What Is Tenofovir?

Tenofovirdisoproxil (Viread) is a new type of nucleotide reverse transcriptase inhibitor. Can effectively fight a variety of viruses, used to treat viral infectious diseases.

Tenofovir

Tenofovirdisoproxil (Viread) is a new type of nucleotides

This product is a nucleotide reverse transcriptase inhibitor. It inhibits reverse transcriptase in a similar way to nucleoside reverse transcriptase inhibitors, and thus has potential anti-HIV-1 activity. The active ingredient of this product, tenofovir bisphosphate, can inhibit viral polymerase by directly competing with natural deoxyribose substrates, and terminate the DNA strand by inserting into DNA. In vitro, this product is effective against a variety of viruses, including those resistant to nucleoside reverse transcriptase inhibitors. In vitro, the IC50 of this product for wild-type HIV-1 is 1.6 micro

Tenofovir is hardly absorbed through the gastrointestinal tract, so it is esterified and salted to become tenofovir disoproxil fumarate hydrochloride. Tenofovir disoproxil is water-soluble and can be quickly absorbed and degraded into the active substance tenofovir. Tenofovir is then converted into the active metabolite tenofovir bisphosphate. Tenofo within 1 to 2 hours after administration

Multiple placebo-controlled trials have verified the efficacy of this product in combination with stable antiretroviral drugs.

For HIV infection

In a study of 186 patients with HIV-1 infection, patients received placebo or one of three doses (75, 150, or 300 mg) of this product in combination with other antiretroviral drugs. 48 weeks. At 24 weeks, the weighted time-averaged logarithmic value of plasma HIV-1 RNA levels changed from the baseline value by 0.02 in the placebo group, and decreased by 0.58 in the treatment group. And the response has continued, and by 48 weeks, the change of this product group from the basic value is reduced by 0.62.

In another study of 550 patients, the average basal plasma HIV-1 RNA level was 3.4 copies / ml, and the average basal CD4 cell count was 427 / ml. Patients in the study received placebo or 245 mg of this product for 24 weeks. At 24 weeks, the former index of the placebo group and the product treatment group decreased by 0.03 copies / ml and 0.61 copies / ml, respectively. The weighted time average of the CD4 cell count also changed significantly from the baseline value, with a rise of 13 / ml in this product group and a decrease of 11 / ml in the placebo group. In addition, at 24 weeks, 45% of patients in this product group had a viral load below the detectable threshold, compared with 13% in the placebo group.

These studies also show that most strains with reduced sensitivity to nucleoside reverse transcriptase inhibitors respond to tenofovir. It is less likely that the sensitivity to tenofovir will be reduced or the sensitivity to nucleoside reverse transcriptase inhibitors will be reduced.

For HBV infection

German scholar van Bommel and others reported at the American AASLD 58th Annual Meeting of Liver Disease in 2007 that they reported 10 cases of chronic recurrence of drug resistance after switching to adefovir (ADV) after resistance to lamivudine (LAM). Hepatitis B patients were treated with tenofovir (TDF) monotherapy for more than 12 months; HBV polymerase gene clone sequencing was performed before and during treatment. The results showed that HBV-DNA decreased by 4.4 (2.8 ~ 5.5) log10copies / ml to 12 months after treatment, and HBV-DNA with an average of 3.3 (1.5 ~ 4.9) log10copies / ml was detected in 8 of 10 cases. During follow-up, 5 patients had HBV-DNA <400copies / ml. No virological breakthrough occurred during the entire course of treatment. The conclusion of the study shows that TDF monotherapy has significant antiviral effects on HBV-DNA associated with ADV-related and combined different resistance mutation sites.

In general, this product is easily tolerated. Unlike nucleoside reverse transcriptase inhibitors, this product does not have bone marrow suppression, peripheral neuropathy or pancreatitis.

Untreated patients

Treatment-induced adverse events

Double-blind controls were performed in 600 untreated patients. Patients received 144 weeks of tenofovir disoproxil fumarate (N = 299) or stavudine (d4T) (N = 301) with lamivudine (3TC) and efavirenz (EFV) ) Combination therapy (Study 903), with the most common adverse reactions being mild to moderate gastrointestinal events and dizziness.

