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Longitudinal observations on mutations conferring ganciclovir resistance in patients with acquired immunodeficiency syndrome and cytomegalovirus retinitis: The Cytomegalovirus and Viral Resistance Study Group Report Number 8

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AMERICAN JOURNAL OF OPHTHALMOLOGY 2001年第5期132卷 700-710页

作者： Jabs, DA Martin, BK Forman, MS Dunn, JP Davis, JL Weinberg, DV Biron, KK Baldanti, F Hu, HL Johns Hopkins Univ Sch Med Dept Ophthalmol Baltimore MD 21205 USA Johns Hopkins Univ Sch Med Dept Med Baltimore MD 21205 USA Johns Hopkins Univ Bloomberg Sch Publ Hlth Dept Epidemiol Baltimore MD USA Johns Hopkins Med Inst Dept Pathol Baltimore MD 21205 USA Univ Miami Dept Ophthalmol Miami FL 33152 USA Northwestern Univ Sch Med Dept Ophthalmol Chicago IL 60611 USA Glaxo Wellcome Inc Res Triangle Pk NC 27709 USA IRCCS Policlin FB Serv Virol Pavia Italy

PURPOSE: Cytomegalovirus retinitis is the most com, mon intraocular infection in patients with acquired immunodeficiency syndrome (AIDS). With prolonged suppressive anticytomegalovirus maintenance therapy, resistance occurs in over 25% of patients. We evaluated longitudinal changes in the cytomegalovirus genotype in patients with cytomegalovirus retinitis who developed ganciclovir resistance that was demonstrated in either the blood or urine. METHODS: Patients with AIDS and previously untreated cytomegalovirus retinitis were followed prospectively for the occurrence of resistance while on treatment. Blood and urine specimens were obtained periodically for cytomegalovirus culture according to a predetermined schedule. Positive isolates were tested for phenotypic susceptibility and for mutations in the UL97 and UL54 genes. RESULTS: A mutation conferring resistance to ganciclovir in either the UL97 or UL54 gene was detected in 18 patients. In general, patients with a genotypically resistant virus developed increasing phenotypic resistance over time. There was a suggestion that unless therapy was changed, UL97 mutations tended to persist. In seven of eight patients, the mutations identified in isolates from the blood and urine were identical. In selected patients, there was a suggestion that a mixed population of cytomegalovirus might be present. Progression of the retinitis in an involved eye (15 of 18), contralateral eye retinitis (10 of 11), and extraocular cytomegalovirus disease (5 of 18) occurred commonly among patients with resistant virus. CONCLUSION: Resistance-conferring mutations in the cytomegalovirus genome emerge and may persist when the selective pressure for resistance is maintained. Some patients appear to harbor complex subpopulations of virus with different mutations and different levels of phenotypic resistance. Changes in therapy may result in a shift in virus population and changes in the cytomegalovirus genotype identified. (C) 2001 by Elsevier Sc

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Human herpesvirus 8 seropositivity and risk of Kaposi's sarcoma and other acquired immunodeficiency syndrome-related diseases

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JOURNAL OF THE NATIONAL CANCER INSTITUTE 1999年第17期91卷 1468-1474页

作者： Rezza, G Andreoni, M Dorrucci, M Pezzotti, P Monini, P Zerboni, R Salassa, B Colangeli, V Sarmati, L Nicastri, E Barbanera, M Pristerà, R Aiuti, F Ortona, L Ensoli, B Ist Super Sanita Ctr Operat AIDS Epidemiol & Biostat Lab I-00161 Rome Italy Ist Super Sanita Virol Lab I-00161 Rome Italy Univ Roma Tor Vergata Dept Infect Dis Rome Italy Univ Milan Sexually Transmitted Dis Clin I-20122 Milan Italy Osped Amedeo di Savoia Div Infect Dis Turin Italy Univ Bologna Infect Dis Clin I-40126 Bologna Italy Osped Riuniti Bergamo Div Infect Dis Livorno Italy Osped Reg Div Infect Dis Bolzano Italy Univ Roma La Sapienza Rome Italy Univ Cattolica Sacro Cuore I-00168 Rome Italy

