The Nonnucleoside Reverse Transcriptase Inhibitors Efavirenz and Nevirapine in the Treatment of HIV

Abstract

Clinical trial data and real-world experience have shown the nonnucleoside reverse transcriptase inhibitors (NNRTIs) to be an important class of agents for the treatment of HIV. Given their long plasma half-lives, in vitro and in vivo potency against HIV, low pill burdens, and ability to be safely combined with other commonly used medications, the NNRTIs nevirapine and efavirenz are widely used in combination antiretroviral therapies. Observational, retrospective cohort studies among antiretroviral treatment (ART)-naive patients have suggested that efavirenz may be superior to nevirapine in terms of efficacy. Recently, data from the 2NN study, a large, multicenter, multinational, prospective, randomized, head-to-head trial comparing efavirenz and nevirapine, have been reported. The results from this study indicate that ART-naive patients achieved good antiviral response after 48 weeks of treatment with nucleoside reverse transcriptase inhibitors (NRTIs) combined with either efavirenz or nevirapine (viral load >50 copies/mL: efavirenz, 70%; nevirapine bid, 65.4%; nevirapine qd, 70%). Even though central nervous system disturbances occurred more frequently among efavirenz-treated patients and nonclinically significant transaminitis occurred more frequently among nevirapine-treated patients, these adverse events were not statistically significant or mutually exclusive. Given the results of the 2NN study, the selection of one agent or the other for use in clinical practice will depend more upon patient-specific factors than expected differences in antiviral responses.

Early initiation of antiretroviral therapy results in decreased morbidity and mortality among patients with TB and HIV

“…Though IRS has been reported in as many as 30% to 40% of TB patients starting HAART, this study, in line with some recent publications [10,11], suggests that this occurs less frequently than previously reported and does not result in discontinuation of either HIV or TB treatment. The proportion of patients with rash in our study is similar to that reported among patients treated with non-nucleoside reverse transcriptase inhibitors (NNRTIs) who were not TB co-infected [12]. In our study, no one discontinued treatment for either IRS or rash; however, a few patients' NNRTIs were changed to alternative regimens.…”

Design, synthesis and biological evaluation of quinoxaline compounds as anti-HIV agents targeting reverse transcriptase enzyme

“…Compounds containing a quinoxaline scaffold have shown high potency as NNRTIs and in the inhibition of HIV-1 replication in cell culture [6]. Derivatives such as HBY [7], HBQ [8] and S-2720 [9], efavirenz (EFV) [10] and quinoline U-78036 [11] and UC38 [12] (Figure 1) are examples of quinoxaline and related compounds with RT inhibitory action. The development of novel NNRTIs using Computer Aided Drug Design (CADD) is well documented in literature [13][14][15][16].…”

Role of Cytochrome P450 2B6 Pharmacogenomics in Determining Efavirenz-Mediated Central Nervous System Toxicity, Treatment Outcomes, and Dosage Adjustments in Patients with Human Immunodeficiency Virus Infection

“…Efavirenz (EFV) has been the backbone of first‐line anti‐HIV combination regimens for many years due to its efficacy against HIV and ease of dosing. EFV is a nonnucleoside reverse transcriptase inhibitor (NNRTI) commonly used as first‐line treatment and is a part of highly active antiretroviral therapy (HAART) against HIV‐1 infection . EFV is a noncompetitive inhibitor of HIV‐1 reverse transcriptase, resulting in allosteric inhibition of RNA‐ and DNA‐dependent DNA polymerase activity, preventing transcribing of viral RNA into DNA …”

“…EFV is a nonnucleoside reverse transcriptase inhibitor (NNRTI) commonly used as first-line treatment and is a part of highly active antiretroviral therapy (HAART) against HIV-1 infection. 1 EFV is a noncompetitive inhibitor of HIV-1 reverse transcriptase, resulting in allosteric inhibition of RNA-and DNA-dependent DNA polymerase activity, preventing transcribing of viral RNA into DNA. 2 0.186 AE 0.072 L/hour/kg.…”