Absence Of Human Immunodeficiency Virus Infection Research Articles

A Longitudinal, Observational Study of Etiology and Long-Term Outcomes of Sepsis in Malawi Revealing the Key Role of Disseminated Tuberculosis.

BackgroundSepsis protocols in sub-Saharan Africa are typically extrapolated from high-income settings, yet sepsis in sub-Saharan Africa is likely caused by distinct pathogens and may require novel treatment strategies. Data to guide such strategies are lacking. We aimed to define causes and modifiable factors associated with sepsis outcomes in Blantyre, Malawi, in order to inform the design of treatment strategies tailored to sub-Saharan Africa.MethodsWe recruited 225 adults who met a sepsis case definition defined by fever and organ dysfunction in an observational cohort study at a single tertiary center. Etiology was defined using culture, antigen detection, serology, and polymerase chain reaction. The effect of treatment on 28-day outcomes was assessed using Bayesian logistic regression.ResultsThere were 143 of 213 (67%) participants living with human immunodeficiency virus (HIV). We identified a diagnosis in 145 of 225 (64%) participants, most commonly tuberculosis (TB; 34%) followed by invasive bacterial infections (17%), arboviral infections (13%), and malaria (9%). TB was associated with HIV infection, whereas malaria and arboviruses with the absence of HIV infection. Antituberculous chemotherapy was associated with survival (adjusted odds ratio for 28-day death, 0.17; 95% credible interval, 0.05–0.49 for receipt of antituberculous therapy). Of those with confirmed etiology, 83% received the broad-spectrum antibacterial ceftriaxone, but it would be expected to be active in only 24%.ConclusionsSepsis in Blantyre, Malawi, is caused by a range of pathogens; the majority are not susceptible to the broad-spectrum antibacterials that most patients receive. HIV status is a key determinant of etiology. Novel antimicrobial strategies for sepsis tailored to sub-Saharan Africa, including consideration of empiric antituberculous therapy in individuals living with HIV, should be developed and trialed.

The Molecular and Phenotypic Profile of Primary Central Nervous System Lymphoma Identifies Distinct Categories of the Disease and Is Consistent With Histogenetic Derivation From Germinal Center–Related B Cells

AbstractPrimary central nervous system lymphoma (PCNSL) is a major cause of morbidity and mortality among human immunodeficiency virus (HIV)-infected individuals. The precise histogenetic derivation and the molecular pathogenesis of PCNSL is poorly understood. In an attempt to clarify the histogenesis and pathogenesis of these lymphomas, 49 PCNSL (26 acquired immunodeficiency syndrome [AIDS]-related and 23 AIDS-unrelated) were analyzed for multiple biologic markers, which are known to bear histogenetic and pathogenetic significance for mature B-cell neoplasms. PCNSL associated frequently (50.0%) with mutations of BCL-6 5′ noncoding regions, which are regarded as a marker of B-cell transition through the germinal center (GC). Expression of BCL-6 protein, which is restricted to GC B cells throughout physiologic B-cell maturation, was detected in 100% AIDS-unrelated PCNSL and in 56.2% AIDS-related cases. Notably, among AIDS-related PCNSL, expression of BCL-6 was mutually exclusive with expression of Epstein-Barr virus (EBV)-encoded latent membrane protein (LMP)-1 and, with few exceptions, also of BCL-2. All but one PCNSL expressed hMSH2, which among mature B cells selectively stains GC B cells. These data suggest that PCNSL may be frequently related to GC B cells and may be segregated into two major biologic categories based on the expression pattern of BCL-6, LMP-1, and BCL-2. BCL-6+/LMP-1−/BCL-2− PCNSL occur both in the presence and in the absence of HIV infection and consistently display a large noncleaved cell morphology. Conversely, BCL-6−/LMP-1+/BCL-2+ PCNSL are restricted to HIV-infected hosts and are represented by lymphomas with immunoblastic features. These data are relevant for the pathogenesis and histogenesis of PCNSL and may be helpful to segregate distinct biologic and prognostic categories of these lymphomas.© 1998 by The American Society of Hematology.

Mitochondrial Toxicogenomics for Antiretroviral Management: HIV Post-exposure Prophylaxis in Uninfected Patients.

