Antiretroviral therapy-induced dominant interleukin-2 HIV-1 Gag CD4+ T cell response: evidence of functional recovery of HIV-1-specific CD4+ T cells.

Prolonged antiretroviral treatment (ART) significantly changes the cytokine secretion capacities of HIV-1-specific T cells. However, it is unclear whether these changes result from decreased viremia or they correspond to true functional recovery of viral-specific immune response. To study this issue, we analysed the quantitative and qualitative differences of HIV-1-specific and polyclonal CD4+ and CD8+ T cells between 26 naive and 52 treated individuals. HIV-1 Gag and staphylococcal enterotoxin B (SEB)-reactive T cells were determined by flowcytometric intracellular secretion of IFN-γ or/and ΙL-2. ART resulted in increase of single IL-2 and decrease of single IFN-γ-secreting HIV-1 CD4+ T cells, while both cytokines secreting HIV-1 CD4+ T cells were presented in comparable frequencies in both groups. Viral loads correlated negatively with single IL-2 and positively with single IFN-γ-secreting HIV-1 CD4+ cells. Single IL-2 HIV-1 CD4+ T cells correlated positively with both cytokines secreting polyclonal CD8+ T cells. By qualitative analysis, a dominant IL-2 HIV-1 CD4+ T cell response (> 70% single IL-2) was identified only in ART suppressed patients, who also generated increased dual specific polyclonal CD8+ T cells. Polyfunctional HIV-1 CD4+ T cell responses were detected even in naive individuals with high viremia. In conclusion, the presence of dominant IL-2 HIV-1 CD4+ T cell response, associated with increased CD8+ T cells capable to produce IL-2, indicates that the recovery of HIV-1-specific CD4+ T cell functionality under ART is a feasible goal. Furthermore, polyfunctional HIV-1 CD4+ T cell responses seem not to be directly involved in viral replication control.

Early detection of subclinical HIV sensory polyneuropathy using intraepidermal nerve fibre density quantification: association with HIV stage and surrogate markers.

The linear intraepidermal nerve fibre density (IENFD) and secondary branching were evaluated from skin biopsy of both the distal calf and the proximal thigh after staining with protein gene product 9.5 in 94 individuals of an HIV outpatient cohort. Possible correlations with clinical and electrophysiological evidence of distal sensory polyneuropathy (DSP), patients' demographics, antiretroviral history and HIV surrogate markers were analysed. Reduced IENFD was recognized in the majority of this population (mean +/- standard deviation [SD] IENFD in the calf and the thigh was 3.19 +/- 1.91 and 7.07 +/- 3.5 fibres/mm, respectively). One-third of the patients with low IENFD had no clinical or electrophysiological evidence of DSP. The level of prior immunosuppression as expressed by lower nadir CD4 count, more advanced HIV stage and prior exposure to combinations of neurotoxic antiretrovirals was associated with more decreased IENFD. Increased SB was associated with symptomatic DSP.

Distal sensory polyneuropathy in HIV-positive patients in the HAART era: an entity underestimated by clinical examination.

The aim of this study was to determine the prevalence of distal sensory polyneuropathy (DSP) in our HIV-positive patients under highly active antiretroviral therapy (HAART) and to investigate correlations with clinical, laboratory and demographic factors. One hundred consecutive HIV-positive patients underwent clinical and electrophysiological evaluation for DSP. Correlations with HIV stage, CD4 count, nadir CD4 count, viral load (VL), disease duration, age, sex and type of antiretrovirals were examined. Thirty-six percent of the patients had DSP (13% clinical, 23% subclinical diagnosed by electrophysiology). The prevalence of DSP was affected in a statistically significant manner by the diagnosis of AIDS (P = 0.00033), age (P = 0.0102), nadir CD4 count (P = 0.0087) and exposure to two neurotoxic antiretrovirals (P = 0.0189). Advanced HIV stage, sex, time from diagnosis, current CD4 count and VL did not seem to affect the prevalence of DSP. Clinical examination plus electrophysiology reveals that DSP affects 36% of patients under HAART, although subclinical in 2/3 of cases. Age, severe prior immunosuppression and the combined use of zalcitabine (ddC), stavudine (d4T) and didanosine (ddI) are important risk factors.

