AIDS-defining Opportunistic Infection Research Articles

Literature Review and Case Histories ofHistoplasma capsulatumvar.duboisiiInfections in HIV-infected Patients

African histoplasmosis caused by Histoplasma capsulatum var. duboisii is an invasive fungal infection endemic in central and west Africa. Most of its ecology and pathogenesis remain unknown. H. capsulatum var. capsulatum is an AIDS-defining opportunistic infection in HIV-infected patients who are living in or have traveled to histoplasmosis-endemic areas. In contrast, reports concerning African histoplasmosis during HIV infection are rare, although both pathogens coexist in those regions. We report 3 cases of imported African histoplasmosis diagnosed in France in HIV-infected patients and a literature review on similar cases.

Incidence of abacavir hypersensitivity and its relationship with HLA-B*5701 in HIV-infected patients in Taiwan

To describe the incidence of hypersensitivity to abacavir and frequency of human leucocyte antigen (HLA)-B*5701 in HIV-infected Taiwanese persons. Medical records of 337 HIV-infected Taiwanese in whom abacavir-containing combination antiretroviral therapy (CART) was prescribed from 1 May 2001 to 31 December 2006 were reviewed, and HLA typing of the patients was performed in 320 patients (232 receiving abacavir and 88 not receiving abacavir) with available blood samples. HLA class I and II polymorphisms were determined by PCR with specific primers. HLA-B*5701 was further confirmed by sequence-based typing. Of the 337 patients, median CD4 count was 166.5 cells/mm3 (range, 1.0-1914.0) and 83 patients (24.6%) had AIDS-defining opportunistic infections. Thirty-eight patients (11.3%) discontinued abacavir within 6 weeks of starting abacavir-containing CART. Among them, 10 patients had successful abacavir re-challenge and another 11 patients had other specific reasons for abacavir discontinuation. Therefore, 14 patients (4.2%) were classified as cases in whom abacavir hypersensitivity could not be excluded, and 3 patients (0.9%) met the criteria of abacavir hypersensitivity. Of the 320 patients undergoing HLA typing, HLA-A02 was the most common allele and only one individual (0.3%) expressed HLA-B*5701. Along with some differences in allele distributions, there was a significant difference in the genetic frequency of HLA-B57 in our patients compared with those of previous studies in other Chinese populations. Abacavir hypersensitivity was less frequently encountered in HIV-infected Taiwanese initiating abacavir-containing CART than in Caucasians, which might be explained by the low frequency of the HLA-B*5701 allele.

Do CD4+ T Cell Functional Responses to Epstein–Barr Virus Provide Protective Immunity Against CNS Lymphoma in AIDS?

Since highly active antiretroviral treatment (HAART) regimens became widely available in North America and Europe in 1996, the incidence of AIDS-defining opportunistic infections and malignancies has declined dramatically. This decline has been attributed to restoration of protective immunity by HAART since HAART improves many of the deficits in T and B cell function that are caused by uncontrolled HIV infection. Some of these deficits include diminished antigen-specific T cell proliferation and cytokine expression, decreased production of new naive T cells by the thymus, and abnormally high levels of CD4+ and CD8+ T cell and B cell activation [1–3]. However, the causal link between the reversal or prevention of these T and B cell functional abnormalities and immune protection against AIDS-defining opportunistic infections and malignancies remains largely hypothetical at present.

Human immunodeficiency virus infection in Saudi Arabian children: transmission, clinical manifestations and outcome.

BACKGROUNDVertical transmission from mother to infant is the most common mode of transmission of HIV infection in children. Data on pediatric HIV in the Middle East and Gulf region are scarce. We describe the spectrum, characteristics and outcome of HIV infection in Saudi children.METHODSWe collected descriptive data on HIV-infected or exposed children seen at the King Faisal Hospital and Research Centre (KFSH&RC) between 1986 and 2003.RESULTSSixty-three children had proven HIV infection. The source of infection was perinatal transmission in 63.5% of cases and contaminated blood or blood products transfusion in 34.5%. Median age at diagnosis was 6 years. In 42 patients for whom complete records were available, 90% were delivered by spontaneous vaginal delivery and 10% by cesarean delivery. Ninety-three percent of infected infants were breastfed throughout infancy. The complete medical records were available for 66% of children; for the remainder, part of the records could not be retrieved. Thirteen percent had an AIDS-defining opportunistic infection, with disseminated cytomegalovirus (CMV) infection being the most common (37.5%). All cases received antiretroviral therapy starting in 1997. Of those who received highly active antiretroviral therapy, 79% were compliant with treatment and had a sustained virologic response below the detectable level. Seventy-five percent of those diagnosed before 1995 died compared with 7.7% diagnosed later.CONCLUSIONEffective preventive measures, such as antiretroviral prophylaxis, cesarean delivery, and abstention from breastfeeding are not being applied. This could be largely due to lack of knowledge among patients and healthcare providers. Physicians must recognize the signs and symptoms of HIV infection, and have a high index of suspicion so that infected children are diagnosed early and referred to a specialized center for treatment and follow-up.