Background: Mitochondrial genome has been used across multiple fields in research, diagnosis, and toxicogenomics. Several compounds damage mitochondrial DNA (mtDNA), including biological and therapeutic agents like the human immunodeficiency virus (HIV) but also its antiretroviral treatment, leading to adverse clinical manifestations. HIV-infected and treated patients may show impaired mitochondrial and metabolic profile, but specific contribution of viral or treatment toxicity remains elusive. The evaluation of HIV consequences without treatment interference has been performed in naïve (non-treated) patients, but assessment of treatment toxicity without viral interference is usually restricted to in vitro assays.Objective: The objective of the present study is to determine whether antiretroviral treatment without HIV interference can lead to mtDNA disturbances. We studied clinical, mitochondrial, and metabolic toxicity in non-infected healthy patients who received HIV post-exposure prophylaxis (PEP) to prevent further infection. We assessed two different PEP regimens according to their composition to ascertain if they were the cause of tolerability issues and derived toxicity.Methods: We analyzed reasons for PEP discontinuation and main secondary effects of treatment withdrawal, mtDNA content from peripheral blood mononuclear cells and metabolic profile, before and after 28 days of PEP, in 23 patients classified depending on PEP composition: one protease inhibitor (PI) plus Zidovudine/Lamivudine (PI plus AZT + 3TC; n = 9) or PI plus Tenofovir/Emtricitabine (PI plus TDF + FTC; n = 14).Results: Zidovudine-containing-regimens showed an increased risk for drug discontinuation (RR = 9.33; 95% CI = 1.34–65.23) due to adverse effects of medication related to gastrointestinal complications. In the absence of metabolic disturbances, 4-week PEP containing PI plus AZT + 3TC led to higher mitochondrial toxicity (−17.9 ± 25.8 decrease in mtDNA/nDNA levels) than PI plus TDF + FTC (which increased by 43.2 ± 24.3 units mtDNA/nDNA; p < 0.05 between groups). MtDNA changes showed a significant and negative correlation with baseline alanine transaminase levels (p < 0.05), suggesting that a proper hepatic function may protect from antiretroviral toxicity.Conclusions: In absence of HIV infection, preventive short antiretroviral treatment can cause secondary effects responsible for treatment discontinuation and subclinical mitochondrial damage, especially pyrimidine analogs such as AZT, which still rank as the alternative option and first choice in certain cohorts for PEP. Forthcoming efforts should be focused on launching new strategies with safer clinical and mitotoxic profile.

Brain microstructural changes support cognitive deficits in HIV uninfected children born to HIV infected mothers

IntroductionAntiretroviral therapy (ART) is considered the most effective way to prevent perinatal transmission of human immunodeficiency virus (HIV). However, there is little knowledge about the effect of ART on the brain of HIV uninfected children born to HIV infected mothers (HUC). The current study evaluated the brain’s microstructural integrity, and cognitive function in HUC compared to healthy children born to normal mothers (CHNM) and HIV infected children born to HIV infected mothers (HIC) to investigate the effect of in-utero exposure of ART on cerebral gray and white matter. Materials and methodsForty nine HIC, 12 HUC and 18 CHNM underwent neuropsychological (NP) assessment and a brain MRI. Diffusion tensor imaging (DTI) data was used to generate fractional anisotropy (FA) and mean diffusivity (MD) maps. Voxel wise comparison for FA and MD was performed between three groups using an analysis of covariance (ANCOVA) including age and sex as covariates, and correction for multiple comparisons (false discovery rate (FDR), p ​< ​0.05 with minimum extended cluster size, 150 voxels). NP test scores were also compared between three groups using ANOVA with Post Hoc Bonferroni multiple comparison corrections (p ​< ​0.05). Significantly changed FA and MD values in different brain regions in HIC and HUC compared to CHNM were used for correlation analysis with NP test scores using Pearson’s correlation. ResultsHIC and HUC groups showed significantly decreased NP test scores in various domain compared to CHNM. Significantly lower NP test scores was observed in HIC than those of HUC. HIC showed decreased FA and increased MD in multiple brain sites as compared to both CHNM and HUC. Decreased FA along with both increased and decreased MD in different brain regions was present in HUC compared to CHNM. Both positive and negative correlation of altered FA and MD values from different brain regions in HIC and HUC with NP test scores was observed. ConclusionThe presence of brain tissue changes and neurocognitive function deficit in absence of HIV infection in HUC indicates that ART may have a detrimental impact on the developing brain. The findings of the current study underscore the need for screening of ART exposed children for neurodevelopment and cognitive abnormalities at an early stage and call for access to early interventions, and nutritional and care programs.

