Nd this have happened for new drug classes as well. This
Nd this have happened for new drug classes as well. This review summarizes the characteristics of raltegravir, the first integrase inhibitor approved for HIV infection, focusing on its use on na e patients. Although not yet recommended by international guidelines, just recently the US FDA approved Necrostatin-1 cost raltegravir for the use in na e patients based on the favorable results of the STARTMRK trial [14]. Its mechanism of action, efficacy and tolerability profile, make raltegravir a very interesting agent for first-line antiretroviral treatment. Raltegravir is the first integrase inhibitor approved for the treatment of HIV infection based on the superior efficacy it showed compared to optimized backbone therapy alone in patients harboring multidrug resistant viruses [13]. Due to the favorable profile in terms of efficacy and tolerability, studies on na e patients began right after. The first clinical trial on na e patients was Protocol 004, a multicenter, randomized, doubleblind, placebo-controlled dose-ranging phase II study which tested the efficacy of raltegravir at four different doses (100, 200, 400 and 600 mg twice daily), in association with two NRTIs [15]. In the first part of the trial 35 patients were randomized to receive eitherEFFICACYNovember 24,EUROPEAN JOURNAL OF MEDICAL RESEARCHplacebo (n = 7) or raltegravir (n = 28) at one of the four dosages as monotherapy for four days [16]. Patients were stratified by HIV-RNA levels or > 50000 copies/ml; mean HIV-RNA was 4.53 to 4.97 Log10 copies/ml and CD4+ cell counts were 256 to 569 cell/ . After 10 days of treatment mean HIV-RNA reduction in the combined raltegravir groups was 2.0 Log10 copies/ml from baseline, significantly greater than what observed in the placebo arm (p<0.001 for the comparison with each raltegravir arm). 50 -70 of patients in the raltegravir arm reached HIVRNA<400 copies/ml by day 10 as compared to none in the placebo arm and at least one patient in each raltegravir arm reached HIV-RNA <50 copies/ml as compared to none in the placebo group. The study then continued in a second part where patients on raltegravir continued on their dosage schedule with the addition PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/26240184 of tenofovir and lamivudine, and patients on the placebo arm started efavirenz also in association with tenofovir and lamivudine. Additional 171 patietns were randomized to receive raltegravir or efavirenz in the second part of Protocol 004, leading to a total of 198 treated patients (5 patient from part I did not continued to part II and 2 randomized patients were not treated) [15]. Results from this 48 weeks study showed no difference in efficacy between raltegravir arms, and although the trial was not powered for efficacy comparison with the standard of care, when raltegravir groups were combined in one group only, there was no difference in response between raltegravir and efavirenz based regimens. After PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/26437915 48 weeks of treatment 86 (137/160) of patients in the raltegravir arm and 87 (33/38) of patients in the efavirenz arm had HIV1 RNA < 50 copies/ml. These results were confirmed at 96 weeks [17] and recently at 144 weeks: 80 of patients in the raltegravir arm and 76 of patients in the efavirenz arm had HIV-1 RNA <50 copies/ml [18]. STARTMRK is the ongoing phase III trial comparing the efficacy and tolerability of raltegravir in comparison to efavirenz, both in association with tenofovir and emtricitabine. The 48 weeks results of this international, double-blind, non inferiority trial have just been rep.
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