Antiretroviral therapy and HIV-related retinal microangiopathy.
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Biomedical subjects
Publications and source records attributed to V Vullo.
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Aim of study is the determination of concentrations of two important cytokines: TNF alfa and IL8 in children with bacterial meningitis to establish a correlation between infection, CSF concentration of cytokines and neurological sequelae. TNF alfa and IL8 concentrations in CSF have been measured by quantitative immunometric enzyme assay during the course of the disease. In the purulent meningitis we observed that CSF concentrations of these cytokines decreased to undectable values 24 to 48 hours after beginning of the antibiotic therapy. Conversely, in the 3 patients with mycobacterial meningitis (TBM) the concentrations of IL8 were higher for a longer period, being detectable in the CSF between 4 and 8 weeks after the beginning of the specific treatment. We found no significant differences of the values of IL8 in children with neurological sequelae compared with children without sequelae.
Thirty healthy blood donors, 15 workers from horse-breeding farms, 69 human immunodeficiency virus (HIV)-negative persons at risk for HIV infection, 125 HIV-infected subjects without Rhodococcus equi infection, and nine HIV-infected patients with Rhodococcus equi pneumonia were evaluated in order to detect serum antibodies to Rhodococcus equi precipitate-soluble antigen by an enzyme immunoassay (EIA). Whereas EIA values for healthy donors, horse farm workers, individuals at risk for HIV infection, and HIV-positive subjects without Rhodococcus equi infection were comparable, HIV-infected patients with rhodococcal disease had significantly higher Rhodococcus equi antibody levels (p < 0.0001). The clinical outcome of Rhodococcus equi pneumonia was more severe in subjects who had low levels of specific antibodies, whereas patients who recovered had elevated Rhodococcus equi antibody levels over time. Immunoblot studies showed that both Rhodococcus equi-infected patients and foals recognized a protein band of approximately 60 kDa in the Rhodococcus equi precipitate-soluble antigen. On the other hand, the Rhodococcus equi-infected patients did not react with the diffuse 15 to 17 kDa virulence-associated proteins that represent important virulence factors both in mice and horses.
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OBJECTIVE: To evaluate the prevalence of Chlamydia pneumoniae antibodies in an Italian population of HIV-infected and uninfected individuals in relation to the presence of HIV risk factors. DESIGN AND METHODS: A prospective evaluation of C. pneumoniae microimmunofluorescence immunoglobulin (Ig) G and IgM titres, in relation to sex, age, HIV clinical stage, and the presence of different HIV acquisition risk factors. SETTING: The Department of Infectious and Tropical Diseases, a secondary and tertiary care institution in the 'La Sapienza' University of Rome, during 1994 and 1995. PARTICIPANTS: HIV-infected and uninfected subjects (n = 322), all of them without respiratory symptoms. RESULTS: A statistically significant higher C. pneumoniae seroprevalence was found to be related, by multivariate analysis, to sex, age, and presence of HIV risk factor, but not to the presence of HIV infection itself. Among HIV-positive subjects, C. pneumoniae seroprevalence appeared to decrease with absolute CD4+ cell count and was low in Centers for Disease Control and Prevention (CDC) stage C of HIV infection. Furthermore, high C. pneumoniae IgG titres (> or = 1:512) were not found in subjects with CDC stage C disease or in those with low CD4+ cell count (< 200 x 10(6)/l). CONCLUSION: C. pneumoniae seroprevalence is higher in injecting drug users and in subjects with promiscuous heterosexual activity. A previous report of a higher C. pneumoniae seroprevalence among HIV-1-infected subjects (in relation to the normal population) was probably due to the presence of HIV risk factor and not to the HIV infection itself. HIV-infected subjects seem to have progressively lost their C. pneumoniae IgG antibodies in middle and advanced stages of HIV infection. High C. pneumoniae IgG titres are rarely found in advanced stage HIV-infected patients.
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Degradation of purified myelin basic protein (MBP) was studied by SDS gel electrophoresis after addition of CSF samples obtained from HIV-1-infected patients. An increase in MBP degradation was detected in patients with neurological complications, such as AIDS dementia complex (ADC) or progressive multifocal leukoencephalopathy (PML), when compared with patients with no neurological symptoms (NA) or with other neurological opportunistic infections (OI). In the ADC and PML patients, in addition to CSF proteolytic activity, an increase in CSF-MBP levels and presence of white matter lesions were also observed by neuroimaging (MRI). In other opportunistic infections of the brain, MBP levels but not anti-MBP proteolytic activity increased. Results suggest the involvement of proteases in the virus-induced demyelination.
