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The introduction of potent combination antiretroviral therapy (cART) has had a remarkable impact on the natural history of HIV infection, leading to a dramatic decline in the mortality rate and a considerable increase in the life expectancy of HIV-positive people. However, cART use is frequently associated with several metabolic complications, mostly represented by lipid metabolism alterations, which are reported very frequently among persons treated with antiretroviral agents. In particular, hyperlipidaemia occurs in up to 70%-80% of HIV-positive subjects receiving cART and is mainly associated with specific antiretroviral drugs belonging to three classes of antiretroviral agents: NRTIs, NNRTIs and PIs. The potential long-term consequences of cART-associated dyslipidaemia are not completely understood, but an increased risk of premature coronary heart disease has been reported in HIV-infected patients on cART, so prompt correction of lipid metabolism abnormalities is mandatory in this population. Dietary changes, regular aerobic exercise and switching to a different antiretroviral regimen associated with a more favourable metabolic profile are the first steps in clinical management, but lipid-lowering therapy with fibrates or statins is often required. In this case, the choice of hypolipidaemic drugs should take into account the potential pharmacokinetic interactions with many antiretroviral agents. [ABSTRACT FROM AUTHOR]

Background:Nucleoside reverse transcriptase inhibitor (NRTI)-sparing antiretroviral therapies may be useful in HIV-infected patients with resistance or intolerance to this class. Methods:We performed an observational study of patients on suppressive antiretroviral therapy containing two NRTIs plus one ritonavir-boosted protease inhibitor who switched to a dual regimen containing raltegravir (400 mg twice daily) and darunavir/ritonavir (800/100 mg once daily) and were followed-up for 48 weeks. Results:As a whole, 82 patients were enrolled. Mean duration of current regimen was 4.6 years and mean duration of plasma HIV RNA < 50 copies/mL before the switch was 46.2 months. Reason for simplification was toxicity in 76 patients and resistance to NRTIs in 13. After switching, the percentage of patients with HIV RNA < 50 copies/mL at week 48 was 92.7% in the intent-to-treat-exposed analysis and 97.6% in the per-protocol analysis. The switch led to a significant reduction in the mean triglyceride value (−85.2 mg/dL), in the prevalence of tubular proteinuria (−56%) and in the mean level of interleukin-6 (−0.94 pg/mL), with a significant increase in the mean phosphoremia (+0.58 mg/dL). Mean trough concentrations of both raltegravir and darunavir were within the therapeutic range. Two patients (2.4%) had virological failure due to suboptimal adherence and 4 subjects (4.9%) discontinued treatment due to adverse events, but no patients experienced Grade 3 or 4 adverse events. Conclusion:In our study, simplification to a dual therapy containing raltegravir plus darunavir/ritonavir after 48 weeks maintained viral suppression in more than 90% of patients and showed a good tolerability with a favourable effect on proteinuria, ipophosphoremia, and lipid metabolism. [ABSTRACT FROM PUBLISHER]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 × 106 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. [ABSTRACT FROM AUTHOR]

The article report that the guidelines for antiretroviral therapy state that nevirapine pharmacokinetics are not significantly affected by pregnancy, although some pregnant HIV-positive women face an increased risk of fatal liver toxicity, often associated with rash. Although the hepatotoxicity of nevirapine is greater than that of efavirenz, the potential for pregnancy and CD4 cell count-related increased hepatotoxicity is uncertain.

An extremely rare case report of HIV-associated gastric adenocarcinoma surgically treated in the year 1998 in a 37-year-old male patient already HIV positive for 10 years, with a complete post-surgery disease-free follow-up of eight years, is described. An international literature search allowed us to report the available details of the only nine cases of HIV-associated gastric cancer yet published. Seven occurred prior to the introduction of highly active antiretroviral therapy (HAART) and were burdened by a rapid disease evolution, while only two patients were reported after the introduction of HAART (like ours) and obtained surgical cure. Detailed data regarding complications, sequelae and overall survival are not given. Notably, even four of the nine published reports came from Japan, and an early disease development was usual (37–50 years of age at diagnosis). Due to its relevant differential diagnosis implications with many other HIV-related gastrointestinal disturbances caused by functional and organic diseases (drug-related disturbances, HIV infection itself, opportunistic infections, and Kaposi's sarcoma and malignant lymphomas being the most frequent disorders) and the possibility of maintaining an adequate life-expectancy when diagnosis and aggressive treatment are not delayed, gastric cancer should be considered carefully by all clinicians dealing with HIV disease. [ABSTRACT FROM AUTHOR]

