Impact of highly active antiretroviral therapy on organ-specific manifestations of HIV-1 infection.

In the last 10 years, interesting results have been reported concerning the impact of highly active antiretroviral therapy (HAART) on the changing pattern of organ-specific manifestations of HIV-1 infection. There has been a clear step-wise reduction in the incidence of several opportunistic infections (OIs), particularly Pneumocystis carinii pneumonia, whereas a nonsignificant reduction in incidence has been observed for other organ-specific diseases, including invasive cervical cancer and Hodgkin disease. In addition, several organ-specific manifestations, including HIV-associated nephropathy, wasting syndrome and cardiomyopathy, are a direct consequence of damage by HIV-1, and so HAART may have a therapeutic effect in improving or preventing these manifestations. Finally, the introduction of HAART has seen the emergence of several complications, termed immune reconstitution inflammatory syndrome, which includes OIs such as cytomegalovirus vitritis, Mycobacterium avium complex lymphadenitis, paradoxical responses to treatment for tuberculosis, and exacerbation of cryptococcosis. Because not all HIV-1 organ-specific manifestations are decreasing in the HAART era, this review will analyse the influence of HAART on several organ-specific manifestations, and in particular OIs related to several organs, cerebral disorders and HIV-1-related neoplasia.

Levels of the bcl-2 protein, fibronectin and alpha(5)beta(1) fibronectin receptor in HIV-1-infected patients with Kaposi's sarcoma.

Kaposi's sarcoma (KS) is an angioproliferative disease characterized by proliferation of neoplastic cells (spindle cells) mixed with endothelial and inflammatory cells. In this study we evaluated the role of the adhesive glycoprotein, fibronectin (FN) and its receptor alpha(5)beta(1) (FNR), and the proto-oncogene bcl-2, an anti-apoptotic protein. Significantly decreased serum levels of FN were noted in HIV-1-infected patients with KS, whereas serum levels of FNR were significantly increased in the same patients. Furthermore, increased FNR expression was observed on CD4 cells from KS patients. Serum levels of bcl-2 protein were significantly decreased in asymptomatic seropositive patients, whereas HIV-1-infected patients with KS showed increased serum levels of bcl-2. These results provide further information about interaction between integrins and the extracellular matrix and bcl-2 protein that can support cell survival either of neoplastic cells or endothelial and inflammatory cells.

Diagnostic value of viral culture, polymerase chain reaction and western blot for HIV-1 infection in 218 infants born to HIV-infected mothers and examined at different ages.

In a prospective longitudinal 10-year (1988 to 1998) study, 308 sequential blood samples from 218 infants born to HIV-1 seropositive women were examined by blood culture, polymerase chain reaction (PCR) and Western Blot (WB) for HIV-1 infection within the first month of life (no. 47 specimens), at 2-6 (no. 125), 7-18 (no. 80), and > 18 (no. 56) months after birth. Clinical status at follow-up after the initial diagnosis of HIV infection was also evaluated. Vertically transmitted HIV infection was diagnosed in 45 children (24 children were diagnosed before 18 months of age), whereas 173 were found to be uninfected (transmission rate 20.6%). Sensitivities of viral culture, PCR and WB were 95.2%, 97.8%, 94.4%, and specificities were 99.5%, 97.6% and 20.7%, respectively. Thus, cumulative positive predictive values (PPV) of blood culture, PCR and WB were 97.5%, 88.2% and 23.4%, while negative predictive values (NPV) were 99.0%, 99.6% and 100.0%, respectively. In view of defining the optimal time of sampling for a correct diagnosis of HIV infection, a PPV of 100.0% was achieved earlier by viral culture (2-6 months of age) than by PCR (7-18 months of age). Meanwhile, a NPV of 100% was obtained earlier by PCR (within the first month of age) than by viral culture (2-6 months). These results indicate that a combination test strategy requiring two blood samples analyzed by viral culture and PCR may confirm or exclude HIV perinatal infection within the first 2 months of life rather than being delayed to later times. Clinical follow-up was performed in 35 children, of whom 7 developed a rapidly progressive disease, 23 showed a slow progression, while 5 children are still younger than 5 years and do not present severe clinical symptoms.