Prevalence of resistance-associated mutations in newly diagnosed HIV-1 patients in Greece.

The prevalence of HIV-1 drug resistance mutations in naïve patients has been previously shown to differ greatly with the geographic origin. The purpose of this study was to prospectively estimate the prevalence of HIV-1 drug resistance in Greece by analyzing a representative sample of newly HIV-1 diagnosed patients, as part of the SPREAD collaborative study. Protease (PR) and partial reverse transcriptase (RT) sequences were determined from 101 newly diagnosed HIV-1 patients, in Greece, during the period September 2002--August 2003, representing one-third of the total newly diagnosed HIV-1 patients in the same time period. The prevalence of HIV-1 drug resistance was estimated according to the IAS-USA mutation table taking into account all mutations in RT and only major mutations in PR region. The overall prevalence of resistance was 9% [95% confidence interval (CI): 4.2--16.2%]. The prevalence of mutations associated with resistance to NRTIs was 5% (95% CI: 1.6--11.2%), for NNRTIs was 4% (95% CI: 1.1--9.8%), while no major resistance mutations were found in PR. No multi-class resistance was detected in the study population. The prevalence of resistant mutations in the recent seroconverters was 22%. For two individuals, there was clear evidence for transmitted resistance based on epidemiological information for a known source of HIV-1 transmission. The prevalence of the HIV-1 non-B subtypes and recombinants was 52%.

Pretransplantation prevalence of human herpes virus 8 antibodies in kidney donors and recipients in Athens, Greece.

AIM: The aim of this study was to estimate the prevalence of anti-human herpes virus 8 (HHV8) antibodies in a cohort of renal donors and recipients in Athens, Greece. HHV8, the etiological agent of posttransplantation Kaposi's sarcoma, causes significant morbidity and mortality. METHODS: Serum samples from 97 subjects (49 donors and 48 recipients) were tested with an enzyme-linked immunosorbent assay (ELISA) prior to renal transplantation. RESULTS: Only 2 subjects (both transplant recipients) were found to be anti-HHV8-positive. Both subjects were of Albanian origin. CONCLUSION: Infection with HHV8 appears to be limited in the Greek population. However, in light of significant long-term morbidity with which HHV8 is related in immunocompromized patients, studies on the general population are needed to estimate the prevalence of HHV8 infection in the country and devise clear guidelines for pretransplantation screening and posttransplantation follow-up.

Downregulation of CD28 surface antigen on CD4+ and CD8+ T lymphocytes during HIV-1 infection.

A progressive significant decrease of CD28 surface antigen expression on CD4+ (mean, 90, 86, 79, 68% in stages I, II, III, and IV, respectively, versus 96% in normals), as well as on CD8+ T lymphocytes (mean, 38, 32, 31, and 29% in stages I, II, III, and IV, respectively, versus 47% in normals) was observed during HIV-1 infection. The increase of cytotoxic/suppressor T cells, in both percentage and absolute numbers, that was observed in almost all HIV-1 patients, was associated with an increase of the CD8+ cells lacking the CD28 surface antigen. The loss of CD28 antigen expression was parallel to the increase of CD38, human leukocyte antigen (HLA)-DR, and CD45RO antigen expression on T lymphocytes throughout the disease. Furthermore, a positive significant correlation within the CD4+ but not the CD8+ subset was observed between the percentage of cells lacking the CD28 antigen and the percentage of cells expressing the HLA-DR and CD38 antigens, a finding suggesting that the loss of CD28 antigen expression on CD4+ lymphocytes may be associated with T-lymphocyte activation. Patients treated with zidovudine showed no significant differences in the percentages of either CD4+CD28+ or CD8+CD28+ T-cell subsets when compared to untreated patients. These phenotypic changes may be associated with the functional defects of T lymphocytes in HIV-1 infected individuals.

