The pavia consensus statement.
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Antiretroviral Therapy, Highly Active↗
Biomedical subjects
Mauro Moroni
Publications and source records attributed to Mauro Moroni.
ADAMTS 13 genotype and vWF protease activity in an Italian family with TTP.
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ADAM Proteins↗
HIV and direct damage of organs: disease spectrum before and during the highly active antiretroviral therapy era.
Evidence derived from numerous studies supports a primary role for HIV in the development of direct damage of different organs eventually being responsible for the appearance of dementia, cardiomyopathy, nephropathy and hematologic abnormalities. As a result of the introduction of effective antiretroviral combination therapies a dramatic decrease of AIDS-associated opportunistic infections and malignancies was observed; however, the role of HAART on HIV organ damage is less well appreciated. In this review we discuss the most common HIV-associated diseases, their pathogenesis as well as the possible changing scenery in the HAART era.
AIDS Dementia Complex↗
Correlates of risk of adipose tissue alterations and their modifications over time in HIV-1-infected women treated with antiretroviral therapy.
OBJECTIVE: To assess the correlates of risk of the different types of lipodystrophy and their modifications over time in a cohort of HIV-positive women receiving antiretroviral therapy (ART). METHODS: A consecutive series of HIV-infected women receiving ART was prospectively enrolled between 1 and 31 March 1998, and followed up for 2 years. Adipose tissue alterations (ATAs) and their variations over time were assessed by means of clinical observation and anthropometric measurements, and logistic regression analysis was used to describe the associated risk factors identified by univariate and multivariate analyses. RESULTS: One-hundred-and-seventeen of the 212 women (55.2%) developed ATAs during the 24 months of follow-up. Central adiposity was observed in 95 patients and peripheral lipoatrophy in 91, with 21 patients (9.9%) showing pure lipoatrophy, 26 (12.3%) pure fat accumulation and 70 (33%) combined forms. Only six of the 223 regional adipose tissue alterations identified in 74 patients during the first 12 months of the study had disappeared by month 24. Of the 43 patients who developed breast enlargement during the first 12 months, 11 (25.6%) showed a decrease in breast size during the second year of follow-up that was unrelated to changes in therapy or therapeutic success. The development of ATAs during the first 12 months of follow-up independently correlated with protease inhibitor (PI) use (OR 2.81, P=0.002) but, by the end of the second year of follow-up, the only factor significantly related to the development of ATAs was the overall duration of ART (OR 1.85, P=0.041). The use of PI significantly increased the risk of developing central adiposity during the first 12 months of the study (OR 2.27, P=0.002), whereas the only variable significantly influencing the risk at month 24 was HIV-infection due to intravenous drug use, which proved to be protective (OR 0.53, P=0.043). During the first 12 months of follow-up, the development of peripheral lipoatrophy was significantly associated with stavudine (OR 2.19, P=0.037) and PI use at enrolment (OR 2.27, P=0.023). At the end of the study, the variables associated with peripheral lipoatrophy were stavudine use at enrolment (OR 2.82, P=0.002), ART exposure for >1000 days at enrolment (OR 2.32, P=0.007), a CD4 cell count of >200/microl at enrolment (OR 2.89, P=0.002) and an age of >28 years (OR 1.91, P=0.036). The only factor significantly associated with an increased risk of breast enlargement during the first 12 months of follow-up was PI use (adjusted OR 2.51; 95% CI: 1.16-5.46, P=0.02); however, at month 24, none of the tested variables was associated with a significantly increased risk of this ATA. CONCLUSIONS: ATAs (particularly central adiposity) are frequent in women treated with ART, and the different forms have different correlates of risk. Once they have become clinically evident, they generally tend to remain or worsen, and improve in only a small minority of cases. The considerable variations in adipomasty over time are apparently unrelated to changes in ART.
Adipose Tissue↗
Genotypic resistance tests for the management of patients with viro-immunological discordant response to highly active antiretroviral therapy.
