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We evaluated rates and determinants of virological failure in triple-class experienced patients receiving raltegravir-based regimens from a national observational study over 48 weeks, defined by any one of the following: (1) no HIV-RNA suppression to undetectable levels (

According to recent studies, women have lower plasma HIV RNA concentrations than men. However, these studies did not take into account the duration of HIV infection.To analyze the relationship between viral load and gender among individuals with known date of seroconversion.Sixty infectious disease clinics in Italy.Cross-sectional analysis of data collected at enrollment in a cohort study.Injecting drug users and heterosexual contacts naive to antiretroviral therapy at enrollment (245 men; 170 women).Plasma HIV RNA concentrations, measured using quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) or signal amplification b-DNA assays before antiretroviral therapy.Plasma HIV RNA concentrations were similar by age and exposure category (p =.80 and p =.39, respectively). Median viral load among women was roughly half that of men (p =.002). The association between viral load and gender remained significant after fitting a two-way analysis of variance (p =.03) and after adjusting for CD4 count, modality of HIV transmission, and age at enrollment in a regression model. Viral load was 0.27 log10 copies/ml (95% confidence interval, 0.05-0.40; p =.01) lower in women (i.e., 50% lower in the raw scale).Plasma HIV RNA concentrations were found to be lower among women, even when considering the duration of HIV infection. Compared with men, it is possible women should be given highly aggressive antiretroviral therapy at lower HIV-RNA concentrations.

The heroin is the main hard drug of abuse among the illicit ones in Italy. The number of overdose episodes increase steadely year by year, indicating the danger of the phenomenon. The policy of several Authorities privileges drug-free treatment approaches and residential communities role while methadone programs still find a sort of ideological opposition.

Tumor growth and survival time were followed in rats transplanted with Morris hepatoma 5123 and previously injected with a crude homogenate of the same tumor by the intradermic or intralymphatic route. Female rats treated by the intralymphatic route showed a longer survival time and impaired tumor growth. Male rats did not show any difference.

A case of identical twins is reported in which only 1 was affected by subacute sclerosing panencephalitis. The affected twin showed a defect of cellular immunity, mainly a decrease of T lymphocytes. This defect therefore appears to be a consequence and not a genetic determinant of the disease.

Lymph node biopsy specimens from 16 intravenous drug abusers with persistent generalized lymphadenopathy were evaluated by immunohistochemical methods using a panel of antisera to detect different cell populations. The 11 cases that we tested on cryostat sections showed an increased number of Leu-2a-positive cells (cytotoxic-suppressor phenotype) in the follicular centers and a significantly reduced helper-to-suppressor T-cell mean ratio when compared with control tissues. In these 11 patients the peripheral helper-suppressor ratio was at the lower normal limit or inverted. Ten cases tested for anti-human T-cell lymphotropic virus type III antibodies were positive. In all 16 cases, immunohistology of paraffin-embedded sections demonstrated a polyclonal B population; 12 of 15 patients tested had polyclonal hypergammaglobulinemia, mostly IgG. The mixed-cell population of the lymph node sinuses was composed mostly of Leu-M1-positive and lysozyme-positive cells and, to a lesser extent, by alpha 1-antichymotrypsin-positive and S100 protein-positive cells. It seems that many of the immunologic dysfunctions found in these patients appear to be reflected in a fairly repetitive immunohistologic pattern.

Alpha-naphthyl acetate esterase (ANAE) reaction of mouse and rat thymus cells was studied. The majority of cells demonstrated ANAE in the form of multiple scattered granules. A reaction of this type appeared particularly labile, was found only when smears were fixed in formalin vapours and was inhibited by NaF. ANAE staining of thymus cells from mice of different ages was studied: the percentage of cells with single-spotted ANAE reaction was found to increase with age, while cells with granular scattered activity showed a progressive slight decrease. The percentage of ANAE positive cells in spleen appeared to be lower than in thymus, and showed only minor variations in different ages. In mouse and rat thymus and bowel lamina propria clusters of lymphocytes were found showing a sickle-shaped ANAE reaction, surrounding diffusely stained large cells which, on the basis of cytochemistry and phagocytosis ability, could be identified as macrophages. Analogous cell clusters were found in human tonsils and adenoids. These cell clusters were found to be similar to those formed by Ia-positive interdigitating cells which have been previously observed in human thymus, tonsils and bowel. The role of these clusters in the education process of lymphocytes is discussed.

