Quality of life in an Italian cohort of people living with HIV in the era of combined antiretroviral therapy (Evidence from I.A.N.U.A. study-investigation on antiretroviral therapy).

The aims of this study were to assess the Health Related Quality of Life (HRQoL) of People Living with HIV/AIDS (PLWHA) who attend outpatient services in Genoa, Italy, and to evaluate the relationship between HRQoL and clinical factors, primarily: CD4+ cell count, viral load and HIV-Hepatitis C Virus (HCV) coinfection. A cross-sectional study was performed involving a sample of 943 consecutive patients. Firstly the EuroQol-Five Dimensions-Three Level (EQ-5D-3L) self-reported questionnaire was used to evaluate HRQoL, while socio-demographic information was collected using a separate self-administered questionnaire. Descriptive statistical analysis was then used to show the socio-demographic and clinical characteristics of the sample. Having characterized the sample, Pearson's correlation technique was used to assess the relationship between HRQoL and socio-demographic and clinical characteristics. Finally, multivariable linear regression was used to determine factors associated with HRQOL. The median EQ-Visual analogue scale (EQ-VAS) score was 75.4 (SD 18.4). We found statistically significant associations between the EQ-VAS score and age, coinfection with HCV+, education, other drugs taken over cART, hospitalization due to HIV and a CD4+ cell count <200 mm3 compared with CD4+ cell count >500 mm3. Factors independently associated with lower HRQoL were: older age, coinfection with HCV+, other drugs used in addition to cART, hospitalization due to HIV and CD4+ cell count <200 mm3 compared with CD4+ cell count >500 mm3.

Incidence and progression to cirrhosis of new hepatitis C virus infections in persons living with human immunodeficiency virus.

OBJECTIVE: To estimate the incidence of hepatitis C virus (HCV) seroconversion and the risk of severe fibrosis/cirrhosis in HCV seroconverters among persons with human immunodeficiency virus (HIV) infection. METHODS: We analysed data on 4059 persons with HIV enrolled in a cohort study in Italy. RESULTS: Incidence rate of seroconversion was 0.6/100 person-years overall, and drug users and men-who-have-sex-with-men were at highest risk. The cumulative risk of progression to severe fibrosis/cirrhosis was 30% by 10 years after seroconversion. CONCLUSIONS: New HCV infections have a rapidly progressive course in this population. Persons with HIV and HCV superinfection should be prioritized for treatment with anti-HCV direct-acting antivirals.

Therapeutical aspects and outcome of HIV/HCV coinfected patients treated with pegylated interferon plus ribavirin in an Italian cohort.

BACKGROUND: One-third of HIV-infected individuals suffer from chronic hepatitis C virus infection (HCV) in Europe. Recommendations from HCV-HIV International Panel advise current treatment with pegylated interferon plus ribavirin. We assessed the impact of interferon and ribavirin combination in 43 patients between 2002 and 2006. PATIENTS AND METHODS: All coinfected patients treated for HCV during the 5-year period were included in retrospective data collection. CD4+ T-lymphocyte count, HAART discontinuation, reasons for treatment interruption and factors correlated to sustained virological response (SVR) were monitored. RESULTS: The mean age was 41 +/- 6.7 years; the risk factor for coinfection was intravenous drug abuse in 32/43 (74%). The baseline CD4+ T-lymphocytes cell count was > 500 in 51% (22/43). Genotype 3a represented 51% (22/43); 37% were on HAART at baseline (16/43) and half of patients showed high HCV RNA levels (> 800,000 IU/ml). High rates of treatment discontinuation were observed (27/43, 63%), caused by voluntary interruptions in 52% (14/27) and virological failure in 26% (7/27). The overall population had an SVR of 30%; genotypes 3a and 1 had SVR of 38% and 24%, respectively. The SVR was significantly lower in three groups: high HCV RNA viral load (chi2 = 6, p < 0.0025), CD4+ T-lymphocyte historical nadir <350 cells/mm3 (chi2 = 3.26, p < 0.01) and genotype 1 with high viral load (chi2 = 4.8, p < 0.005). CONCLUSIONS: Although factors such as HCV viral load rates and genotype 1 have been confirmed to threaten the response to therapy, we observed a significant response rate when patients had a history of CD4+ T-lymphocyte nadir >350 per mm3. The high dropout rates due to voluntary discontinuations complicated the patients' case management.

Papular-purpuric gloves and socks syndrome in HIV-positive patients.

Three HIV-positive women showed clinical signs of papular-purpuric gloves and socks syndrome and serologic evidence of acute Parvovirus B19 infection. The course of the disease was complicated by anemia and persistent skin lesions, probably related to inadequate immune response. Because anemia in AIDS patients may be due to many causes, the history of recent Parvovirus B19 infection is helpful in suggesting the etiologic diagnosis.

