Immunization for persons infected with human immunodeficiency virus

Immunization is an important measure to protect HIV-infected children and adults against certain vaccine preventable diseases. However, the antibody response, which is associated with the level of CD4+ T cell count, is frequently impaired in this group of patients. Certain vaccines enhance virus replication and transiently increase HIV viral load. Theoretically, vaccination should be given before the immune status of the patients is suppressed. Inactivated vaccines are generally safe and are beneficial for HIV-infected patients. These vaccines should be administered at appropriate age recommended for immunocompetent individuals. Live vaccines should be used with caution since some of the vaccines may be harmful to patients with severe immunologic suppression. Recommendations for immunization in HIV-infected patients may differ from country to country, depending on the availability and affordability of each vaccine, and the prevalence of each preventable disease. Vaccine trial in HIV-infected patients is needed in order to establish the most appropriate vaccine recommendation for this group of patients.     

Correlation between the presence of antibodies to the Epstein-Barr virus nuclear antigen type 2 and antibodies to the rheumatoid arthritis nuclear antigen in patients with rheumatoid arthritis

The incidence of antibodies to Epstein-Barr nuclear antigen type 2 (EBNA-2) was determined in sera from rheumatoid arthritis (RA) patients and control subjects, by protein immunoblotting. Sixty-eight percent of the RA patients and 48% of the controls possessed anti-EBNA-2 antibodies. The titer of anti-rheumatoid arthritis nuclear antigen (RANA) in RA patient sera showed a stronger correlation with serum reactions to EBNA-2 than with reactions to EBNA-1. Our results indicate that the presence of EBNA-2 may make a major contribution to the RANA reaction.     

Prophylaxis against opportunistic infections in persons infected with human immunodeficiency virus

This article outlines the current official recommendations for the prevention of opportunistic disease in adults and adolescents infected with human immunodeficiency virus, including specific guidelines for discontinuing primary and secondary prophylaxis when immune reconstitution has occurred as a result of highly active antiretroviral therapies. The recommendations, developed by the U. S. Public Health Service and the Infectious Diseases Society of America for clinicians and healthcare providers, were originally published in 1995 and revised in 1997, 1999, and 2002. The 2002 recommendations are summarized in this article.     

Selenium and interleukins in persons infected with human immunodeficiency virus type 1

An important role for selenium in human immunodeficiency virus (HIV) disease has been proposed. Decreased selenium levels, as found in persons with HIV infection or AIDS, are sensitive markers of disease progression. Selenium deficiency, an independent predictor of mortality in both HIV-1-infected adults and children, is an essential micronutrient that is associated with an improvement of T cell function and reduced apoptosis in animal models. In addition, adequate selenium may enhance resistance to infections through modulation of interleukin (IL) production and subsequently the Th1/Th2 response. Selenium supplementation up-regulates IL-2 and increases activation, proliferation, differentiation, and programmed cell death of T helper cells. Moreover, selenium supplementation may down-regulate the abnormally high levels of IL-8 and tumor necrosis factor-alpha observed in HIV disease, which has been associated with neurologic damage, Kaposi's sarcoma, wasting syndrome, and increased viral replication. Together, these findings suggest a new mechanism through which selenium may affect HIV-1 disease progression.     

Risk factors for community-acquired pneumonia among persons infected with human immunodeficiency virus

Two hundred eleven adults with human immunodeficiency virus (HIV) infection hospitalized for community-acquired pneumonia, including Pneumocystis carinii pneumonia (PCP; patients), and 192 matched HIV-infected hospitalized patients without pneumonia (controls) were interviewed to determine risk factors for pneumonia. Multivariate logistic regression showed that patients were less likely than controls to have used trimethoprim-sulfamethoxazole (TMP-SMZ) prophylaxis (odds ratio [OR], 0.22; 95% confidence interval [CI], 0.12-0.41) and more likely to have been hospitalized previously with pneumonia (OR, 6.25; CI, 3.40-11.5). Patients were also more likely than controls to have gardened (OR, 2.24; CI, 1.00-5.02) and to have camped or hiked (OR, 4.95; CI, 1.31-18.7), but stratified analysis by etiologic agent showed this association only for PCP. These findings reconfirm the efficacy of TMP-SMZ in preventing community-acquired pneumonia. In addition, hospitalization for pneumonia might represent a missed opportunity to encourage HIV-infected patients to enter into regular medical care and to adhere to prescribed antiretroviral and prophylaxis medications.     