Background: The incidence of Kaposi's sarcoma (KS) is increased severalfold in individuals infected with human immunodeficiency virus-1 (HIV). Human herpesvirus 8 (HHVS) has also been implicated in KS. We investigated several factors that may determine the onset of KS, particularly HHVS infection in individuals after becoming seropositive for HIV. Methods: We studied 366 individuals belonging to different HIV-exposure categories (i.e., homosexual activity, intravenous drug use, and heterosexual contact) for whom a negative HIV serologic test and then a positive HIV serologic test were available within a 2-year period. HHV8 antibody testing was performed by use of an immunofluorescence assay on the first serum sample available after the first positive HIV test. Actuarial rates of progression of KS and of other acquired immunodeficiency syndrome (AIDS)-defining diseases were estimated by use of time-to-event statistical methods. All statistical tests were two-sided. Results: Twenty-one of the 366 study participants developed AIDS-related KS, and 83 developed AIDS without KS. One hundred forty (38.3%) participants had detectable anti-HHV8 antibodies. The actuarial progression rate to KS among persons co-infected with HIV/HHV8 was nearly 30% by 10 years after HIV seroconversion. Increasing HHV8 antibody titers increased the risk of developing KS (for seronegative versus highest titer [1 :125 serum dilution], adjusted relative hazard [RH] = 51.82;95% confidence interval [CI] = 6.08-441.33) but not of other AIDS-defining diseases (adjusted RH = 1.14;95% CI = 0.72-1.80). HHV8-seropositive homosexual men compared with HHV8-seropositive participants from other HIV-exposure categories showed an increased risk of KS that approached statistical significance (adjusted RH = 6.93;95% CI = 0.88-54.84). Conclusions: Approximately one third of individuals coinfected with HIV/HHV8 developed KS within 10 years after HIV seroconversion. Progression to KS increased with time after HIV se

关键词：艾滋病相关机会致病菌感染/病毒学保险统计分析抗体病毒/血液 CD4淋巴细胞计数疾病恶化 HIV感染/并发症疱疹病毒科感染/并发症疱疹病毒4型人/免疫学疱疹病毒8型人/免疫学意大利危险肉瘤卡波西/病毒学青少年成年人老年人女(雌)性人类男(雄)性中年人

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Cervicovaginal human papillomavirus infection in human immunodeficiency virus-1 (HIV)-positive and high-risk HIV-negative women

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JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE 1999年第3期91卷 226-236页

作者： Palefsky, JM Minkoff, H Kalish, LA Levine, A Sacks, HS Garcia, P Young, M Melnick, S Miotti, P Burk, R Univ Calif San Francisco Dept Lab Med San Francisco CA 94143 USA SUNY New York NY USA New England Res Inst Watertown MA 02172 USA Univ So Calif Los Angeles CA USA Mt Sinai Med Ctr New York NY 10029 USA Northwestern Univ Chicago IL 60611 USA Georgetown Univ Washington DC USA NCI Bethesda MD 20892 USA NIAID Bethesda MD 20892 USA Albert Einstein Coll Med New York NY USA

Background: Human papillomavirus (HPV) infection is associated with precancerous cervical squamous intraepithelial lesions commonly seen among women infected with human immunodeficiency virus-1 (HIV), We characterized HPV infection in a large cohort of HIV-positive and HIV-negative women participating in the Women's Interagency HIV Study to determine the prevalence of and risk factors for cervicovaginal HPV infection in HIV-positive women, Methods: HIV-positive (n = 1778) and HIV-negative (n = 500) women were tested at enrollment for the presence of HPV DNA in a cervicovaginal lavage specimen. Blood samples were tested for HIV antibody status, level of CD4-positive T cells, and HIV RNA load (copies/mL), An interview detailing risk factors was conducted. Univariate and multivariate analyses were performed. Results: Compared with HIV-negative women, HIV-positive women with a CD4(+) cell count of less than 200/mm(3) were at the highest risk of HPV infection, regardless of HIV RNA load (odds ratio [OR] = 10.13;95% confidence interval [CI] = 7.32-14.04), followed by women with a CD4+ count greater than 200/mm3 and an HIV RNA load greater than 20 000 copies/mL (OR = 5.78;95% CI = 4.17-8.08) and women with a CD4(+) count greater than 200/mm3 and an HIV RNA load less than 20 000 copies/mL (OR = 3.12;95% CI = 2.36-4.12), after adjustment for other factors. Other risk factors among HIV-positive women included racial/ethnic background (African-American versus Caucasian, OR = 1.64;95% CI = 1.19-2.28), current smoking (yes versus no;OR = 1.55;95% CI = 1.20-1.99), and younger age (age <30 years versus greater than or equal to 40 years;OR = 1.75;95% CI = 1.23-2.49). Conclusions: Although the strongest risk factors of HPV infection among HIV-positive women were indicators of more advanced HIV-related disease, other factors commonly found in studies of HIV-negative women, including racial/ethnic background, current smoking, and age, were important in HIV-positive women as well.