Clinical Parameters, Routine Inflammatory Markers, and LTA4H Genotype as Predictors of Mortality Among 608 Patients With Tuberculous Meningitis in Indonesia.

Damaging inflammation is thought to contribute to the high morbidity and mortality of tuberculous meningitis (TBM), but the link between inflammation and outcome remains unclear. We performed prospective clinical and routine laboratory analyses of a cohort of adult patients with TBM in Indonesia. We also examined the LTA4H promoter polymorphism, which predicted cerebrospinal fluid (CSF) leukocyte count and survival of Vietnamese patients with TBM. Patients were followed for >1 year. We included 608 patients with TBM, of whom 67.1% had bacteriological confirmation of disease and 88.2% had severe (ie, grade II or III) disease. One-year mortality was 43.7% and strongly associated with decreased consciousness, fever, and focal neurological signs. Human immunodeficiency virus (HIV) infection, present in 15.3% of patients, was associated with higher mortality and different CSF characteristics, compared with absence of HIV infection. Among HIV-uninfected patients, mortality was associated with higher CSF neutrophil counts (hazard ratio [HR], 1.10 per 10% increase; 95% confidence interval [CI], 1.04-1.16), low CSF to blood glucose ratio (HR, 1.16 per 0.10 decrease; 95% CI, 1.04-1.30), CSF culture positivity (HR, 1.37; 95% CI, 1.02-1.84), and blood neutrophilia (HR, 1.06 per 109 neutrophils/L increase; 95% CI, 1.03-1.10). The LTA4H promoter polymorphism correlated with CSF mononuclear cell count but not with mortality (P = .915). A strong neutrophil response and fever may contribute to or be a result of (immuno)pathology in TBM. Aggressive fever control might improve outcome, and more-precise characterization of CSF leukocytes could guide possible host-directed therapeutic strategies in TBM.

Human Herpesvirus 8–Related Castleman Disease in the Absence of HIV Infection

Castleman disease (CD) in the context of human immunodeficiency virus (HIV) infection is well described. It is almost always multicentric (MCD) and linked to human herpesvirus 8 (HHV-8). There are limited published data surrounding HHV-8-related CD among HIV-negative patients. From January 1995 through June 2012, we identified in a single center 18 HIV-seronegative patients with HHV-8-related CD. We report on their clinical, pathological, and laboratory features. All cases were multicentric. Patients were aged 42-83 years and were referred with a relapsing remitting syndrome of fever (94%), constitutional symptoms (100%), peripheral lymphadenopathy (100%), splenomegaly (72%), hepatomegaly (50%), and edema (28%). Kaposi sarcoma was observed in 9 cases. Anemia and serum markers of inflammation were present in all cases. Polymerase chain reaction for HHV-8 DNA was positive on blood samples in all cases, whereas only 12 of 16 patients tested had positive HHV-8 serology at diagnosis. All cases showed the classic histological features of MCD, and LANA-1 immunostaining identified HHV-8-infected plasmablasts in 16 of 16 tested cases. Reactive hemophagocytic syndrome (44%), autoimmune hemolytic anemia (33%), and lymphoma (22%) were the commonest associated complications. Remission was obtained with etoposide in 13 of 15 cases. Rituximab allowed prolonged remission off therapy in 10 cases. Death occurred in 3 patients not treated with rituximab. These features were similar to those described in HIV-positive HHV-8-related MCD. Comparison between these 18 cases and 12 HIV-negative HHV-8-unrelated MCD cases showed marked discrepancies. HHV-8-associated MCD may be considered as a single clinicopathological entity regardless of HIV status.

Paludismo importado e infección por VIH en Madrid. Perfil clínico y epidemiológico

IntroductionFew data are available in Spain data on human immunodeficiency virus (HIV) patients coinfected with malaria. This study has aimed to determine the epidemiological and clinical characteristics of imported malaria in patients coinfected with HIV. Patients and methodsA case-series retrospective study was performed using the patient's medical records. The study population consisted on patients diagnosed with malaria attended in our center from january 1, 2002 to december 31, 2007. ResultsA total of 484 episodes of malaria, 398 of which were included in this study, were identified. Co-infection with HIV was described in 32 cases. All of them occurred in individuals presumably with some degree of semi-immunity. In the coinfected group, there were 13 cases (40.6%) asymptomatic, whereas this event occurred in 99 cases of patients not coinfected (37.2%) (P=0.707). The greater presence of anemia in co-infected patients (62.5% vs 32.3% in non-coinfected [P=0.001]) stands out. ConclusionsIn present study, the clinical presentation forms were similar, regardless of the presence or absence of HIV infection. Although the study population does not reflect all possible scenarios of malaria and HIV coinfection, our results indicate the reality of patients attended in the Autonomous Community of Madrid.

