今日の臨床サポート

HIVスクリーニング陽性

著者: 塚田訓久 国立国際医療研究センター エイズ治療・研究開発センター

監修: 山本舜悟 京都市立病院 感染症科/京都大学 医療疫学(非常勤講師) 

著者校正/監修レビュー済:2021/09/29
参考ガイドライン:
  1. 厚生労働省研究班:抗HIV治療ガイドライン 2021年3月
  1. 日本エイズ学会HIV感染症治療委員会: HIV感染症 治療の手引き 第24版
  1. 日本エイズ学会日本臨床検査医学会:診療におけるHIV-1/2感染症の診断ガイドライン2020版(日本エイズ学会・日本臨床検査医学会 標準推奨法)日本エイズ学会誌 23(1):39-43, 2021.
患者向け説明資料

概要・推奨   

  1. HIVスクリーニング検査が陽性となった場合は、抗体確認検査ならびに核酸増幅検査による確認を行う必要がある(推奨度1)。
  1. 治療薬の選択に肝腎機能の評価が必要であるため、HIV診断時に血算、生化学、肝機能を調べることが推奨される(推奨度2)。
  1. 抗HIV薬開始によって脂質代謝異常を起こすことがあるため、治療薬開始前のベースラインとして脂質機能の評価を行っておくことが推奨される(推奨度2)。
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薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、林太祐、渡邉裕次、井ノ口岳洋、梅田将光による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、
著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適用の査定において保険適用及び保険適用外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適用の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
塚田訓久 : 特に申告事項無し[2021年]
監修:山本舜悟 : 特に申告事項無し[2021年]

改訂のポイント:
  1. HIVスクリーニング検査が陽性となった場合の確認検査方法が変更となった.

病態・疫学・診察

疫学情報・病態・注意事項  
  1. HIV感染症とは、ヒト免疫不全ウイルス(HIV)が主としてCD4陽性リンパ球などの免疫担当細胞に感染することで、治療を行わなければ細胞性免疫能が進行性に障害されてゆく疾患である。
 
HIV感染の自然経過

HIV感染後のウイルス量とCD4値の自然経過および病期との関係

 
HIVウイルス

HIV粒子の構造

出典

 
  1. HIVは感染者からの血液、精液、膣分泌液などの体液、母乳を介して感染する。性行為、注射器具の共用、母子感染などが主な感染経路である。
  1. 診断方法としては、まず第4世代検査(抗原・抗体検査)などの高感度のスクリーニング検査を行う。偽陽性のことがあるので、診断の確定には抗体確認検査、核酸増幅検査による確認検査が必要である。
  1. 感染急性期の場合はスクリーニング検査が陽性にならない場合がある。スクリーニング陰性の場合でも、急性感染期が強く疑われる患者では、より早期に検出可能となるHIV-RNA量の測定を検討する。
  1. 診断が確定した場合には、治療に向けて早めに専門医に紹介する。
  1. HIV感染症は現時点では完治できないが、早期に適切な治療を行うことで、良好な予後を期待できる慢性疾患となっていること、また医療費の補助体制や相談窓口も整っていることを伝える。
  1. 感染予防のカウンセリングを行う。
問診・診察のポイント  
ポイント:
  1. ほかの感染症、あるいは日和見感染症を合併していることがあるので、問診、診察は全身くまなく丁寧にする。特に口腔内、リンパ節、皮膚、陰部の診察を忘れないこと。本人に自覚症状がないこともあるほか、陰部の症状や病変があっても患者本人から言い出しにくいこともある。

これより先の閲覧には個人契約のトライアルまたはお申込みが必要です。

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文献 

著者: P L Myskowski, R Ahkami
雑誌名: Med Clin North Am. 1996 Nov;80(6):1415-35.
Abstract/Text Cutaneous disorders occur with great frequency in patients with HIV infection and increase in number and severity as the disease progresses and immune function declines. In addition, the first findings related to HIV infection are often on the skin. Cutaneous infections with herpesviruses may be severe and atypical in their presentations; papillomaviruses and MC are common as well. Bacterial infections may be primary or secondary to other skin diseases; superficial and deep fungal infections are also prevalent. Papulosquamous disorders, including seborrheic dermatitis, psoriasis, and eczema, may be disfiguring and result in secondary complications. Neoplastic disorders, especially Kaposi's sarcoma, demand early diagnosis, to afford the patient maximal treatment options. All physicians must be aware of these cutaneous manifestations to decrease morbidity and improve quality of life in the HIV-infected individual.