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Immune-recovery uveitis in patients with cytomegalovirus retinitis taking highly active antiretroviral therapy

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AMERICAN JOURNAL OF OPHTHALMOLOGY 2000年第1期130卷 49-56页

作者： Robinson, MR Reed, G Csaky, KG Polis, MA Whitcup, SM NEI NIH Bethesda MD 20892 USA NIAID NIH Bethesda MD 20892 USA

PURPOSE: To investigate the clinical features associated with immune recovery in human immunodeficiency virus (HIV)-infected patients with cytomegalovirus retinitis who are taking highly active antiretroviral therapy. METHODS: Sixteen patients were evaluated prospectively at the National Eye Institute, Bethesda, Maryland. Evaluation included a medical history and a complete ophthalmologic examination. The examination included best corrected visual acuity score measured by means of logarithmic charts, slit-lamp biomicroscopy, dilated retinal examination, retinal photography, and fluorescein angiography. Immune-recovery uveitis was defined as the ocular inflammation associated with clinical immune the presence of moderate to severe macular edema on fluorescein angiography and vitreous haze (P less than or equal to .001). CONCLUSIONS: Immune-recovery uveitis is an important cause of visual morbidity in HIV-infected patients with cytomegalovirus retinitis in the era of highly active antiretroviral therapy. Although immune recovery associated with highly active antiretroviral therapy has allowed some patients to discontinue specific anticytomegalovirus therapy, the rejuvenated immune response can be associated with sight-threatening inflammation. Published by Elsevier Science Inc.

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Large plantar wart caused by human papillomavirus-66 and resolution by topical cidofovir therapy

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JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY 2000年第2期43卷 340-343页

作者： Davis, MDP Gostout, BS McGovern, RM Persing, DH Schut, RL Pittelkow, MR Mayo Clin & Mayo Fdn Dept Dermatol Rochester MN 55905 USA Mayo Clin & Mayo Fdn Sect Gynecol Surg Rochester MN 55905 USA Mayo Clin & Mayo Fdn Dept Lab Med & Pathol Rochester MN 55905 USA Hennepin Cty Med Ctr HIV AIDS Program Minneapolis MN 55415 USA

Warts can be difficult to diagnose and to treat in the setting of human immunodeficiency virus (HIV) infection. A 37-year-old woman with a background of HIV presented with a large verrucous plaque involving her right foot. Human papillomavirus (HPV)-66 was identified in the lesional skin biopsy sample and in scrapings obtained from her cen ix. The wart rapidly responded to topical cidofovir therapy. HPV-66 is a novel HPV type to be associated with verruca vulgaris. Topical cidofovir should be further investigated as an alternative treatment modality for verruca vulgaris.