Lung squamous cell carcinoma presenting with brain metastases in an HIV-positive patient.

The case history of a patient with squamous cell carcinoma of the lung and HIV infection is described, who presented clinically with CNS symptomatology. No association of the tumor with human papilloma virus was found.

Virological and immunological response to HAART therapy in a community-based cohort of HIV-1-positive individuals.

PURPOSE: To determine virological and immunological response to highly active antiretroviral therapy (HAART) and to investigate factors influencing response in a community-based setting. METHOD: Plasma HIV RNA levels and CD4 cell counts were studied in 168 unselected individuals starting HAART including indinavir or ritonavir or hard-gel saquinavir-containing regimens. RESULTS: Overall, 60% of the patients reduced their HIV RNA to below 500 Eq/mL, but half of them experienced a subsequent virologic rebound. Patients with higher baseline HIV RNA, higher baseline CD4 cell count, and simultaneous initiation of combination therapy and patients on indinavir or ritonavir regimen were more likely to have virologic response within 6 months since HAART initiation. Patients with lower baseline CD4 cell count and with lower rates of viral clearance had a higher probability of a subsequent virologic rebound. Forty percent of the patients had increased their CD4 cell counts by more than 100 cells/microL (immunologic response). The probability of immunologic response was independent of baseline HIV RNA levels and CD4 cell count; however, the more complete the virologic suppression, the higher the probability of immunologic response. Thirty percent of the patients had discordance between virologic and immunologic responses. CONCLUSION: The rate of virologic failure in this unselected group of patients was higher than that observed in randomized clinical trials, but only a minority (11%) of the patients were treatment naïve. Starting combination therapy simultaneously and initiating antiretroviral therapy before advanced HIV disease has developed predict virologic response, whereas the magnitude of viral suppression predicts mid to long immunological response.

Facial heliotrope rash as the initial manifestation of acute myelomonocytic leukemia.

The association of leukocytoclastic vasculitis or dermatomyositis with malignancies has been reported. We describe a patient who developed a skin rash, histologically compatible with dermatomyositis, which during the course of the disease switched to leukocytoclastic vasculitis, which was accompanied with peripheral blood pancytopenia in the absence of any specific pathological manifestation from the bone marrow three years prior to the diagnosis of acute myelomonocytic leukemia (AMML).

Extranodal non-Hodgkin lymphoma presenting as a soft tissue mass in the proximal femur in a HIV(+) patient.

Primary soft tissue non-Hodgkin lymphomas (NHL) are very rare especially among HIV-1 infected patients. We describe a patient with HIV-1 infection who presented with acute pain of the right proximal femur. The clinical and laboratory investigation revealed a high grade centroblastic B-cell lymphoma of soft tissue. The patient was treated by surgical resection of the tumor, chemotherapy and local radiotherapy with no serious side effects. After 36 mdnths of follow up he is in excellent clinical condition, with his lymphoma in complete remission.

Non-organ specific autoantibodies against cellular components in HIV-1 infected individuals.

OBJECTIVE: To detect the presence of autoantibodies against cellular components in HIV-1 infected individuals. METHODS: Serum samples from 87 patients with HIV-1 infection and from 17 healthy HIV-seronegative controls were tested using sensitive and specific techniques (immunoblot, RNA precipitation), as well as counterimmunoelectrophoresis and indirect immunofluorescence. RESULTS: Four sera (4.6%) showed reactivity in immunoblot against various unidentified cytoplasmic autoantigens. The four positive sera were obtained from patients belonging in equal numbers to the non-AIDS and AIDS groups. CONCLUSION: It appears that the production of antibodies against cellular components rarely occurs during the clinical course of HIV infection.

Serum concentrations of soluble intercellular adhesion molecule-1 and progress towards disease in patients infected with HIV.

