Natural history of HIV-infection in hemophiliacs: Clinical,immunological, and virological findings

Summary At our institution 686 hemophiliacs are being treated. Of them 402 (59%) are anti-HIV-seropositive. The general use of heat-treated clotting factor products was begun in July 1983, and from May 1984 all patients exclusively used heat-treated clotting factors. Thus, one can assume that infection occurred no later than early 1984 in our patients. Since December 1985 HIV-positive hemophiliacs have regularly been clinically and immunologically examined. Most of the 306 patients who could be investigated were clinically symptom-free at the time of their first visit. However, 45 patients have developed AIDS from 1982 through August 1988. The mean survival time of hemophiliacs with AIDS is less than 6 months. In 36% of those 274 patients who have been followed for a mean period of 14 months the clinical stage of the disease worsened by at least one stage according to the classification system proposed by the Centers for Disease Control. We did not find a correlation between clotting-factor consumption during the years 1984–1986 and the actual clinical stage of the patients. Virus isolation from peripheral blood lymphocytes (PBIs) answered the question whether anti-HIV seropositive hemophiliacs are not only immunized but really infected in many more cases than those revealed by detection of p24 antigen or decline of p24 antibody. Positive viral culture correlated strongly with a drop in CD4⁺ lymphocytes under the level of 400/µl. However, HIV could not be cultured regularly in advanced cases, suggesting that virus replication in PBLs is not necessarely the cause of depletion of T-helper cells. There is no evidence that the natural history of HIV infection in hemophiliacs is different from that in other HIV-infected patients.Abbrevations AIDS Acquired immunodeficiency syndrome - ARC AIDS-related complex - AZT Azidothymidine - CDC Centers for Disease Control - CD4 (T4) lymphocytes Lymphocytes bearing the cluster of differentiation antigen 4 - CD8 (T8) lymphocytes Lymphocytes bearing the cluster of differentiation antigen 8 - CD5 lymphocytes Lymphocytes bearing the cluster of differentiation antigen 5 - CD20 lymphocytes Lymphocytes bearing the cluster of differentiation antigen 20 - CPE Cytopathic effect - ELISA Enzyme linked immunosorbent assay - F VIII Blood-clotting factor VIII - F IX Blood-clotting factor IX - HIV Human immunodeficiency virus - HNK-1 cells Human natural killer cells (CD8⁺ subset) - IL-2 Interleukin-2 - PHA Phythemagglutinin - p24 HIV core protein, molecular weight 24 kd     

Slow subcutaneous human intravenous immunoglobulin in the treatment of antibody immunodeficiency: Use of an old method with a new product

J Allergy Clin Immunol 1998;101:848-9.     

Bacillary angiomatosis in a German patient with AIDS

Summary A 52-year old male homosexual patient with acquired immunodeficiency syndrome (AIDS) presented in our clinic with multiple nodular papules (more than 100) spread over the whole body which had developed within 3 months. Bacillary angiomatosis was suspected, which is a bacterial infectious disease recognized recently mainly in patients with AIDS. Histological and immunohistochemical examinations of extirpated skin lesions were in agreement with the diagnosis, and the detection of rod-shaped bacteria in the lesions by Warthin-Starry silver stain confirmed it. The patient was treated with 2 × 100 mg doxycycline per day. The fever disappeared, and the cutaneous lesions showed a slight tendency to improve. However, after 5 days of therapy the patient showed increasing weakness, with muscle and bone pain. The patient died 10 days after the doxycyline therapy had been started. The cutaneous lesions in bacillary angiomatosis may resemble Kaposi's sarcoma and may therefore be misdiagnosed. The disease may be fatal, but timely antibiotic treatment is usually effective; therefore the diagnosis of bacillary angiomatosis is important. Although many cases have been reported from the United States, only one case is known from Europe. Our finding of bacillary angiomatosis in a German AIDS patient supports the concept of a worldwide distribution of this bacterial agent.Abbreviations HIV human immunodeficiency virus type 1 - AIDS acquired immunodeficiency syndrome     