Assessment of the efficacy of total lymphocyte counts as predictors of AIDS defining infections in HIV-1 infected people

Background: The CD4 count is a dominant prognostic and predictive factor in HIV infection. This study assessed the utility of the total lymphocyte count (TLC) in place of the CD4...

Increasing Risk of 5% or Greater Unintentional Weight Loss in a Cohort of HIV-Infected Patients, 1995 to 2003

Although the incidence of most AIDS-defining opportunistic infections, including HIV wasting syndrome, has dramatically decreased since the introduction of highly active antiretroviral therapy (HAART), previous studies have shown that weight loss and wasting are still common in HIV-infected persons. We examined the 6-month risk and determinants of > or =5% weight loss during the period when the use of combination antiretroviral therapy and HAART was commonplace among 713 participants enrolled in the Nutrition for Healthy Living cohort in Boston, Massachusetts between 1995 and 2003. There was a significant 50% increase in the 6-month risk of > or =5% weight loss in the later HAART years (1998-2003) compared with the early HAART years (1995-1997) among most of the participants who reported they were not trying to lose weight (P = 0.002). In addition to calendar time, several other variables were significantly independently associated with risk of > or =5% weight loss, including use of injection drugs; living below the federal poverty level; higher body mass index (BMI; > or =25 kg/m(2)); lower CD4 cell count; higher HIV viral load; and presence of diarrhea, nausea, or fever. The characteristics of weight loss in the later HAART years did not differ from the early HAART years with respect to initial body composition (eg, weight, BMI, triceps skinfold thickness) or changes in body composition during the periods of weight loss. In summary, we have found that the risk of > or =5% unintentional weight loss over 6-month intervals is on the rise in our cohort of HIV-infected participants, despite better control of HIV infection in recent years. Although we still do not know the exact cause of this increase, the fact that it exists indicates the need for clinicians who take care of HIV-infected patients to continue to pay attention to weight loss among particular segments of their patient population. This is particularly important because recent studies have shown that even a 5% weight loss in 6 months markedly increases the risk of death.

Endoscopic appearance of GI mycobacteriosis caused by the Mycobacterium avium complex in a patient with AIDS: case report and review

Disseminated Mycobacterium avium complex (MAC) infection, an important AIDS-defining opportunistic infection in patients with advanced HIV infection (generally those with CD4 lymphocyte counts <50 cells/μL), is associated with significant morbidity and mortality, and with shortened survival.1,2 The incidence of disseminated MAC (DMAC) infection increased during the period 1982 to 1994, with the maturation of the AIDS epidemic,3 to an estimated cumulative incidence of 15% to 24% of patients with AIDS.

0836 Incidence and progression of central nervous system AIDS-defining opportunistic infections (CNS-OI) after introduction of highly active antiretroviral therapy (HAART)

0836 Incidence and progression of central nervous system AIDS-defining opportunistic infections (CNS-OI) after introduction of highly active antiretroviral therapy (HAART)

Treatment of Anemia with Aranesp® (Darbepoetin-alfa) Given Once Every Two Weeks in HIV Seropositive Patients.