Meningoencephalitis caused by human herpesvirus-6 in an immunocompetent adult patient: case report and review of the literature.

Human herpesvirus-6 (HHV-6) is the etiologic agent of roseola infantum, and has been implicated as a possible cause of encephalitis in pediatric and adult patients. A case of meningoencephalitis in an otherwise healthy, immunocompetent 59-year-old woman is described. The diagnosis of HHV-6 meningoencephalitis was confirmed by detecting viral DNA in cerebrospinal fluid collected in the acute stage of the disease by polymerase chain reaction. The patient was treated with acyclovir and recovered without any sequelae. The current knowledge of the pathophysiology, clinical course and outcome of HHV-6 meningoencephalitis in immunocompetent adult patients is also reviewed.

A retrospective study of treatment of cerebral toxoplasmosis in AIDS patients with trimethoprim-sulphamethoxazole.

AIMS OF THE STUDY: a retrospective study was designed to evaluate efficacy and tolerance of trimethoprim-sulphamethoxazole (TMP-SMZ) in AIDS patients with cerebral toxoplasmosis (TE). PATIENTS AND METHODS: we reviewed 471 patients with AIDS, and we analysed 71 AIDS patients with TE, who received intravenous therapy with TMP-SMZ (TMP: 10 mg/kg/day, SMZ: 50 mg/kg/day) for 4 weeks. RESULTS: 35 patients (49.2%) had a complete regression of clinical signs, and a complete resolution of radiological lesions was noted in 41 patients (57.7%). Improvement of clinical signs and radiological lesions were observed in 27 patients (38%), and in nine patients (12.6%), respectively. In contrast, nine patients (12.6%) did not show any clinical change, or worsened. Twenty-two patients (30.9%) suffered from adverse cutaneous reactions, whereas many patients had haematological toxicity. CONCLUSIONS: TMP-SMZ seems to be an efficient therapy for TE in AIDS patients, although further prospective, randomized therapeutic trials are required to confirm these results.

A retrospective study on the efficacy and safety of amphotericin B in a lipid emulsion for the treatment of cryptococcal meningitis in AIDS patients.

To evaluate the efficacy and safety of Amphotericin B dissolved in dextrose (Amb) or in a lipid emulsion (Intralipid, Amb-IL) in AIDS patients with cryptococcal meningitis, we conducted a retrospective study in 30 AIDS patients with cryptococcal meningitis. A clinical complete resolution was obtained in 11 patients (55%) treated with Amb, and in six patients (60%) treated with Amb-IL. Intralipid did not decrease the infusion-related adverse effects, in particular nephrotoxicity and anaemia. Our results indicate that Amb-IL formulation is useful in the treatment of cryptococcal meningitis in AIDS patients, but it does not reduce the infusion-related adverse events.

Serum levels of Fas/Apo-1 and Bcl-2 in children with HIV-1 infection.

Apoptosis of CD4-positive T cells is considered to be involved in depletion of CD4-positive T cells in adult patients with HIV-1 infection. In this report we evaluated serum levels of soluble Fas/Apo-1 and circulating bcl-2 protein (an antiapoptotic molecule) in HIV-1-infected children, and 30 HIV-1 seronegative children. Significantly higher levels of Fas/Apo-1 were observed in 13 HIV-1-infected children than in non-infected control children (p < 0.001), whereas serum levels of bcl-2 were significantly decreased (p=0.002). Seronegative children born to HIV-infected mothers displayed significantly decreased (p < 0.05) serum levels of bcl-2. By contrast, children born to HIV-seronegative mothers and suffering from acute lower respiratory infection had normal levels of bcl-2 and Fas/Apo-1. These data suggest that upregulation of Fas/Apo-1 along with downregulation of bcl-2 protein may contribute to apoptosis in children with HIV-1 infection.

Increased levels of nitrite in the sera of children infected with human immunodeficiency virus type 1.