A unique occurrence of two subsequent episodes of HIV-associated Cryptococcus neoformansfollowed by C. laurentii meningoencephalitis (successfully cured with fluconazole after demonstrated amphotericin B resistance) is presented and discussed. The available literature reported only two cases of HIV-associated C. laurentii infection to date, while a concurrent infection by C. neoformans and C. laurentii has been reported only once in a patient without HIV disease. The absence of prior descriptions of documented central nervous system infection by C. laurentii in non-HIV–infected patients is emphasized as well as the unpredictable in vitro and in vivo antifungal susceptibility of this non- neoformans Cryptococcus spp., and its apparent prevalence in hospitalized patients who received prior antifungal treatments. All epidemiologic, diagnostic, clinical, and therapeutic implications are discussed on the basis of the evolving characteristics of opportunism in the era of highly active antiretroviral therapy (HAART). [ABSTRACT FROM AUTHOR]

Objective and methods: The aim of our study was to analyse retrospectively the nature and frequency of antiretroviral prescriptions for 990 HIV-infected patients followed at our outpatient centre in Bologna, Italy, from January 2003 to March 2004. The main focus of the study was to identify the most commonly prescribed combinations and their related expenses, in order to identify the most competitive treatment regimens with regard to costs. Prescriptions were given directly to patients at monthly intervals, and drug treatment adherence data was stored in an electronic database. Antiretroviral regimens administered for the longest period to each patient during the 15 months of the study were selected for the study. All patients treated for <9 consecutive months and/or with treatment adherence levels <90% were excluded. Physicians assessed antiretroviral therapy at least quarterly according to efficacy and safety criteria, but not in terms of pharmacoeconomic considerations. Direct pharmacy expenses were obtained for the 24 most commonly used therapeutic regimens, covering 80.1% of patients. Results: The zidovudine-lamivudine-efavirenz combination proved to be the most prescribed combination (7.3%), followed by zidovudine-lamivudine- nevirapine (7.1%), lamivudine-stavudine (6.2%), zidovudine-lamivudine- lopinavir-ritonavir (5.2%), didanosine-stavudine-lopinavir-ritonavir (4.8%), and lamivudine-stavudine-nevirapine (4.7%). Anti-HIV combinations varied from a minimum yearly cost of €3895.6 for lamivudine-stavudine to €9422.8 for the zidovudine-lamivudine-lopinavir-ritonavir combination (+241.9%) [year of costing 2003]. There was a significant difference between the two first-line regimens for antiretroviral-naive subjects, with lopinavir-ritonavir-based combinations costing more than €9000 per patient/year compared with efavirenz-containing combinations, which were 28% less expensive. Mean daily costs varied substantially, from a minimum of €10.7 per day for lamivudine-stavudine to a maximum of €25.8 per day (+241.1%) for zidovudine-lamivudine-lopinavir-ritonavir. Regimens based on non-nucleoside reverse transcriptase inhibitors (NNRTIs) were less costly than most of those including protease inhibitors (PIs). The increased expense of each combination was compared with the cheapest therapeutic selection (lamivudine-stavudine), and costs of all triple combinations were also compared. Regimens based on NNRTIs accounted for 29.3% of our cohort (nevirapine-containing therapies 15.1%, and efavirenz-based ones 14.2%), while PIs were used in the majority of cases (37.3%), with lopinavir-ritonavir as the leading combination (13.6% of patients), followed by nelfinavir (9.9%) and indinavir (9.2%). When drug-related costs were examined, dual nucleoside analogues showed the lowest expense (€10.7–€11.6 per day), while triple nucleoside/nucleotide analogue combinations cost nearly twice as much (€18.5–€20.4 per day). Among the NNRTIs, there were comparable costs for nevirapine-based combinations (€18.3–€18.7 per day), while efavirenz-including regimens were 10% more costly (€19.2–€20.l per day). A very broad range of combinations and related costs were found with PIs, but apart from indinavir and saquinavir combinations (€15.7–€21.7 per day), all other regimens had a higher daily cost (from €22.0 per day for ritonavir-based regimens to €23.4–€24.3 per day for nelfinavir combinations, and up to €24.9–€25.8 per day with lopinavir-ritonavir). When considering nelfinavir- and lopinavir-containing combinations, the difference compared with NNRTI-based regimens varied from 41% when nevirapine- and lopinavir-ritonavir were compared, to 11.6% when efavirenz and nelfinavir were compared. Conclusions: Investigations that link prescribing patterns and related costs in the setting of HIV disease therapy are needed to improve patient management and help with the planning of healthcare resource allocation. [ABSTRACT FROM AUTHOR]