Treatment of diarrhoea in human immunodeficiency virus-infected patients with immunoglobulins from bovine colostrum

Summary Diarrhoea and weight loss are found in more than 50% of patients with the acquired immunodeficiency syndrome (AIDS). In some patients the symptoms can be very severe, leading to death even in the absence of opportunistic infections. In 30% of these patients, enteric pathogens cannot be identified, and approximately only half of the identifiable aetiologic agents of diarrhoea in patients infected with the human immunodeficiency virus (HIV) were treatable with antibiotics. Immunoglobulins from bovine colostrum (Lactobin, Biotest, Dreieich, FRG) contain high titers of antibodies against a wide range of bacterial, viral and protozoal pathogens as well as against various bacterial toxins. Lactobin (LIG) is quite resistant to 24-h incubation with gastric juice. In a multi-center pilot study 37 immunodeficiency patients with chronic diarrhoea [29 HIV-infected patients, 2 patients with common variable immunodeficiency (CVID), one unidentified immunodeficiency, five patients with graft versus host disease (GvHD) following bone marrow transplantation] were treated with oral LIG (10 g/day for 10 days). Good therapeutic effects were observed. Out of 31 treatment periods in 29 HIV-infected patients 21 gave good results leading to transient (10 days) or long-lasting (more than 4 weeks) normalisation of the stool frequency. The mean daily stool frequency decreased from 7.4 to 2.2 at the end of the treatment. Eight HIV-infected patients showed no response. The diarrhoea recurred in 12 patients within 4 weeks (32.4%), while 19 patients were free of diarrhoea for at least 4 weeks (51.3%). In 5 patients intestinal cryptosporidiosis disappeared following oral LIG treatment. LIG treatment was also beneficial in 4 out of 5 GvHD patients. No serious side effects were recorded in any of the treated patients.Abbreviations AIDS acquired immunodeficiency syndrome - ALL/3 acute lymphoblastic leukaemia (FAB classification type 3) - AML/1 acute myeloblastic leukaemia (FAB classification type 1) - CDC center of disease control - CML/CP chronic myelocytic leukaemia (chronic phase) - CMV cytomegalovirus - CVID common variable immunodeficiency - DHPG 1,3-dihydroxy-2-propoxymethyl-guanine (gancyclovir) - ELISA enzyme-linked immunosorbent assay - GvHD graft versus host reaction - HIV human immunodeficiency virus - IgA immunoglobulin A - IgG immunoglobulin G - IgM immunoglobulin M - INH isoniazid - LIG Lactobin - MAI mycobacterium avium intracellulare - RAEB-T refractory anaemia with excess of blasts-transformation - SD standard deviation     

Human immunodeficiency virus type 1 gp120 C5 region mimics the HLA class I α1 peptide-binding domain

Molecular mimicry of major histocompatibility (MHC) antigens by viral glycoproteins has been suggested as one of the possible mechanisms of induction of an autoimmune response by human immunodeficiency viruses. A monoclonal antibody (M38) was previously shown to bind to both human immunodeficiency virus type 1 (HIV-1) gp120 and β-2 microglobulin-free HLA class I heavy chains encoded by an HLA C allele. Using HLA C recombinant proteins and synthetic peptides, the M38 class I binding site was mapped to a stretch of 44 amino acids of the al domain. The amino acid residues recognized are clustered in two non-contiguous regions at positions 66-69 (KYKR) and 79-82 (RKLR) shared by almost all HLA C alleles. On HIV-1 gp120, M38 binds to two non-contiguous sequences (KYK and KAKR) at positions 490-492 and 505-508 located at the edges of a large hydrophobic region that is apparently involved in binding the transmembrane glycoprotein gp41. The C-terminal gp120 M38-reactive region (KAKR) lies within the immunodominant sequence APTKAKRRVVQREKR, against which the majority of HIV-infected individuals produce antibodies. The results indicate that a functionally important region of HIV-1 gp120 shares similar amino acid sequence motifs with the antigen recognition site of most HLA class I C alleles. The molecular mimicry may be the basis for autoimmune responses in HIV infection.     