Male rats were immunized against bovine albumin injected by either intradermic or intralymphatic routes. A significantly higher number of animals treated by the latter route did respond, probably because antigens introduced by this route directly reach lymph nodes, by passing blood and tissue lytic enzymes.

The effect of Hodgkin patient cytotoxic sera on the electrophoretic mobility of normal and Hodgkin peripheral blood allo-lymphocytes has been studied. Contact with cytotoxic serum determined a significant decrease in the electrophoretic mobility of lymphocytes, due to the presence of cytotoxic antibody on the lymphocyte surface. The antibody seems to be directed against T-lymphocytes. The results are discussed in the light of the preceding data by the authors on the role of anti-T-autoantibodies in Hodgkin's disease.

Treatment of human perypheral blood lymphocytes with phytohaemagglutinin (PHA), for 30 min and for 72 h, increases their ability to form E-rosettes. Possible interpretations of the phenomenon are discussed.

Lymphocyte subpopulations in cerebrospinal fluid (CSF) and peripheral blood (PB) were studied using monoclonal antibodies and the common membrane markers. The results in three groups of patients were compared: 36 subjects with 'non-immunological disorders' (NID), 14 subjects with multiple sclerosis (MS) and 6 with subacute sclerosing panencephalitis (SSPE). It was found that, in patients with NID, (1) 90% of cells were T lymphocytes, reactive with OKT3; (2) the helper/suppressor (T4/T8) ratios were the same in the CSF and the PB; (3) the OKIa1 percentage was lower in the CSF than in the PB; and (4) only a few cells were 'immature', reacting with OKT10. Using the membrane markers (E rosettes, Fc IgG receptors and surface immunoglobulins), on the other hand, it was noted that the majority of cells in the CSF were identified as suppressor T lymphocytes and surface immunoglobulin-positive B cells were less common than the Ia1 marker suggested. There were no significant differences between the CSF results in patients with NID and MS but the OKT3 lymphocytes were reduced in CSF samples from patients with SSPE.

The presence of alpha-2-macroglobulin (alpha-2-M) on the surface of peripheral blood lymphocytes from normal human subjects and from patients with chronic lymphatic leukaemia (CLL) and with ataxia-teleangectasia was studied by indirect immunofluorescence technique. Same experiments were done on purified subpopulations of normal blood peripheral lymphocytes (B and T). The percentage of alpha-2-M bearing lymphocytes is 17 +/- 6% as regard to normal subjects (Ig-bearing cells are 14%): in CLL the percentage of alpha-2-M bearing cells generally is significantly lower than that of Ig-bearing cells (IgM-IgD). On selected subpopulations, 90% of alpha-2-M bearing cells are present among non T-cells and only 5% among T-cells (probably due to not absolute purification). Blocking experiments using anti-Ig sera did not affect significantly the percentage of alpha-2-M bearing cells and using anti-alpha-2-M sera did not affect that of Ig-bearing cells. The percentage of E-rosette forming cells is not affected by pretreatment of peripheral lymphocytes with anti-Ig and/or anti-alpha-2-M sera. Hypothesis is set forth that alpha-2-M bearing cells could be a lymphocytes subpopulation made by a subgroup of B-cells and by K-cells, taking part in that immunoregulatory system in which collaborate many serum alpha-globulins and T-suppresor cells.

Surface markers of cerebrospinal fluid (CSF) cells have been studied in comparison with those of peripheral blood lymphocytes. The great majority (about 95%) of CSF cells bear surface markers of thymus-dependent lymphocytes (E rosettes with uncoated sheep red blood cells), while being devoid of bone-marrow derived cell markers (EAC rosettes with complement-coated red blood cells). In contrast with lymphocytes from peripheral blood, CSF cells form predominantly 'early' and 'sphere'-shaped E rosettes, and bear receptors for the complement-fixing segment of immunoglobulins G. Treatment with concentrated CSF does not affect rosette forming ability of peripheral blood lymphocytes.