Laboratory anomaly

Except that the fasting cholesterol and fasting triglyceride elevations (40% and 9%, respectively) were more common in the stavudine group than the tenofovir disoproxil fumarate group (19% and 1%, respectively), Other laboratory abnormalities observed in the study were similar in the tenofovir disoproxil fumarate and stavudine treatment groups.

Treated patients

Treatment-induced adverse events

Adverse reactions in treated patients are usually consistent with untreated patients and include mild to moderate gastrointestinal events such as nausea, diarrhea, vomiting, and flatulence. <1% of patients withdrawn from clinical studies due to gastrointestinal adverse events (Study 907).

Laboratory anomaly

The incidence of laboratory abnormalities observed in the study was similar in the tenofovir disoproxil fumarate and placebo treatment groups.

Lactic acidosis / severe hepatomegaly with steatosis When using nucleoside analogs alone or in combination with other antiretroviral drugs, lactic acidosis and severe hepatomegaly with steatosis have been reported, including fatal Case. Most of these cases occur in women. Obesity and long-term exposure to nucleosides may be risk factors. Special care should be taken when administering nucleoside analogs in patients with known risk factors for liver disease; however, cases have been reported in patients without known risk factors. Any patient with clinical or laboratory results suggesting lactic acidosis or significant liver toxicity (which may include hepatomegaly and steatosis, even if the aminotransferase is not significantly elevated) should be suspended with tenofovir disoproxil fumarate treatment.

Patients with co-infection with HIV and hepatitis B virus are advised that all HIV patients be tested for chronic hepatitis B virus (HBV) before starting antiretroviral therapy. Tenofovir disoproxil fumarate is not approved for the treatment of chronic HBV infection, and the safety and efficacy of tenofovir disoproxil fumarate have not been proven in patients with HBV and HIV co-infection. Severe acute exacerbations of hepatitis B have been reported in patients with HBV and HIV co-infection who discontinued tenofovir disoproxil fumarate treatment. Patients with co-infection with HIV and HBV who discontinue treatment with tenofovir disoproxil fumarate must closely monitor liver function, including clinical and laboratory follow-up, for at least several months. If conditions are right, patients can be allowed to start anti-HBV treatment.

Renal impairment is mainly cleared by the kidney. Cases of renal impairment, including acute renal failure and Fanconi syndrome (tubular injury with hypophosphatemia) have been reported to be associated with the use of tenofovir disoproxil fumarate ^[1]

When coadministered with tenofovir disoproxil fumarate, the maximum serum concentration (Cmax) and the area under the plasma concentration time curve (AUC) of desoxycreatinine sustained-release tablets or enteric preparations (Videx, VidexEC) increased significantly high. The mechanism of this interaction is unclear. Higher levels of didemic creatinine have the potential to lead to adverse events associated with didemic creatinine, including pancreatitis and kidney disease. A decrease in CD4 cell count was observed in patients receiving tenofovir disoproxil fumarate and didanosine creatinine 400 mg daily. In adults weighing> 60kg, the dose of hydroxycreatinine when combined with tenofovir disoproxil fumarate should be reduced to 250 mg. In patients <60 kg in weight, no data are currently available on the recommended dose adjustments for creatinine. When combined, tenofovir disoproxil fumarate and dyscreatin enteric solvent can be taken on an empty stomach or after eating light food (<400Kcal, 20% fat). Sustained-release oxycreatinine tablets and tenofovir disoproxil fumarate should be administered in combination on an empty stomach. Caution should be exercised when taking tenofovir disoproxil fumarate in combination with oxycreatinine, and patients receiving the combination should closely monitor adverse events related to oxycreatinine. In patients with deoxycreatinine-related adverse events, deoxycreatinine should be discontinued. ^[1]

Tenofovir TDF is listed as a component of second-line treatment in the National Free AIDS Antiviral Treatment Manual (Second Edition).

In the case of meeting two criteria, you can switch to second-line therapy: 1, first-line drugs can be switched to second-line drugs after failure. 2. Some serious or irreversible side effects occur after first-line antiviral treatment, and second-line drugs can be used if necessary.

Hepatitis B and AIDS co-infected patients can use TDF as a first-line drug. The program has been launched in some provinces.

Tenofovir was listed as a component of first-line treatment in the National Free AIDS Antiviral Treatment Manual (Third Edition) ^[2] , published in 2012.