Prevalence and prognostic significance of infection with TT virus in patients infected with human immunodeficiency virus

No clear association between human disease and TT virus (TTV) has been documented. A possible pathogenic role of TTV was investigated in patients infected with human immunodeficiency virus (HIV). TTV serum concentrations were estimated in 185 HIV-infected patients by dilution polymerase chain reaction. Of these, 149 (76%) were TTV-positive, compared with 18 (7%) of 252 Danish blood donors (P<. 001). Of the HIV-infected patients who were TTV-positive, 72 (51%) had high TTV viremia (>/=5 times the highest concentration observed among blood donors, i.e., >/=3.5x105 TTV/mL of serum). High TTV viremia was associated with decreased survival (P<.001; relative hazard [RH], 2.0). There was a correlation between lower CD4+ T cell counts and higher TTV titers (P<.01). In a Cox regression model, CD4+ T cell count (P<.001), age (P<.001), HIV viral load (P<.001), beta2 microglobulin (P<.02), and high TTV viremia (P<.01; RH, 1.9) were independent predictors of survival. TTV is suspected to be an opportunistic pathogen with an independent influence on HIV progression.     

Transient induction of a nuclear antigen unrelated to Epstein-Barr nuclear antigen in cells of two human B-lymphoma lines converted by Epstein-Barr virus.

Infection of cells of the Epstein-Barr virus (EBV)-negative human B-lymphoma lines BJAB and Ramos with EBV preparations from P3HR-1 or B 95-8 cells converted these cells to EBV genome carriers expressing Epstein-Barr nuclear antigen (EBNA) in almost 100% of these cells. Induction of these cells as well as of clones from P3HR-1 EBV-converted BJAB cells with iododeoxyuridine, aminopterin, and hypoxanthine resulted in the appearance of a nuclear antigen in about 1-6% of the cells 1-4 days after induction. The antigen is different from known EBV-induced antigens like EBNA, viral capsid antigen (VCA) or the D- and R-subspecificities of the early antigen (EA) complex. It is demonstrated by indirect immunofluorescence and inactivated after acetone fixation. The antigen was not detectable after induction of uninfected BJAB and Ramos cells nor has it been found in noninduced or induced P3HR-1 and Raji cells. Thus, it appears that EBV-infection mediates the expression of this antigen, for which the name TINA (transiently induced nuclear antigen) is suggested. Sera reacting against TINA generally contained high antibody titers against EBV-induced EA. Only a limited number of highly EA-reactive sera, however, were also positive for TINA. Among 200 sera tested thus far, TINA reactivity was most frequently observed in sera of patients with nasopharyngeal carcinoma (7 out of 28), in sera of the only two patients with immunoblastoma tested and occasionally in sera from patients with Hodgkin's disease and chronic lymphatic leukemia. Among 70 sera from nontumor patients, TINA reactivity was observed three times: two patients suffered from "chronic" infectious mononucleosis, the other revealed persistent splenomegaly.     

Blood donors infected with the hepatitis B virus but persistently lacking antibodies to the hepatitis B core antigen

BACKGROUND AND OBJECTIVES: Antibodies to the core of hepatitis B virus (anti-HBc) are considered to be the best serologically reliable markers of hepatitis B virus (HBV) infection. Through a national epidemiological survey, two young and first-time blood donors, originating from HBV-endemic areas, were identified as HBV carriers with an absence of anti-HBc reactivity. MATERIALS AND METHODS: We followed up these two subjects in order to investigate the evolution of their HBV serological profiles. Nucleotide sequencing was performed of the entire pre-C/C region of the strains infecting these donors. RESULTS: The same serological profile of active viral replication with an apparent persistent lack of anti-HBc and normal alanine aminotransferase (ALT) levels was found for both subjects throughout a follow-up of 19 months and 4 months, respectively. Neither donor was immunocompromised. Nucleotide sequence analysis of the pre-C/C region did not show mutations or deletions in encoded proteins. CONCLUSION: The hypothesis of an in utero HBV infection responsible for an immune tolerance to HBV seems to be the most probable explanation for this particular immunological situation. Such occurrences in the blood donor population are probably rare as less than 0.1% of hepatitis B surface antigen (HBsAg)-positive donors exhibit such a profile, in our experience. Moreover, this phenomenon does not impose a risk of HBV transmission by blood donation, as the exclusion of HBV-infected blood donation is based on HBsAg detection. However, such a risk might be encountered with the hepatitis C virus (HCV) for which at present only antibodies to HCV are screened.     