Background: Anemia is common in patients (pts) infected with the Human Immunodeficiency Virus (HIV). In these pts, anemia is associated with diminished quality of life (QoL) and is an independent prognostic factor for mortality. Aranesp® (darbepoetin-alfa) is a recombinant erythropoiesis-stimulating protein with extended serum half-life allowing for less frequent dosing than conventional recombinant erythropoietin. We studied Aranesp® in anemic HIV-positive pts to evaluate safety, hemoglobin (Hgb) response, and quality of life (QoL).Methods: Entry criteria included HIV infection, Hgb < 11.5 g/dL, and adequate renal and liver function. Patients with anemia due to bleeding, malignancy, B12, folate, or iron deficiency were excluded. Aranesp® 3.0 mg/kg was given sc every 2 weeks (Q2W) for 24 weeks. Treatment response was defined as Hgb increase of ≥ 1.5 g/dL from baseline sustained for ≥ 4 weeks duration at any time during the study. If no response by wk 8, Aranesp® was escalated to 5.0 μg/kg.Results: Thirteen female and 10 male pts have been enrolled to date. Median age was 43 years (range 27–67), median entry Hgb was 10.6 g/dL (range 8.6–11.5), and median CD4 count was 197 cells/mm3 (range 29–821). Nine (39%) pts had a prior clinical AIDS-defining illness or opportunistic infection, 19 (87%) pts received concurrent HAART therapy; 11 (58%) were receiving a zidovudine- containing regimen with either combivir (n=6) or trizivir (n=5). Aranesp® was well tolerated. The only treatment-associated side effect was mild pain at the injection site. Pts who received ≥ 8 wks of Aranesp® were analyzed (n=20). 17 of the 20 pts (85%) had a Hgb response (median duration 12+ weeks [range 4+ to 22+]). One of these pts required a dose escalation. Evaluation of change in QoL using a Linear Analog Scale in 20 evaluable patients showed a mean improvement in energy level (+23.2 mm), activity level (+19.8 mm) and overall QoL (+15.5 mm) over the first 8 wks of treatment.Conclusions: In HIV-infected pts with anemia, Aranesp® at a dose of 3.0 mg/kg Q2W is well tolerated, is associated with a Hgb response in the majority of pts, effectively maintains Hgb levels, and improves QoL. Further work is on-going.

Prevalence of Resistance: High in the Newly Diagnosed, Extremely High in Those Under Care

Management of antiretroviral drug resistance has become a central component of HIV clinical care. Studies of the prevalence of drug resistance in newly diagnosed patients and in individuals already under care are often limited by small size and relatively narrow patient demographics. These two large surveys provide a much broader estimation of the scope of the resistance problem in the U.S. From 1997-2001, Weinstock and colleagues from the CDC gathered information on newly diagnosed HIV-positive adults from 39 sites in 10 U.S. cities. Subjects were eligible for inclusion if they had been diagnosed within the previous 12 months, were antiretroviral-therapy naive, had a CD4 count of at least 200 cells/mm3, and had no history of an AIDS-defining opportunistic infection. Patients with non-reactive results on a modified …

Serum and cerebrospinal fluid levels of interleukin-18 in human immunodeficiency virus type 1–associated central nervous system disease

Interleukin-18 (IL-18) is a proinflammatory cytokine released by macrophages that strongly stimulates the production of interferon-gamma, thereby linking innate and acquired immunity. Its role in human immunodeficiency virus (HIV) pathogenesis is under debate and little is known about its role in neuro-AIDS (acquired immunodeficiency syndrome). Serum and cerebrospinal fluid (CSF) levels of IL-18 were determined by a commercially available enzyme-linked immunosorbent assay (ELISA) in 22 HIV-seropositive patients without neurological symptoms (HIV+), 21 patients with AIDS dementia complex (ADC), and 31 patients with AIDS-defining opportunistic infections (OIs) of the brain. Thirty-two HIV seronegative patients (HIV-) served as controls. Compared to HIV- controls, serum IL-18 levels were increased in HIV+ and ADC but not in OI patients. In contrast, CSF IL-18 levels were elevated in OI patients whereas HIV+ and ADC patients were not different from HIV- controls. We provide evidence for an significantly increased IL-18 level in the CSF of HIV+ patients with cerebral OIs, suggestive of a role for IL-18 in the intrathecal host response to OIs.

Pneumocystis carinii BCK1 functions in a mitogen-activated protein kinase cascade regulating fungal cell-wall assembly

Pneumocystis pneumonia remains the most common AIDS-defining opportunistic infection in people with HIV. The process by which Pneumocystis carinii constructs its cell wall is not well known, although recent studies reveal that molecules such as β-1-3-glucan synthetase (GSC1) and environmental pH-responsive genes such as PHR1 are important for cell-wall integrity. In closely related fungi, a specific mitogen-activated protein kinase (MAPK) cascade regulates cell-wall assembly in response to elevated temperature. The upstream mitogen-activated protein kinase kinase kinase (MAPKKK, or MEKK), BCK1, is an essential component in this pathway for maintaining cell-wall integrity and preventing fungal cell lysis. We have identified a P. carinii MEKK gene and have expressed it in Saccharomyces cerevisiae to gain insights into its function. The P. carinii MEKK, PCBCK1, corrects the temperature-sensitive cell lysis defect of bck1Δ yeast. Further, at elevated temperature PCBCK1 restored the signaling defect in bck1Δ yeast to maintain expression of the temperature-inducible β-1-3-glucan synthetase gene, FKS2. PCBCK1, as a functional kinase, is capable of autophosphorylation and substrate phosphorylation. Since glucan machinery is not present in mammals, a better understanding of this pathway in P. carinii might aid in the development of novel medications which interfere with the integrity of the Pneumocystis cell wall.