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Infectious and tropical diseases affecting the human mouth

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PERIODONTOLOGY 2000 1998年第1期18卷 47-70页

作者： Scully, C Monteil, R Sposto, MR Univ London Eastman Dent Inst Oral Hlth Care Sci London England Univ Nice Fac Chirurg Dent Nice France Univ Estadual Paulista Fac Odontol Sao Paulo Brazil

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Usefulness of the cytomegalovirus (CMV) antigenemia assay for predicting the occurrence of CMV disease and death in patients with AIDS

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CLINICAL INFECTIOUS DISEASES 1999年第4期28卷 758-763页

作者： Chevret, S Scieux, C Garrait, V Dahel, L Morinet, F Modaï, J Decazes, JM Molina, JM Hop St Louis Serv Malad Infect Dept Biostat F-75010 Paris France Hop St Louis Dept Virol F-75010 Paris France Hop St Louis Dept Infect Dis F-75010 Paris France

A cohort study of 214 human immunodeficiency virus (HIV)-infected patients was performed to assess the usefulness of the cytomegalovirus (CMV) antigenemia assay for predicting the occurrence of CMV disease and death. Multivariate analysis revealed that only positive baseline CMV antigenemia assays (relative risk [RR], 7.2;95% confidence interval [CI], 3.7-14.2;P = .0001) and CD4 cell counts (RR, 0.98;95% CI, 0.97-0.99;P = .009) were associated with CMV disease. A positive baseline CMV antigenemia assay was also associated with death by multivariate analysis (RR, 2.2;95% CI, 1.5-3.4;P = .0003). Increasing levels of CMV antigenemia during follow-up were associated with increased risks of CMV disease and death. A positive CMV antigenemia assay that shelved >10 cells per 2 x 10(5) polymorphonuclear leukocytes during follow-up was 91% sensitive and 84% specific for predicting a diagnosis of CMV disease: the negative predictive value for this positive test was high (97%). Therefore, the CMV antigenemia assay appears to be a simple, rapid, and inexpensive test for predicting the occurrence of CMV disease and death in patients with advanced HIV infection.

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KS enters Y2K still riddled with many questions

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JOURNAL OF THE NATIONAL CANCER INSTITUTE 1999年第19期91卷 1612-1614页

作者： Miller, M

Discusses the mysteries surrounding Kaposi's sarcoma (KS), an AIDS-related malignancies. How Robert Gallo, director of the Institute of Human Virology in Baltimore, Maryland, described KS; Puzzling aspects of KS; ... 详细信息

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Comparison of intraocular to plasma HIV-1 viral burden in patients with cytomegalovirus retinitis

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AMERICAN JOURNAL OF OPHTHALMOLOGY 1999年第2期127卷 221-223页

作者： Ciulla, TA Schnizlein-Bick, CT Danis, RP Frank, MO Wheat, LJ Indiana Univ Sch Med Dept Ophthalmol Indianapolis IN 46202 USA Indiana Univ Sch Med Dept Internal Med Div Infect Dis Indianapolis IN 46202 USA

PURPOSE: To determine the relationship between plasma and intraocular human immunodeficiency virus-1 (HIV-1) viral loads in 12 consecutive patients undergoing ganciclovir implant surgery for cytomegalovirus (CMV) retinitis. METHODS: Aqueous and vitreous specimens were assayed for HIV-1 viral load by polymerase chain reaction analysis (Roche Amplicor HIV Monitor;Roche Diagnostics Systems, Inc, Branchburg, New Jersey). RESULTS: It was possible to quantitatively assay HIV-1 burden in intraocular fluids using polymerase chain reaction analysis. In general, patients with plasma viral loads less than 250,000 copies/ml had undetectable (<200 copies/ml) HIV-1 in their aqueous and vitreous. CONCLUSIONS: It is likely that intraocular viral levels have several determinants in addition to plasma viral loads, with which they only partially correlate. (Am J Ophthalmol 1999;127:221-223. (C) 1999 by Elsevier Science Inc. All rights reserved.).

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Persistent fever as the only manifestation of chronic coxsackievirus B4 infection in the brain of a human immunodeficiency virus type 1-infected child

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CLINICAL INFECTIOUS DISEASES 1999年第4期28卷 912-913页

作者： Palomba, E Tovo, PA Univ Turin Dept Pediat I-10126 Turin Italy

Reports the case of a child infected with HIV-1 in whom persistent fever was the only symptom of chronic coxsackievirus B4 infection in the brain. Therapy conducted; Effects of high doses of intravenous immunoglobulin... 详细信息

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