Partial restoration of cytokine profile despite reconstitution of cytomegalovirus-specific cell-mediated immunity in human immunodeficiency virus-infected patients during highly active antiretroviral treatment.

We reconstituted cytomegalovirus (CMV)-specific T-cell responses in human immunodeficiency virus-1-positive, CMV-positive patients receiving highly active antiretroviral treatment (HAART). We used several combinations of functionality parameters to determine the degree of T-lymphocyte reconstitution obtained during 1 year of treatment. Untreated patients displayed CMV-specific cytotoxic T-lymphocyte (CTL) activity despite the absence of CMV-specific lymphoproliferative responses (LPRs) and despite the fact that interferon-gamma (IFN-gamma) and interleukin-2 (IL-2) were not secreted. The absence of LPRs, IFN-gamma and IL-2 before antiretroviral treatment suggests that CMV-specific immunity was deregulated despite the high CD4+ T-cell counts presented by our cohort, which are critical to the reactivation of CMV disease. After 6 months of HAART, CTL activity had increased compared with the baseline, as had the levels of secreted IFN-gamma and LPR. However, the levels of specific IL-2 produced did not change during therapy, and no specific IL-2 was detected during the follow-up period. Taken together, our findings suggest that 1 year of HAART led to the recovery of some, but not all, CMV-specific responses in our cohort of patients.

Temporary restoration of immune response against Toxoplasma gondii in HIV-infected individuals after HAART, as studied in the hu-PBMC-SCID mouse model.

We studied immune reconstitution against the parasite T. gondii in HIV-infected patients treated for 1 years with highly active antiretroviral therapy (HAART). We used SCID mice, humanized with peripheral blood mononuclear cells (PBMC) from patients, which were then infected with T. gondii cysts. Mice humanized with PBMC from patients before the start of HAART were highly susceptible to infection. In contrast, mice humanized with PBMC from patients who had received HAART for 6 months displayed higher survival rates, correlating with lower intracerebral parasite loads. However, this resistance was lost during follow up because mice humanized with PBMC from patients treated with HAART for 12 months survived for no longer than mice that had not been humanized. Specific lymphocyte proliferation assays showed that the increase in proliferative response depended on treatment duration and that HAART induced changes in IFN-gamma secretion in the presence of Toxoplasma antigens. Thus, our results indicate partial immune reconstitution against T. gondii in HIV-infected patients following HAART, possibly due to changes in the patterns of specific IFN-gamma production and redistribution of functional memory CD4+ cells.

Effect of adding clofazimine to combined clarithromycin-ethambutol therapy for Mycobacterium avium complex septicemia in AIDS patients.

This study compared the efficacies of clarithromycin-ethambutol and clarithromycin-ethambutol-clofazimine for the treatment of Mycobacterium avium complex (MAC) in AIDS patients. Thirty-four patients were randomized into two groups to receive clarithromycin 2 g/day and ethambutol 20 mg/kg/day, with or without clofazimine 200 mg/day. The evaluation was based primarily on blood cultures becoming negative after 2 months of therapy, but survival at 12 months and clinical evolution were also assessed. Inclusions were prematurely stopped because of a communication reporting increased mortality associated with clofazimine. At 2 months, the blood cultures of 55% of the clarithromycin-ethambutol group patients versus 81% of the clarithromycin-ethambutol-clofazimine group were negative; this difference is not significant (P=0.42). Only one relapse was observed during the study. No clarithromycin-resistant strain was isolated. No apparent difference in either survival or clinical evolution was observed in this small number of patients (median survival, 144 days in the clarithromycin-ethambutol group and 236 days in the clarithromycin-ethambutol-clofazimine group, P=0.44). The clarithromycin-ethambutol combination appears to be an effective and well-tolerated first-line therapy against MAC infections in AIDS patients.

Oral transmission of Candida albicans between partners in HIV-infected couples could contribute to dissemination of fluconazole-resistant isolates.

