Sex differences in the clinical, immunological and virological parameters of HIV-infected patients treated with HAART

OBJECTIVE: To compare the clinical, virological and immunological parameters of men and women at baseline and during antiretroviral treatment. METHODS: Analysis over time of data collected prospectively from of 2620 patients in a large cohort of HIV-infected patients followed for 12 months after initiating a nelfinavir-based antiretroviral regimen. RESULTS: Women had higher CD4 cell counts (P < 0.001), lower viral load (P < 0.001) and more favourable clinical profile (P < 0.001) than men at baseline. Following treatment, antiretroviral drug-naive women had higher CD4 cell count (P = 0.01) over time than drug-naive men but similar virological responses (P = 0.6); among drug-experienced individuals, women had also better immunological (P = 0.06) and similar virological (P = 0.3) responses compared with men. Consequently, the viroimmunological profile was significantly more favourable in women at each time point. The rates of clinical progression or death were also lower in women (P = 0.008), although drug toxicity was observed more commonly in women (P = 0.09). The highest viroimmunological responses were observed during the first 3 months of therapy in both sexes, although virological responses were achieved up to the 6th month in drug-naive patients. Sex was significantly associated with clinical (P = 0.01), virological (P = 0.01) and immunological (P = 0.006) responses to antiretroviral treatment in multivariate analyses after adjustment for other variables. The differences between genders were not explained by different adherence to therapy. CONCLUSIONS: Women have more favourable clinical and viroimmunological patterns than men both at baseline and during antiretroviral treatment. Sex has a small but significant influence on the clinical and laboratory outcomes of HIV infection.     

Reconstitution of antimycobacterial immune responses in HIV-infected children receiving HAART

OBJECTIVE: Recent epidemiological studies in adults suggest that HAART can prevent the development of tuberculosis in HIV-infected individuals, but the mechanisms are incompletely understood and no data exist in children. We investigated whether changes in mycobacterial-specific immune responses can be demonstrated in children after commencing antiretroviral therapy. DESIGN: We measured mycobacterial growth in vitro using a novel whole-blood assay employing reporter-gene tagged bacillus Calmette-Guérin (BCG) in a prospective cohort study in the tuberculosis-endemic environment of South Africa. Key cytokines were measured in supernatants collected from the whole-blood assay using cytometric bead array. PATIENTS: A cohort of 15 BCG-vaccinated HIV-infected children was evaluated prospectively for in-vitro antimycobacterial immune responses before and during the first year of HAART. All children had advanced HIV disease. Nine children completed all study timepoints. RESULTS: Before HAART, blood from children showed limited ability to restrict the growth of mycobacteria in the functional whole-blood assay. The introduction of HAART was followed by rapid and sustained reconstitution of specific antimycobacterial immune responses, measured as the decreased growth of mycobacteria. IFN-gamma levels in culture supernatants did not reflect this response; however, a decline in TNF-alpha was observed. CONCLUSION: This is the first study using a functional in-vitro assay to assess the effect of HAART on immune responses to mycobacteria in HIV-infected children. Our in-vitro data mirror the in-vivo observation of decreased susceptibility to tuberculosis in HIV-infected adults receiving antiretroviral agents. This model may be useful for further characterizing immune reconstitution after HAART.     

Successful treatment of Castleman's disease with HAART in two HIV-infected patients

Castleman's disease is a heterogeneous group of lymphoproliferative disorders of unknown aetiology. Recently, human herpesvirus type 8 (HHV-8) has been associated with various diseases in individuals with HIV infection, including Kaposi's sarcoma, B cell non Hodgkin's lymphomas, and Castleman's disease.In Castleman's disease it has been hypothesized that HHV-8, encoding a number of various virokines, can be responsible for clinical manifestations of the disease.Previously, two reports have described a clinical recovery from HIV-associated Castleman's disease: by administration of a monoclonal antibody neutralizing human IL-6 in one case, and in another case by treatment with highly antiretroviral therapy and anti-herpesvirus therapy, following splenectomy. We report two cases where HAART alone led to clinical recovery from Castleman's disease.In both the cases reported here, although follow-up biopsy was not performed, it is likely that the inhibition of HHV-8 replication and of virokine release, through the restoration of immunity by HAART, was the basis for the disappearance of the clinical symptoms.     