U2 region of Epstein-Barr virus DNA may encode Epstein-Barr nuclear antigen 2.

Sequence analysis of the U2 regions of the B95-8 and AG876 Epstein-Barr virus (EBV) isolates reveals divergence within a long open reading frame previously identified as encoding 1.5 kilobases of the 3' end of a viral RNA expressed in latently infected, growth-transformed, B-lymphocyte cell lines. Differences among EBV isolates within the U2 open reading frame are shown to correlate with differences in an EBV nuclear antigen, EBNA2. B95-8, W91, Raji, Cherry, and Lamont EBV isolates have similar U2 domains and encode similar-size EBNA2 proteins, while AG876, Jijoye, and P3HR-1 have variant or absent U2 domains and variant or absent EBNA2 proteins. The AG876 U2 open reading frame and EBNA2 protein are both shorter than those of B95-8. These data indicate that the U2 open reading frame encodes EBNA2.     

Response of latent syphilis or neurosyphilis to ceftriaxone therapy in persons infected with human immunodeficiency virus.

OBJECTIVE: To evaluate the effect of ceftriaxone in treating latent syphilis or asymptomatic neurosyphilis in patients infected with the human immunodeficiency virus (HIV). DESIGN: Follow-up study of patients treated at two HIV-based clinics during 16 months from 1989 to 1991. PATIENTS: Patients were those in whom a clinical diagnosis of latent syphilis or asymptomatic neurosyphilis was made, who received all recommended doses of antimicrobial therapy, and who returned for follow-up visits for 6 or more months. RESULTS: Forty-three patients were treated with ceftriaxone, 1 to 2 g daily for 10 to 14 days. Thirteen underwent lumbar puncture before treatment; 7 (58%) had documented neurosyphilis (pleocytosis in 5, elevated protein levels in 6, VDRL reactive in cerebrospinal fluid [CSF] in 7), and 6 had documented latent syphilis (entirely normal CSF). The remaining 30 were said to have presumed latent syphilis. There was no relation between the diagnosis and the selected dosage of ceftriaxone. Response rates were similar in those who had documented neurosyphilis and documented or presumed latent syphilis. Overall, 28 patients (65%) responded to therapy, 5 (12%) were serofast, 9 (21%) had a serologic relapse, and 1 (2%) who experienced progression to symptomatic neurosyphilis was a therapeutic failure. Thirteen patients received benzathine penicillin for presumed latent syphilis; results were similar to those observed after ceftriaxone therapy, with 8 (62%) responders, 1 (8%) serofast, 2 (15%) relapses, and 2 (15%) failures. CD4 cell counts in responders were not different from those who failed to respond. CONCLUSIONS: Even in the absence of neurologic symptoms, half of the HIV-infected persons who have serologic evidence of syphilis may have neurosyphilis. Although ceftriaxone achieves high serum and CSF levels, 10 to 14 days of treatment with this drug were associated with a 23% failure rate in HIV-infected patients who had latent syphilis or asymptomatic neurosyphilis. Three doses of benzathine penicillin did not have a significantly higher relapse rate and may provide appropriate therapy, at least for documented latent syphilis in persons co-infected with HIV. Studies comparing ceftriaxone with 10 to 14 doses of procaine penicillin are needed to determine the most cost-effective treatment for asymptomatic neurosyphilis or presumed latent syphilis in this group of patients.     

The use of 2 health-related quality-of-life measures in a sample of persons infected with human immunodeficiency virus.

The purpose of this analysis was to examine the ability of the MOS-HIV (Medical Outcomes Study-Human Immunodeficiency Virus) Health Survey and the EuroQol Group's EQ-5D questionnaire to discriminate between subjects in predefined disease-severity groups on the basis of clinical-indicator status (i.e., CD4 cell counts, HIV type 1 [HIV-1] RNA copies). This study used medical records of and instruments completed by 242 HIV-infected patients. The ability of the health-related quality-of-life instruments to discriminate between subjects stratified by disease severity was assessed by means of receiver-operating characteristic (ROC) curve analysis. The EQ-5D (P<.05) and MOS-HIV physical health summary (PHS) scores (P<.01) were able to discriminate between groups of subjects stratified by disease severity on the basis of either CD4 cell counts or HIV-1 RNA copies. These findings provide further evidence of the validity of the use of EQ-5D and the MOS-HIV questionnaire and suggest that they may be practical tools for the monitoring of health status from the HIV-infected patient's perspective.     