Evidence for Translocation of Microbial Products in Patients with Idiopathic CD4 Lymphocytopenia

Translocation of microbial products has been described in chronic human immunodeficiency virus (HIV) infection and correlates with activation of the immune system. We investigated the potential translocation of microbial products in idiopathic CD4 lymphocytopenia (ICL), a rare disorder characterized by low CD4 T cell counts in the absence of HIV infection. Plasma lipopolysaccharide (LPS) levels and T cell activation were measured in a cross-sectional cohort study of patients with ICL and HIV infection and healthy control subjects. Increases in CD4 T cell proliferation but not CD8 T cell proliferation were observed in patients with ICL. LPS levels were significantly elevated both in patients with ICL and in patients with HIV infection, and they were strongly correlated with the proportion of proliferating CD4 T cells in the cohort of patients with ICL (r = 0.88; P= .003). The proportions of T helper (Th) 17 and Th1 CD4 cells in peripheral blood were similar between patients with ICL, patients with HIV infection, and control subjects. These findings suggest a potential association of translocation of microbial products with perturbed CD4 T cell homeostasis in individuals with CD4 lymphopenic states other than HIV infection.

Idiopathic collapsing glomerulopathy in children

Collapsing glomerulopathy (CG) is a clinically and pathologically distinct variant of focal segmental glomerulosclerosis (FSGS). Pathologically similar lesions have been reported in adults and children with human immuno-deficiency virus (HIV) infection. However, there is a recent interest in the recognition of this variant in the absence of HIV infection. To evaluate the clinical presentation and outcome of our pediatric patients with idiopathic CG. A sum of six children with idiopathic CG, aged 1-7 years at presentation, were retrospectively identified. Clinical data and renal biopsy were reviewed for all patients. Serum creatinine and estimated GFRs at presentation and last follow-up were compared using the Wilcoxon signed rank test and the risk factors for occurrence of ESRD analyzed using the Cox proportional hazard models. Steroid-resistant nephrotic syndrome with or without azotemia was the presenting clinical finding in all the cases. The median serum creatinine values at onset and last follow-up were 1.05 and 1.25 mg/dl, respectively (p = 0.128). Following immunosuppressive therapy one patient achieved complete remission of proteinuria, and four were in partial remission. The remaining one patient did not show any change in proteinuria at 6 months of therapy. Two of the six patients progressed to end-stage renal disease within a median follow-up period of 27 months (range 14-96 months). Collapsing glomerulopathy is an aggressive variant of focal segmental glomerulosclerosis. All patients with CG should be screened for the underlying etiology, and patients with idiopathic CG should be offered a trial of immunosuppressive therapy.

A Case of Idiopathic CD4+ T-lymphocytopenia Associated with Autoimmune Hemolytic Anemia

Idiopathic CD4+ T-lymphocytopenia (ICL) is defined by the CDC as depressed numbers of circulating CD4+ T-lymphocytes (<300 cells/μL or <20% of the total T cells) on more than one determination, with the absence of HIV infection and other known causes of immunodeficiency. The clinical spectrum of ICL ranges from asymptomatic laboratory abnormalities to severe opportunistic infections that mimic the clinical course of human immunodeficiency virus (HIV) infected patients. There are a few reports of ICL associated with different diseases such as Sjogren's syndrome, pulmonary sarcoidosis, Down syndrome or non-Hodgkin's lymphoma. We describe here a 5-year-old male patient with a three-year history of recurrent otitis media and pulmonary infection, and he was without any risk factors for HIV infection; this patient presented with autoimmune hemolytic anemia and was ultimately found to have idiopathic CD4+ T-lymphocytopenia. (Korean J Hematol 2007;42:53-57.)