Single withess: Drug resistance is one of the main factors limiting the success of antiretroviral therapy. Some other factors, such as individual enzymatic pattern and immune system function, play a role in the outcome of therapy in HIV infection. Moreover, adherence to treatment could also be a pivotal factor. Thus, there is a complex network that influences patients' response and ultimately contributes to the development of drug resistance. A particular situation among HIV-infected individuals is the finding of a 'discordant' response, which means a virological failure with the maintenance of an optimal immune function. In these subjects, the mere determination of the genotypic pattern of drug resistance is not necessary. Rather, the quantification of phenotypic drug resistance together with the measurement of viral fitness and/or CD4+ T-cell dynamics will help in defining further therapeutic strategies.
Antiretroviral Therapy, Highly Active↗
Increased risk of developing peripheral neuropathy in patients coinfected with HIV-1 and HTLV-2.
One thousand one hundred fifty-two HIV-1-positive patients were screened for HTLV-2 infection, and the AIDS-free coinfected individuals were consecutively included in a longitudinal study with the aim of investigating the role of HTLV-2 in the progression to AIDS and the development of specific neurologic diseases. Two matched HIV-1-positive/HTLV-2-negative controls for each coinfected individual were also enrolled in the study. HTLV-2 infection was found in 95 (8.2%) of the HIV-1-positive patients, 30 of whom were followed up for a median of 28.5 months. No significant differences were observed between them and the patients infected with HIV-1 alone in terms of the rate of decline in CD4 cell counts, progression to AIDS, or AIDS mortality, but they had an increased risk of developing peripheral neuropathy (hazard ratio, 3.3; 95% confidence interval, 1.3-8.0; p =.009). One coinfected patient developed myelopathy during the follow-up. In the second part of the study, aimed at preliminarily assessing the effect of highly active antiretroviral therapy (HAART) on the incidence of peripheral neuropathy, we extended our observations to two groups of coinfected and singly infected individuals receiving HAART. An 80% decrease in incidence of peripheral neuropathy was observed among both groups without any significant difference between them. These results support the hypothesis that HTLV-2 plays a role in the development of neurologic abnormalities in HIV-1-infected patients and suggest that the immune reconstitution due to HAART may limit the activity of HTLV-2 as an opportunistic agent.
Acquired Immunodeficiency Syndrome↗
Low-dose prolonged intermittent interleukin-2 adjuvant therapy: results of a randomized trial among human immunodeficiency virus-positive patients with advanced immune impairment.
Twenty-two patients with CD4(+)cell counts <or=200 cells/microL after 12 months of stable highly active antiretroviral therapy (HAART; "immunologic nonresponders") were randomly assigned to receive subcutaneous low-dose prolonged intermittent interleukin (IL)-2 in addition to HAART (n=12) or to continue HAART alone (n=10). At 48 weeks of follow-up, no IL-2-related serious adverse events and no significant differences in plasma human immunodeficiency virus (HIV) RNA level were observed in the 2 groups. A higher incidence of HIV-related clinical events was observed among patients receiving HAART alone (3/10) than among subjects receiving HAART plus IL-2 (0/12). Significant increases in CD4(+), naive, and CD4(+)CD7(+) cells and plasma levels of IL-7 were observed in patients receiving IL-2 versus patients receiving HAART alone. A significant increase in cell turnover did not lead to a decrease in the frequency of T cell receptor excision circles, which remained stable. Rather, increased numbers of T cell receptor excision circles per microliter of blood were observed (not statistically significant). Thus, adjuvant IL-2 therapy in immunologic nonresponders resulted in a clinical benefit, suggesting that the quantitative cell recovery involves functionally competent immune cells.
Adult↗
Determination of free and total (free plus protein-bound) melatonin in plasma and cerebrospinal fluid by high-performance liquid chromatography with fluorescence detection.