Reactivation of latently infected hepatitis B virus in a leukemia patient with antibodies to hepatitis B core antigen

Received: June 15, 2000 / Accepted: September 22, 2000     

Prevalence of antibodies to human herpesviruses and hepatitis B virus in patients at different stages of human immunodeficiency virus (HIV) infection

Summary The results of antibody assays for viruses of the herpes group (HSV, EBV, VZV and CMV) and for hepatitis B virus (HBV) were retrospectively evaluated in 439 HIV-seropositive patients classified into different stages of HIV infection. The prevalence of specific IgG, IgM and IgA antibodies in these groups was compared with that of a control group of HIV-negative unselected hospital patients. Antibodies to herpes viruses and HBV were more prevalent amongst HIV-seropositives, especially LAS and AIDS patients than in controls. However, marked differences were found only with CMV-IgG and anti-HBc-IgG, both with a comparatively low prevalence in HIV-negative persons (64.5% and 23.2%). Significantly more seropositives were found among asymptomatic HIV carriers (83.3% and 50%) and still more in patients with full-blown AIDS (95.4% and 82.5%). The increased frequency of CMV and HBV antibodies, already seen in asymptomatic HIV patients reflects their higher risk for sexually transmitted infections. Moreover, IgA antibodies to CMV were detected in 25.4% of LAS and 37.3% of AIDS patients, respectively, but only in 7.6% of the controls. Elevated CMV-IgA titres were found exclusively in HIV-infected persons. The differences in the antibody patterns found in this cross-sectional study may reflect the progression of the HIV disease. However, prospective follow-up studies are required to assess the value of these markers as indicators of prognosis in HIV-infected subjects.

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Prävalenz von Antikörpern gegen humane Herpesviren und Hepatitis-B-Virus bei HIV-Patienten in verschiedenen Krankheitsstadien

Zusammenfassung Bei 439 HIV-positiven Patienten verschiedener Krankheitsstadien wurden retrospektiv die Ergebnisse der Antikörpertests gegen Viren der Herpesgruppe (HSV, EBV, VZV und CMV) und gegen Hepatitis-B-Virus (HBV) ausgewertet. Die Prävalenz spezifischer IgG-, IgM- und IgA-Antikörper wurde zwischen den verschiedenen Stadien der HIV-Infektion und mit einem Kontrollkollektiv HIV-negativer Krankhenhauspatienten verglichen. Die Durchseuchung mit Herpesviren und Hepatitis B war insgesamt bei HIV-positiven und insbesondere LAS-und AIDS-Patienten höher als im Kontrollkollektiv. Die größten Unterschiede zeigten sich für das CMV-IgG und das anti-HBc-IgG, beide mit einer vergleichsweise niedrigen Prävalenz bei HIV-negativen Personen (64,5% bzw. 23,2%). Der Anteil CMV und HBV-Seropositiver war deutlich höher in der Gruppe der asymptomatischen HIV-Träger (83,3% bzw. 50%) und noch mehr bei Patienten mit dem Vollbild AIDS (95,4% bzw. 82,5%). Die höhere Prävalenz von CMV- und HBV-Antikörpern bei asymptomatischen HIV- positiven Patienten entspricht ihrem erhöhten Risiko für sexuell übertragene Infektionen. Ferner wurde CMV-IgA bei 25,4% und 37,3% der LAS- bzw. AIDS-Patienten gegenüber nur 7,6% im Kontrollkollektiv nachgewiesen. Hohe CMV-IgA-Titer wurden ausschließlich bei HIV-infizierten Patienten gefunden. Der Vergleich der in dieser Querschnittsstudie gefundenen Antikörperprofile scheint die Progression der HIV-Krankheit widerzuspiegeln. Allerdings sind prospektive Verlaufsuntersuchungen erforderlich um den Wert dieser Marker als Prognosefaktoren sicher zu beurteilen.

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Dedicated to Prof.G. Maas, Münster, for his sixty-fifth birthday.