Intercellular adhesion molecule-1 (ICAM-1) is a membrane-bound molecule that is primarily involved in cell to cell adhesive interactions of the immune system. Concentrations of soluble ICAM-1 (s-ICAM-1) shed into the circulation were measured by a quantitative ELISA in HIV-infected persons without AIDS, patients with AIDS with or without evidence of acute opportunistic infection at the time of sampling, and HIV-seronegative patients with toxoplasmosis, community-acquired pneumonia, leishmaniasis and rickettsial infections. Patients were classified on the basis of clinical condition and CD4+ T-cell counts according to the 1993 revised HIV classification of the USA Centers for Disease Control. Concentrations of s-ICAM-1 in the serum of HIV-infected persons without AIDS-indicator conditions (categories A1, A2, B1 and B2) as well as in the serum of patients with AIDS (categories A3, B3, C1, C2 and C3) were significantly higher than normal (mean +/- S.E.M. 469 +/- 23, n = 60 and 780 +/- 73, n = 56, respectively, versus 329 +/- 15 ng/ml, P < 0.0001 and < 0.0001 respectively) and differed also significantly from each other (P < 0.0001). Raised concentrations of s-ICAM-1 in the serum of afebrile patients with AIDS but without acute opportunistic infection at the time of sampling (mean +/- S.E.M. 672 +/- 76, n = 29) did not differ from those of the remaining patients with AIDS or from those of HIV-seronegative patients with the infections studied. A steady and significant increase of serum concentrations of s-ICAM-1 with progress of disease according to clinical category (categories A-->B-->C, p = 0.0007) as well as with the loss of circulating CD4+ T-cells (categories 1-->2-->3, p = 0.009) was observed. Individual serum concentrations of s-ICAM-1 showed negative correlations with individual total lymphocyte (P = 0.004), CD4+ T-cell (P = 0.05), CD8+ T-cell counts (P = 0.03) as well as positive correlation with serum concentrations of soluble interleukin-2 receptors (P < 0.0001), an indirect marker of progress of HIV-related disease. Serum concentrations of s-ICAM-1 did not differ between patients with AIDS who were receiving or not receiving zidovudine at the time of sampling. A longitudinal survey is needed in order to determine whether measuring serum concentrations of s-ICAM-1, although not specific, has any predictive or prognostic value in these patients as well as whether this bioactive molecule has any pathogenetic role in the progress of disease in HIV infection.

Bone marrow infection caused by Actinobacillus ureae in a rheumatoid arthritis patient.

A patient with rheumatoid arthritis is described who presented with low-grade fever for 3 months, in whom Actinobacillus ureae was cultured from bone marrow aspirate. Fever responded favourably to penicillin therapy. It is the first reported isolation of A. ureae from bone marrow.

Lactobacillus rhamnosus endocarditis complicating colonoscopy.

We report the first case of endocarditis caused by Lactobacillus after an uneventful colonoscopy. The initial empiric treatment with the standard regimen of penicillin-aminoglycoside failed; subsequent treatment with a combination of antibiotics, selected according to the in vitro studies, was successful.

The prevalence of hepatitis B and C in HIV-positive Greek patients: relationship to survival of deceased AIDS patients.

OBJECTIVES: To determine the prevalence of hepatitis viruses B (HBV) and C (HCV) co-infections in HIV-infected patients and the overall impact of these co-infections on deceased AIDS patients survival. METHODS: One hundred and eighty-one patients (159 males, 22 females) infected with HIV, attending an academic AIDS unit in Athens, Greece, constituted the study population. The study population consisted of 124 homo/bisexual men, 34 heterosexuals, 12 intravenous drug users (IDU) and 11 blood transfusion recipients. Virological markers tested for HBV infection included HBsAg, anti-HBs and total anti-HBc by enzyme-linked immunoassays. Detection of HCV antibodies was carried out by third generation enzyme-linked immunoassay, and repeatedly positive samples were further tested by a supplemental enzyme-linked immunoassay; only sera reactive by both methods were considered to be HCV-positive. RESULTS: The prevalence of HBV markers was 67.4%: 71.8% in homo/bisexuals, 35.3% in heterosexuals, 91.7% in IDUs and 90.9% in blood transfusion recipients (P = 0.00004). The prevalence of HCV antibodies was 13.8%: 8.1% in homo/bisexuals, 8.8% in heterosexuals, 58.3% in IDU and 45.5% in blood transfusion recipients (P<0.000001). The prevalence of HCV antibodies was not significantly higher in homo/bisexuals than in heterosexuals (P= 0.8). Coinfection with HBV or HCV, or both, did not influence the survival of deceased AIDS patients (n = 73). CONCLUSIONS: HBV infection was equally prevalent among homo/bisexuals and IDU with HIV infection, whereas HCV infection was more prevalent in IDU than in homo/bisexuals with HIV infection. The prevalence of HCV infection was equal among heterosexuals and homo/bisexuals, indicating that if sexual transmission of HCV occurs, homo/bisexuals are not at greater risk than heterosexuals. Finally, the survival of deceased AIDS patients was not affected by the presence of HBV and HCV co-infections.

