Coinfection with multiple strains of the Epstein-Barr virus in human immunodeficiency virus-associated hairy leukoplakia.

Epstein-Barr virus DNA was analyzed from specimens of hairy leukoplakia, an oral lesion that occurs in patients infected with the human immunodeficiency virus. The simultaneous presence of both type 1 and type 2 Epstein-Barr virus was demonstrated by Southern blot analysis and polymerase chain reaction assay. Restriction fragment length polymorphisms in the BamHI WYH region and in clones of the EcoRI C region suggested the presence of multiple strains of type 1 and type 2 viruses. The demonstration of multiple variably sized BamHI H fragments on Southern blot analysis and cloning of the EBNA-2 gene coding region also suggested the presence of multiple viral strains or variants coinfecting hairy leukoplakia. Recombination of the viral genome in and around the EBNA-2 gene apparently generated viral variants that replicated efficiently, one of which appeared to increase in abundance in a lesion over time. These data indicate that hairy leukoplakia involves coinfection with multiple strains of replicating Epstein-Barr virus and the endogenous generation of viral variants, some of which have mutations of the EBNA-2 gene.     

Positive Epstein-Barr virus heterophile antibody tests in patients with primary human immunodeficiency virus infection

PURPOSE: To describe three cases of primary human immunodeficiency virus (HIV) infection in patients who had laboratory studies consistent with infectious mononucleosis. SUBJECTS: We describe 3 patients who presented with a viral syndrome, had a positive heterophile antibody test, and were diagnosed with primary HIV infection. RESULTS: The results of Epstein-Barr virus serology studies in each of these patients were consistent with chronic, but not acute, Epstein-Barr virus infection. HIV antibody tests were negative, and HIV RNA was >500,000 copies/mL in each patient. CONCLUSIONS: Clinicians should recognize that a positive heterophile antibody test in the setting of an acute viral illness does not exclude the diagnosis of primary HIV infection, although reactivation of latent Epstein-Barr virus infection cannot be ruled out. Patients presenting with nonspecific viral syndromes should be assessed for HIV risk behaviors and tested for primary HIV infection when appropriate.     

Epstein-Barr virus-related oral T-cell lymphoma associated with human immunodeficiency virus immunosuppression

Epstein-Barr virus (EBV) is generally held to infect B cells and epithelial cells, although there are now reports of EBV infection in normal T cells and neoplastic T-cell diseases. In patients with human immunodeficiency virus (HIV) infection, EBV is associated with the benign epithelial lesion, hairy leukoplakia, and has been reported in up to 80% of acquired immunodeficiency syndrome (AIDS)-related B-cell lymphoma. This study shows the presence of EBV in malignant oral T-cell lymphoma in three AIDS patients, two of whom had concurrent manifestation of hairy leukoplakia. The T-cell lineage of the tumor cells was determined by positive immunophenotyping for T-cell markers and lack of B-cell or nonhematopoietic (cytokeratin) determinants. All tumors contained monoclonal T-cell populations shown by polymerase chain reaction, which showed amplification of T-cell receptor gamma chain DNA without evidence of Ig heavy chain gene rearrangement. Furthermore, these lesions showed the presence of EBV DNA and expression of EBV latent gene products in the tumor cells. EBV involvement in AIDS-related T-cell lymphoma has not been widely reported and may represent a further manifestation of opportunistic EBV infection arising in the HIV-immunocompromised host.     

Association of Epstein-Barr virus with human immunodeficiency virus-negative peripheral T-cell lymphomas in Japan

The association of Epstein-Barr virus (EBV) with human immunodeficiency virus-negative T-cell lymphoma was examined in 68 patients using the polymerase chain reaction (PCR) with DNA obtained from formalin-fixed paraffin-embedded tissues and an in situ hybridization technique. EBV-encoded RNA (EBER) was detected in 43 of 68 cases (63%) of peripheral T-cell lymphoma: in 100% (11 of 11 cases) of NK/T-cell lymphomas, 70% (14 of 20 cases) of angioimmunoblastic T-cell lymphomas (AILT) and 49% (18 of 37 cases) of other types of peripheral T-cell lymphoma. A positive band was also detected at high incidence (36 of 65 cases; 55%) in a PCR analysis using primers to detect the Bam HI-W fragment of EBV. In the immunohistochemical analysis using a monoclonal antibody to latent membrane protein 1 (LMP-1) of EBV, one of the EBV-encoded latent gene products, LMP-1, was found to be expressed in 13 of 64 cases (20%), but EBNA-2 was not expressed in all the cases examined (0 of 59 cases; 0%). The 5-yr survival rate was 28% for peripheral T-cell lymphomas overall, 0% for NK/T-cell lymphomas, 38% for AILTs and 28% for other types of peripheral T-cell lymphoma. The difference in the overall survival rate between NK/T-cell lymphoma and non-NK/T-cell lymphoma was significant (P = 0.0498 by Log-rank test). Among peripheral T-cell lymphoma patients overall, the group severely infected with EBV (EBER-ISH ++) had a lower 5-yr survival rate (8%) than the group slightly (EBER-ISH +) or not infected (38%; P = 0.0013).     