PMID 8941229  Med Clin North Am. 1996 Nov;80(6):1415-35.
著者: N J Mehta, I A Khan, R N Mehta, D A Sepkowitz
雑誌名: Chest. 2000 Oct;118(4):1133-41.
Abstract/Text OBJECTIVE: To report two new cases of HIV-related pulmonary hypertension and to review and analyze the existing reports on the subject.
METHOD: Two new cases of HIV-related pulmonary hypertension are described, and the cases, case series, and related articles on the subject in all languages were identified through a comprehensive MEDLINE search.
RESULTS: Among the 131 reviewed cases, 54% were male, and the age range was 2 to 56 years (mean, 33 years). The interval between the diagnosis of HIV disease and the diagnosis of pulmonary hypertension was 33 months. In 82% of cases, pulmonary hypertension was related solely to HIV infection. Presenting symptoms were progressive shortness of breath (85%), pedal edema (30%), nonproductive cough (19%), fatigue (13%), syncope or near-syncope (12%), and chest pain (7%). The mean (+/- SD) pulmonary arterial systolic BP was 67 +/- 18 mm Hg (n = 116), and diastolic BP was 40+/-11 mm Hg (n = 39). Pulmonary vascular resistance was 983+/-420 dyne. s. cm(-5) (n = 29). Chest radiographs demonstrated cardiomegaly (72%) and pulmonary artery prominence (71%). Right ventricular hypertrophy was the most common electrocardiographic finding (67%). Dilatation of the right heart chambers was the most common echocardiographic finding (98%). Plexogenic pulmonary arteriopathy was the most common histopathology (78%). Pulmonary function tests demonstrated mild restrictive patterns with variably reduced diffusing capacities. The responses to vasodilator agents and antiretroviral therapy was variable. Sixty-six patients died during a median follow-up period of 8 months. The median length of time from diagnosis to death was 6 months.
CONCLUSION: HIV infection is an independent risk factor for the development of pulmonary hypertension. The appearance of unexplained cardiopulmonary symptoms in HIV-infected individuals should suggest pulmonary hypertension.

PMID 11035689  Chest. 2000 Oct;118(4):1133-41.
著者: E Mylonakis, M Paliou, M Lally, T P Flanigan, J D Rich
雑誌名: Am J Med. 2000 Nov;109(7):568-76. doi: 10.1016/s0002-9343(00)00583-0.
Abstract/Text The enzyme-linked immunosorbent assay (ELISA) and the Western blot are the primary tests for the diagnosis and confirmation of human immunodeficiency virus (HIV) infection. The ELISA, an inexpensive screening test for antibodies to HIV-1, is both sensitive and specific. The HIV-1 Western blot is a reliable confirmatory test following a repeatedly reactive ELISA. False-positive HIV-1 results with this sequence of tests are extremely rare but can occur, and test results that are inconsistent with clinical or other laboratory information should be questioned, repeated, or supplemented. The US Food and Drug Administration has also approved rapid and more accessible testing methods. Oral mucosal transudate and urine testing are noninvasive testing methods; rapid and home sample collection kits offer easier access to testing.

PMID 11063959  Am J Med. 2000 Nov;109(7):568-76. doi: 10.1016/s0002-93・・・
著者: Judith A Aberg, Joel E Gallant, Khalil G Ghanem, Patricia Emmanuel, Barry S Zingman, Michael A Horberg, Infectious Diseases Society of America
雑誌名: Clin Infect Dis. 2014 Jan;58(1):1-10. doi: 10.1093/cid/cit757.
Abstract/Text Evidence-based guidelines for the management of persons infected with human immunodeficiency virus (HIV) were prepared by an expert panel of the HIV Medicine Association of the Infectious Diseases Society of America. These updated guidelines replace those published in 2009. The guidelines are intended for use by healthcare providers who care for HIV-infected patients. Since 2009, new antiretroviral drugs and classes have become available, and the prognosis of persons with HIV infection continues to improve. However, with fewer complications and increased survival, HIV-infected persons are increasingly developing common health problems that also affect the general population. Some of these conditions may be related to HIV infection itself or its treatment. HIV-infected persons should be managed and monitored for all relevant age- and sex-specific health problems. New information based on publications from the period 2009-2013 has been incorporated into this document.

