Clinical trials of HIV antiretroviral therapy: Non-nucleoside reverse transcriptase inhibitors
- Paul E Sax, MD
Paul E Sax, MD
- Clinical Director, Division of Infectious Diseases
- Brigham and Women's Hospital
- Professor of Medicine
- Harvard Medical School
The non-nucleoside reverse transcriptase inhibitors (NNRTIs) are a class of potent oral antiretroviral (ARV) drugs. One member of this class, efavirenz, is currently a preferred first-line agent for antiretroviral-naïve patients according to several treatment guidelines [1,2].
There are currently five approved NNRTIs (efavirenz, nevirapine, rilpivirine, etravirine, and delavirdine). Efavirenz, rilpivirine and nevirapine are predominantly used in treatment-naïve patients, while etravirine is indicated for treatment-experienced patients. Due to its less favorable pill burden, dosing frequency, and adverse event profile, delavirdine is rarely used. This topic will summarize the comparative clinical trial data in both treatment-naive and treatment-experienced patients supporting the use of these agents in various patient populations.
Information regarding selecting antiretroviral regimens, toxicity, and dosing is found elsewhere. (See "Selecting antiretroviral regimens for the treatment-naïve HIV-infected patient" and "Overview of antiretroviral agents used to treat HIV", section on 'Non-nucleoside reverse transcriptase inhibitors (NNRTIs)' and "Overview of antiretroviral agents used to treat HIV".)
Antiretroviral treatment (ART) regimens should have at least three active antiretroviral medications. In treatment-naïve patients, recommended therapy will have two nucleoside reverse transcriptase inhibitors (NRTIs) (one of them lamivudine or emtricitabine) and a third active drug consisting of either a non-nucleoside reverse transcriptase inhibitor (NNRTI) or a ritonavir-boosted protease inhibitor (PI). (See "Selecting antiretroviral regimens for the treatment-naïve HIV-infected patient".)
The major advantages of the NNRTIs are their relative potency and low pill burden, the latter especially notable with efavirenz, which can be given co-formulated with the NRTIs tenofovir and emtricitabine as one pill daily. A major disadvantage for nevirapine, delavirdine, and efavirenz is that a single resistance mutation can lead to complete loss of antiviral activity; this property is sometimes referred to as a "low genetic barrier" to resistance. (See "Primer on interpretation of HIV drug resistance testing" and "Overview of antiretroviral agents used to treat HIV", section on 'Non-nucleoside reverse transcriptase inhibitors (NNRTIs)'.)
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- GENERAL PRINCIPLES
- Abbreviations used
- TREATMENT-NAIVE PATIENTS
- Efavirenz and nevirapine (2NN study)
- Efavirenz versus rilpivirine
- TREATMENT-EXPERIENCED PATIENTS
- Switch strategies (NEFA study)
- Etravirine versus PI-based ART (TMC125-227 trial)
- Etravirine in patients with drug resistance (DUET trials)
- SUMMARY AND RECOMMENDATIONS