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OBJECTIVES: Nevirapine is a non-nucleoside reverse transcriptase inhibitor of HIV-1 which exhibits synergy in vitro with zidovudine (ZDV) and also is active against ZDV-resistant HIV. We evaluated the activity and safety of nevirapine in combination with ZDV in patients receiving long-term ZDV therapy. METHODS: We conducted a randomized, open-label, controlled 28-week study of nevirapine (200 mg daily for 2 weeks followed by 200 mg twice daily for 26 weeks) and continued ZDV (500-600 mg daily) versus continued ZDV alone in 49 HIV-1 p24 antigenaemic patients with CD4+ lymphocyte counts < 500 x 10(6)/l and who had been treated with ZDV for at least 6 months. RESULTS: Addition of nevirapine to ZDV resulted in a significant and rapid reduction in circulating RNA load (mean, 0.65), a mean CD4+ lymphocyte rise of 34 x 10(6)/l, a reduction in serum beta 2-microglobulin and a median fall in immune complex dissociated p24 antigen levels of 69%. These changes remained statistically significant for 4, 4, 12 and at least 28 weeks, respectively. The principal adverse event due to nevirapine was a hypersensitivity reaction comprising rash with or without fever and mucositis in eight (32%) patients, which was dose-limiting in seven patients. CONCLUSION: Nevirapine exhibits significant although transient anti-HIV activity in ZDV-pretreated patients but its use is frequently associated with a hypersensitivity reaction.

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In this study the authors report the case of HIV patients with visceral leishmaniasis. He presented a pancreatitis with evident clinical signs and high increase of amilasis (9876 U/L) the twelfth day of treatment with meglumine antimoniate. The interruption of therapy was followed by a rapid disappearance of signs and symptoms and a normalization of amilasis. In accordance with the most recent studies, it is expedient, for every patients treated with antimonial drugs, to undergo an accurate amilasis monitoring.

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In this study the presence of brain antiganglioside antibodies in the cerebrospinal fluid (CSF) of patients with HIV infection was analysed. CSF samples were collected from 45 patients with AIDS and from 45 anti-HIV negative subjects, 15 of whom presented aseptic meningitis. Nineteen AIDS patients had clinically well-documented encephalopathy. Thirteen of these patients had white matter lesions shown by magnetic resonance imaging (MRI). Both IgG and IgM antiganglioside antibodies were detected by immunostaining on thin layer chromatography plates in three CSF samples from AIDS patients with progressive encephalopathy with signs of a diffuse demyelination, as revealed by MRI. Two of these CSF samples reacted specifically with GM3, GM1 and GD1a and one with GD1a. In none of the HIV infected patients without demyelinating encephalopathy, but with opportunistic infections or cerebral lymphoma, nor in the anti-HIV negative control subjects were antiganglioside antibodies detected. No association with JCV DNA, CMV DNA, EBV DNA, detected by nested PCR, nor HIV antigen p24 was found. These findings show the presence of brain antiganglioside antibodies in the CSF of AIDS patients for the first time. However, the findings do not suggest relating the presence of these antibodies to HIV encephalopathy or particular viral agents, but indicate that the antibodies are detectable in subjects with progressive encephalopathy with a diffuse demyelination.

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Cytomegalovirus (CMV) encephalitis has been reported with increasing frequency in patients with AIDS. Nevertheless, the management of CMV-related encephalitis appears to be problematic and data in the literature on the clinical efficacy of ganciclovir therapy is sparse and controversial. We describe two patients with AIDS who developed CMV encephalitis while receiving ganciclovir maintenance therapy for CMV retinitis. Moreover, there was no improvement in neurological status or virological and radiological response during a further induction course of ganciclovir. These observations suggest that the currently recommended therapeutic protocols with ganciclovir are not effective in the prevention and treatment of CMV encephalitis in patients with AIDS.

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The relationship between tumour necrosis factor-alpha (TNF-alpha) and the interleukin-2 (ILL-2) system in HIV-1 infection is important in understanding the dynamics of early immune response before the development of acquired immunodeficiency syndrome. Levels of TNF-alpha, IL-2 and soluble IL-2 receptor (sIL-2R) in serum and cerebrospinal fluid (CSF) samples from 31 asymptomatic HIV-1 seropositive individuals were measured. High levels of TNF-alpha were detected in CSF of 17 (55%) and serum of 22 (71%) subjects, 15 (88%) of whom had elevated CSF IL-2 levels and 16 (94%) had high sIL-2R levels. Moreover, CSF levels of TNF-alpha significantly correlated with CSF levels of IL-2 and sIL-2R. TNF-alpha, IL-2 and sIL-2R seem to be released within the intrathecal compartment early in the course of HIV-1 infection. In view of the known cytotoxic effects of TNF-alpha, an early release may contribute to subsequent development of neurological complications.