Painful peripheral neuropathy (PPN) in HIV-infected patients has been increasingly associated with cytomegalovirus (CMV) infection at other sites. In the last few years, the detection of CMV lower matrix phosphoprotein (pp65) antigen in leukocytes has become a major tool in the diagnosis of CMV systemic infection in immunocompromised patients. In this study, CMV antigen detection was assessed in 13 HIV-infected patients with PPN and, as controls, in 82 HIV seropositive patients without any evidence of peripheral nerve syndromes (10 with CMV retinitis and 72 without CMV end-organ disease). CMV antigenemia was found in 10 (76.9%) patients with PPN, in 5 (6.9%) without CMV disease, and in all 10 patients (100%) with CMV retinitis. Of the 10 PPN patients with CMV antigenemia, only 3 presented with CMV retinitis, while the remaining 7 had no clinical evidence of overt CMV infection at other sites. CMV pp65-positive cells were also found in three of the four cerebrospinal fluid (CSF) samples collected from PPN patients. Ganciclovir was effective in improving neurological symptoms in two of the four treated patients. The findings suggest that active CMV infection may be associated with PPN in HIV infection even in the absence of CMV disease at other sites. The detection of CMV-matrix pp65 antigen in the blood and CSF leukocytes could represent a simple and rapid tool of selecting PPN patients for antiviral therapy.
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.
OBJECTIVES: This study evaluated prospectively the frequency, clinical outcome and pathologic findings of acute global left ventricular dysfunction in human immunodeficiency virus (HIV) infection during the various stages of the disease. BACKGROUND: Acute global left ventricular dysfunction in the course of HIV infection is still a poorly defined clinical entity, and little is known about the outcome after the acute onset. METHODS: Between January 1988 and June 1992, 136 HIV-positive (HIV+) patients without clinical, electrocardiographic or echocardiographic evidence of cardiovascular dysfunction on admission were prospectively studied with serial echocardiograms. Patients were assigned to three groups: 1) anti-HIV+ asymptomatic (17 patients, 12.5%); 2) acquired immunodeficiency syndrome (AIDS)-related complex (26 patients, 19.1%); 3) AIDS (93 patients, 68.4%). RESULTS: During a mean follow-up period of 415 +/- 220 days, seven patients, all in the AIDS subgroup, developed clinical and echocardiographic findings of acute global left ventricular dysfunction; of these, six (85%) died of congestive heart failure. Mean survival time from symptom onset was 41 +/- 13 days. Necropsy findings in five patients revealed acute lymphocytic myocarditis in three, cryptococcal myocarditis in one and interstitial edema and fibrosis in one. In only one patient was left ventricular dysfunction reversible with treatment. CONCLUSIONS: Although infrequent, acute global left ventricular dysfunction is not rare in the course of HIV infection. It seems to occur exclusively during the AIDS stage. Acute global left ventricular dysfunction is often fatal but may be reversible and is mainly associated with the pathologic findings of acute myocarditis.
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 antiprotozoan and antifungal agent, the terbinafine, was investigated for its potential activity against Pneumocystis carinii infection of the A549 cell line culture and on immunosuppressed Sprague Dawley rats in comparison with trimethoprim-sulphamethoxazole and pentamidine isethionate. Terbinafine suppressed P. carinii growth at doses up to 3 g/L within 24 h and it was able to inhibit cyst forms at 60 h post inoculation. With respect to trimethoprim-sulphamethoxazole and pentamidine isethionate P. carinii organisms decreased at the same time interval but cyst form elimination was less apparent than with terbinafine. The results of the in-vitro culture were consistent with the in-vivo observations. Of the 3 groups of rats tested, the occurrence of P. carinii pneumonia was documented in 18 (60%) of the control rats (group 3) which showed a high degree of P. carinii burden and a marked weight loss with respect to the beginning of the experiment. Among terbinafine treated rats (group 1), P. carinii pneumonia was present in one rat (3.3%), while no P. carinii infection occurred in the pentamidine isethionate and in trimethoprim-sulphamethoxazole treatment rat groups (group 2). All the agents investigated showed no particular signs of toxicity. These preliminary results suggest further explorations of the terbinafine in clinical trials for treatment and prophylaxis of P. carinii pneumonia.
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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.
Several reports indicate that systemic carnitine deficiency could occur in acquired immunodeficiency disease syndrome (AIDS), and that primary and secondary carnitine deficiency leads to critical metabolic dysfunctions. L-carnitine supplementation to peripheral blood mononuclear cells (PBMCs) of AIDS patients resulted in significant enhancement of the phytohemagglutinin (PHA)-driven proliferative response. High dose L-carnitine administration (6 gr per day for two weeks) to AIDS patients treated with zidovudine also led to increased PBMCs proliferation and reduced blood levels of triglycerides. In addition, a reduction of beta 2-microglobulin serum levels as well as circulating tumor necrosis factor (TNF)-alpha, mostly in patients exhibiting highly elevated levels, were found at the end of the treatment period. Our data suggest that in vivo L-carnitine could prove useful in ameliorating both the immune response and lipid metabolism in patients with AIDS, irrespective of initial serum carnitines levels. The mechanism(s) accounting for the observed results are currently not clear. Further studies are needed to confirm the hypothesis that L-carnitine affects the expression of HIV-induced cytokine.
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