Possible malignant transformation of benign lymphoepithelial parotid lesions in human immunodeficiency virus-infected patients: report of three cases.

Benign lymphoepithelial parotid lesions (BLL) are intraparotid pathological changes that are commonly thought to be an early manifestation of human immunodeficiency virus (HIV) infection. It is not well known whether BLL may undergo malignant transformation into B cell lymphoma and may therefore be a sort of precancerous lesion. We report 3 cases of possible malignant transformation of BLL in HIV-infected patients.

Detection of apoptotic T lymphocytes in peripheral blood of human immunodeficiency virus (HIV)-infected subjects by apostain.

Apoptosis has been indicated as a mechanism of T cell depletion in HIV-infected subjects and useful in monitoring disease progression. We investigated for the presence of apoptotic T lymphocytes in 130 HIV subjects in various stages of disease by the newly developed cell permeant DNA dye Apostain. Blood was collected in EDTA, lysed in buffered ammonium chloride, fixed in freshly prepared 1% paraformaldehyde and stored in aliquots at -80 degrees C. Samples were thawed and double stained with FITC conjugated-CD3 monoclonal antibody and Apostain. Flow cytometry was then performed and T cells gated on a CD3 versus side scatter dot plot. Normal samples treated in the same manner served to establish the boundary separating non-apoptotic from apoptotic cells. There was no statistically significant association between the proportion of subjects with detectable apoptotic cells and CDC clinical categories A, B and C at the time of admission to the study, although a trend toward a lower apoptotic rate in category A (A= 29%, B=40% and C=41%) was noticed. Conversely, CDC T cell categories 2 and 3 contained significantly higher proportions of Apostain positive patients (1=6%, 2=32% and 3=49%, P=0.072, by chi(2) test). Most importantly, Apostain test identified subjects at risk of disease progression during a 3.5-7 months follow-up in CDC category B and 2 (P=0.008 and P=0.0003, by Fisher's exact test, respectively). A similar, albeit not statistically significant trend was observed also in the other categories. Not requiring extensive manipulation of fresh samples nor cumbersome culture techniques, Apostain test appears suitable for identifying HIV subjects at higher risk of disease progression in clinical settings.

Expression of CD10 by human T cells that undergo apoptosis both in vitro and in vivo.

This study shows that human postthymic T cells express CD10 when undergoing apoptosis, irrespective of the signal responsible for initiating the apoptotic process. Cells from continuous T-cell lines did not normally express CD10, but became CD10(+) when induced into apoptosis by human immunodeficiency virus (HIV) infection and exposure to CD95 monoclonal antibody, etoposide, or staurosporin. Inhibitors of caspases blocked apoptosis and CD10 expression. Both CD4(+) and CD8(+) T cells purified from normal peripheral blood expressed CD10 on apoptotic induction. CD10 was newly synthesized by the apoptosing cells because its expression was inhibited by exposure to cycloheximide and CD10 mRNA became detectable by reverse transcription-polymerase chain reaction in T cells cultured under conditions favoring apoptosis. To show CD10 on T cells apoptosing in vivo, lymph node and peripheral blood T cells from HIV(+) subjects were used. These suspensions were composed of a substantial, although variable, proportion of apoptosing T cells that consistently expressed CD10. In contrast, CD10(+) as well as spontaneously apoptosing T cells were virtually absent in peripheral blood from normal individuals. Collectively, these observations indicate that CD10 may represent a reliable marker for identifying and isolating apoptosing T cells in vitro and ex vivo and possibly suggest novel functions for surface CD10 in the apoptotic process of lymphoid cells.

Serum IgG antibodies to human herpesvirus-6 (HHV-6) do not predict the progression of HIV disease to AIDS. Italian Seroconversion Study group.

OBJECTIVES: To evaluate if different levels of human herpesvirus 6 (HHV-6) antibodies can predict HIV disease progression. DESIGN: Longitudinal study of individuals with a documented date of HIV seroconversion. SETTING: Clinical centers located throughout Italy. PATIENTS: Individuals who serconverted for HIV between 1983 and 1995 in Italy. METHODS: Sera were tested for IgG antibodies to HHV-6 using a commercial enzyme immunoassay. A serum sample with an optical density (OD) > or =242 (i.e. the mean value of 10 negative controls +4x standard deviation) was considered as HHV-6 positive; the progression of HIV disease was evaluated estimating the relative hazards (RH) of AIDS (by Cox models) for individuals with higher levels vs. lower levels of HHV-6 antibodies or considering levels of antibodies based on 10% increase of the distribution (deciles). Rates of CD4 decline fitting linear regression were also estimated. RESULTS: A total of 381 persons were followed for a median time of 4 years (range: 0.15-9 years) following the date of collection of the serum sample. The median OD value of HHV-6 antibodies was 306, with an interquartile range of 241-440 and a range of 48-2330. A slight inverse correlation was found between HHV-6 antibody levels and age of the individual at the time of serum collection (Spearman rank correlation coefficient, -0.16; p = 0.0013). No association was found between HHV-6 and CD4 level or between HHV-6 and CD8 level at the date of serum collection. The unadjusted RH of progression to AIDS was 0.63 (95% CI: 0.42-0.96) for HHV-6 positive individuals vs. HHV-6 negative; when adjusting for possible confounders (CD4, age, pre-AIDS HIV-related pathologies at the date of sera collection, and previous anti-herpes treatment), the RH of AIDS increased to 0.80 (95% CI: 0.51-1.23). No particular association with HIV disease progression was found when using the deciles of the distribution of HHV-6 antibodies. The median CD4 cell loss was 5.0x10(6) cells/l per month among HHV-6 positive individuals and 5.7x10(6) cells/l per month among the others. CONCLUSIONS: The presence of high levels of HHV-6 antibodies does not seem to predict the clinical or immunologic progression of HIV disease.