Two-year prospective study of major depressive disorder in HIV-infected men

OBJECTIVE: The risks and factors contributing to major depressive episodes in HIV infection remain unclear. This 2-year prospective study compared cumulative rates and predictors of a major depressive episode in HIV-infected (HIV+) men (N=297) and uninfected (HIV-) risk-group controls (N=90). METHODS: By design participants at entry were without current major depression, substance dependence or major anxiety disorder. Standardized neuromedical, neuropsychological, neuroimaging, life events, and psychiatric assessments (Structured Clinical Interview for DSM III-R) were conducted semi-annually for those with AIDS, and annually for all others. RESULTS: Lifetime prevalence of major depression or other psychiatric disorder did not differ at baseline between HIV+ men and controls. On a two-year follow-up those with symptomatic HIV disease were significantly more likely to experience a major depressive episode than were asymptomatic HIV+ individuals and HIV-controls (p<0.05). Episodes were as likely to be first onset as recurrent depression. After baseline disease stage and medical variables associated with HIV infection were controlled, a lifetime history of major depression, or of lifetime psychiatric comorbidity (two or more psychiatric disorders), predicted subsequent major depressive episode (p<0.05). Neither HIV disease progression during follow-up, nor the baseline presence of neurocognitive impairment, clinical brain imaging abnormality, or marked life adversity predicted a later major depressive episode. LIMITATIONS: Research cohort of men examined before era of widespread use of advanced anti-HIV therapies. CONCLUSIONS: Symptomatic HIV disease, but not HIV infection itself, increases intermediate-term risk of major depression. Prior psychiatric history most strongly predicted future vulnerability.     

High-dose intravenous immunoglobulins: an option in the treatment of systemic lupus erythematosus

Despite encouraging reports on the efficacy of intravenous immunoglobulin (IVIG) therapy in systemic lupus erythematosus (SLE), the clinical value of this treatment is not well established, and most of the data are based on case reports and small series of patients. IVIG has been used successfully to treat SLE patients with a broad spectrum of clinical manifestations, such as refractory thrombocytopenia, pancytopenia, central nervous system (CNS) involvement, secondary antiphospholipid syndrome, and lupus nephritis. The beneficial effects of IVIG on overall disease activity are usually prompt, with marked improvement within a few days, but they are often of limited duration. Improvement lasts for several weeks after the last infusion, although clinical response could be maintained by continuous monthly IVIG infusions. IVIG therapy immunomodulates autoimmune diseases by interacting with various Fcgamma receptors in such a way that it downregulates activating FcRIIA and FcRIIC and/or upregulates inhibitory FcRIIB. However, in SLE, additional mechanisms include inhibition of complement-mediated damage, modulation of production of cytokines and cytokine antagonists, modulation of T- and B-lymphocyte function, induction of apoptosis in lymphocytes and monocytes, downregulation of autoantibody production, manipulation of the idiotypic network, and neutralization of pathogenic autoantibodies. At present, IVIG in SLE is indicated either in severe cases that are nonresponsive to other therapeutic modalities, or when SLE can be controlled only with high-dose steroids; in such patients, IVIG thus becomes a useful steroid-sparing agent. However, this needs to be confirmed in double-blind, placebo-controlled studies.     

Use of intravenous immunoglobulin and adjunctive therapies in the treatment of primary immunodeficiencies: A working group report of and study by the Primary Immunodeficiency Committee of the American Academy of Allergy Asthma and Immunology

There are an expanding number of primary immunodeficiency diseases (PIDDs), each associated with unique diagnostic and therapeutic complexities. Limited data, however, exist supporting specific therapeutic interventions. Thus, a survey of PIDD management was administered to allergists/immunologists in the United States to identify current perspectives and practices. Among 405 respondents, the majority of key management practices identified were consistent with existing data and guidelines, including the provision of immunoglobulin therapy, immunoglobulin dosing and selective avoidance of live viral vaccines. Practices for which there are little specific data or evidence-based guidance were also examined, including evaluation of IgG trough levels for patients receiving immunoglobulin, use of prophylactic antibiotics and recommendations for complementary/alternative medicine. Here, variability applied to PIDD patients was identified. Differences between practitioners clinically focused upon PIDD and general allergists/immunologists were also identified. Thus, a need for expanded clinical research in PIDD to optimize management and potentially improve outcomes was defined.     