A simple, sensitive and accurate method for the estimation of free and total (free plus protein-bound) melatonin (MLT) in human plasma and cerebrospinal fluid (CSF) is described. Via Chem-Elut cartridges, free and total MLT (the latter obtained after a deproteinization step) were quantified in dichloromethane-extracted samples and analyzed in one chromatographic run by high-performance liquid chromatography (HPLC) with fluorimetric detection. The column used was an Extrasil ODS-2 (3 microm, 150 x 4.6 mm I.D.), while the mobile phase consisted of 75 mM sodium acetate-acetonitrile (72:28, v/v) (pH 5.0). Repeatability and reproducibility of the method were 3.24 and 9.4%, respectively. The recovery of melatonin from plasma and CSF was 99.9+/-4.0% for non-deproteinized samples and 93.2+/-4.8% for deproteinized samples. The detection limit of the assay was 0.5 pg/ml. In human plasma, the mean+/-SD concentrations in the darkness period were 23.18+/-7.44 pg/ml for free melatonin and 82.5+/-36.48 pg/ml for total melatonin, while the lowest concentrations detected during daytime were 2.23+/-2.22 and 7.40+/-5.68 pg/ml, respectively. Detection of MLT in CSF was 5.01+/-2.31 and 28.55+/-6.95 pg/ml for the free and total fraction, respectively.
Chromatography, High Pressure Liquid↗
Virologic and immunologic response to regimens containing nevirapine or efavirenz in combination with 2 nucleoside analogues in the Italian Cohort Naive Antiretrovirals (I.Co.N.A.) study.
This nonrandomized study compared the virologic and immunologic responses to potent regimens containing either efavirenz or nevirapine after considering potential systematic differences between patients receiving these drugs. Virologic failure was defined as the first of 2 consecutive measurements of virus load >500 human immunodeficiency virus RNA copies/mL. Of the 694 patients included in the analysis, 460 (66.3%) started nevirapine and 234 (33.7%) started efavirenz. The adjusted relative hazard of virologic failure for patients who started nevirapine, compared with those who started efavirenz, was 2.08 (95% confidence interval, 1.37-3.15; P=.0006). In addition, patients receiving efavirenz tended to recover 5 CD4 cells/microL more per quarter (P=.05). Although comparisons of drug efficacy in nonrandomized studies should be viewed with caution, no results from randomized controlled comparisons of these drugs are thought to be available. The findings of this study are in agreement with those of other observational studies.
Acquired Immunodeficiency Syndrome↗
Body habitus changes and metabolic alterations in protease inhibitor-naive HIV-1-infected patients treated with two nucleoside reverse transcriptase inhibitors.
BACKGROUND: Cross-sectional and retrospective surveys suggest that nucleoside reverse transcriptase inhibitors (NRTIs) contribute to the metabolic and morphologic alterations observed in patients on antiretroviral therapy (ART). OBJECTIVES: To assess the risk of developing body habitus changes (BHCs) and metabolic abnormalities in protease inhibitor (PI)-naive HIV-1-infected patients treated with two NRTIs, and the risk associated with each of these drugs. DESIGN: Prospective cohort study. PATIENTS AND METHODS: The BHCs occurring in 335 patients treated with two NRTIs were evaluated every 3 months. The laboratory tests included determination of CD4 cell counts and the measurement of HIV RNA, serum glucose, cholesterol, and triglyceride levels. Cox proportional hazard models were used to describe the factors associated with the development of BHCs. RESULTS: During a median exposure of 747.5 days, 46 patients (13.7%) developed BHCs: nine fat accumulation alone, 12 fat loss alone, and 25 combined fat loss and accumulation in different body regions. Fat loss alone occurred after a significantly longer median duration of treatment than the other two forms (p =.004). The risk of developing any BHC was significantly higher in female patients (p <.0001). Fat loss was the prevalent alteration in males. Hypertriglyceridemia was observed in 76 patients (22.7%), hypercholesterolemia in 35 (10.5%), and hyperglycemia in 48 (14.3%). The adjusted risk of developing hypertriglyceridemia was higher in the stavudine-treated patients (p =.04) and in those who had previously received ART (p =.02). The only independent factor associated with the development of hypercholesterolemia was to be ART experienced at baseline (p =.02), whereas age was associated with the development of hyperglycemia (p =.0096). CONCLUSIONS: Treatment with NRTIs may be responsible for the same morphologic alterations as those observed in patients treated with PIs. Moreover, altered triglyceride levels are also frequently observed. The different timing of presentation and gender distribution of BHCs suggest that multiple pathogenetic mechanisms are involved.
