Daria Pocaterra

Substitution of nevirapine or efavirenz for protease inhibitor versus lipid-lowering therapy for the management of dyslipidaemia.

Objectives:To evaluate simplified protease inhibitor (PI)-sparing antiretroviral treatment versus lipid-lowering therapy for the management of highly active antiretroviral therapy (HAART)-induced hyperlipidaemia. Design:Randomized, open-label clinical trial assessing the efficacy on hyperlipidaemia of a switching therapy from PI to non-nucleoside reverse transcriptase inhibitor (NNRTI) nevirapine or efavirenz versus a hypolipidaemic treatment (with pravastatin or bezafibrate) added to current, unchanged antiretroviral combination. Methods:All HIV-infected patients on their first HAART regimen, with stable immuno-virological features, naive to all NNRTIs, and with mixed hyperlipidaemia, were randomized to replace PI with nevirapine (arm A) or efavirenz (arm B), or to receive pravastatin (arm C) or bezafibrate (arm D) with unchanged HAART regimen, and were followed-up for 12 months. Results:One hundred and thirty patients were evaluated: 29 patients were randomized to arm A, 34 to arm B, 36 to arm C, and 31 to arm D. At the end of the 12-month follow-up, a reduction of 25.2, 9.4, 41.2 and 46.6% in mean triglyceridaemia versus respective baseline values was reported in groups A, B, C and D, respectively, with statistically significant difference between arms A–B and C–D (P < 0.01). Similar results were reported for total and low-density lipoprotein cholesterol levels. Viro-immunological efficacy and tolerability profile were comparable in all considered arms. Conclusion:Pravastatin and bezafibrate proved significantly more effective in the management of HAART-related hyperlipidaemia than the switching therapy from PI to nevirapine or efavirenz.

Rosuvastatin for the treatment of hyperlipidaemia in HIV-infected patients receiving protease inhibitors: a pilot study.

Sixteen HIV-infected patients with protease inhibitor (PI)-related, persisting hypercholesterolaemia were treated with 10 mg a day rosuvastatin for 24 weeks. At the end of the observation period, the median reductions in total cholesterol and triglyceride levels versus median baseline values were 21.7 and 30.1%, respectively (P < 0.01). In our small pilot study, rosuvastatin was found to be effective for the treatment of PI-associated hyperlipidaemia, in association with a favourable tolerability profile, without significant clinical or laboratory adverse events.

Risk of premature atherosclerosis and ischemic heart disease associated with HIV infection and antiretroviral therapy

The use of new potent protease inhibitor-based antiretroviral therapies in patients with human immunodeficiency virus (HIV) infection has been increasingly associated with cardiovascular risk factors, including hyperlipidaemia, fat redistribution syndrome, insulin resistance, and diabetes mellitus. The introduction of highly active antiretroviral therapy (HAART) in clinical practice has remarkably changed the natural history of HIV disease, leading to a notable extension of life expectancy, and prolonged lipid and glucose metabolism abnormalities are expected to lead to significant effects on the long-term prognosis and outcome of HIV-infected patients. Prediction modeling, surrogate markers and hard cardiovascular endpoints suggest an increased incidence of cardiovascular diseases in HIV-infected subjects receiving HAART, even though the absolute risk of cardiovascular complications remains still low, and must be balanced against the evident virological, immunological, and clinical benefits descending from combination antiretroviral therapy. Nevertheless, the assessment of cardiovascular risk should be performed on regular basis in HIV-positive individuals, especially after initiation or change of antiretroviral treatment. Appropriate lifestyle measures (including smoking cessation, dietary changes, and aerobic physical activity) are critical points, and switching HAART may be considered, although maintaining viremic control should be the main goal of therapy. Pharmacological treatment of dyslipidaemia (usually with statins and fibrates), and hyperglycaemia (with insulin-sensitizing agents and thiazolidinediones), becomes suitable when lifestyle modifications and switching therapy are ineffective or not applicable.

The Burden of Metabolic Diseases Amongst HIV Positive Patients on HAART Attending the Johannesburg Hospital

South Africa has the highest prevalence of human immunodeficiency virus (HIV) infection in the world. The improved life expectancy, due to the recent introduction of highly active antiretroviral therapy (HAART), may lead to an increased health burden related to metabolic disorders, resulting in an increased pressure on health-care services. The main objective of this study was to determine the prevalence of hypertension, diabetes, obesity and dyslipidemia in a sample of HAART-treated HIV infected patients, attending an HIV clinic in the Gauteng province. This was a cross-sectional study of 304 HIV positive patients enrolled between January 2009 and March 2009, including patients aged 18 to 45 years, on HAART for more than one year. Hypertension prevalence was 19.1% (95% confidence interval (CI) 14.7-23.5): 23.9% in men and 17.7% in women (P=0.10). Diabetes was diagnosed in 4 women. Hypercholesterolemia (total cholesterol >5.00 mmol/mL) was found in 32.2% (95% CI 27.0-37.5), low HDL cholesterol (<1.20 mmol/mL) in 45.7% (95% CI 40.1-51.3) and elevated LDL cholesterol (>4.10 mmol/mL) in 9.5% (95% CI 6.2-12.8); these prevalences were not different between sexes, whereas hypertriglyceridemia (>2.25 mmol(mL) (15.8%, 95% CI 11.7-19.9) was significantly more frequent in men (28.4% versus 12.2%, P=0.002). TC and LDL-C were positively correlated with CD4+ cell count (r=0.13, P=0.03 and r=0.12, P=0.03). In this sample, the traditional risk factors for cardiovascular disease had a high prevalence, despite the young age of our patients. Women seemed to be at higher risk than man, unlike other HIV populations where these comparisons were made (Uganda, Italy and Norway). Obesity and lipid abnormalities, highly prevalent in the general population, also appeared related to HIV-infection and CD4+ cell count, presumably as a consequence of ART exposure. Further studies are needed in order to survey a population where HIV infection is turning into a chronic disease, with its complications.