The Impact of Cirrhosis on CD4+ T Cell Counts in HIV-Seronegative Patients

Studies of the progression liver fibrosis in human immunodeficiency virus (HIV) and hepatitis C virus-coinfected patients suggest that cirrhosis is associated with immunosuppression, as measured by low absolute CD4(+) T cell counts. However, we hypothesized that, in patients with advanced liver disease, low CD4(+) T cell counts may occur secondary to portal hypertension and splenic sequestration, regardless of the presence or absence of HIV infection. Sixty HIV-seronegative outpatients with cirrhosis were enrolled during the period 2001-2003 in a prospective, cross-sectional study of the association between liver disease and CD4(+) T cell counts and percentages. Demographic characteristics, liver disease-related characteristics, and laboratory results--including CD4(+) T cell parameters--were collected. A total of 39 patients (65%) had a low CD4(+) T cell count; 26 patients (43%) and 4 patients (7%) had CD4(+) T cell counts <350 and <200 cells/mm(3), respectively. Abnormal CD4(+) T cell counts were associated with splenomegaly (P=.03), thrombocytopenia (P=.002), and leukopenia (P<.001). The percentage of CD4(+) T cells was normal in 95% of patients who had a low absolute CD4(+) T cell count. CD4(+) T cell counts were significantly lower among cirrhotic patients than among 7638 HIV-seronegative historic control subjects without liver disease. Cirrhosis is associated with low CD4(+) T cell counts in the absence of HIV infection. Discordance between low absolute CD4(+) T cell counts and normal CD4(+) T cell percentages may be attributable to portal hypertension and splenic sequestration. Our findings have significant implications for the use and interpretation of absolute CD4(+) T cell counts in HIV-infected patients with advanced liver disease.

AIDS‐related lymphomas: from pathogenesis to pathology

Human immunodeficiency virus (HIV)-associated lymphomas include: (1) lymphomas also occurring, although sporadically, in the absence of HIV infection. The vast majority of these lymphomas are high-grade B-cell lymphomas: Burkitt lymphoma (BL), diffuse large B-cell lymphoma (DLBCL) with centroblastic (CB) features and DLBCL with immunoblastic (IBL) features; (2) unusual lymphomas occurring more specifically in HIV-positive patients and include two rare entities, namely 'primary effusion lymphoma' (PEL) and 'plasmablastic lymphoma' of the oral cavity. The pathological heterogeneity of acquired immunodeficiency syndrome-associated non-Hodgkin's lymphomas (AIDS-NHL) reflects the heterogeneity of their associated molecular lesions. In AIDS-BL, the molecular lesions involve activation of cMYC, inactivation of P53, and infection with Epstein-Barr virus (EBV). AIDS-IBL infected with EBV are characterised by frequent expression of latent membrane protein 1--an EBV oncoprotein. The biological heterogeneity of AIDS-NHL is highlighted by their histogenetic differences. Kaposi's sarcoma-associated herpesvirus/human herpesvirus 8 (KSHV/HHV8)-associated lymphomas, which often develop in persons with advanced AIDS, present predominantly as PEL. KSHV/HHV8 has also been recently detected in solid extracavitary-based lymphomas. The KSHV/HHV8-associated solid lymphomas are (1) unusual lymphomas that occur more specifically in HIV-positive patients; (2) extracavitary and arise in nodal and/or extranodal sites; and (3) histologically, they usually display a PEL-like morphology and plasma cell-related phenotype.

Clinical characteristics and outcomes of cytomegalovirus retinitis in persons without human immunodeficiency virus infection

Purpose To describe the characteristics and outcomes of patients with cytomegalovirus (CMV) retinitis in the absence of human immunodeficiency virus (HIV) infection. Design Retrospective cohort study. Methods Consecutive patients with CMV retinitis in the absence of HIV infection were identified at a university hospital. Demographic and clinical characteristics were noted at the time of CMV retinitis. Outcomes were determined retrospectively. Main outcome measures were rates of second eye involvement, vision loss, rhegmatogenous retinal detachment (RD), immune recovery uveitis, progression of retinitis, and mortality. Results The clinical characteristics of CMV retinitis in 18 patients (30 eyes) without HIV infection diagnosed between January 1, 1984, and April 13, 2003, were similar to those of patients with HIV infection. The incidences of visual loss to the levels of 20/50 or worse and of 20/200 or worse were 17% per eye-year and 14% per eye-year, respectively. The observed incidence of RD was 3.7% per eye-year, and the mortality rate was 23% per person-year. Following reduction of immunosuppression, 10 patients (56%) who discontinued anti-CMV therapy remained free of retinitis progression. The incidence of immune recovery uveitis was 13% per person-year. Conclusions In our series, CMV retinitis in patients without HIV infection had a clinical course similar to that in patients with AIDS treated with highly active antiretroviral therapy (HAART), except the incidence of RD was lower for patients without AIDS. A substantial number of patients no longer required long-term anti-CMV therapy after adjustment of immunomodulatory therapy.