[Anthracyclines and the heart]. / Le antracicline e il cuore.

Cardiotoxicity is the most important side effect of the highly effective chemotherapeutic drugs anthracyclines. The total dose that must not be surpassed to avoid cardiotoxicity is specific for each anthracycline. For doxorubicin the maximal dose is 450-550 mg/mq. Nevertheless cardiotoxicity can be observed in some cases even with doses smaller than the critical ones. Clinical signs of cardiotoxic damage can appear at any stage during the course of therapy. The prevention of cardiac damage can be tried in three ways. Firstly one should extend the administration period of the total dose of the drug for about 6 hours. The second way is based on the use of anthracycline analogs less toxic and possibly equally effective than doxorubicin. Finally one can associate to the anthracycline a cardioprotective drug such as ICRF187. The diagnosis of cardiotoxicity is usually reached evaluating the reduction of left ventricular ejection fraction either with echocardiography or with angiocardiography. Other parameters, particularly those evaluating the diastolic function, are under study to make the diagnosis more quick and accurate. Both cardiac scintigraphy and tomography also seem to offer promising tools for the diagnosis of anthracycline cardiotoxicity. Endomyocardiac biopsy is highly effective for the diagnosis, but is indicated only for selected cases. The therapy of anthracycline cardiomyopathy is directed mainly to the control of congestive heart failure. In the initial phase the treatment is based on the use of digitalis and diuretics, that are substituted in the following maintaining phase by ACE inhibitors.

Recognition of antigenic clusters of Candida albicans by T lymphocytes from human immunodeficiency virus-infected persons.

The fine specificity of the cellular immune response to Candida albicans (i.e., recognition of different antigenic components) between normal controls and human immunodeficiency virus-infected patients in various stages of disease was compared. C. albicans-specific T cells, enriched by antigen stimulation and interleukin-2 expansion, were challenged with antigenic fractions of different molecular weight obtained by SDS-gel fractionation of C. albicans extracts in the presence of autologous mononuclear cells as antigen-presenting cells. Proliferative responses showed similar patterns of reactivity between controls and category A and B seropositive subjects. Category C patients with concurrent C. albicans infections did not give rise to C. albicans-specific T cell lines, confirming the T cell defect. Patients without clinically evident C. albicans infection had a low but broad reactivity pattern of C. albicans-specific T cells. These results suggest that depletion of C. albicans-specific T cells, independent of their fine specificity, occurs along with disease progression.

Anti-V3 loop spectrotype in HIV-infected individuals during zidovudine therapy.

In order to investigate the role played by zidovudine (ZDV) as immune modulator, particularly on B-cell response, the anti-V3 loop spectrotype in 115 sera from 26 HIV-infected individuals was evaluated, prior to and during treatment with ZDV, by isoelectric focusing and reverse blotting (IEF-RB), a technique useful for indirectly measuring the activity and the number of B-cell clones. All 18 patients showing seroreactivity by IEFRB displayed a clear oligoclonal banding pattern, with no change in the spectrotype (i.e. new bands), in sequential analysis over the course of therapy. Only minor changes in band intensity were found, without any correlation with ZDV treatment or CD4+ cell count. In addition, among the sera reactive in spectrotypic analysis, the percentage of those with p24 antigen positivity was significantly lower than those with no detectable p24 antigen (19.8% vs 80.2%, respectively, p = < 0.0001, Fisher's exact test). In conclusion, it could not be demonstrated by IEFRB that there was any effect of ZDV on the activity and the number of anti-V3 specific B-cell clones. This data is in line with previous studies showing the constancy of anti-gp120 antibody spectrotype over the long course of the disease.

[Sedation, combined anesthesia, and total intravenous anesthesia (TIVA) with propofol in the pediatric surgical patient]. / Sedazione, anestesia combinata e anestesia totalmente endovenosa (TIVA) con propofol nel paziente chirurgico pediatrico.