Graves' disease during immune reconstitution in HIV-infected patients treated with HAART

Autoimmune phenomena after immune recovery due to HAART are not frequently described. Recently we found 3 patients with Graves' disease after starting HAART, outnumbering the expected incidence; 13 patients have been reported in the literature up to the present time.A probable relation between immune restoration and development of Graves' disease might be suspected.     

Neurocognitive impairment and survival in a cohort of HIV-infected patients treated with HAART

Before the introduction of HAART, HIV-associated neurocognitive impairment (NCI) was recognized as an independent risk factor for death. Since 1996, we conducted a prospective study to assess whether NCI still represents a negative prognostic factor for mortality. Patients were administered measures of neurocognitive function (a battery of 17 neuropsychological tests), clinical and neurological evaluation, laboratory testing, and brain imaging studies. Among the 412 enrolled patients, 224 (54.4%) were neurocognitively impaired and 188 (45.6%) were neurocognitively unimpaired. A durable virological suppression under highly active antiretroviral therapy (HAART) was achieved by 63.3% of unimpaired patients and by 49.6% of impaired patients (p = 0.007). Overall, 47 deaths were recorded, 38 among impaired and 9 among unimpaired patients. At 84 months, the estimated survival proportions in impaired and unimpaired patients were 68.5% and 84.9%, respectively (p < 0.001). At univariate analysis the virological response to HAART was the variable most strongly associated with survival, since patients with virological failure had a nearly 10-fold increased risk of death than those with durable virological suppression (HR = 9.9, 95% CI: 3.9-25.0). After stratification for virological response to HAART, an increased risk of death for neurocognitively impaired patients was seen only among the 182 patients with virological failure (HR: 2.9, 95% CI: 1.2-7.1), while the survival probability of the 230 patients with durable virological suppression was not affected by neurocognitive impairment (p = 0.89). Our results highlight the clinical relevance of HIV-related central nervous system (CNS) involvement in the HAART era, and raise concerns regarding the clinical relevance of CNS involvement as potent antiretroviral therapies become less effective.     

HAART in HIV-infected patients: restoration of antigen-specific CD4 T-cell responses in vitro is correlated with CD4 memory T-cell reconstitution, whereas improvement in delayed type hypersensitivity is related to a decrease in viraemia.

OBJECTIVE: To analyse prospectively the effect of highly active antiretroviral treatment (HAART) on CD4 T-cell responses in vitro and in vivo in HIV-infected patients. DESIGN: Prospective study with 49 protease inhibitor-naive adult patients. Data were collected at baseline and after 3 and 6 months of HAART. METHODS: In vitro CD4 T-cell reactivity was analysed by stimulation of peripheral blood mononuclear cells with several antigens. In vivo CD4 T-cell reactivity (delayed type hypersensitivity) was assessed by Multitest Merieux. Both measurements were correlated to CD4 (memory) T-cell count and HIV-1 viraemia. RESULTS: Restoration of specific CD4 T-cell proliferation was observed in most patients. The in vitro T-cell response was restored more frequently against antigens to which the immune system is constantly exposed (Candida albicans, Mycobacterium tuberculosis, M. avium) as compared with a low-exposure antigen (tetanus toxoid). Overall, delayed type hypersensitivity detection rate increased under HAART. Multivariate analysis showed improvement of antigen-specific T-cell proliferation to be significantly associated with an increase in memory CD4 T-cells, whereas improvement of the delayed type hypersensitivity response was associated with a decrease in plasma HIV-1 RNA. CONCLUSIONS: HAART for 6 months restored antigen-specific CD4 T-cell response to several antigens. In vitro immune reconstitution was closely correlated with an increase in memory CD4 cells. Restoration of delayed type hypersensitivity was associated with suppression of viraemia. It appears that in addition to expansion of memory CD4 cells, suppression of viraemia following HAART may allow an improved inflammatory reaction, thus providing even stronger immune reconstitution.     

