Abstract
Efavirenz, a non-nucleoside reverse-transcriptase inhibitor (NNRTI) is one of the most commonly prescribed antiretroviral drugs. The present article provides a systematic overview and meta-analysis of clinical trials comparing efavirenz and other active drugs currently recommended for treatment of HIV-infected, antiretroviral-naive patients. Electronic databases (Pubmed, Embase, the Cochrane Library, Trip Database) were searched up till 23 December 2013 for randomized controlled clinical trials published as a peer-reviewed papers, and concerning efavirenz-based regimens used as initial treatment for HIV infection. Thirty-four studies were included in the systematic review, while twenty-six trials were suitable for the meta-analysis. Efavirenz was compared with drugs from four different classes: NNRTIs other than efavirenz (nevirapine or rilpivirine), integrase strand transfer inhibitors (InSTIs), ritonavir-boosted protease inhibitors (bPI) and chemokine (C-C motif) receptor 5 (CCR5) antagonists (maraviroc), all of them were added to the background regimen. Results of the current meta-analysis showed that efavirenz-based regimens were equally effective as other recommended regimens based on NNRTI, ritonavir-boosted PI or CCR5 antagonist in terms of efficacy outcomes (disease progression and/or death, plasma viral HIV RNA <50 copies/ml) while statistically significant more patients treated with InSTI achieved plasma viral load <50 copies/ml at week 48. In comparison with both InSTI-based and CCR5-based therapy, efavirenz-based treatment was associated with a higher risk of therapy discontinuation due to adverse events. However, comparisons of efevirenz-based treatment with InSTI-based and CCR5-based therapy were based on a limited number of trials, therefore, conclusions from these two comparisons must be confirmed in further reliable randomized controlled studies. Results of our meta-analysis support the present clinical guidelines for antiretroviral-naive, HIV-infected patients, in which efavirenz is one of the most preferred regimens in the analyzed population. Beneficial safety profile of InSTI-based and CCR5-based therapy over efavirenz-based treatment needs further studies.
Highlights
Highly-active antiretroviral therapy (HAART) with three or more antiretroviral drugs is nowadays a “gold standard” of HIV treatment
Results of the current meta-analysis showed that efavirenz-based regimens were effective as other recommended regimens based on nucleoside reverse-transcriptase inhibitor (NNRTI), ritonavir-boosted PI or chemokine receptor type 5 (CCR5) antagonist in terms of efficacy outcomes while statistically significant more patients treated with integrase strand transfer inhibitors (InSTIs) achieved plasma viral load
Two different regimens adequate for comparisons with efavirenz were identified: NNRTI, InSTI, boosted protease inhibitors (bPI), and CCR5 (CC chemokine receptor type 5), all added to the specified background regimens
Summary
Highly-active antiretroviral therapy (HAART) with three or more antiretroviral drugs is nowadays a “gold standard” of HIV treatment. Its effectiveness in antiretroviral-naive and treatment-exposed HIV-infected patients was compared with various regimens (mostly PI-based), there is still a lack of comprehensive review regarding comparison of efavirenz-based therapy with other, recommended regimens. Recent practice guidelines of initial treatment in HIV-infected patients, among preferred combinations of antiretroviral drugs mentioned two nucleoside reverse transcriptase inhibitors (NRTIs) plus either a non-nucleoside reverse-transcriptase inhibitor (NNRTI), ritonavir-boosted protease inhibitor (ritonavir-boosted PI) or integrase strand transfer inhibitor (InSTI) [6,7,8]. In the light of numerous trials regarding the use of efavirenz in HIV-infected, antiretroviral-naive patients, we performed systematic review and meta-analysis of randomized controlled trials in order to establish differences between efavirenz-based regimens and other regimens recommended by clinical experts to be used in HIV-infected patients previously untreated with antiretroviral therapy
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