Comparison of two types of intravenous immunoglobulins in the treatment of neonatal sepsis.

In a prospective double-blind study, standard intravenous immunoglobulin (IVIG) was compared with an IgM-enriched IVIG in the treatment of neonatal sepsis. The two treatment groups were also compared with matched controls. One hundred and thirty babies (65 in each group) ranging from 0 to 24 days old, 480 to 4200 g in weight and born between 24 and 42 weeks of gestation who had, or were suspected of having, sepsis were given either standard IVIG or IgM-enriched IVIG (250 mg/kg per day) for 4 days in addition to supportive and antibiotic therapy. A further 65 babies who received similar supportive, antibiotic and fluids but not IVIG were used as matched controls. Mortality from infection in 'culture proven sepsis' was 3/44 (6.8%) in the IgM-enriched IVIG group, 6/42 (14.2%) in the standard IVIG group, and 11/43 (25.5%) in the control group (P = 0.017, IgM versus control, P = 0.19 standard IVIG versus control). There was no statistical difference in the outcome between the two immunoglobulin therapy groups (P = 0.25). The study indicates that IVIG improves outcome in neonatal sepsis when used as an adjunct to supportive and antibiotic therapy, but larger studies are required to confirm this.     

Pneumococcal parotitis and cervical lymph node abscesses in an HIV-infected patient

The case of a 33-year-old patient with rapid onset of bilateral parotid gland and lymph node abscesses is described. The patient was positive for human immunodeficiency virus 1 and presented with a history of interstitial lymphocytic pneumonia and pneumococcal meningitis prior to admission. The patient received cotrimoxazole as primary prophylaxis againstPneumocystis carinii pneumonia. Fine needle aspiration from the abscesses yieldedStreptococcus pneumoniae. Penicillin G treatment in combination with surgical drainage of the lesions led to healing with minimal residual lymph node enlargement. No relapse was noted until 12 months after presentation.Abbreviations HIV human immunodeficiency virus - ELISA enzyme-linked immunosorbent assay Correspondence to: H.-J. Stellbrink     

HIV/AIDS患者肝组织HIV-1 p24抗原的免疫组化检测

目的　检测HIV抗原标志物在肝组织的表达情况,探讨HIV AIDS患者肝损伤发生的可能机制。方法　采用免疫组织化学方法对14例HIV AIDS患者的肝活检组织切片进行HIV 1p2 4抗原检测,比较不同病变肝组织中HIV 1p2 4抗原的表达数量。结果　在14例肝组织切片的Kupffer细胞、内皮细胞、肝细胞均发现HIV 1p2 4抗原表达;阳性肝细胞计数分析显示,表达数量随病变严重程度而增加(P <0 0 5 )。结论　HIV能够在HIV AIDS患者的肝脏内表达,并且可能参与肝细胞的凋亡。     

女性HIV感染者甲状腺功能与性激素水平的研究

目的 研究人类免疫缺陷病毒(HIV)感染的女性患者是否存在甲状腺功能障碍及性激素水平变化,观察甲状腺激素变化与性激素变化之间的关系.方法 采用放射免疫法测定研究对象的甲状腺激素及性激素,分析2者间的相关性.结果 34%的患者出现一种或多种甲状腺激素的改变,19%的发生亚临床甲减;睾酮(T)、雌激素(E2)、孕酮(P)、泌乳素(PRL)改变差异显著(P＜0.05);甲状腺激素值有变化的患者比甲状腺激素值无变化的患者T下降更明显(P＜0.05).结论 HIV感染女性患者存在甲状腺激素的紊乱;HIV感染女性患者存在性激素的紊乱:存在甲状腺激素紊乱的HIV感染女性患者性激素紊乱更明显.     

