Efficacy and safety of atazanavir-ritonavir plus abacavir-lamivudine or tenofovir-emtricitabine in patients with hyperlipidaemia switched from a stable protease inhibitor-based regimen including one thymidine analogue.
ABSTRACT Randomized, open-label, prospective clinical trial assessing efficacy and safety on hyperlipidemia of a switching from a regimen including one protease inhibitor and one thymidine analogue to atazanavir/ritonavir plus abacavir/lamivudine or tenofovir/emtricitabine. Adult HIV-infected patients on their first antiretroviral therapy (of at least 48-week duration), including one protease inhibitor and zidovudine or stavudine, with stable immunovirologic features, and having diagnosis of persisting hyperlipidemia, were randomized to replace current treatment with atazanavir/ritonavir plus abacavir/lamivudine (arm A) or tenofovir/emtricitabine (arm B), and were followed for 48 weeks. Eighty-nine patients were enrolled: 42 patients were randomized to arm A, and 47 to arm B. At the end of the 48-week follow-up, incidence of virologic failure was comparable in both arms, and associated with a poor drug compliance. Increase in CD4 lymphocyte count was significantly higher in arm A after a 24-week study period (62.5 versus 39.2 x 10(6) cells/L; p < 0.05), while immunologic responses were comparable at the end of 48-week follow-up (91.5 versus 83.6; p > 0.05). A statistically significant reduction (-15.4%) in mean triglyceridaemia versus respective baseline values was reported in both groups (p < 0.05), without statistically significant difference between arm A and B. Similar results were reported for total cholesterol and low-density lipoprotein (LDL) cholesterol levels. Safety and tolerability profiles were comparable in both groups. Switching from a protease inhibitor- and thymidine analogue-based antiretroviral regimen to atazanavir/ritonavir plus abacavir/lamivudine or tenofovir/emtricitabine proved effective in the management of hyperlipidemia, without significant differences in lipid-lowering effect, virologic efficacy, and safety profile between these regimens.
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ABSTRACT: In the absence of a cure, HIV-infected patients are being successfully treated with antiretroviral therapies (ART) and living longer. Indeed, an increasing number of HIV-infected patients are living beyond the age of 50, and in that regard, the use of ART has transformed HIV to a chronic medical condition. As more HIV-infected patients are virologically controlled and living longer, the trajectory of disease morbidity has shifted, however, primarily from opportunistic infections and immune dysfunction to metabolic complications. Evidence suggests that HIV-infected patients acquire significant metabolic risks, including lipodystrophic changes, subclinical atherosclerosis, and insulin resistance. The etiology of these metabolic complications specifically in HIV-infected patients is not entirely clear, but may be related to a complex interaction between long term consequences of infection and HIV itself, chronic use of antiretrovirals, and underlying inflammatory processes. Previous classes of ART, such as protease inhibitors and reverse transcriptase inhibitors, have been implicated in altering fat redistribution and lipid and glucose homeostasis. Advances in drug development have introduced newer ART with strategies to target novel mechanisms of action and improve patient adherence with multi-class drug combinations. In this review, we will focus on these newer classes of ART, including selected entry inhibitors, integrase inhibitors, and multi-class drug combinations, and two newer protease inhibitors, and the potential of these newer agents to cause metabolic complications in HIV-infected patients. Taken together, further reduction of morbidity in HIV-infected patients will require increasing awareness of the deleterious metabolic complications of ART with subsequent management to mitigate these risks.European Journal of Endocrinology 02/2014; · 3.14 Impact Factor
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ABSTRACT: Background: The Raltegravir Switch for Toxicity or Adverse Events (RASTA) Study is a 2-arm randomized pilot study exploring the safety and efficacy at 48 weeks of a treatment switch to raltegravir associated with tenofovir/emtricitabine or abacavir/lamivudine in patients with regimens with optimal virological control. Methods: Patients treated with stable protease inhibitor (PI)-, non-nucleoside reverse transcriptase inhibitor (NNRTI)-, or nucleoside reverse transcriptase inhibitor (NRTI)-based regimens, with HIV-RNA levels < 50 copies/ml for ≥ 3 months and a CD4 cell count > 200 cells/μl were eligible. Enrollment of 40 patients was planned: at baseline patients were randomized 1:1 to switch to raltegravir plus tenofovir/emtricitabine (arm A) or abacavir/lamivudine (arm B). Laboratory parameters, raltegravir plasma levels, self- reported adherence, quality of life parameters, neurocognitive performance, bone composition, and body fat distribution were monitored. Virological failure was defined as HIV-RNA > 50 copies/ml on 2 consecutive determinations. Results: After 48 weeks, 5/40 (12.5%) regimen discontinuations occurred: 2 were for low-level viremia virological failure (both in arm A, at weeks 24 and 48) and 3 were for adverse events (neurological disturbances and skin rash in arm B; proximal tubulopathy in arm A). Overall, a significant CD4 increase was observed at weeks 36 and 48, and a significant decrease in total cholesterol, non-high density lipoprotein cholesterol, and triglycerides was observed at each study visit. Physical health/satisfaction in therapy scores and neuropsychological performance improved. The lumbar column Z-score improved, with no modification in other bone composition and fat distribution parameters. Conclusions: The investigated switch strategy was associated with rare virological failure. Improvements in lipid levels, quality of life measures, neuropsychological performance, and bone composition suggest good tolerability of raltegravir-based regimens.Scandinavian Journal of Infectious Diseases 10/2013; · 1.71 Impact Factor
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ABSTRACT: Lamivudine and emtricitabine are considered equivalent by several guidelines, but evidence of comparable efficacy is conflicting. We searched two databases up to June 30 2013 to identify randomized and quasi-randomized trials in which lamivudine and emtricitabine were used as part of combination antiretroviral therapy for treatment-naïve or experienced HIV-positive adult patients. We only included trials where partner drugs in the regimen were identical or could be considered to be comparable. We allowed for comparisons between tenofovir and abacavir provided the study population did not begin treatment with a viral load >100,000 copies/ml. 12 trials contributed 15 different randomized comparisons providing data on 2251 patients receiving lamivudine and 2662 patients receiving emtricitabine. Treatment success was not significantly different in any of the 12 trials. In the three trials that directly compared lamivudine and emtricitabine, the relative risk for achieving treatment success was non-significant (RR 1.03 95%CI 0.96-1.10). For all trials combined, the pooled relative risk for treatment success was not significantly different (RR 1.00, 95%CI 0.97-1.02). No heterogeneity was observed (I (2) = 0). Similarly, there was no difference in the pooled relative risk for treatment failure (RR 1.08, 95%CI 0.94-1.22, I (2) = 3.4%). The findings of this systematic review suggest that lamivudine and emtricitabine are clinically equivalent.PLoS ONE 01/2013; 8(11):e79981. · 3.73 Impact Factor