BACKGROUND: Fluconazole resistance has emerged among Candida albicans isolates and has been associated with the prolonged or repeated use of the drug. This study was designed to discover whether transmission of oral isolates could occur between sexual partners and thereby explain fluconazole resistance in patients never treated with the drug. MATERIALS AND METHODS: The oral flora of 10 HIV-infected couples (five heterosexual and five homosexual) were studied. In vitro susceptibility testing and genotyping (restriction fragment length polymorphism with EcoRI and HinfI) were used to delineate strain relatedness for 230 clones (five clones per sample, one to four samples per patient). RESULTS: The genetic diversity of the clones with one DNA subtype was specific to a given patient or a given couple, except in one case in which unrelated patients shared clones of the same genotype. The persistence of clones between partners was stable over time in six out of 10 couples and only transient in one couple. Fluconazole resistance in isolates from patients who had never been treated with azoles was associated in three patients with the first episode of oropharyngeal candidiasis and treatment failure. CONCLUSION: The observation that couples tended to share genetically indistinguishable clones was highly suggestive of transmission between partners. This phenomenon may, in part, explain the pathogenesis of oropharyngeal candidiasis and the increased frequency of fluconazole resistance both in vitro and in vivo.

Infections associated with totally implantable venous access devices (TIVAD) in human immunodeficiency virus-infected patients.

We report on a retrospective study evaluating infectious morbidity associated with totally implantable venous access devices (TIVAD) (Port-A-Cath) in HIV-infected patients. This study of 84 consecutive HIV-infected patients requiring 89 TIVAD between January 1990 and October 1993 was performed in the Department of Infectious Diseases Hôpital de l'Institut Pasteur, Paris, France. The total number of catheter days was 11,595. Eighteen of 89 patients with TIVAD (20%) were infected, causing 25 infectious events (25/89: 28%) among 17 different patients (17/84: 20%). The infection rate was 0.22 per 100 catheter days. Mean onset of infection was 82 days. Twenty microorganisms were isolated: Staphylococcus aureus in eight cases (40%), coagulase-negative Staphylococcus in six cases (30%), Streptococcus D faecalis in one case; Gram-negative bacilli were found in five cases (25%). All patients received an intravenous antibiotherapy combined with a local lock treatment in eight cases. Nine TIVAD removals were performed. One death was related to the TIVAD infection. No additional predisposing factor for infection was identified other than the implied condition of the HIV infection. The population and material in this study were homogeneous. The TIVAD infection rate was comparable to other published reports. Prospective evaluation comparing tunneled catheter and TIVAD in HIV-infected patients is needed.

Acute retinal necrosis in the course of AIDS: study of 26 cases.

OBJECTIVE: To report 26 cases of acute retinal necrosis (ARN) in HIV-infected patients, to compare these data with the literature and to discuss the clinical spectrum of ARN during HIV infection. DESIGN AND SETTING: Twenty-six HIV-infected patients with ARN, collected from five ophthalmology departments in Paris (France) between 1985 and 1993, were analysed retrospectively. PATIENTS: Twenty-eight patients were enrolled; two were lost of follow-up. Diagnosis of ARN was established on the following criteria: (1) inflammation of the anterior segment and the characteristic triad, and (2) peripheral circular necrosis with centripetal progression toward the posterior pole associated with occlusive periarteritis and inflammation of the vitreous. RESULTS: ARN is a late event in the course of immunosuppression (CD4+ lymphocyte count < 100 x 10(6)/l). The most frequent presenting syndrome is a decrease of visual acuity, but signs related to a retrobulbar optic neuritis may also be present. In 60-90% of cases, vesicular viral eruption, usually shingles, precedes the onset of ARN by several days. Occasionally, neurological impairment is also present. Progression to blindness occurs in 76-85% of cases, bilaterally in 59%, and is usually induced by retinal detachment. This study and literature data suggest that varicella zoster virus (VZV) is directly implicated in the onset of ARN. At present, the most efficient therapeutic schedule is unknown. CONCLUSION: ARN is a rare and serious disease in AIDS patients. It is often associated with VZV infection. There is no preventive or curative efficient treatment. ARN might be considered as another opportunistic infection because of its rapid clinical evolution and severe prognosis.

[Infectious complications of implantable catheters in HIV infected patients. Retrospective study of 46 patients]. / Complications infectieuses des cathéters à chambre implantable chez des malades infectés par le VIH. Etude rétrospective de 46 patients.