The frequency, the microbiology and clinical features of AIDS-related primary episodes and relapses of cryptococcosis, before and after the introduction of highly active antiretroviral therapy (HAART), were compared. The study covered 58 cases diagnosed before the introduction of HAART, and eight episodes since 1997. Because of negative cultures, we sought a sensitive laboratory assay such as detection of polysaccharide antigen. Despite later diagnosis, there was reduced disease mortality. Clinical suspicion for HIV-associated cryptococcosis should be maintained in immunocompromised subjects. The introduction of HAART has led to significant clinical and laboratory changes of HIV-related cryptococcosis. [Copyright &y& Elsevier]

A wide range of abnormalities of lipid metabolism have been recently described in HIV-infected patients receiving a protease inhibitor (PI)-based highly active antiretroviral therapy, including hypertriglyceridaemia and hypercholesterolaemia. The increase of plasma lipid concentrations may involve up to 70–80% of HIV-positive subjects treated with a PI-containing regimen and are frequently (but not always) associated with the fat redistribution or the lipodystrophy syndrome. Multiple pathogenetic mechanisms by which antiretroviral agents lead to dyslipidaemia have been hypothesized, but they are still controversial. The potential clinicopathological consequences of HIV-associated hyperlipidaemia are not completely known, but several anecdotal observations report an increased risk of premature coronary artery diseases in young HIV-positive individuals receiving PIs, besides peripheral atherosclerosis and acute pancreatitis. A limited-to-significant improvement of increased triglyceride and cholesterol plasma levels was described in patients who replaced PIs with nevirapine, efavirenz or abacavir, but the risks of long-term toxicity and virological relapse of this treatment switching are not completely defined. A hypolipidaemic diet and regular physical exercise may act favorably on dyslipidaemia, but pharmacological therapy becomes necessary when hyperlipidaemia is severe or persists for a long time. The choice of hypolipidaemic drugs is problematic because of potential pharmacological interactions with antiretroviral compounds and other antimicrobial agents, associated with an increased risk of toxicity and intolerance. Statins are considered the first-line therapy for the PI-related hypercholesterolaemia, while fibrates are the cornerstone of drug therapy when predominant hypertriglyceridaemia is of concern. [Copyright &y& Elsevier]

Evaluates the frequency, features, activity and tolerability of combination antiretroviral therapy in HIV-infected patients aged 55 years or older.

A rare case report of acute myelogenous 46 XY, inv(16)(p13q22) leukaemia occurring in a patient with his HIV infection controlled by highly active antiretroviral therapy is reported, in the context of a review of the available literature evidences. The initial localization as an isolated thyroid mass has no clinical equivalents to date. Although at its initial presentation the haematological disease had a very advanced (M5) stage expressing a predominant monocytic phenotype, two 1-week cytotoxic chemotherapy cycles carried out with cytarabin-daunorubicin, achieved complete remission (as assessed by combined diagnostic imaging, and repeated bone marrow studies). At the present 11-month follow-up time, eventual bone marrow transplantation is under evaluation, since the chromosomal translocation was still present. A such favourable clinical response to acute, advanced myelogenous leukaemia with an insidious recognition is considered infrequent, especially in the setting of HIV disease. [ABSTRACT FROM AUTHOR]

An abstract of the article ""Self-Managed", Inadequate "Adherence" to Antiretroviral Therapy, Limited to One Half of Standard Dosages, Followed by an Unexpected, Sustained Virological and Immunological Success," by Roberto Manfredi is presented.

An abstract of the article "Non-AIDS Related Malignancies 13 Years After the Availability of Combined Antiretroviral Therapy," by Roberto Manfredi is presented.

An abstract of the article "Fusion Inhibitors and Their Evolving Role During Salvage Antiretroviral Therapy: Seven Years of Experience With Enfuvirtide," by Roberto Manfredi is presented.

Examines the occurrence of liver toxicity in HIV-infected patients receiving isolated dual nucleoside analogue antiretroviral therapy. Transaminase level; Liver function tests; Liver enzyme elevation.