What
is Viread?
•
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.
•
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?
•
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.
•
Viread is not approved for children younger than 18 years of age.
•
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?
•
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
•
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.
•
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?
•
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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