Clinical trials of HIV antiretroviral therapy: Protease inhibitors versus 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
There has been great interest in defining which combination therapy approach may be most beneficial for treatment-naive HIV-infected patients.
This topic will discuss the major clinical trials that have been performed in the era of potent antiretroviral therapy (ART), which have compared regimens employing either non-nucleoside reverse transcriptase inhibitors (NNRTIs) versus protease inhibitors (PIs). Some of the studies were performed using older or currently unavailable formulations of antiviral agents, and hence have limited applicability to current practice.
Antiretroviral treatment (ART) regimens should have at least three active antiretroviral medications. In treatment-naïve patients, recommended regimens should consist of two nucleoside reverse transcriptase inhibitors (NRTIs), with one of them being lamivudine or emtricitabine, and either a non-nucleoside reverse transcriptase inhibitor (NNRTI) or a ritonavir-boosted protease inhibitor (PI). Decision-making for the selection of antiretroviral therapy is discussed elsewhere. (See "Selecting antiretroviral regimens for the treatment-naïve HIV-infected patient".)
Abbreviations used — The table shows commonly used abbreviations for the medications discussed in this topic (table 1).
Pharmacokinetic boosting with ritonavir — Low doses of ritonavir are often used in conjunction with a PI to raise serum concentrations of the parent drug. Use of low-dose ritonavir in a "boosted" regimen is often indicated with a small "r" (eg, "lopinavir/r" or LPV/r). Pharmacokinetic boosting is discussed in detail elsewhere. (See "Overview of antiretroviral agents used to treat HIV", section on 'Protease inhibitors (PIs)'.)
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- http://retroconference.org/2010/Abstracts/39789.htm (Accessed on November 27, 2010).
- Puls RL, Srasuebkul P, Petoumenos K, et al. Efavirenz versus boosted atazanavir or zidovudine and abacavir in antiretroviral treatment-naive, HIV-infected subjects: week 48 data from the Altair study. Clin Infect Dis 2010; 51:855.
- GENERAL PRINCIPLES
- Abbreviations used
- Pharmacokinetic boosting with ritonavir
- STUDIES IN TREATMENT-NAIVE PATIENTS
- Nelfinavir versus efavirenz (ACTG 384)
- Atazanavir versus efavirenz
- Saquinavir versus efavirenz (FOCUS)
- Amprenavir versus efavirenz (CLASS)
- Nelfinavir versus nevirapine (COMBINE)
- PI versus NNRTI-based ART (FIRST)
- PI versus NNRTI-based strategy (ACTG 5142, ACTG 5202, ALTAIR)
- SUMMARY AND RECOMMENDATIONS