Caterina Salvadori

Incidence of renal toxicity in HIV-infected, antiretroviral-naïve patients starting tenofovir/emtricitabine associated with efavirenz, atazanavir/ritonavir, or lopinavir/ritonavir

Abstract Objectives: We performed a retrospective cohort study of HIV-infected antiretroviral-naïve patients starting a first antiretroviral therapy with tenofovir/emtricitabine plus efavirenz (EFV), atazanavir/ritonavir (ATV/r), or lopinavir/ritonavir (LPV/r). Methods: The incidence of renal impairment or proximal tubular dysfunction was evaluated during a 12-month follow-up. Renal impairment was diagnosed by a reduced estimated glomerular filtration rate (eGFR) calculated using the Modification of Diet in Renal Disease (MDRD) formula, and tubular dysfunction was diagnosed when ≥ 2 among proteinuria, glucosuria, hypouricaemia, hypophosphataemia, and hypokalaemia, were identified. Results: A total of 235 patients were enrolled: 82 taking EFV, 78 ATV/r, and 75 LPV/r. The mean decline in eGFR after the 12-month follow-up was significantly greater in subjects treated with ATV/r (−10.4 ml/min/1.73 m2) than in those receiving EFV (− 5.1; p = 0.002) or LPV/r (−4.8; p = 0.003). Similarly, a significantly higher incidence of proximal tubulopathy was observed among ATV/r-treated patients (14.1%) compared with patients receiving EFV (4.9%) or LPV/r (5.3%). Conclusions: In our retrospective study, naïve patients receiving tenofovir/emtricitabine and ATV/r for 12 months showed a significantly higher decline in eGFR and a significantly higher incidence of proximal tubulopathy than those receiving tenofovir/emtricitabine plus EFV or LPV/r, even though clinically evident renal toxicity associated with tenofovir-based treatment is a very uncommon event.

Two-Year Treatment with Rosuvastatin Reduces Carotid Intima-Media Thickness in HIV Type 1-Infected Patients Receiving Highly Active Antiretroviral Therapy with Asymptomatic Atherosclerosis and Moderate Cardiovascular Risk

Recent studies have shown that rosuvastatin significantly decreases serum levels of inflammatory biomarkers and slows progression of carotid atherosclerosis in the general population. However, there are no data about its effect on progression of atherosclerosis in HIV-infected patients. Adult patients with HIV infection, on stable antiretroviral therapy, with asymptomatic carotid atherosclerosis and hypercholesterolemia, who started a rosuvastatin treatment at 10 mg daily during the period 2007-2009 were enrolled and followed-up for 24 months. Thirty-six patients (30 males) were enrolled, with a mean age of 49 years, a mean duration of current antiretroviral therapy of 38 months, and a mean 10-year risk of myocardial infarction of 18.5%. Rosuvastatin led to a significant decrease in mean values of intima-media thickness in all extracranial carotid arteries, with the greatest magnitude observed in carotid bifurcations (a mean decrease of 18.7% in the right artery and of 21.4% in the left artery) and in internal carotid arteries (a mean decrease of 23.7% in the right artery and of 25.6% in the left artery). Moreover, there was a significant reduction in mean levels of total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides versus respective baseline values associated with a significantly decreased mean cardiovascular risk. The treatment with rosuvastatin was well tolerated, and serious adverse events were not reported. A 24-month treatment with rosuvastatin in HIV-infected patients on highly active antiretroviral therapy (HAART) with subclinical atherosclerosis and a moderate cardiovascular risk seems to promote significantly favorable changes in carotid atherosclerosis, associated with a favorable effect on serum lipid levels and a good tolerability profile.

Tenofovir/emtricitabine/efavirenz plus rosuvastatin decrease serum levels of inflammatory markers more than antiretroviral drugs alone in antiretroviral therapy-naive HIV-infected patients.

Abstract Objectives: Statins are lipid-lowering drugs that exhibit anti-Inflammatory and immune-modulatory properties, leading to a reduction of serum levels of C-reactive protein (CRP) in the general population. Design: To assess the anti-inflamatory effects of statins in HIV-infected patients, because very limited data are available today. Methods: Longitudinal, observational study of HIV-infected adult patients naive to antiretroviral therapy who started tenofovir/emtricitabine/efavirenz and were followed-up for 48 weeks. Patients with baseline normal cholesterol level and taking only antiretroviral drugs (group A) were compared to those with baseline hypercholesterolemia who received rosuvastatin (10 mg daily) in association with antiretroviral treatment (group B). The primary observation was change in serum markers of inflammation (high-sensitivity C-reactive protein [hsCRP], interleukin-6 [IL-6], interleukin-8 [IL-8]) and tumor necrosis factor-α [TNF- α]) in both groups, whereas secondary observations include variations in CD4 lymphocyte count, HIV viral load, and occurrence of adverse events. Results: Eighty-six patients were enrolled into the study: 46 in group A and 40 in group B. After 48 weeks, patients treated with antiretroviral therapy plus rosuvastatin had significantly greater decreases in serum concentrations of all Inflammatory markers than those taking antiretroviral therapy only. Changes in mean levels of hsCRP and TNF-α were -35.1% and -22.4% in group B and -8.2% and 5.4% in group A, respectively (P) .001, for both parameters). No significant differences in immunovirological parameters and safety profile were reported across the compared groups. Conclusions: Our findings suggest that tenofovir/emtricitabine/efavirenz plus rosuvastatin has a greater antiInflammatory effect than antiretroviral drugs only.

Lopinavir/ritonavir trough concentrations with the tablet formulation in HIV-1-infected women during the third trimester of pregnancy

Abstract Objectives: An observational, open-label study was performed to assess changes of lopinavir/ritonavir plasma concentrations during pregnancy. Methods: Adult HIV-1-infected women during the third trimester of pregnancy and on stable antiretroviral treatment including zidovudine/lamivudine plus lopinavir/ritonavir tablets (400/100 mg twice daily) were asked to participate. This group was compared with a group of non-pregnant HIV-1-infected women receiving the same antiretroviral regimen. The trough plasma concentration (Ctrough) of lopinavir and ritonavir was assessed at steady-state by a validated high-performance liquid chromatography (HPLC)-tandem mass spectrometry method. Results: A total of 41 HIV-positive female patients were enrolled in the study, with a median age of 28 y (range 20–37 y). These patients were stratified into 2 groups: 21 women in the third trimester of pregnancy (group A) and 20 non-pregnant women (group B). The geometric mean (95% confidence interval (CI)) plasma Ctrough of lopinavir was 4205 (2418–6896) ng/ml in group A and 5098 (3187–8084) ng/ml in group B. The reduction in lopinavir plasma levels observed in group A was not significant (geometric mean ratio 0.87, 95% CI 0.62–1.32; p = 0.411). No correlation was found between lopinavir plasma levels and adverse events (such as diarrhoea and hyperlipidaemia) or immunological parameters of HIV disease, and no changes in plasma HIV viral load were reported. Conclusion: In this study, a slight but not significant decrease in the plasma lopinavir Ctrough was found during the third trimester of pregnancy, suggesting that standard dosing of the tablet formulation is also appropriate during the later stages of pregnancy.