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Received May 10, 2017; Accepted Jul 16, 2017
This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
1. Introduction
Darunavir (DRV) is a once-daily second-generation protease-inhibitor [1, 2] that is administered with low-dose ritonavir (DRV/r) and two nucleoside reverse transcriptase inhibitors (NRTI) for treatment of HIV infection. In vitro studies have shown that resistance to DRV develops much more slowly and that it has a higher genetic barrier for the development of resistance relative to current protease inhibitors [3]. DRV has a very low resistance profile [3], requires boosting with ritonavir, and is used in combinations with two NRTIs, such as abacavir (ABC) + lamivudine (3TC) or tenofovir (TDF) + emtricitabine (FTC).
DRV/r + two NRTIs is the third option in the United States (US) Department of Health and Human Services’ and the European AIDS Clinical Society’s six recommended initial regimens for antiretroviral-naïve HIV-infected patients [4, 5]. The British HIV Medical Association has also recommended it as one of six third-line agents to be used with a two-drug NRTI backbone [6]. In contrast World Health Organization (WHO) guidelines only recommend DRV/r with two NRTIs as second- and third-line regimens for adults and adolescents who have failed initial therapy [7]. Different studies have shown that DRV/r combination therapy is less expensive than other combination therapies such as ritonavir-boosted lopinavir (LPV/r) [8] and ritonavir-boosted atazanavir (ATV/r) [8] but less cost effective compared to dolutegravir (DTG) [9] and raltegravir (RAL) [10].
In this paper, we systematically review the efficacy and safety of DRV/r in combination with two NRTIs compared to the current WHO standard regimens of efavirenz (EFV), DTG, LPV/r, ATV/r, and RAL with two NRTIs.
2. Methods
We used Cochrane Collaboration methods throughout the review process [11]. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidance in reporting our results [12]. Before beginning our review, we registered its protocol...