Acquired immunodeficiency syndrome and Epstein-Barr virus

Epstein-Barr virus is an important aetiological factor in certain HIV-related syndromes, with its opportunist expression related to the level of host immunodeficiency. In asymptomatic people co-infected with HIV, EBV activity is reflected by increased viral shedding and rises in anti-EBV titres; as immunodeficiency ensues EBV manifests as epithelial hyperproliferation in OHL, and later as B-cell lymphoma in AIDS. The suggested role of EBV as a co-factor in the progression of HIV infection and development of AIDS has not been established, although another herpesvirus, cytomegalovirus, might play such a role. Advances in our understanding of HIV regulation and its interaction with other latent (herpes) viruses should provide important molecular and pharmacological approaches to the clinical management of advanced HIV disease.     

Heart rate variability in human immunodeficiency virus-positive individuals

Torsade de pointes is a form of polymorphic ventricular tachycardia occurring in a setting of prolonged QT interval on surface electrocardiogram. Congenital causes of prolonged QT interval occur in individuals with genetic mutations in genes that control expression of potassium and sodium channels and acquired causes are numerous, predominantly drugs causing prolonged QT interval by blockade of potassium channels. Among the drugs, antiarrhythmic agents most notably quinidine, sotalol, dofetilide and ibutilide have the potential to induce the fatal torsade de pointes. Many non-antiarrhythmic drugs can also cause torsade de pointes. Although it is important to distinguish between the congenital and the acquired forms of long QT syndrome as the later can often be reversed by correction of the underlying disorder or discontinuation of the offending drug, both forms are not mutually exclusive. Clinical considerations and management of torsade de pointes are described.     

Progression to acquired immunodeficiency syndrome in 94 human immunodeficiency virus-positive hemophiliacs with long-term follow-up

BACKGROUND AND OBJECTIVES: Human immunodeficiency virus (HIV) infection was transmitted to many hemophilics treated with non-inactivated factor concentrates before 1986. The aim of this study was to know the long-term incidence of AIDS and risk factors for its development in HIV-infected hemophiliacs. DESIGN AND METHODS: This study was a retrospective analysis of 94 HIV-infected hemophilics. The cumulative incidence of AIDS during a follow-up of 16 years from seroconversion was determined by Kaplan-Meier analysis,and potential risk factors were also studied by multivariate analysis. RESULTS: The 16-year estimated incidence of AIDS was 38% (95%CI 27%-52%). The AIDS incidence was significantly higher in patients with hemophilia B (p <0.0001), older age at seroconversion (p=0.0004), lower CD4 counts at seroconversion (p=0.004), and lower concentrate consumption during follow-up (p=0.02), than it was in those patients without these characteristics. However, only hemophilia type and age at seroconversion remained significant in the multivariate analysis, with a relative risk of 0.06 (95%CI 0.02-0.20) for hemophilia A and 1.04(95%CI 1.01-1.06) for every year of increase in age at seroconversion. The severity of hemophilia, history of inhibitors and concentrate consumption before seroconversion were not significantly associated with AIDS development. INTERPRETATION AND CONCLUSIONS: A considerable proportion of HIV-infected hemophiliacs remained AIDS-free 16 years after seroconversion. The risk of AIDS was particularly high in patients with hemophilia B and for patients who were older at seroconversion.     

Subtypes of Epstein-Barr virus in human immunodeficiency virus-associated non-Hodgkin lymphoma.