Nitric oxide (NO) is a newly discovered gas that plays an important role in cell communication and host resistance to infection. The production of NO was examined in the sera of seven children infected with human immunodeficiency virus type 1 (HIV-1) and in the sera of 14 children who became seronegative for HIV-1 during the first year of life. In addition, we determined serum levels of various cytokines, such as interleukin (IL)-1 beta, tumor necrosis factor (TNF)-alpha, and gamma interferon (IFN-gamma), inasmuch as these cytokines are potent inducers of NO production. Production of NO, detected as circulating serum levels of nitrite, was measured with use of the Griess reagent. Serum levels of cytokines were determined by enzyme immunoassay. Increased serum levels of nitrite were observed in children with HIV-1 infection (0.4 +/- 0.2 mumol/L; P = .013), and in those who became seronegative for HIV-1 during the first year of life (0.5 +/- 0.3 mumol/L; P = .04). Furthermore, serum levels of IL-1 beta and TNF-alpha were significantly elevated in children with HIV-1 infection (37.5 +/- 23.6 pg/mL and 91.2 +/- 45.1 pg/mL, respectively). Prophylactic administration of intravenous immune globulin provoked a significant decrease of circulating levels of nitrite in children with HIV-1 infection. In conclusion, NO may play a role as a cytostatic or cytotoxic factor for invading microorganisms, and thus it is probably involved in limiting and/or eradicating infection.

Circulating fibronectin and fibronectin receptor in children with pertussis.

AIM: To determine concentrations of fibronectin and fibronectin receptor in children with pertussis. METHODS: Concentrations of circulating fibronectin and serum fibronectin receptor were detected in eight children affected by pertussis, eight children with acute upper or lower respiratory tract infections, and in 14 healthy control children. The single radial immunodiffusion technique and a solid phase enzyme immunoassay were used to detect circulating serum concentrations of fibronectin and fibronectin receptor. RESULTS: On admission, a significant decrease in fibronectin was detected in children with pertussis (p = 0.0006). Significant and decreased concentrations of fibronectin were also observed in children with upper or lower respiratory tract infections (p = 0.0002). On the other hand, serum fibronectin receptor concentrations were significantly increased in patients with pertussis, whereas patients with upper or lower respiratory tract infections had normal circulating fibronectin receptor concentrations. CONCLUSIONS: Fibronectin deficiency in children with pertussis may be related to diffusion and deposition of this protein in bronchial and alveolar spaces to limit infection, while increased fibronectin receptor concentrations are probably the expression of T cell activation and cell-mediated immunity during Bordetella pertussis infection.

Aseptic meningitis caused by Leptospira australis.

Meningeal involvement in leptospiral infection is quite common, usually mild and often overlooked. In contrast, cases of isolated involvement of the central nervous system, including aseptic meningitis, have been reported only rarely. A case of a patient with acute aseptic meningitis caused by Leptospira australis serovar bratislava is reported. This is believed to be the first report of aseptic meningitis due to Leptospira australis. This case indicates the need to consider human leptospirosis in the differential diagnosis of aseptic meningitis.

Levels of circulating fibronectin receptor in adult and pediatric patients with human immunodeficiency virus type 1 infection.

We found a significant increase in fibronectin receptor (FNR) levels in the sera of adult human immunodeficiency virus type 1 (HIV-1)-infected patients, especially in those with AIDS (1,026.9 +/- 583.9 ng/ml; P < 0.0001). In contrast, AIDS patients with neurologic disorders and HIV-1-seropositive patients showed normal levels of FNR in serum. In addition, HIV-1-infected children showed increased levels of FNR in serum (824.4 +/- 333.5 ng/ml; P = 0.03). We suggest that an increase of FNR levels in AIDS patients is related to enhanced expression of FNR on HIV-1-infected cells.

Cerebrospinal fluid concentration of fibronectin in patients with HIV-1 infection and central nervous system disorders.

