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Viread (Tenofovir)
Viread
Capsule
Articles on Viread
Full US Prescribing Information

Patient Information
What is Viread?
What is known about Viread?
What about drug interactions?
Resistance and Cross-Resistance
What Are the Side Effects?
www.viread.com


Articles on Viread


Meta-analysis Finds Tenofovir Linked to Modest Kidney Impairment, No Increase in Bone Fractures
9-14-2010

CAPRISA Microbicide Trial Shows Tenofovir Vaginal Gel Reduces HIV Transmission Risk by 39%

7-23-2010

Tenofovir-related Kidney Toxicity Linked to High Drug Concentrations, May Not Always Be Reversible
5-18-2010

Kaiser Study Finds Link between First-line Tenofovir (Viread) Use and Kidney Impairment
2-09-2010


TDF-containing Antiretroviral Regimens in Pregnancy: Findings from the Antiretroviral Pregnancy Registry
9-15-2009

Antiretroviral Pregnancy Registry Indicates Use of Tenofovir (Viread) by Pregnant Women Does Not Raise Risk of Birth Defects
9-15-2009

Abacavir (Ziagen) Backbone Suppresses HIV as well as Tenofovir (Viread) in UK CHIC Study
8-21-2009

Studies Show Tenofovir (Viread) Is Linked with Impaired Kidney Function
6-16-2009


Tenofovir (Viread) during Pregnancy: Findings from the Antiretroviral Pregnancy Registry

3-24-2009


Is Tenofovir an Option for Prevention of mother-to-child HIV transmission?

3-24-2009


A Pilot Study to Determine the Effect on Dyslipidemia of the Addition of Tenofovir to Stable ART in HIV-infected Subjects: Results from A5206 Study Team
2-21-2009

Once-daily Regimen of Nevirapine (Viramune), Tenofovir (Viread), and Lamivudine (Epivir) Is Associated with Early Virological Failure
2-03-2009

In Vivo Viral Dynamics and Pharmacokinetics of Tenofovir Disoproxil Fumarate (TDF) and Abacavir (ABC): Evidence of a Non-Additive Antiviral Effect
2-10-2009

Single Dose Tenofovir Disoproxil Fumarate (TDF) with and without Emtricitabine (FTC) in HIV-1 Infected Pregnant Women and Their Infants: Pharmacokinetics (PK) and Safety
2-10-2009

Structural Basis for HIV-1 Reverse Transcriptase Drug Resistance to Zidovudine (AZT) and Tenofovir
2-10-2009

Lack of Minority K65R Resistant Viral Populations Detected after Repeated Interruptions of Tenofovir DF/ Zidovudine/Lamivudine
2-10-2009

Tenofovir (TDF)- or Abacavir (ABC)-selected Minority Subpopulations in Viremic Subjects Detected by Ultra-deep Sequencing
11/05/2008


Tenofovir (Viread) Associated with Mild Kidney Function Impairment, but not Clinically Relevant Renal Disease
10/14/08


Tenofovir (Viread) Administered Orally, by Injection, or as a Rectal Microbicide Protects Monkeys from Infection with HIV-like Virus
10/07/08

PrEP using Tenofovir plus Emtricitabine May Offer Benefits even if HIV Infection Occurs
10/07/08

Study Presentation Overstates Tenofovir Kidney Toxicity Risk
8/15/2008


What is the Risk of Kidney Toxicity Associated with Tenofovir (Viread)?
8/12/08


Impact of Gender on Response to Lopinavir/ritonavir (LPV/r) Tablets Dosed QD or BID Administered with Tenofovir Disoproxil Fumarate (TDF) and Emtricitabine (FTC) in Antiretroviral-naÔve (ARV) Subjects: Results from Study M05-730
8/10/08

Comparable HIV-1 Viral Suppression and Immunologic Recovery of White and Non-White Antiretroviral-NaÔve Subjects Taking Lopinavir/ritonavir (LPV/r) Tablets + Tenofovir Disoproxil Fumarate (TDF) and Emtricitabine (FTC) through 48 Weeks
8/10/08

Simplification with Easier Emtricitabine and Tenofovir (SWEET): Results of a 48 Week Analysis of Patientsí Perceptions of Treatment and Adherence
8/10/08

An Open-Label Multicenter Study to Assess Efficacy, Tolerability and Adherence of a Once Daily (OD) TDF-Containing HAART in HIV-1-Infected Former IVDU-Patients Receiving Opiate Substitution - Final 48 Weeks Analysis of 3OD
8/10/08

Renal Safety Profile of Tenofovir DF (TDF)-containing vs. Thymidine Analog-containing Regimens Through 144 Weeks in Antiretroviral-naÔve Patients
8/10/08

High CD4 Count, Shorter Time to Viral Suppression and Association with NNRTI were Predictive of Lower Risk of Virologic Rebound in Patients Receiving TDF-containing Regimens
8/10/08

The Safety and Efficacy of Switching Stavudine to Tenofovir DF in Combination with Lamivudine and Efavirenz in HIV-1-Infected Patients: A Four-Year Follow-up
8/10/08

Tenofovir Effect on Renal Function Factoring in Both MDRD-Calculated Glomerular Filtration Rate (GFR) and Spot Urine Protein-to-Creatinine (UPC) Ratio
8/10/08


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.