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OBJECTIVE: Reduced levels of serum carnitines (3-hydroxy-4-N-trimethyl-ammonio-butanoate) are found in most patients treated with zidovudine. However, since serum carnitines do not strictly reflect cellular concentrations we examined whether a carnitine depletion could be found in peripheral blood mononuclear cells (PBMC) from AIDS patients with normal serum carnitine levels. In addition, we explored whether it was possible to relate the host's immunoreactivity to the content of carnitine in PBMC and whether carnitine levels can be corrected by oral supplementation of L-carnitine. DESIGN: Immunopharmacologic study. METHODS: Twenty male patients with advanced AIDS (Centers for Disease Control and Prevention stage IVCI) and normal serum levels of carnitines were enrolled. Patients were randomly assigned to receive either L-carnitine (6 g/day) or placebo for 2 weeks. At baseline and at the end of the trial, we measured carnitines in both sera and PBMC, serum triglycerides, CD4 cell counts, and the frequency of cells entering the S and G2-M phases of cell cycle following mitogen stimulation. RESULTS: Concentrations of total carnitine in PBMC from AIDS patients was lower than in healthy controls. A significant trend towards the restoration of appropriate intracellular carnitine levels was found in patients treated with high-dose L-carnitine and was associated with an increased frequency of S and G2-M cells following mitogen stimulation. Furthermore, at the end of the trial we found a strong reduction in serum triglycerides in the L-carnitine group compared with baseline levels. CONCLUSIONS: Our data indicate that carnitine deficiency occurs in PBMC from patients with advanced AIDS, despite normal serum concentrations. The increase in cellular carnitine content strongly improved lymphocyte proliferative responsiveness to mitogens. Because carnitine status is an important contributing factor to immune function in patients with advanced AIDS, we therefore believe that L-carnitine supplementation could have a role as a complementary therapy for HIV-infected individuals.

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The relationship between retinal microangiopathy and some features of human immunodeficiency virus (HIV) infection such as HIV antigenemia, antibodies to the viral proteins, T lymphocyte subsets, were studied in 71 patients with acquired immunodeficiency syndrome (AIDS). The absence of antibodies to the HIV p24 protein was significantly related to retinal microangiopathy (p = 0.0051) and more closely to retinal cotton-wool spots (p = 0.0007); the combination of positive antigenemia with the absence of antibodies to p24, which is typical of the later phases of HIV infection, was found in a larger percentage of patients with cotton-wool spots (p = 0.0013) than in subjects with every sign of microangiopathy (p = 0.0546). T-helper (CD4+) cells count below 200 cells/mm3 was also detected in a higher percentage of patients with HIV-related retinal microangiopathy (p = 0.009). These findings suggest that retinal microangiopathy and especially retinal cotton-wool spots are related to the progression of immunodeficiency.

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The relationship between the interleukin-2 (IL-2) system and the humoral response against human immunodeficiency virus type-I (HIV-1) is important in understanding the immune reaction before the development of AIDS. Levels of IL-2 and soluble IL-2 receptor (sIL-2R) in serum and cerebrospinal fluid (CSF) samples from 31 asymptomatic HIV-1 seropositive individuals were measured and correlated with levels of anti-1 IgG and IgM antibodies. High IL-2 levels were detected in the CSF of 20 (65%) subjects, 18 (90%) of whom had evidence of intrathecal synthesis of HIV-1-specific IgM antibodies. Similarly, IgG antibodies were detected in 10 subjects who had elevated IL-2 levels in the CSF. Moreover, intrathecal levels of IL-2 and sIL-2R correlated with intrathecal synthesis of both IgG and IgM antibodies. Local release of IL-2 seems to play an important role in the initiation of the antibody response against HIV-1 in early stages of infection and may be utilised in devising effective therapeutic strategies.

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The pathogenesis of brain inflammation and damage by human immunodeficiency virus (HIV) infection is unclear. Because blood-brain barrier damage and impaired cerebral perfusion are common features of HIV-1 infection, we evaluated the role of tumour necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) in mediating disruption of the blood-brain barrier. Levels of TNF-alpha were more elevated in cerebrospinal fluid (CSF) than in serum of HIV-1 infected patients and were mainly detected in those patients who had neurologic involvement. Intrathecal TNF-alpha levels correlated with signs of blood-brain barrier damage, manifested by high CSF to serum albumin quotient, and with the degree of barrier impairment. In contrast, intrathecal IL-1beta levels did not correlate with blood-brain barrier damage in HIV-1 infected patients. TNF-alpha seems to be related to active neural inflammation and to blood-brain barrier damage. The proinflammatory effects of TNF-alpha in the nervous system are dissociated from those of IL-1beta.