OBJECTIVES: Investigate the rate of infection in HIV positive patients with an implantable venous access device. METHODS: Forty-six totally implantable venous access devices (port-a-cath, PAC) were inserted in 46 HIV infected patients between January 1990 and May 1992. We analyzed the rate of infectious complications and tried to find predictive factors. RESULTS: There were five infectious complications in five patients. The total complication rate was 0.06 per 100 catheter days. Staphylococcus aureus was responsible in two cases, Staphylococcus epidermidis was responsible in one case and Acinetobacter in one case. No predictive factor was recognized. CONCLUSION: The rate of PAC infection was lower than in other published studies concerning HIV-infected patients. Totally implantable central venous access devices play an increasingly important role in the clinical management of HIV-related diseases. We have shown that the PAC device is safe and convenient in HIV-infected patients.

Cerebral glial tumors and human immunodeficiency virus-1 infection. More than a coincidental association.

BACKGROUND: The authors describe the clinical and morphologic patterns in four patients with acquired immune deficiency syndrome (AIDS) who developed intracranial glial tumors. METHODS: This retrospective study reports 70 patients at various stages of human immunodeficiency virus-1 (HIV-1) infection who underwent stereotactic brain biopsy for an intracerebral space-occupying lesion. RESULTS: Of these patients, four had glial tumors: one astroblastoma, two astrocytomas, and one glioblastoma. Glial tumors probably arise from a complex interplay of factors; possibilities include the activation of a dominant oncogene or viral inactivation of a tumor suppressor gene by a viral promoter (like the tat protein), impairment of immune defenses (which facilitates the growth of astrocytomas in acute lymphoblastic leukemia), production of cellular growth factors, cytokines, possible infection of glial cells by HIV, and the potentiation of a coinfectious agent. CONCLUSIONS: These cases illustrate that glial tumors should be considered in the differential diagnosis of brain masses in HIV-1 infection, especially because specific treatment for these tumors is available. Moreover, the occurrence of glial tumors in AIDS patients is not only an important event from a clinical point of view, but may also have implications for the pathogenesis of tumors in AIDS.

Infection due to Klebsiella rhinoscleromatis in two patients infected with human immunodeficiency virus.

Two cases of rhinoscleroma in patients infected with the human immunodeficiency virus (HIV) who had stayed in an area of endemic Klebsiella rhinoscleromatis are reported. One of the patients presented with oropharyngeal lesions, an unusual clinical picture. Both patients suffered from a major cellular immune deficiency. The importance of Klebsiella rhinoscleromatis infection in AIDS-related oropharyngeal pathology and the possible treatment of such infection in HIV-positive patients are not yet clearly established.

[Cerebral glioblastoma: a new complication of HIV-1 infection]. / Glioblastome cérébral: nouvelle complication de l'infection par le VIH 1.

A new case of supratentorial malignant glioma is reported in an HIV-1 infected male homosexual. Tumours of the nervous system account for only 5 to 10 percent of neurological complications of AIDS, and most of them are lymphomas or metastases from Kaposi's sarcomas. In fact, HIV-1 is a neurotropic lentivirus, not transforming by definition. Our patient had a frontal tumoral syndrome resistant to the conventional anti-toxoplasmic treatment. Pathological examination of a tumoral fragment obtained by stereotactic biopsy showed that according to the WHO criteria the tumour was a glioblastoma. The mechanism through which HIV infection results in malignant transformation of astrocytes is conjectural. There is no consensus on whether the virus is located in glial cells, but the transgenic animal technique suggests that the tat gene might play a certain role. Other hypotheses concerning the indirect neurotoxicity of HIV have been put forward, notably that of viral coinfection with viruses of the papova group.

Toxoplasma colitis in the acquired immunodeficiency syndrome.

In patients with acquired immunodeficiency syndrome (AIDS), toxoplasmosis almost exclusively involves the central nervous system (CNS), and extra-CNS organ infection is rare. We report a case of Toxoplasma gondii colitis in a patient with AIDS characterized by the following: 1) onset of diarrhea was simultaneous with disseminated toxoplasmosis; 2) T. gondii was found in colonic biopsies, whereas other infectious causes of diarrhea had been ruled out; 3) diarrhea was cured by anti-Toxoplasma therapy.

Pentamidine-induced acute pancreatitis in a patient with AIDS.

We report pentamidine-induced acute pancreatitis in a patient with the acquired immunodeficiency syndrome (AIDS). The course of this pancreatitis was prolonged but favorable. Pentamidine was detected in serum as late as one month after discontinuation of therapy. The special pharmacokinetics of this drug may account for the potential severity of pentamidine-induced acute pancreatitis.