Pneumocystis carinii BCK1 complements the Saccharomyces cerevisiae cell wall integrity pathway.

Journal of Eukaryotic MicrobiologyVolume 50, Issue s1 p. 676-677 Pneumocystis carinii BCK1 Complements the Saccharomyces cerevisiae Cell Wall Integrity Pathway PAWAN K. VOHRA, PAWAN K. VOHRA Thoracic Diseases Research Unit, Muyo Clinic, Rochestel, MN 55905Search for more papers by this authorTHEODORE J. KOTTOM, THEODORE J. KOTTOM Thoracic Diseases Research Unit, Muyo Clinic, Rochestel, MN 55905Search for more papers by this authorANDREW H. LIMPER, ANDREW H. LIMPER Thoracic Diseases Research Unit, Muyo Clinic, Rochestel, MN 55905Search for more papers by this authorCHARLES F. THOMAS JR., Corresponding Author CHARLES F. THOMAS JR. Thoracic Diseases Research Unit, Muyo Clinic, Rochestel, MN 55905Corresponding author: C.F. Thomas, Jr. Telephone: 507-284-2301; Fax: 507-284-4521; Email: thomas.charles@mayo.eduSearch for more papers by this author PAWAN K. VOHRA, PAWAN K. VOHRA Thoracic Diseases Research Unit, Muyo Clinic, Rochestel, MN 55905Search for more papers by this authorTHEODORE J. KOTTOM, THEODORE J. KOTTOM Thoracic Diseases Research Unit, Muyo Clinic, Rochestel, MN 55905Search for more papers by this authorANDREW H. LIMPER, ANDREW H. LIMPER Thoracic Diseases Research Unit, Muyo Clinic, Rochestel, MN 55905Search for more papers by this authorCHARLES F. THOMAS JR., Corresponding Author CHARLES F. THOMAS JR. Thoracic Diseases Research Unit, Muyo Clinic, Rochestel, MN 55905Corresponding author: C.F. Thomas, Jr. Telephone: 507-284-2301; Fax: 507-284-4521; Email: thomas.charles@mayo.eduSearch for more papers by this author First published: 11 July 2005 https://doi.org/10.1111/j.1550-7408.2003.tb00682.xCitations: 7Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article.Citing Literature Volume50, Issues1July 2003Pages 676-677 RelatedInformation

Disseminated Histoplasmosis Complicated by Small-Bowel Perforation in a Patient With Acquired Immune Deficiency Syndrome

Disseminated Histoplasmosis Complicated by Small-Bowel Perforation in a Patient With Acquired Immune Deficiency Syndrome

Multidrug resistance (MDR-1) expression in aids-related lymphomas

P-glycoprotein is a product of the multidrug resistance (MDR-1) gene. In non-Hodgkin's lymphoma, less than 20% of untreated de novo lymphomas express MDR-1 compared with approximately 50% after failure of chemotherapy. We wished to study the expression of MDR-1 in AIDS-related non-Hodgkin's lymphoma (AIDS-NHL). Tissue biopsies from 50 patients with newly diagnosed AIDS-NHL were studied by immunohistochemical analysis using C494, a monoclonal antibody specific for the MDR-1 isoform of P-gp. MDR-1 expression was correlated with patient demographics, lymphoma characteristics, response to chemotherapy, and survival. Forty-six males and four females with a median age of 38 years (range 26–63) were studied. A prior AIDS-defining opportunistic infection was reported in 35 patients (70%). The median CD4+ lymphocyte count was 69/mm 3 (range 0–920). Thirty-two patients (63%) had received prior anti-HIV therapy, including a protease inhibitor in five (10%). Pathologic types consisted of diffuse large cell in 13 (26%), immunoblastic in 13 (26%), small non-cleaved in 22 (44%), and high grade not otherwise specified in two (4%). The majority of patients (76%) had stage III/IV disease. Pre-treatment lymphoma tissues from 33 patients (66%) stained positively for MDR-1. MDR-1 positive patients had a significantly lower complete remission rate compared to MDR-1 negative patients (33 versus 65%, P=0.042). Duration of complete response was significantly longer in MDR-1 negative patients compared with MDR-1 positive patients (not reached versus 9.9 months, P=0.003). Strategies to overcome MDR-1 expression may be important for initial treatment in patients with AIDS-NHL.

Lack of change in the distribution of AIDS-defining opportunistic diseases and the related degree of immunodeficiency during the periods before and after the introduction of highly active antiretroviral therapy.