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

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.

The feature of Metabolic Syndrome in HIV naive patients is not the same of those treated: Results from a prospective study

Metabolic Syndrome (MS) is a common disorder combining obesity, dyslipidemia, hypertension, and insulin resistance. Its prevalence among HIV-infected people is still debated. Besides, how antiretroviral therapy and HIV infection per se are related to MS is still unclear. All treatment-naïve patients attending scheduled visits at CISAI group hospitals between January and December 2007 were eligible for the study. Patients without MS at enrolment were followed-up for 3 years or until they developed MS, diagnosed according to the National Cholesterol Education Program (NCEP) definition. The main objective was to assess the 3-years incidence of MS. MS was evaluated for 188 subjects. Out of them, 62 (33.0%) had started HAART at enrolment, whereas 67 (35.6%) more started during the observation. 59 (31.4%) were still treatment-naive at the study end. MS was newly diagnosed in 14 patients. The incidence was 2.60 cases/100 person-years (95% CI 1.47-4.51), 2.75 (1.11-5.72) among HAART-naïve patients and 2.65 (1.23-5.03) in subjects on HAART. Blood pressure did not change in the study period, whereas in naive patients the HDL level significantly lowered (median -6.0 vs. 4.0, P<0.0001) compared to HAART-treated patients. Triglicerides increased significantly in HAART subjects (median 12.0 vs. 1.0, P=0.02), as well as blood glucose (median 6.0 vs. 1.0, P=0.01). In our population, the overall MS incidence was low and largely similar in patients who started HAART or remained naive. However, the feature of MS was different in the two groups, suggesting that in untreated and treated patients MS developed through different metabolic pathways.

Cardiovascular risk factors and ultrasound evaluation of carotid atherosclerosis in patients with HIV-1 infection

A cross-sectional study was performed to evaluate classical risk factors for cardiovascular diseases and subclinical atherosclerosis by carotid ultrasonography in HIV-positive subjects, naïve or treated with antiretroviral agents. A total of 66 patients were enrolled into the study: 21 subjects were naïve to all antiretroviral agents (group A) and 45 patients were treated with antiretroviral therapy for ≧36 months (group B). The prevalence of carotid plaques was significantly higher in group B than in group A (44.7% versus 0%; P = 0.014). In group B, patients with high 10-year risk of coronary heart disease showed a significantly higher intima-media thickness and prevalence of carotid lesions than those with low risk. Moreover, carotid lesions were structurally comparable to classical atherosclerotique plaques observed in the general population, with iso-hyperechonegic aspects and irregular surfaces. The prevalence of carotid atherosclerosis in experienced patients is higher than in those naïve to highly active antiretroviral therapy and seems mostly associated with a longer duration of HIV infection, more severe lipid metabolism alterations, presence of lipodystrophy syndrome and a more elevated 10-year risk of cardiovascular diseases.

Abacavir-induced reaction with fever and severe skin rash in a patient tested human leukocyte antigen-B*5701 negative

The most serious adverse event caused by abacavir is the hypersensitivity reaction, which is usually associated with the presence of the human leukocyte antigen (HLA) subtype B*5701, as shown in recent studies. We describe the case of a 41-year-old Caucasian female patient, who tested HLA-B*5701 negative and developed fever and severe skin rash 10 weeks after the start of abacavir therapy. Similar reports suggest that not all severe abacavir-induced adverse events occur as a result of classic hypersensitivity reactions, and can present also in HLA-B*5701-negative patients.

Efficacy and tolerability of a fosamprenavir-ritonavir-based versus a lopinavir-ritonavir-based antiretroviral treatment in 82 therapy-naïve patients with HIV-1 infection:

Recent data indicate that fosamprenavir/ritonavir as part of an initial antiretroviral regimen in HIV-1 -infected patients is associated with favourable efficacy and tolerability and in the KLEAN study (kaletra versus lexiva with epivir and abacavir in antiretroviral-naive patients) it was found to be non-inferior to lopinavir/ritonavir in association with abacavir/lamivudine. In our open-label, observational study conducted in 82 therapy-naíve HIV-1-infected patients followed-up for 18 months, virological and immunological efficacy was comparable in subjects receiving a fosamprenavir/ritonavir-based and a lopinavir/ritonavir-based treatment (proportions of patients with HIV RNA <50 copies/mL at month 18 were 76.9% and 74.4%, respectively, when discontinuations were counted as failures). At the same time, frequency of treatment discontinuations and adverse events were similar in both groups, whereas incidence of diarrhoea and hypertriglyceridaemia was significantly higher in lopinavir-treated patients than in fosamprenavir-treated ones (53.5% vs. 25.6% and 69.8% vs. 43.6%, respectively; P < 0.01). In subjects with virological failure, no viral protease resistance mutations were detected by genotype analysis.