Total intravenous anaesthesia (TIVA) has recently obtained a wide diffusion in paediatrics, thanks to the pharmacological properties of propofol. The authors make a review on sedation, combined anaesthesia and Tiva in paediatric anesthesia, particularly on propofol and its characteristics. They describe the practical use of TIVA with recent knowledge in this field.

Defective burst-promoting activity of T lymphocytes from anemic and nonanemic elderly people.

Erythroid stem cell proliferation is regulated by lymphokines and erythropoietin. The helper subset of T lymphocytes is known to produce the erythroid growth factor IL-3 or burst-promoting activity (BPA), while the suppressor subset seems to inhibit the erythroid growth. Leukocyte-conditioned media derived from white cells of nonanemic elderly were reported to provide defective support to the erythropoiesis. In two groups of elderly, nonanemic and anemic, we studied the ability of T lymphocytes to stimulate the BFU-E growth and the in vitro effect of cimetidine, as a drug that inhibits the suppressor T lymphocytes. Culture data were then compared with the peripheral blood lymphocyte picture. The study shows that defective mononuclear cell support to the BFU-E growth, namely due to reduced absolute number of the T4 subset of T lymphocytes, can be observed in both anemic and nonanemic elderly. It is suggested that isolated defective BPA production is not always sufficient to induce anemia. In most cases, anemia of unexplained origin in senescence would be due to the concomitance of both BFU-E impairment and defective BPA production. The simultaneous evaluation of BFU-E growth, lymphokine production, and the T-lymphocyte blood picture offers the best way to investigate the erythropoiesis of the elderly.

[Necrotizing vasculitis induced by cytomegalovirus in a woman with acquired immunodeficiency syndrome]. / Vasculite nécrosante produite par le cytomégalovirus chez une malade atteinte du syndrome d'immunodéficience acquise.

INTRODUCTION: Skin lesions induced by cytomegalovirus are rare and usually non-characteristic. CASE REPORT: A 32-year-old women with AIDS developed about twenty unpainful ulceronecrotic lesions on the extension aspect of the members and the trunk. Histology examination and in situ hybridization favoured cytomegalovirus infection of the skin. DISCUSSION: Despite the exceptional nature of this case, this particular clinical presentation should be recognized as it could be useful for early diagnosis of cytomegalovirus infection in immunodepressed subjects.

Zidovudine therapy of HIV-1 infection during pregnancy: assessment of the effect on the newborns.

Zidovudine (ZDV) administration during pregnancy has been suggested for the prevention of mother-to-child HIV-1 transmission. Reliable levels of the drug have been observed in the fetus and in the newborn. Seven HIV-1-infected pregnant women who declined to have abortions and whose immunological status required antiretroviral treatment were administered oral ZDV 18 mg/kg in four daily doses, the initial dose being administered anytime from the 16th to the 30th week of gestation up until the time of delivery. Follow-up of the seven infants from birth with a mean duration of 22 months (range 16-32 months) revealed mild drug-related toxicity: anemia in two infants and macrocytosis in all seven, both conditions resolved by the second month of life. All infants remained HIV-1 seronegative, according to the 1987 CDC classification, and all stayed clinically well. Other virological parameters including virus culture, in vitro antibody production, and polymerase chain reaction, repeatedly performed in the infants, remained negative. Although none of the mothers transmitted HIV-1 infection to the offspring, the size of this study and the relatively low transmission rate (13%) in Europe do not permit us to draw a definite conclusion about treatment efficacy in preventing maternal-fetal transmission. However, the drug caused only limited toxicity among the infants, and its administration to large numbers of mothers in treatment trials should be considered relatively safe for both mother and child.

[The clinical assessment and intensive treatment of meningoencephalitis in newborns and children of subsequent ages]. / Valutazione clinica e trattamento intensivo delle meningo-encefaliti in età neonatale e successive età pediatriche.

We focused on the best timing and management when admitting into intensive care unit a pediatric patient with central nervous system infection. The modified scales for pediatric patients did not prove satisfactory and reliable for making such decision. In fact the final score is obtained by adding the partial scores regarding the different clinical aspects. That bears a loss of informations. For this reason we think that the cardiorespiratory and metabolic parameters, assessed in a period of time, may indicate the moment when it is necessary to start an intensive care in these patients, regardless of consciousness. We therefore discussed the monitoring precociously required in these patients after assessing the initial clinical status. We also discussed the intensive care procedure employed in severely ill patients with cardio-circulatory and metabolic problems due to septic shock caused by bacterial meningoencephalitis (infants) and meningitis (other pediatric ages). In patients affected by infectious or post-infective encephalitis with respiratory failure and/or brain edema, it is essential to apply the organ protection procedures and particularly neuroprotection.