In a retrospective study of 86 patients with AIDS-defining diseases diagnosed from 1997 to June 2000, i.e. following consolidated and large-scale introduction of highly active antiretroviral therapy (HAART), and 342 control patients diagnosed with AIDS from 1985 to 1995, i.e. the decade preceding the HAART era, the etiological spectrum and the related level of immunodeficiency of each individual AIDS-defining opportunistic infection were compared. The results show that, despite the progress attained in the management of HIV infection since the introduction of HAART, clinicians facing newly diagnosed cases of AIDS will likely encounter a spectrum of opportunistic diseases and a level of underlying immunodeficiency similar to those observed during the decade preceding the introduction of HAART. Even in recent years, the large majority of patients newly diagnosed with AIDS have not been able to take advantage of HAART prior to diagnosis of their disease.

Pneumocystis carinii pneumonia: a review of current issues in diagnosis and management.

Pneumocystis carinii pneumonia: a review of current issues in diagnosis and management.

Mucosal transmission and induction of simian AIDS by CCR5-specific simian/human immunodeficiency virus SHIV(SF162P3).

Nonhuman primate models are increasingly used in the screening of candidate AIDS vaccine and immunization strategies for advancement to large-scale human trials. The predictive value of such macaque studies is largely dependent upon the fidelity of the model system in mimicking human immunodeficiency virus (HIV) type 1 infection in terms of viral transmission, replication, and pathogenesis. Herein, we describe the efficient mucosal transmission of a CCR5-specific chimeric simian/human immunodeficiency virus, SHIV(SF162P3). Female rhesus macaques were infected with SHIV(SF162P3) after a single atraumatic application to the cervicovaginal mucosa. The disease course of SHIV(SF162P3)-infected monkeys is similar and as varied as natural HIV infection in terms of viral replication, gradual loss of CD4(+) peripheral blood mononuclear cells, and the development of simian AIDS-defining opportunistic infections. The SHIV(SF162P3)/macaque model should facilitate direct preclinical assessment of HIV vaccine strategies in addition to antiviral compounds directed towards envelope target cell interactions. Furthermore, this controlled model provides the setting to investigate immunologic responses and putative host-specific susceptibility factors that alter viral transmission and subsequent disease progression.

Correlates of opportunistic infections in children infected with the human immunodeficiency virus managed before highly active antiretroviral therapy.

Opportunistic infections (OIs) are an important cause of morbidity and mortality in children infected with HIV. However, few data are available regarding the overall prevalence, incidence and immunologic correlates associated with these diseases in the pediatric HIV population. The Pediatric AIDS Clinical Trials Group (PACTG) has conducted multicenter studies in HIV-infected children since 1988 and through these studies has collected prospective data on the immunologic and virologic status of study participants and recorded complications, including infectious diseases, related to HIV infection and its treatments. Therefore data were analyzed from across 13 PACTG studies, performed before treatment with highly active antiretroviral therapy was given, to determine the rates of various infectious complications and the immunologic correlates, specifically CD4 cell counts, associated with these diseases. OIs were tabulated from 3331 HIV-infected children who participated in 13 clinic trials undertaken before highly effective antiretroviral therapy was available. Five OIs occurred at event rates of >1.0 per 100 patient years (person years): serious bacterial infections, 15.1; herpes zoster, 2.9; disseminated Mycobacterium avium complex (DMAC), 1.8; Pneumocystis carinii pneumonia, 1.3; and tracheobronchial and esophageal candidiasis, 1.2. Six other OIs evaluated, cytomegalovirus (CMV) disease, cryptosporidiosis, tuberculosis, systemic fungal infections, toxoplasmosis and progressive multifocal leukoencephalopathy, occurred at event rates of <1.0 per 100 person years. Pneumonia (11.1 per 100 person years) and bacteremia (3.3 per 100 person years) were the most common bacterial infections. An AIDS-defining OI before entry was a risk factor for the development of a new OI during a trial. Bacterial infections, herpes zoster and tuberculosis occurred frequently at all stages of HIV infection; whereas DMAC, P. carinii pneumonia, CMV and other OIs occurred primarily in children with severe immunosuppression. The frequency of OIs in HIV-infected children in the pre-highly active antiretroviral therapy era varies with age, pathogen, prior OI and immunologic status. Analysis of CD4 counts at the time of DMAC, CMV and PCP provide validation for current prophylaxis guidelines in children > or =2 years old. This information on infectious complications of pediatric HIV will be especially valuable for contemporary management of HIV infection that is poorly responsive to highly active antiretroviral therapy.

Cidofovir May Improve Outcome of AIDS Patients with PML

Progressive multifocal leukoencephalopathy (PML) is an AIDS-defining opportunistic infection caused by JC virus. PML is characterized by deteriorating