Lamivudine/Zidovudine/Nevirapine

 
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More about Lamivudine/Zidovudine/Nevirapine

What is/are Lamivudine/Zidovudine/Nevirapine?

Nevirapine (NVP), also marketed under the trade name Viramune (Boehringer Ingelheim), is a non-nucleoside reverse transcriptase inhibitor (NNRTI) used to treat HIV-1 infection and AIDS.

As with other antiretroviral drugs, HIV rapidly develops resistance if nevirapine is used alone, so recommended therapy consists of combinations of three or more antiretrovirals.

Medical uses

Nevirapine in triple combination therapy has been shown to suppress viral load effectively when used as initial antiretroviral therapy (i.e., in antiretroviral-naive patients). Some clinical trials have demonstrated comparable HIV suppression with nevirapine-based regimens to that achieved with protease inhibitors (PIs) or efavirenz. Although concerns have been raised about nevirapine-based regimens in those starting therapy with high viral load or low CD4 count, some analyses suggest that nevirapine may be effective in these patients.

Nevirapine may also form a useful component of salvage regimens after virological failure, usually in combination with one or more PIs as well as nRTIs, especially in those who have not previously taken an NNRTI.

Adverse effects

The most common adverse effect of nevirapine is the development of mild or moderate rash (13%).Severe or life-threatening skin reactions have been observed in 1.5% of patients, including Stevens–Johnson syndrome, toxic epidermal necrolysis and hypersensitivity.

Nevirapine may cause severe or life-threatening liver toxicity, usually emerging in the first six weeks of treatment.In 2000, the U.S. Food and Drug Administration issued a black box label on nevirapine, warning that it could cause severe liver damage, including liver failure. Unacceptably high risk of serious liver symptoms in certain patient groups (women with CD4 count >250 and men >400) has led the U.S. DHSS to recommend the restriction of nevirapine use to those at lower risk, unless the benefit to the patient clearly outweighs the risk; although in the 2NN study which found these CD4 limits, the effect was seen only in patients recruited from Thailand. More recent studies on the use of Nevirapine in people with higher CD4 cell counts have come to the following conclusion: Treatment-experienced patients who start NVP-based combination therapy with low pre–ART and high current CD4 cell counts and an undetectable VL have a similar likelihood for discontinuing NVP therapy because of hypersensitivity reactions (HSRs), compared with treatment-naive patients with low CD4 cell counts. This suggests that NVP-based combination therapy may be safely initiated in such patients. However, in similar patients with a detectable VL, it is prudent to continue to adhere to current CD4 cell count thresholds. The U.S. Public Health Service Task Force advocates caution in the use of nevirapine in pregnancy due to toxicity issues, which may be exacerbated during pregnancy

Mechanism of action

Nevirapine falls in the non-nucleoside reverse transcriptase inhibitor (NNRTI) class of antiretrovirals Both nucleoside and non-nucleoside RTIs inhibit the same target, the reverse transcriptase enzyme, an essential viral enzyme which transcribes viral RNA into DNA. Unlike nucleoside RTIs, which bind at the enzyme's active site, NNRTIs bind allosterically at a distinct site away from the active site termed the NNRTI pocket.

Nevirapine is not effective against HIV-2, as the pocket of the HIV-2 reverse transcriptase has a different structure, which confers intrinsic resistance to the NNRTI class.

Resistance to nevirapine develops rapidly if viral replication is not completely suppressed.[3] The most common mutations observed after nevirapine treatment are Y181C and K103N, which are also observed with other NNRTIs. As all NNRTIs bind within the same pocket, viral strains which are resistant to nevirapine are usually also resistant to the other NNRTIs, efavirenz and delavirdine.

This article uses material from the Wikipedia article Lamivudine/Zidovudine/Nevirapine, which is released under the Creative Commons Attribution-Share-Alike License 3.0.

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