Simple adherence assessments to predict virologic failure among HIV-infected adults with discordant immunologic and clinical responses to antiretroviral therapy

We evaluated the association between two antiretroviral therapy (ART) adherence measurements--the medication possession ratio (MPR) and patient self-report--and detectable HIV viremia in the setting of rapid service scale-up in Lusaka, Zambia. Drug adherence and outcomes were assessed in a subset of patients suspected of treatment failure based on discordant clinical and immunologic responses to ART. A total of 913 patients were included in this analysis, with a median time of 744 days (Q1, Q3: 511, 919 days) from ART initiation to viral load (VL) measurement. On aggregate over the period of follow-up, 531 (58%) had optimal adherence (MPR > or =95%), 306 (34%) had suboptimal adherence (MPR 80-94%), and 76 (8%) had poor adherence (MPR <80%). Of the 913 patients, 238 (26%) had VL > or =400 copies/ml when tested. When compared to individuals with optimal adherence, there was increasing risk for virologic failure in those with suboptimal adherence [adjusted relative risk (ARR): 1.3; 95% confidence interval (CI): 1.0, 1.6] and those with poor adherence (ARR: 1.7; 95% CI: 1.3, 2.4) based on MPR. During the antiretroviral treatment course, 676 patients (74%) reported no missed doses. The proportion of patients with virologic failure did not differ significantly among those reporting any missed dose from those reporting perfect adherence (26% vs. 26%, p = 0.97). Among patients with suspected treatment failure, a lower MPR was associated with higher rates of detectable viremia. However, the suboptimal sensitivity and specificity of MPR limit its utility as a sole predictor of virologic failure.     

Pneumocystis carinii pneumonia in HIV-infected patients in the HAART era

Since the advent of highly active antiretroviral therapy (HAART), the incidence of opportunistic infections (OI) in patients with HIV has markedly decreased. Despite this, there are still large numbers of Pneumocystis carinii pneumonia (PCP) cases at Cook County Hospital (CCH). To better understand this patient group, we performed a retrospective chart review of 120 pathologically proven cases of PCP from January 1998 to June 2001. One hundred four patients were included in the study. Sixty-nine percent of our patients were active substance abusers and 50% had previous knowledge of HIV disease. Of our patients, fewer than 5% were on HAART or PCP prophylaxis on study admission. The overall mortality rate was 14%. Of discharged patients, 65% were placed on HAART therapy and 59% of these achieved a viral load of less than 1000 copies per milliliter in the year postdischarge. Patients who failed to achieve a viral load less than 1000 copies per milliliter were more likely active substance abusers or had a viral load greater than 100,000 copies per milliliter prior to study admission. Our study shows that patients are still being admitted with PCP in the HAART era. Active substance abuse and failure to recognize HIV status contributed heavily to this late presentation of HIV disease. An aggressive approach toward HIV identification and substance abuse treatment may decrease admissions to the hospital for PCP and improve response to HAART therapy.     

Protease inhibitor-based HAART, HDL, and CHD-risk in HIV-infected patients

ObjectiveTo study the effects of HIV-infection and protease inhibitor (PI)-based highly active anti-retroviral therapy (HAART) on the lipid and high-density lipoprotein (HDL) subpopulation profile and to relate the changes to coronary heart disease (CHD)-risk.Methods and designThe lipid and HDL subpopulation profiles of HIV-positive subjects (n = 48) were studied prospectively by comparing pre- and post-PI-HAART data as well as cross-section by comparing the profiles to HIV-negative subjects with (n = 96) and without CHD (n = 96).ResultsHIV-infected HAART-naïve subjects had lower concentrations of low-density lipoprotein cholesterol (LDL-C) and HDL-C and higher concentration of triglycerides (TG) than healthy controls. After receiving PI-based HAART, LDL-C and TG concentrations increased, while HDL-C concentrations remained unchanged. The HDL subpopulation profiles of HAART-naïve HIV-positive patients were significantly different from those of healthy controls and were similar to those with CHD. Moreover, the HDL subpopulation profile changed unfavorably after PI-based HAART, marked with increased concentrations of the small, lipid-poor pre-β-1 HDL (32% or 3.9 mg/dl; p < 0.001), and decreased concentration of the large, cholesterol-rich α-1 HDL(9% or 1 mg/dl ns).ConclusionAn already unfavorable lipid and HDL subpopulation profile of HIV-positive HAART-naïve subjects further deteriorated after receiving PI-based treatment, which may cause increased CHD-risk in these subjects.     