An unusual presentation of body cavity lymphoma

6699 Background: BCL (Body Cavity Lymphoma) is an uncommon primary NHL (Non-Hodgkin's lymphoms) that proliferates within serous body cavities - pleural, pericardial or peritoneal, resulting in recurrent effusions. It is common in young to middle-aged HIV (Human Immunodeficiency Virus) positive homosexual males. In the absence of HIV infection, it almost universally develops in the background of HHV-8/KSHV (Human Herpes Virus-8/ Kaposi's Sarcoma Herpes Virus) infection with or without EBV (Epstein Barr Virus). Rare BCLs have been reported in elderly populations, which are both HIV negative and HHV-8 negative. We report an unusual case of BCL, which is HHV-8 negative and EBV positive. Abstract: 75 yrs old Immigrant Ashkenazi Jew from Russia was admitted with shortness of breath for 1 month and leg edema. No B-symptoms. His Karnofsky performance status was 80. He is heterosexual, monogamous, non-smoker and denied alcohol or intravenous drug abuse. Clinical examination revealed a right-sided pleural effusion only. Complete Blood Count showed mild normocytic normochromic anemia with hemoglobin -11.5 gm/dl. Total white count, differential, renal and liver function tests were normal. Serum LDH 200 U/L, serum β2 Microglobulin 2.8. Pleural fluid was frankly hemorrhagic with 80,000 RBC/cu mm, 16,800 WBC/ cu mm with 65% lymphocytes and 26% monocytes. Pleural fluid LDH 4500 U/L and cytology revealed Large cell lymphoma. CT scan of chest, abdomen and pelvis failed to demonstrate any lymphadenopathy or organomegaly. There was no pericardial effusion or ascites. Pleural fluid flow-cytometry demonstrated monoclonal lambda B-cell population lacking CD5 or CD10. The cells were positive for CD19, CD20, CD22 and CD45 and negative for CD2, CD3, CD4, CD5, CD7, CD9, CD10, CD11c and CD13/33. Bone marrow aspiration biopsy and flow-cytometry were negative for disease. Serum PCR for HHV-8, Human T Cell Leukemia Virus 1 and 2, Hepatitis C Virus negative, serum EBV IgG positive. CD4 count was 400 and CD8 was 300 with a ratio of 1.3. A diagnosis of BCL was made. He underwent therapeutic thoracentesis with relief of respiratory symptoms.Standard CHOP-like chemotherapy has been planned for this patient. No significant financial relationships to disclose.

An unusual presentation of body cavity lymphoma

6699 Background: BCL (Body Cavity Lymphoma) is an uncommon primary NHL (Non-Hodgkin's lymphoms) that proliferates within serous body cavities - pleural, pericardial or peritoneal, resulting in recurrent effusions. It is common in young to middle-aged HIV (Human Immunodeficiency Virus) positive homosexual males. In the absence of HIV infection, it almost universally develops in the background of HHV-8/KSHV (Human Herpes Virus-8/ Kaposi's Sarcoma Herpes Virus) infection with or without EBV (Epstein Barr Virus). Rare BCLs have been reported in elderly populations, which are both HIV negative and HHV-8 negative. We report an unusual case of BCL, which is HHV-8 negative and EBV positive. Abstract: 75 yrs old Immigrant Ashkenazi Jew from Russia was admitted with shortness of breath for 1 month and leg edema. No B-symptoms. His Karnofsky performance status was 80. He is heterosexual, monogamous, non-smoker and denied alcohol or intravenous drug abuse. Clinical examination revealed a right-sided pleural effusion only. Complete Blood Count showed mild normocytic normochromic anemia with hemoglobin -11.5 gm/dl. Total white count, differential, renal and liver function tests were normal. Serum LDH 200 U/L, serum β2 Microglobulin 2.8. Pleural fluid was frankly hemorrhagic with 80,000 RBC/cu mm, 16,800 WBC/ cu mm with 65% lymphocytes and 26% monocytes. Pleural fluid LDH 4500 U/L and cytology revealed Large cell lymphoma. CT scan of chest, abdomen and pelvis failed to demonstrate any lymphadenopathy or organomegaly. There was no pericardial effusion or ascites. Pleural fluid flow-cytometry demonstrated monoclonal lambda B-cell population lacking CD5 or CD10. The cells were positive for CD19, CD20, CD22 and CD45 and negative for CD2, CD3, CD4, CD5, CD7, CD9, CD10, CD11c and CD13/33. Bone marrow aspiration biopsy and flow-cytometry were negative for disease. Serum PCR for HHV-8, Human T Cell Leukemia Virus 1 and 2, Hepatitis C Virus negative, serum EBV IgG positive. CD4 count was 400 and CD8 was 300 with a ratio of 1.3. A diagnosis of BCL was made. He underwent therapeutic thoracentesis with relief of respiratory symptoms.Standard CHOP-like chemotherapy has been planned for this patient. No significant financial relationships to disclose.