Anti-lymphocyte antibodies of cold-reactive IgM-type in Systemic Lupus Erythematosus (SLE) and IgG-type in Hodgkin's disease (HD) by means of immunofluorescent technique have been demonstrated. The contemporaneous attachment of SLE and HD sera on selected peripheral lymphocytes demonstrate that the target cell is T-lymphocyte and that the two kinds of antibodies coat the same cell. Co-capping experiments have shown that the phenomenon has the same behaviour as regard to SLE and HD antibody, indicating that the antigen is the same. Hypothesis about the meaning of these antibodyies have been made.

In 32 patients with Hodgkin's disease the electrophoretic mobility of peripheral blood lymphocytes and, at the same time, some clinical, hematological, and immunological parameters of the disease were determined. The mean mobility of lymphocytes was normal; nevertheless, the lymphocytic mobility of 8/32 patients was significantly decreased. No correlation with clinical, hematological, and immunological parameters of the disease was detected. However, the functional deficiency of hodgkinian T lymphocytes seems to play a role in their abnormal electrophoretic behaviour. In 9 out of these 32 patients the electrophoretic mobility of peripheral erythrocytes was also determined. The average mobility was significantly (P less than 0.05) decreased. No correlation with clinical, hematological, and immunological parameters nor with electrophoretic mobility of lymphocytes was detected.

Benzodiazepine (BDZ) binding sites were studied by using 3H-diazepam and 3H-Ro 5-4864 in intact lymphocytes from peripheral blood (PBL), in comparison to kidney and cerebellum. Experiments with 3H-diazepam performed at equilibrium and measuring kinetics revealed that BDZ binding sites are indeed present in rat PBL. The binding is saturable (Bmax 557 fmoles/10(6) cells), with high affinity (KD = 9.3 nM) and reversible. Specific binding sites are also observed by saturation experiments with 3H-Ro 5-4864 (Bmax 175 fmoles/10(6) cells, KD 2.2 nM). In addition, analysis of saturation isotherms obtained with 3H-diazepam indicates that BDZ binding sites are also present in human PBL. Scatchard plot of binding isotherms revealed an apparent single population of sites in all cases. The pharmacological characterization of BDZ binding sites in PBL, as compared with those of kidney and cerebellum, showed that these sites belong to the so-called "peripheral type."

An epidemiologic survey of the distribution of lymphoadenopathy syndrome in six Italian cities and its correlation with human T-lymphotropic retrovirus III (HTLV-III) is reported. Serum samples of nine patients with acquired immune deficiency syndrome (AIDS) were tested, 180 from patients with lymphoadenopathy and 349 from individuals belonging to groups such as homosexuals, drug addicts, hemophiliacs, and polytransfused considered at increased risk for AIDS. Prevalence of HTLV-III antibodies was 78% in AIDS patients and 61% in 180 patients with lymphoadenopathy syndrome (variation among drug abusers by city from 51% in Cagliari to 87% in Rome). The percentage of positive sera in individuals at risk for AIDS or lymphoadenopathy ranged from 0% in polytransfused to 8.5% in homosexuals, 14% in drug addicts, and 19.5% in hemophiliacs. No positive sera were found among 660 healthy individuals including relatives of patients with AIDS or lymphoadenopathy or in 342 patients suffering from immunologic or infectious diseases. These results strongly suggest that HTLV-III is the causative agent of AIDS and lymphoadenopathy. Since none of the healthy subjects were positive while a substantial percentage of people at risk for AIDS showed antibodies to HTLV-III, it may be presumed that this infection is also prevalent in the Italian population group in which AIDS and lymphoadenopathy are most likely to develop.

In a previous paper it was demonstrated that the treatment of human peripheral lymphocytes with phytohaemagglutinin increases their ability to form E-rosettes, probably inducing rosette formation also by B-lymphocytes. In this paper new data are reported concerning the machanism of this phenomenon.