Gallbladder contraction after administration of intravenous amino acids and long-chain triacylglycerols in humans.

We examined the possible physiologic effects of intravenous (IV) amino acids (AAs) and long-chain triacylglycerols (LCTs) on gallbladder (GB) motility and release of cholecystokinin (CCK) on humans. GB contraction was studied in normal volunteers after administration of a fatty meal and IV infusion of AA and LCT. The GB contraction volume was calculated with ultrasound. Cholecystokinin-8 (CCK-8) and cholecystokinin-33/39 (CCK-33/39) were measured by radio-immunoassay. Administration of a fatty meal resulted in GB contraction by 60% of its basal volume and was accompanied by an increase in the serum levels of both CCK-8 and CCK-33/39. Administration of IV AA and LCT resulted in GB contraction by 17 and 37%, respectively, of its basal volume. The latter contractions were accompanied by increased levels of CCK-8 only. We conclude that IV administration of AA and LCT can result in human GB contraction and induce the release of only CCK-8. Continuous IV administration of AA and LCT for greater than 2h causes exhaustion of CCK-8 release, so that the GB returns to its initial volume.

Eosinophilic granuloma of the femur in an HIV-1-positive patient.

A case of eosinophilic granuloma in the right femur of an HIV-1-infected patient is described, and the possible pathogenetic role of HIV infection in eosinophilic granuloma formation is discussed.

Herpes simplex virus types 1 and 2 and cytomegalovirus in peptic ulcer disease and non-ulcer dyspepsia.

The prevalence and the serum levels of IgG antibody to Herpes simplex virus type 1 or 2 (HSV1, HSV2) and to cytomegalovirus (CMV) were studied by ELISA in patients with active peptic ulcer -- duodenal and gastric -- and non-ulcer dyspepsia. Two hundred and forty-two consecutive patients with endoscopically confirmed active peptide ulcer -- 170 duodenal ulcers, 72 gastric ulcers -- and 95 consecutive patients who fulfilled the criteria for the diagnosis of non-ulcer dyspepsia were included in the study. The patients, aged 17-80 years, were well matched for age and sex. Antibody to cytomegalovirus was found in 83% of duodenal ulcer, 85% of gastric ulcer and 75% of non-ulcer dyspepsia patients; differences were not significant. The prevalence of HSV1 antibody was significantly higher in patients with duodenal ulcer than in those with non-ulcer dyspepsia (p < 0.025); the prevalence of HSV2 antibody was significantly higher in patients with duodenal or gastric ulcer, than in those with non-ulcer dyspepsia (p < 0.05, p < 0.01, respectively); however, antibody levels (mean optical density) to the viruses studied were similar for all groups of patients. These results provide some evidence that HSV might be implicated in the pathogenesis of peptic ulcer disease.

An unusual case of brucellar spondylitis involving both the cervical and lumbar spine.

We report an unusual case of brucellar spondylitis, involving both the cervical and lumbar spine. Diagnosis was established using magnetic resonance imaging (MRI). An initial plain radiograph of the lumbar spine, showing mild degenerative lesions, was misleading. Therefore, institution of a proper treatment was delayed.