Adult↗
Salivary stone lithotripsy in the HIV patient.
OBJECTIVE: To investigate the use of shock-wave lithotripsy in the treatment of salivary gland disease in HIV-positive patients. STUDY DESIGN: Four patients infected with human immunodeficiency virus with ultrasonographically confirmed sialolithiasis (three male patients, mean age 33.5 years, range 19-41 years) were treated with extracorporeal electromagnetic shock-wave lithotripsy. RESULTS: All but one of the patients were successfully treated or experienced relief, with complete stone clearance demonstrated by ultrasonography 12 months after lithotripsy. CONCLUSION: Extracorporeal shock-wave lithotripsy is a safe, effective and minimally invasive technique for the nonsurgical treatment of HIV-positive patients with sialolithiasis.
Adult↗
Incidence of adipose tissue alterations in first-line antiretroviral therapy: the LipoICoNa Study.
BACKGROUND: Adipose tissue alterations (ATAs) are a frequent untoward effect of antiretroviral therapy, the causes of which remain incompletely explained. OBJECTIVES: To assess the incidence of ATAs and to identify the associated risk factors in patients infected with human immunodeficiency virus type 1 starting their first-line antiretroviral treatment. METHODS: In a multicenter investigation designed to study issues related to the treatment of patients starting antiretroviral therapy, physicians were requested to assess the presence of ATAs at enrollment and every 6 months thereafter. The ATAs were considered altogether and grouped as fat loss (lipoatrophy), adipose tissue accumulation (lipohypertrophy), and combined forms. RESULTS: A total of 655 patients were followed up for a median of 86 weeks; 128 patients (19.6%) were diagnosed as having at least 1 morphologic alteration during the study. Female gender and positivity for hepatitis C virus were independently linked to an increased risk of developing morphologic alterations. Age was another independent correlate of risk of developing ATAs. To have been infected through drug injection was a correlate of reduced risk of ATAs. Stavudine exposure was predictive at borderline statistical significance of lipoatrophy (but not of the other forms), and indinavir exposure was associated with a significantly higher risk of developing combined forms. Patients who started therapy with 2 nucleoside reverse transcriptase inhibitors and subsequently added a protease inhibitor during the follow-up had a significantly higher risk of having ATAs compared with patients who continued taking 2 nucleoside reverse transcriptase inhibitors up to the end of follow-up. CONCLUSIONS: Different types of ATAs might derive from distinct pathways and multifactorial causes. Adipose tissue alterations are a frequent and relatively early finding during first-line antiretroviral therapy.
Adipose Tissue↗
Prospective observational study of fever in hospitalized returning travelers and migrants from tropical areas, 1997-2001.
BACKGROUND: An estimated 50 million people each year from industrialized countries visit tropical areas: 3% to 11% of these travelers report a febrile illness on their return. We conducted a 5-year prospective observational study on the causes of fever in patients admitted to a university teaching hospital after returning from the tropics. METHODS: We enrolled in this study all consecutive patients admitted to the Division of Infectious Diseases of the University of Milan, Italy, between January 1997 and December 2001 presenting with fever (oral temperature > or =37.5 degrees C) and a history of travel to a tropical country in the previous 6 months. RESULTS: Seven percent (147/2,074) of all hospital admissions in the study period were due to fever in travelers and migrants returning from the tropics. Malaria accounted for 47.6 % of all admissions (70/147), followed by presumed self-limiting viral infections (12%). Pretravel screening and vaccination strategies could have prevented a considerable number of hospitalizations (e.g., hepatitis A and typhoid fever). The most useful investigations were blood examination and PCR for malaria, which gave positive results in 65% of cases in which they were performed. CONCLUSIONS: During a 5-year period, the number of patients returning from tropical areas who were admitted with fever to a university hospital in northern Italy remained stable; malaria was the most frequent diagnosis, and should be considered in any febrile patient returning from the tropics. With the exception of hepatitis A and dengue fever infections, in a real-world setting serology is of modest utility and is probably overused.
Adult↗
Therapeutic targeting of epidermal growth factor receptor with monoclonal antibodies.
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Antibodies, Monoclonal↗