Final 192-week efficacy and safety of once-daily darunavir/ritonavir compared with lopinavir/ritonavir in HIV-1-infected treatment-naïve patients in the ARTEMIS trial.
ABSTRACT OBJECTIVE: This paper presents the final analysis of once-daily darunavir/ritonavir (DRV/r) vs. lopinavir/ritonavir (LPV/r) in treatment-naïve HIV-1-infected adults. METHODS: ARTEMIS (AntiRetroviral Therapy with TMC114 ExaMined In naïve Subjects; NCT00258557) was a randomized, open-label, phase-III, 192-week trial. Patients were stratified by baseline HIV-1 RNA and CD4 count, and randomized to once-daily DRV/r 800/100 mg or LPV/r 800/200 mg total daily dose (either once or twice daily) plus tenofovir/emtricitabine. RESULTS: Of 689 randomized patients receiving treatment (DRV/r: 343; LPV/r: 346), 85 and 114 patients in the DRV/r and LPV/r arms, respectively, had discontinued by week 192. Noninferiority was shown in the primary endpoint of virological response (HIV-1 RNA < 50 copies/mL) [DRV/r: 68.8%; LPV/r: 57.2%; P < 0.001; intent to treat (ITT)/time to loss of virological response; estimated difference in response 11.6% (95% confidence interval 4.4-18.8%)]. Statistical superiority in virological response of DRV/r over LPV/r was demonstrated for the primary endpoint (P = 0.002) and for the ITT non-virological-failure-censored analysis (87.4% vs. 80.8%, respectively; P = 0.040). No protease inhibitor (PI) primary mutations developed and only low levels of nucleoside reverse transcriptase inhibitor (NRTI) resistance developed in virological failures in both groups. Significantly fewer discontinuations because of adverse events were observed with DRV/r (4.7%) than with LPV/r (12.7%; P = 0.005). Grade 2-4 treatment-related diarrhoea was significantly less frequent with DRV/r than with LPV/r (5.0% vs. 11.3%, respectively; P = 0.003). DRV/r was associated with smaller median increases in total cholesterol and triglyceride levels than LPV/r. Changes in low- and high-density lipoprotein cholesterol were similar between groups. Similar increases in aspartate aminotransferase and alanine aminotransferase for DRV/r and LPV/r were observed. CONCLUSION: Over 192 weeks, once-daily DRV/r was noninferior and statistically superior in virological response to LPV/r, with a more favourable gastrointestinal profile, demonstrating its suitability for long-term use in treatment-naïve patients.
- Clinical Infectious Diseases 02/2013; 56(11). DOI:10.1093/cid/cit087 · 9.42 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Introduction: The number of HIV patients receiving antiretroviral therapy is increasing worldwide, as new infections continue to occur and access to drugs is scaling up in most developing regions. Due to the efficacious nature of combination antiretroviral therapy in most drug-adherent patients, the concerns on the safety profile of these lifelong medicines have attracted great attention. Areas covered: Side effects of antiretroviral agents can be clinically symptomatic or manifest only as laboratory abnormalities. Drug-related toxicities can be grouped by antiretroviral drug class or damage of distinct body organs/systems. By mechanism, antiretroviral-associated adverse events generally result from hypersensitivity reactions, direct cytopathic effect, or idiosyncratic phenomena. Expert opinion: A good knowledge of the toxicity profile of antiretroviral agents is warranted for HIV care providers in order to prevent and avoid unwanted complications.Expert Opinion on Drug Safety 06/2013; 12(5). DOI:10.1517/14740338.2013.806480 · 2.74 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: It is unclear whether regular CD4 testing is necessary for all patients during long-term antiretroviral treatment, after patients achieve full HIV-1 RNA suppression. In the ARTEMIS trial, 689 treatment-naïve patients were randomised to tenofovir/emtricitabine plus either darunavir/ritonavir or lopinavir/ritonavir. The number of patients with CD4 counts equal or above 200 copies/mL and HIV-1 RNA <50 copies/mL at Week 48 was assessed. For these patients, we assessed whether CD4 counts fell below 200 cells/uL from Week 49 to Week 192, while HIV-1 RNA suppression was maintained. Of the 520 responders, 5 (1.0%) progressed to an AIDS defining event during the first 48 weeks of the trial, while 19 of the 169 non-responders (11.2%) developed AIDS defining events during this time (p = 0.001, Fisher's Exact test). Of the 449 patients with sustained HIV-1 RNA suppression <400 copies/mL from Week 49-192, 5 patients (1.1%) had reductions in CD4 count below 200 cells/μL on two consecutive visits. These were all short-term reductions, with follow up results equal or above 200 cells/μL. There was a benefit to testing for CD4 count in the first 48 weeks of treatment, to identify patients who have immuno-virological discordance and therefore a higher risk of progression to AIDS. However, after 48 weeks of antiretroviral treatment, for the "responder" patients in the ARTEMIS trial who had both HIV-1 RNA <50 copies/mL and rises in CD4 count equal or above 200 cells/uL, there appears to be little clinical benefit from continued testing for CD4 count.AIDS (London, England) 07/2013; 27(17). DOI:10.1097/01.aids.0000432458.98851.c1 · 6.56 Impact Factor