Effect of HAART on salivary composition and oxidative profile in HIV-infected patients

Although it has been widely suggested that oxidative stress contributes to the pathogenesis of HIV infection, salivary composition and its oxidative related aspects have never been studied in HIV patients, both HAART-treated and untreated. Human saliva and serum were collected and analyzed for various biochemical, redox related and immunological parameters from 43 consenting HIV-infected patients (20 untreated and 23 treated with HAART) and 20 healthy controls, age and gender matched. Saliva composition of HIV infected patients was completely altered but returned to normal following HAART. HIV patients had significantly-increased levels of oxidative stress damaging markers, compared to healthy controls. Carbonyl levels increased by 110% (p=0.005), and superoxide dismutase enzyme (SOD) and antioxidant capacity (ImAnOx) levels by 45% and 16% (0.035) respectively, but returned to normal levels in treated patients (p=0.005, p=0.03 and 0.02 respectively). Also, the significantly-altered salivary composition (pH and lactate dehydrogenase (LDH) enzyme) and concentration (calcium (Ca), magnesium (Mg), albumin, salivary total protein, secretory IgA) of HIV-infected patients reverted to normal following HAART treatment. Salivary analysis may be used for assessing patient status: treated vs untreated, based on the increase or decrease in the concentration of a given salivary parameter in the HIV-untreated group vs controls, and a return to normal following the HAART treatment. Salivary collection is simple, non-invasive and not associated with risk of infection spread. Antioxidants in HIV patients may be recommended, as well as local oral means aimed at resuming salivary functions compromised in HIV patients.     

Adherence to HAART among HIV-infected persons in rural Louisiana

The purpose of this study was to examine factors associated with nonadherence to highly active antiretroviral therapy (HAART) in patients seen in HIV clinics throughout nonurban Louisiana. A convenience sample of 273 patients from 8 areas in nonurban Louisiana were interviewed to obtain demographic, clinical and adherence information. Associations between demographic, clinical, and behavioral factors and nonadherence were examined. Ideally, non-adherence should not exceed 5% in patients for whom HAART was prescribed. Mean age was 38.6 years (range, 19-66), 29.3% were female, 60.1% were African American, 34.4% reported nonadherence to their HAART medication (defined as the subject's self-report of missing any doses of HAART medication in the prior week). In the prior month, participants reported the following behaviors: binge drinking (12.8%), problem drinking (12.8%), and illicit drug use (16.5%). Depression was found in 49.8% of the respondents. In logistic regression analysis, problem drinking odds ratio [OR] (95% confidence interval [CI]): 3.92 (1.69,9.09) was found to be associated with nonadherence. Demographic and behavioral factors such as illicit drug use and depression were not associated with nonadherence on multivariable analysis. Problem drinking was associated with lack of adherence to HAART over the past week. Interventions to treat problem drinking are needed and may improve adherence to medication for HIV-infected persons living in rural, town, and small-city areas.     

Neurocognitive impairment influences quality of life in HIV-infected patients receiving HAART

The objective of the study was to determine the association of neurocognitive impairment with health-related quality of life (HRQoL) in patients receiving highly active antiretroviral therapy (HAART). Seventy subjects were cross-sectionally analysed with a standardized neuropsychological test battery and a questionnaire including an Italian translation of the MOS-HIV Health Survey. The presence of neurocognitive impairment was significantly associated with lower HRQoL scores: pain (P = 0.03), physical functioning (P = 0.01), role functioning (P = 0.01), social functioning (P = 0.029), mental health (P = 0.001), energy (P = 0.036), health distress (P = 0.002), cognitive functioning (P = 0.05), current health perception (P <0.001), physical health summary score (PHS) (P = 0.005), mental health summary score (MHS) (P = 0.002). Years of education (odds ratio [OR] 0.79; 95% confidence interval [CI] 0.65-0.96), PHS (OR 0.71; 95% CI 0.54-0.95) and MHS (OR 0.67; 95% CI 0.51-0.88) were also associated with cognitive impairment. Neurocognitive impairment in patients receiving HAART was associated with reduced HRQoL. Identifying cognitive impairment may provide motivation for additional treatment to help patients to compensate for deficits in functioning.     