Biopsy samples obtained from 20 patients with human immunodeficiency virus (HIV)-associated non-Hodgkin lymphoma (NHL) were assessed for evidence of Epstein-Barr virus (EBV) and HIV sequences. DNA was extracted from formalin-fixed, paraffin-embedded NHL tissue and specific viral gene sequences were sought using the polymerase chain reaction (PCR). EBV sequences were found in 10 NHL samples (50%), with five tumors showing A-type and five B-type sequences. By serologic testing, 18 of 19 patients had antibodies to EBV, with 14 patients having antibodies to A-type EBV and 11 to B-type EBV. Serology confirmed the high prevalence of type B EBV in HIV-infected patients, but was not a reliable indicator of the EBV subtype present in the lymphomas. HIV sequences were present in biopsy tissue but at a level consistent with an origin from bystander HIV-infected cells. All 20 patients were negative by enzyme-linked immunosorbent assay for antibodies to human T-cell leukemia virus-type I. The high prevalence of type B EBV in these tumors is similar to the findings in endemic Burkitt's lymphoma, where 40% of the tumors have type B viral sequences. In normal populations, type B EBV is rarely found outside the nasopharynx. These studies support the hypothesis that EBV is an important cofactor in NHL in HIV-infected persons. The finding that B-type EBV is present in 25% of HIV-associated NHL suggests that this EBV subtype may be an important human pathogen with a wider geographic distribution than originally thought.     

Hepatitis A virus infection and hepatitis A vaccination in human immunodeficiency virus-positive patients: A review

Hepatitis A virus(HAV)is one of the most common infectious etiologies of acute hepatitis worldwide.The virus is known to be transmitted fecal-orally,resulting in symptoms ranging from asymptomatic infection to fulminant hepatitis.HAV can also be transmitted through oral-anal sex.Residents from regions of low endemicity for HAV infection often remain susceptible in their adulthood.Therefore,clustered HAV infections or outbreaks of acute hepatitis A among men who have sex with men and injecting drug users have been reported in countries of low endemicity for HAV infection.The duration of HAV viremia and stool shedding of HAV may be longer in human immunodeficiency virus(HIV)-positive individuals compared to HIV-negative individuals with acute hepatitis A.Current guidelines recommend HAV vaccination for individuals with increased risks of exposure to HAV(such as from injecting drug use,oral-anal sex,travel to or residence in endemic areas,frequent clotting factor or blood transfusions)or with increased risks of fulminant disease(such as those with chronic hepatitis).The seroconversion rates following the recommended standard adult dosing schedule(2doses of HAVRIX 1440 U or VAQTA 50 U administered6-12 mo apart)are lower among HIV-positive individuals compared to HIV-negative individuals.While the response rates may be augmented by adding a booster dose at week 4 sandwiched between the first dose and the 6-mo dose,the need of booster vaccination remain less clear among HIV-positive individuals who have lost anti-HAV antibodies.     

Natural history of primary Epstein-Barr virus infection in children of mothers infected with human immunodeficiency virus type 1

The natural history of Epstein-Barr virus (EBV) infection in 556 infants born to 517 human immunodeficiency virus (HIV) type 1-infected mothers was studied in a prospective, multicenter, cohort study. HIV-1-infected children had a cumulative EBV infection rate similar to HIV-1-uninfected children at age 3 years (77.8% vs. 84. 9%) but had more frequent oropharyngeal EBV shedding (50.4% vs. 28. 2%; P<.001). The probability of shedding decreased with longer time from EBV seroconversion and was similar to that of HIV-1-uninfected children 3 years after seroconversion. HIV-1-infected children identified as rapid progressors shed EBV more frequently than nonrapid progressors (69.4% vs.41.0%; P=.01). HIV-1-infected children with EBV infection had higher mean CD8 cell counts. EBV infection did not have an independent effect on mean CD4 cell counts, percent CD4, IgG levels, HIV-1 RNA levels, lymphadenopathy, hepatomegaly, or splenomegaly. Early EBV infection is common in children born to HIV-1-infected mothers. Children with rapidly progressive HIV-1 disease have more frequent EBV shedding.     

Prevalence of antibodies to Epstein-Barr virus nuclear antigen 2B in persons infected with the human immunodeficiency virus

We measured the presence of antibodies to the Epstein-Barr virus (EBV) nuclear antigen 2B (EBNA2B) in patients with AIDS and related disorders, persons with human immunodeficiency virus (HIV) infection, persons at risk for HIV infection, and normal persons. Sera from 38% (16 of 43) of the patients with AIDS and 35% (43 of 123) of HIV-positive individuals reacted with EBNA2B, versus 25% (21 of 83) of the high-risk patients and 7.5% (5 of 65) of the normal persons. Screening these sera against cell lines that express EBNA2B, EBNA2A, or neither antigen revealed that only a proportion of these sera contained EBNA2B-specific antibodies. Many sera reacted with both antigens. Of the EBNA2B-specific sera, 14% (6 of 43) were from patients with AIDS, 16% (20 of 123) from HIV-positive individuals, 5% (4 of 83) from high-risk individuals, and 4.5% (3 of 65) from normal persons. The presence of antibodies to the EBNA2B in HIV-infected individuals indicates that they may be infected with type B strains of EBV.