Langerhans’ cell count and HLA class II profile in cervical intraepithelial neoplasia in the presence or absence of HIV infection

Objectives: The progression of immunosuppression in human immunodeficiency virus (HIV)+ women has been correlated with elevated incidence of squamous intraepithelial lesions (SIL), probably indicating the role of local immune milieu. In this study, we analysed S100, and HLA class II molecule expression in cervical biopsies according to HIV status, to the severity of SIL and to human papillomavirus (HPV) type. Methods: Biopsies from 34 HIV+ and 44 HIV− patients with normal cervix or low- or high-grade SIL were studied. Langerhans’ cells (LC) (S100), HLA class II and HLA-DQ molecules were evaluated by immunohistochemistry. HPV detection was performed using polymerase chain reaction (PCR). For statistical analysis Mann–Whitney ( P≤0.05) and Spearman test were used. Results: Epithelial S100 and HLA class II density were significantly increased with the severity of lesion ( P=0.032; P=0.005). Epithelial S100 + increased in HPV+ ( P=0.038), and HLA class II density decreased in HPV 16+ ( P=0.035) or 18+ ( P<0.0001) samples. HIV infection was associated with increased stromal S100 + ( P=0.0005) and decreased HLA class II densities ( P=0.0001). Decreased stromal S100 + was observed in women with CD4<500 cells/μl ( P=0.050). Among HIV+ patients with SIL, the lowest S100 and epithelial HLA class II densities were detected in women with CD4<200 cells/μl ( P=0.045). Conclusions: After the establishment of AIDS, increased numbers of immature LCs and a reduction in HLA class II occurred, possibly turning the cervical milieu more favourable to HPV persistence. HPV 16 and 18 infections may interfere with the antigen presenting activity, possibly as an evasion mechanism.

Measures of Mortality in the Study of Individuals Infected with the Human Immunodeficiency Virus in the UK Haemophilia Population

Summary Two statistical issues that have arisen in the course of a study of mortality and disease related to the human immunodeficiency virus (HIV) in the haemophilia population of the UK are discussed. The first of these concerns methods of standardization for age and it is shown that, when the mortality of HIV-infected individuals with different severities of haemophilia are compared, an analysis based on the ratio of observed to national expected deaths suggests that mortality in HIV-infected individuals depends on the severity of their haemophilia. This conclusion is inappropriate and mortality in HIV-infected individuals is, in fact, similar regardless of severity of haemophilia. The second part of the paper discusses the effect of using various end points for studies of survival and progression of HIV-related disease. In the present example it was possible to calculate relative survival in HIV-infected individuals, i.e. survival after correcting for mortality expected in the absence of HIV infection. An analysis based on absolute survival gave a very similar picture of the effect of age at infection to an analysis based on relative survival, whereas an analysis based on the time to diagnosis of acquired immune deficiency syndrome (AIDS) underestimated the effect substantially and the possible alternative end point of time to AIDS or HIV-related death was shown to be subject to considerable misclassification error.

Microsporidial Keratoconjunctivitis in a Patient without Human Immunodeficiency Virus Infection

To describe a case of microsporidial keratoconjunctivitis in a patient without human immunodeficiency virus (HIV) infection. Case report. An epithelial corneal scraping from a woman with chronic bilateral keratoconjunctivitis was evaluated by Giemsa stain. Giemsa stain of an epithelial corneal scraping disclosed intracellular and extracellular spores characteristic of microsporidia. An HIV enzyme-linked immunosorbent assay (ELISA) test was negative. The signs and symptoms of the bilateral keratoconjunctivitis resolved after treatment with albendazole. Microsporidia may cause a chronic epithelial keratoconjunctivitis in the absence of HIV infection.