Response to HAART in treatment-naive HIV-infected patients with a prior diagnosis of tuberculosis or other opportunistic infections

We aimed to evaluate immunological, virological and clinical response to HAART, as well as all-cause mortality, in treatment-naive patients with a diagnosis of tuberculosis (TB) in the prior 6 months, compared to subjects with another AIDS-defining illness (ADI) or event-free individuals in an open, prospective and multicenter hospital-based cohort of HIV-infected naive adults (2004-2008). All cause mortality rates were calculated by Cox regression models. Among 4407 patients, 2400 (54.5%) started HAART: 110 (4.6%) had had previous TB and 414 (17.3%) another ADI. Median time from TB diagnosis to inititation of HAART was 53 days (IQR: 25.75-83.25), and for other ADI was 22 days (IQR: 8-42). Overall, 151 (6.3%) patients developed a new ADI during follow-up; 63% reached virological suppression and 69.4% had increases of ≥50 CD4+/μl, at 6 months. No statistically significant differences were found according to a previous history of TB or another ADI. Overall, 85 subjects died in 4031 person-years of follow-up with a mortality rate of 2.1 (95%CI: 1.7-2.6). When compared to subjects who started HAART in the absence of a previous ADI (HR 1), a prior diagnosis of an ADI other than TB was significantly associated with an increased risk of death. (HR 1.6; 95%CI: 1.1-2.3), but not a diagnosis of TB (HR 1.15; 95%CI: 0.5-2.5). In conclusion, a previous diagnosis of TB or another ADI before HAART did not compromise short-term virological and immunological response to treatment. A prior diagnosis of an ADI different to TB significantly increased all cause mortality.     

Helper and suppressor T-cell function in HIV-infected hemophilia patients

T-lymphocyte helper and suppressor functions were assessed in 61 hemophilia patients. Twenty one patients were HIV-negative (Group 1), 27 were HIV-positive without having AIDS-related complex (ARC)/AIDS (Group 2), and 13 had ARC/AIDS (Group 3). T, CD4-positive, or CD8- positive T lymphocytes were cocultured with B lymphocytes and pokeweed mitogen for 6 days and immunoglobulin producing cells were assessed in a reverse hemolytic plaque assay. In HIV-infected patients, T cells as well as the CD4-positive T cell subset exhibited reduced helper (P less than .01, Group 2; P less than .0005, Group 3) and elevated suppressor activity (P less than .02, Group 2; P less than .005, Group 3), whereas no significant difference was found between HIV-negative patients and controls. The number of CD4-positive cells was not correlated with CD4 cell function. CD4-positive cells showed no helper activity (less than 10% of control T cells) in 8/11 (73%), but an excessive suppressor activity (greater than 80% suppression of plaque formation) in 6/11 (55%) Group 3 patients. Our results show that defective helper and elevated suppressor functions of T cells in HIV-infected patients are caused not only by a change in the CD4/CD8 cell counts but also by functional abnormalities of the CD4-positive T-cell subset. These abnormal helper and suppressor functions may play a role in the development of the immunodeficiency state of AIDS patients.     

Positive outcomes of HAART at 24 months in HIV-infected patients in Cambodia

OBJECTIVES: African and Asian cohort studies have demonstrated the feasibility and efficacy of HAART in resource-poor settings. The long-term virological outcome and clinico-immunological criteria of success remain important questions. We report the outcomes at 24 months of antiretroviral therapy (ART) in patients treated in a Médecins Sans Frontières/Ministry of Health programme in Cambodia. METHODS: Adults who started HAART 24 +/- 2 months ago were included. Plasma HIV-RNA levels were assessed by real-time polymerase chain reaction. Factors associated with virological failure were analysed using logistic regression. RESULTS: Of 416 patients, 59.2% were men; the median age was 33.6 years. At baseline, 95.2% were ART naive, 48.9% were at WHO stage IV, and 41.6% had a body mass index less than 18 kg/m. The median CD4 cell count was 11 cells/microl. A stavudine-lamivudine-efavirenz-containing regimen was initiated predominantly (81.0%). At follow-up (median 23.8 months), 350 (84.1%) were still on HAART, 53 (12.7%) had died, six (1.4%) were transferred, and seven (1.7%) were lost to follow-up. Estimates of survival were 85.5% at 24 months. Of 346 tested patients, 259 (74.1%) had CD4 cell counts greater than 200 cells/microl and 306 (88.4%) had viral loads of less than 400 copies/ml. Factors associated with virological failure at 24 months were non-antiretroviral naive, an insufficient CD4 cell gain of less than 350 cells/microl or a low trough plasma ART concentration. In an intention-to-treat analysis, 73.6% of patients were successfully treated. CONCLUSION: Positive results after 2 years of advanced HIV further demonstrate the efficacy of HAART in the medium term in resource-limited settings.     