A Comparative Study of Intravenous Immunoglobulin and Subcutaneous Immunoglobulin in Adult Patients with Primary Immunodeficiency Diseases: A Systematic Review and Meta-Analysis

Subcutaneous immunoglobulin (SCIG) is a new therapeutic procedure for patients with primary immunodeficiency (PI). This research is a systematic review of studies on the efficacy and safety of intravenous immunoglobulin (IVIG) and SCIG in adult patients with PI. This study includes a systematic review of cohorts and randomized clinical trials (24 articles) from 5 databases with no time limits. Random effects meta-analysis was performed for outcomes such as efficacy and safety. Standard mean difference (SMD) of serum immunoglobulin level was equal to 0.336 (P <0.01; 0.205-0.467) and the odds ratio (OR) of side effects was 0.497 (P=0.1; 0.180-1.371). The results indicate that SCIG leads to a higher level of immunoglobulin and a reduction in side effects but shows the same infection rate as IVIG. Our analysis shows that shifting from IVIG to SCIG therapy can have clinical benefits for PI patients.     

Neuropathology of the Central Nervous System in Acquired Immune Deficiency Syndrome (AIDS) in Japan

The neuropathologiesl features of the central nervous system in IS autopsy cases of Japanese male with AIDS were reported. Nine patients had various histological changes including a variety of opportunistic infections in six patients (40%), primary malignant lymphoma of the brain in two (13%), AIDS encephalopathy in four (27%) and vacuolar myelopathy in one (7%). Usually, these pathological changes were present concomitantly. AIDS encephalopathy was characterized by infiltration of mono and multinucleated cells and myelin pallor with astrogliosis located predominantly in the cerebral white matter and subcortical gray matter. Furthermore, unevenly distributed neuronal loss of the cerebral cortex was apparent in one case. Diffuse astrocytosis of the gray matter out of proportion to neuronal loss was also an outstanding finding in another case. The present study suggested that not only the white matter changes but also gray matter alterations might be the morphological substrates of AIDS encephalopathy.     

Prevalence of intestinal parasitic infections in HIV-infected individuals and their relationship with immune status

Background and Objectives: Intestinal parasitic infection is a common entity in patients infected with human immunodeficiency virus (HIV). These infections may lead to fatal complications in the immuno suppressed individuals. The aim of the present study was to determine the prevalence of intestinal parasitic infections in HIV sero-positive patients and their relationship with the immune status of individuals. Materials and Methods: Fecal samples from 100 HIV sero-positive and an equal number of HIV sero-negative individuals were collected and examined for enteric parasites by direct microscopy. CD4 counts were carried out in only HIV sero-positive patients. Prevalence of intestinal parasites in patients with CD4 count <200 cells/μl, 200-499 cells/μl, and ≥500 cells/μl in HIV-infected patients were compared. Results: Enteric parasites were detected in 59.3% HIV-infected patients with CD4 count <200 cells/μl as compared with 23.5% in patients with CD4 count>200 cells/μl (P < 0.01). Prevalence of coccidian parasites was significantly (P < 0.01) higher (14%) in HIV sero-positive subjects compared with HIV sero-negative subjects (2%). Isospora belli (25%) was the most common parasite with CD4 count <200 cells/μl, followed by Cryptosporidium parvum (12.5%). Prevalence of intestinal parasitic infections was significantly higher in patients with diarrhea, 73.6% than without diarrhea, 25.9%, (P < 0.05). The mean CD4 count of HIV sero-positive patients presenting with diarrhea was significantly (P < 0.01) lower (181.26 ± 135.14) than without diarrhea (352.02 ± 204.03). Conclusion: This study emphasizes the need for routine screening of parasites especially in patients with lower CD4 count so as to decrease the morbidity by ensuring the early treatment of the cases.