Hepatitis C (HCV) genotype and viral titer distribution among Argentinean hemophilic patients in the presence or absence of human immunodeficiency virus (HIV) co‐infection

Hepatits C (HCV) infection is frequent among hemophilic patients treated with non-inactivated factor-concentrates. Both HCV genotype and viral load have been suggested to be important prognostic markers of disease progression and treatment outcome. In addition, co-infection with the human immunodeficiency virus (HIV) has been associated with increased level of HCV replication and higher risk of developing liver failure. Thus, HCV genotype, viral load, and HIV co-infection are important factors in HCV infection. Using restriction fragment length polymorphism analysis (RFLP) and the branched-DNA (bDNA) assay, we retrospectively investigated the HCV genotypes and viral loads present in 59 Argentinean hemophiliacs, in the presence or absence of HIV infection. HCV genotype 1 was the predominant viral variant detected among HIV-negative (HIV−) (76%) and HIV-positive (HIV+) (82.5%) patients, followed by genotypes 3 (10.4%), 2(2%) and a small proportion of multiply co-infected patients including genotypes 4 and 5 (6.25%). HIV+ patients had higher plasma HCV RNA levels than HIV− patients (88.4 ± 16.5 × 105 Eq/ml vs. 24.7 ± 5.8 × 105 Eq/ml) (P < 0.001); however, no correlation between HCV replication and level of immune suppression, evaluated by CD4+ T-cell measurement, was observed among HIV+ patients (r = 0.017). Abnormal and higher ALT levels were more frequently detected among HIV+ (93%; 123.6 ± 15.7 U/liter) than HIV− (41%; 70.2 ± 24.2 U/liter) patients (P < 0.001; P < 0.05). Although we were able to confirm previous reports suggesting the existence of increased HCV replication in HIV/HCV co-infected hemophiliacs, our data did not support the conclusion that HIV-induced immune suppression is directly responsible for this phenomena. It is possible that other factors induced by HIV are responsible for the increased levels in HCV replication observed. J. Med. Virol. 52:219–225, 1997. © 1997 Wiley-Liss, Inc.

Hepatitis C (HCV) genotype and viral titer distribution among Argentinean hemophilic patients in the presence or absence of human immunodeficiency virus (HIV) co-infection

Hepatitis C (HCV) infection is frequent among hemophilic patients treated with non-inactivated factor-concentrates. Both HCV genotype and viral load have been suggested to be important prognostic markers of disease progression and treatment outcome. In addition, co-infection with the human immunodeficiency virus (HIV) has been associated with increased level of HCV replication and higher risk of developing liver failure. Thus, HCV genotype, viral load, and HIV co-infection are important factors in HCV infection. Using restriction fragment length polymorphism analysis (RFLP) and the branched-DNA (bDNA) assay, we retrospectively investigated the HCV genotypes and viral loads present in 59 Argentinean hemophiliacs, in the presence or absence of HIV infection. HCV genotype 1 was the predominant viral variant detected among HIV-negative (HIV-) (76%) and HIV-positive (HIV+) (82.5%) patients, followed by genotypes 3 (10.4%), 2 (2%) and a small proportion of multiply co-infected patients including genotypes 4 and 5 (6.25%). HIV+ patients had higher plasma HCV RNA levels than HIV- patients (88.4 +/- 16.5 x 10(5) Eq/ml vs. 24.7 +/- 10(5) Eq/ml) (P < 0.001); however, no correlation between HCV replication and level of immune suppression, evaluated by CD4+ T-cell measurement, was observed among HIV+ patients (r = 0.017). Abnormal and higher ALT levels were more frequently detected among HIV+ (93%; 123.6 +/- 15.7 U/liter) than HIV- (41%; 70.2 +/- 24.2 U/liter) patients (P < 0.001; P < 0.05). Although we were able to confirm previous reports suggesting the existence of increased HCV replication in HIV/HCV co-infected hemophiliacs, our data did not support the conclusion that HIV-induced immune suppression is directly responsible for this phenomena. It is possible that other factors induced by HIV are responsible for the increased levels in HCV replication observed.