AIMS: To evaluate the fibronectin concentrations in the cerebrospinal fluid of HIV-1 infected patients with central nervous system disorders. METHODS: Fibronectin was determined by an immunoturbidimetric assay in 41 HIV-1 infected patients with AIDS dementia complex, progressive multifocal leucoencephalopathy, and opportunistic infections. RESULTS: A significant decrease in fibronectin concentrations in the cerebrospinal fluid of patients with AIDS and dementia complex and progressive multifocal leucoencephalopathy was observed, as well as in those with opportunistic infections of the central nervous system (p < 0.0001). In particular, a significant decrease in fibronectin concentration in cerebrospinal fluid was observed in patients with cerebral toxoplasmosis and cryptococcal meningitis (p < 0.0001). CONCLUSIONS: Because fibronectin can bind to several viruses, fungi, and protozoa, it is conceivable to suppose that the consumption of fibronectin in the cerebrospinal fluid of patients with neurological disorders may be related to the binding of fibronectin to HIV itself, or to viral proteins, or to organisms responsible for opportunistic infections.

Acute-phase proteins and levels of interleukin 1B, interleukin 6, tumor necrosis factor alpha, and interleukin 8 in children with pertussis.

OBJECTIVE: To determine serum levels of acute-phase proteins and interleukin 1B, interleukin 6, tumor necrosis factor alpha, and interleukin 8 in children with pertussis. DESIGN: Cross-sectional study. SETTING: Divisions of Infectious Diseases, Regional Hospital, and Pediatrics, University of Pavia, Varese, Italy. PARTICIPANTS: Eight children with pertussis, six with acute febrile infections, and eight healthy control children matched for sex, age, and time presentation over a 32-month study period. INTERVENTIONS: None. MEASUREMENTS/MAIN RESULTS: An immunoenzymatic assay was used to detect serum levels of all cytokines. Normal values of C-reactive protein, alpha 1-acid glycoprotein, and erythrocyte sedimentation rate were observed in the serum of patients with pertussis. The mean (+/- SD) detectable levels of tumor necrosis factor alpha (65.0 +/- 50.4 pg/mL) and interleukin 6 (32.3 +/- 17.8 pg/mL) were observed in the serum of patients with pertussis. In contrast, a nonsignificant increment of interleukin 1B levels (66.5 +/- 83.7 pg/mL) and interleukin 8 levels (12.7 +/- 17.8 pg/mL) was noted in the serum of the same patients. Increased and significant levels of all four cytokines were noted in most of the serum samples of patients with acute febrile infections. CONCLUSIONS: Acute-phase response is absent in patients with pertussis, whereas detectable and significant serum levels of tumor necrosis factor alpha and interleukin 6 were observed in some such patients.

Ventriculoatrial shunt infection caused by Staphylococcus warneri: case report and review.

Staphylococcus warneri, a coagulase-negative species, is a rare cause of infection of cerebrospinal fluid (CSF) shunts. In one recently studied case of ventriculoatrial shunt infection, the repeated isolation of S. warneri (i.e., from all of six blood cultures and from a CSF sample obtained directly from the valve of the shunt) suggested that this organism can be clinically significant. Review of the literature clearly indicates that S. warneri is a rare but potentially dangerous pathogen in both immunocompetent and immunocompromised hosts with prosthetic devices. The removal of the infected shunt in association with systemic and local antibiotic administration probably constitutes the treatment of choice in such infections. Further experience is needed to determine the prevalence and the pathogenic significance of S. warneri and of the related organisms Staphylococcus epidermidis and Staphylococcus saprophyticus in patients with prosthetic devices.

Cerebrospinal fluid levels of IL-6 in patients with acute infections of the central nervous system.

Interleukin-6 (IL-6) activity was measured in the cerebrospinal fluid (CSF) of patients with acute bacterial or viral meningitis and in AIDS patients with various cerebral disorders. Increased levels of IL-6 were detected in the CSF of patients with bacterial meningitis. On the contrary, most of the samples from patients with viral meningitis (predominantly caused by mumps virus) had no detectable IL-6 activity in CSF. A moderate increase of IL-6 levels was detected in the CSF of AIDS patients with AIDS dementia complex (ADC), progressive multifocal leukoencephalopathy and cerebral toxoplasmosis. Moreover, higher levels of IL-6 were detected in the CSF of patients with cryptococcal meningitis. We conclude that the initial events of CSF inflammation in patients with acute viral meningitis are different from those in patients with acute bacterial meningitis, and the role of IL-6 is less critical to the process.