Mortality after myocardial infarction in HIV-infected patients who have initiated HAART

We identified all Danish HIV patients registered with myocardial infarction (MI) when on HAART (44 patients) and compared their mortality with that of matched patients with MI and no HIV and patients with HIV and no MI. Mortality in HIV-infected MI patients was not significantly different to that of MI only patients in the first 90 days post-MI and thereafter was not significantly different to that of HIV patients without MI.     

Osteoprotegerin and bone turnover markers in heavily pretreated HIV-infected patients

OBJECTIVES: To characterize osteoprotegerin (OPG) levels, bone remodelling and bone mineral density (BMD) in heavily pretreated HIV-infected patients on antiretroviral therapy, and to evaluate the clinical factors associated with bone density decline. METHODS: Heavily pretreated (> 5 years) HIV-positive patients were enrolled in this cross-sectional, observational study, which was based on a total body bone densitometry examination and a comprehensive evaluation of bone and mineral parameters. RESULTS: Sixty-eight patients (55 male and 13 female) with a median age of 41 years (range 25-60 years) were included in the study. Their antiretroviral treatment lasted for 82 months. On the basis of the World Health Organization criteria, nine patients (13.2%) were osteoporotic [T-score < -2.5 standard deviation (SD)] and 19 patients (27.9%) were osteopenic (T-score between -1 and -2.5). The principal outcomes associated with the presence of a low BMD were high OPG and lysylpyridinoline/creatinine ratio (Dpd) values. Most of the patients (39 of 48; 81.25%) showed vitamin D insufficiency [Vitamin D (25(OH)D) < 18 ng/mL] with secondary hyperparathyroidism (13 of 50 patients: 26%), which proved to be correlated to osteocalcin (BGP) levels [parathyroid hormone (PTH) vs. BGP: r = 0.34; P < 0.01]. There was an inverse correlation between T-scores and serum osteocalcin and alkaline phosphatase (AP) levels, on one hand, and Dpd, on the other. High AP and Dpd values were associated with relative risks of 4.1 [95% confidence interval (CI) = 1.01-17.6] and 7.2 (95% CI = 1.67-31.03), respectively, of a pathological T-score. Multivariate analysis revealed that the factors associated with the presence of osteopenia or osteoporosis were older age and lower body mass index. CONCLUSIONS: About 40% of our heavily pretreated subjects with advanced HIV infection had a low BMD, and 56% (24 of 44 patients) showed a high bone turnover rate with marked osteoclast activation. High OPG levels may protect against bone resorption.     

Statins and fibrates for the treatment of hyperlipidaemia in HIV-infected patients receiving HAART

OBJECTIVES: The aim of our work is to evaluate the role of statins and fibrates in the management of hyperlipidaemia in HIV-infected patients receiving highly active antiretroviral therapy. DESIGN: Open-label, randomized, prospective study of the efficacy and safety of bezafibrate, gemfibrozil, fenofibrate, pravastatin and fluvastatin as pharmacologic treatment for protease inhibitor-related dyslipidaemia. METHODS: Plasma lipid levels of 656 HIV-infected patients who referred to our tertiary care centre and were on protease inhibitor-based antiretroviral therapy for at least 12 months have been evaluated. All patients had HIV viral load < 50 copies/ml and presented with hypertriglyceridaemia of at least 6 months duration that was unresponsive to a hypolipidaemic diet; all have been treated with bezafibrate, gemfibrozil, fenofibrate, pravastatin, or fluvastatin for 12 months. RESULTS: Of the 656 patients observed 113 (17.2%) received pharmacological therapy, while seven patients were excluded from evaluation due to early drop-out. Of the 106 evaluable subjects, bezafibrate was used in 25 cases, gemfibrozil in 22, fenofibrate in 22, pravastatin in 19, and fluvastatin in 18. At the close of 1-year follow-up, fibrates led to a reduction of 40.7% and 21.9% versus baseline triglyceridaemia and cholesterolaemia, respectively (P < 0.001), and statins led to a reduction of 34.8% and 25.2% versus baseline triglyceride and total cholesterol levels, respectively (P < 0.001), without significant differences according to each different administered hypolipidaemic drug. CONCLUSIONS: All administered statins and fibrates revealed a similar, significant efficacy in the treatment of diet-resistant hyperlipidaemia, and showed a favourable tolerability profile.