation in patients treated with Viread
and other antiretrovirals found that that it
was an uncommon occurrence - occurring in only
1-3% of the patients treated with Viread. The
K65R mutation may also occur with and affect
HIV-1 sensitivity to Ziagen (abacavir), Hivid
(zalcitabine) and Videx (didanosine).
•
Viread cross-resistance with other RTIs has
been found to be associated with zidovudine-associated
mutations, including M41L, D67N, K70R, L210W,
T215Y/F and K219Q/E/N. M41L and L210W appear
to have particular significance for Viread resistance.
HIV-1 with 3 or more zidovudine-associated mutations
had a reduced response to Viread, and the response
to Viread was decreased further if these mutations
included either M41L or L210W. The T69S double
insertion mutation is also associated with marked
Viread resistance.
•
M184V, a mutation associated with Ziagen and
Epivir use, appears to increase HIV-1 sensitivity
to Viread. This effect of M184V on HIV-1 sensitivity
to Viread occurs regardless of whether zidovudine-related
mutations are present or not.
Viread does not appear to have any cross-resistance
with NNRTIs or PIs.
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An appropriate cutoff for phenotypic resistance
to Viread appears to be a four fold change in
susceptibility from wild type. Patients with
≤ 4 fold change had a decrease in viral
load of 0.61 log10 copies/mL, while patients
with >4 fold change had a decrease in viral
load of only 0.12 log10
copies/mL.
What are the side effects?
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Black Box Warnings:
Viread, like all RTIs, has a black box warning
regarding the risk of lactic acidosis and
severe hepatomegaly with steatosis, including
fatal cases, associated with the use of
RTIs alone or in combination with other antiretrovirals.
Patients on RTIs should be carefully monitored
for signs or symptoms of these conditions and
liver function tests and enzymes should be checked
on a regular basis (See below).
The most common side effects associated
with Viread, when given in combination with
other antiretrovirals, are mild to moderate
gastrointestinal events, including nausea [11%],
vomiting [5%], diarrhea [9%] and flatulence
[4%]. Other relatively common side effects included
asthenia [8%], headache [6%], abdominal pain
[3%] and anorexia [3%].
Abnormal
laboratory tests associated with Viread included
neutropenia (low white cell count) [1%], increased
amylase (pancreas enzyme) [5%], increased liver
enzymes including alanine aminotransferase (ALT)
[2%] or aspartate aminotransferase (AST) [4%],
increased creatine kinase (muscle enzyme) [12%],
increased urine glucose (sugar) [3%], increased
serum glucose [2%] and increased triglycerides
(fat in blood) [8%].
The
RTI class of anti-HIV drugs has an adverse
side effect that can be fatal. This is
a grouping of abnormalities called lactic acidosis
(too much acid in the blood) and hepatomegaly
with steatosis (an enlarged, fatty liver).
Symptoms associated with these conditions can
include weakness, nausea, stomach/intestinal
pain, vomiting, shortness of breath and a fast
heart beat. Not all symptoms need to be present.
The majority of cases have occurred in women
and other risk factors include increasing length
of time taking an RTI drug(s) and being overweight.
There
is also some data that suggest that those with
pre-existing liver disease (e.g., chronic hepatitis
B or C or cirrhosis) may also be at higher risk.
The diagnosis of this condition is made by symptoms,
blood tests and physical examination to check
for a large liver and other abnormalities. Blood
tests may include liver enzymes, lactic acid
levels and other tests. Treatment with Viread
should be immediately suspended if this condition
is diagnosed or suspected based upon clinical
or laboratory findings indicating lactic acidosis
or hepatic injury, even if liver enzymes are
normal.
The
RTI class of anti-HIV drugs appears also be
associated with fat redistribution ("lipodystrophy")
as a side effect. Currently, researchers are
actively investigating the cause or causes of
fat redistribution associated with anti-HIV
therapy. At this time, the combination of protease
inhibitor drugs and RTI drugs appear to have
the highest association with this condition.
The risk may be higher in Caucasians.
Other
possible risk factors for fat redistribution
include total duration of HIV infection, genetic
background, body weight (body mass index or
weight divided by height), gender (females tend
to have more central fat gain and males more
peripheral fat loss), and age. Fat redistribution
may include fat loss and fat gain. Fat loss
under the skin tends to occur in the face, arms,
legs and buttocks. Fat gain may occur in the
abdomen ("paunch"), breasts, base
of the neck ("buffalo hump") and in
other, less specific locations. Lipomas (fatty
lumps under the skin) can also occur. Other
abnormalities sometimes associated with fat
redistribution are increased blood lipids
(fats, including cholesterol and triglycerides)
and increased blood sugar (hyperglycemia),
but these are usually associated with protease
inhibitor usage.
There
is increasing evidence that the RTI class of
anti-HIV drugs can cause damage to DNA
(genes) in the mitochondria (energy producers)
of cells. (Note this is separate DNA from that
in the nucleus that is a part of the chromosomes.)
This interaction with mitochondrial DNA may
be the cause of many of the significant toxicities
associated with each drug in this class. However,
each of the drugs appears to have somewhat different
toxicity profiles associated with various types
of cells. This might explain why different drugs
in this class manifest somewhat differing toxicities.
Preliminary, in vitro data indicate that
Viread is a weak inhibitor of mitochondrial
DNA polymerase ? and that Viread may be the
RTI least likely to cause mitochondrial dysfunction.
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