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The mechanism for the initiation of blood-brain barrier damage and intrathecal inflammation in patients infected with the human immunodeficiency virus (HIV) is poorly understood. We have recently reported that tumour necrosis factor-alpha (TNF-alpha) mediates active neural inflammation and blood-brain barrier damage in HIV-1 infection. Stimulation of endothelial cells by TNF-alpha induces the expression of intercellular adhesion molecule-1 (ICAM-1), which is an important early marker of immune activation and response. We report herein for the first time the detection of high levels of free circulating ICAM-1 in serum and cerebrospinal fluid of patients with HIV-1 infection. Free circulating ICAM-1 in these patients correlated with TNF-alpha concentrations and with the degree of blood-brain barrier damage and were detected predominantly in patients with neurologic involvement. These findings have important implications for the understanding and investigation of the intrathecal inflammatory response in HIV-1 infection.

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A total of 124 patients with lower respiratory tract (44) or urinary tract infections (80) were enrolled in an open, multicenter study to evaluate the efficacy and tolerability of sulbactam/ampicillin, administered at the dosage of 3 g/die by intramuscular route. Pretreatment pathogens from patients with lower respiratory tract infections included: Streptococcus alpha-haemolyticus in 8 cases, Streptococcus beta-haemolyticus in 2 cases, Staphylococcus albus in 7 cases, Haemophilus influenzae in 7 cases, Staphylococcus aureus in 6 cases, Klebsiella oxytoca in 5 cases, Staphylococcus epidermidis in 3 cases, Streptococcus pneumoniae in 3 cases, Escherichia coli in 2 cases; in one subject (2.75%), no microorganisms were isolated. In vitro, 36 isolates (84%) were sensitive to SA and 7 (16%) were resistant. At the end of therapy, all the causative pathogens sensitive to sulbactam/ampicillin were eliminated. In patients with urinary tract infections, pretreatment pathogens were: E. coli in 40 cases, S. albus in 16 cases, Proteus mirabilis in 8 cases, Enterobacter agglomerans in 6 cases, Proteus vulgaris in 3 cases, Streptococcus faecalis in 3 cases, Streptococcus liquefaciens in 2 cases, Pseudomonas aeruginosa in 2 cases. In vitro, 64 isolates (80%) were sensitive to sulbactam/ampicillin and 16 (20%) were resistant. At the end of therapy, 63 out of the 64 pathogens sensitive to sulbactam/ampicillin were eliminated; in one case the therapy was interrupted due to adverse effect. Clinical efficacy: in subjects with lower respiratory tract infections, sulbactam/ampicillin cured 32 patients (72.72%) and ameliorated the clinical status of 8 patients (18.18%); efficacy rate: 90.9%).(ABSTRACT TRUNCATED AT 250 WORDS)

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HIV infection is thought to exacerbate the virulence of normal saprophytic vaginal microflora. We studied the vaginal ecosystem of HIV patients to detect the quantitative and qualitative variation of vaginal microorganisms. 15 patients (5 with AIDS and 10 with ARC) were investigated. Vaginal candidiasis was more frequent in this group than in the control groups. Gardnerella was present in 60% of patients generally in association with anaerobic bacteria and Mycoplasma. Among anaerobia, Bacteroides sp and other Gram-negative rods were the most common bacteria. Neisseria gonorrhoeae was absent in all patients tested. Chlamydia trachomatis was recovered in two out of the 15 HIV-positive patients. Aerobic Gram-negative flora was 100-fold that of the control group and anaerobic Gram-negative flora 10-fold.

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Alveolar lymphocytosis, in the face of blood lymphopenia, is a common finding among patients with AIDS. We studied by bronchoalveolar lavage (BAL), the alveolar cell profile of 43 human immuno deficiency virus (HIV) seropositive patients divided into three groups involving the advanced stages of the disease: group A (n = 9; CDC III), ambulatory individuals without systemic or respiratory symptoms; group B (n = 15; CDC IV) patients admitted for evaluation of fever of unknown origin (FUO) without pulmonary involvement; group C (n = 19; CDC IV), patients admitted for evaluation of an acute pulmonary condition. Sex, age and risk factor were comparable among the groups. Alveolar lymphocytosis was found in no group A patients, in 2 out of 15 group B patients (both with P. carinii lung infection) and in all group C patients, where pulmonary involvement was due to opportunistic infection or to nonspecific interstitial pneumonitis. Our findings suggest that in patients with advanced HIV infection alveolar lymphocytosis may be an expression of a concomitant process within the lungs either clinically manifest or inapparent, or possibly related to HIV primary lung involvement.

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