PMID 24343580  Clin Infect Dis. 2014 Jan;58(1):1-10. doi: 10.1093/cid/・・・
著者: J Servais, D Nkoghe, J C Schmit, V Arendt, I Robert, T Staub, M Moutschen, F Schneider, R Hemmer
雑誌名: J Acquir Immune Defic Syndr. 2001 Nov 1;28(3):221-5. doi: 10.1097/00042560-200111010-00003.
Abstract/Text The relationship between HIV-1 replication and hematologic parameters was examined in two separate studies. The first study was a cross-sectional evaluation of 207 untreated patients. In this study, the proportion of patients with hematologic disorders increased with disease progression. There was a significant inverse correlation between HIV-1 plasma viral load and all hematologic values (r = -0.266 to -0.331). The second study was a longitudinal evaluation of patients on combination antiretroviral therapy (HAART) with hematologic alterations before treatment ( N = 27 with platelets <150,000/microl, 24 with hemoglobin <12 g/dl, 36 with neutrophils <2000/microl and 29 with leukocytes <3000/microl). Samples were analyzed every 3 months for 2 years. At 2 years, >50% of patients experienced a sustained virologic response, with viral loads <500 RNA copies/ml. Hematologic reconstitution occurred progressively for all blood cell lineages and became statistically significant after the sixth month of therapy ( p <.001). Mean values increased from 110 to 180 x 10(3)/microl for platelets, from 10.7 to 12.3 g/dl for hemoglobin (stabilizing finally at 11.4 g/dl), from 1,260 to 2,240/microl for neutrophils, and from 2,260 to 3,600/microl for leukocytes. In conclusion, hematologic disorders are corrected by combination antiretroviral therapy. This suggests a causative role of HIV-1 in hematologic disorders.

PMID 11694827  J Acquir Immune Defic Syndr. 2001 Nov 1;28(3):221-5. do・・・
著者: J A Winston, L A Bruggeman, M D Ross, J Jacobson, L Ross, V D D'Agati, P E Klotman, M E Klotman
雑誌名: N Engl J Med. 2001 Jun 28;344(26):1979-84. doi: 10.1056/NEJM200106283442604.
Abstract/Text
PMID 11430327  N Engl J Med. 2001 Jun 28;344(26):1979-84. doi: 10.1056・・・
著者: E Fontas, F van Leth, C A Sabin, N Friis-Møller, M Rickenbach, A d'Arminio Monforte, O Kirk, M Dupon, L Morfeldt, S Mateu, K Petoumenos, W El-Sadr, S de Wit, J D Lundgren, C Pradier, P Reiss, D:A:D Study Group
雑誌名: J Infect Dis. 2004 Mar 15;189(6):1056-74. doi: 10.1086/381783. Epub 2004 Mar 2.
Abstract/Text Levels of triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c), as well as the TC:HDL-c ratio, were compared in patients receiving different antiretroviral therapy regimens. Patients receiving first-line regimens including protease inhibitors (PIs) had higher TC and TG levels and TC : HDL-c ratios than did antiretroviral-naive patients; patients receiving 2 PIs had higher levels of each lipid. Ritonavir-containing regimens were associated with higher TC and TG levels and TC : HDL-c ratios than were indinavir-containing regimens; however, receipt of nelfinavir was associated with reduced risk of lower HDL-c levels, and receipt of saquinavir was associated with lower TC : HDL-c ratios. Patients receiving nonnucleoside reverse-transcriptase inhibitors had higher levels of TC and LDL-c than did antiretroviral-naive patients, although the risk of having lower HDL-c levels was lower than that in patients receiving a single PI. Efavirenz was associated with higher levels of TC and TG than was nevirapine.

PMID 14999610  J Infect Dis. 2004 Mar 15;189(6):1056-74. doi: 10.1086/・・・
著者: Kathryn Anastos, Dalian Lu, Qiuhu Shi, Phyllis C Tien, Robert C Kaplan, Nancy A Hessol, Steven Cole, Cheryl Vigen, Mardge Cohen, Mary Young, Jessica Justman
雑誌名: J Acquir Immune Defic Syndr. 2007 May 1;45(1):34-42. doi: 10.1097/QAI.0b013e318042d5fe.
Abstract/Text BACKGROUND: The effects of HIV infection, highly active antiretroviral therapy (HAART), and specific antiretroviral agents on lipoproteins in women are not well described.
METHODS: In a cross-sectional substudy of the Women's Interagency HIV Study with 623 HIV-negative and 1556 HIV-positive women (636 untreated, 419 on non-protease inhibitor [PI] HAART, and 501 on PI-containing HAART), we performed multivariate analyses of associations among fasting lipoprotein levels, HIV infection, and HAART.
RESULTS: Untreated HIV-positive women had lower high-density lipoprotein cholesterol (HDL-C) and higher triglycerides (TGs) but not lower low-density lipoprotein cholesterol (LDL-C) than HIV-negative women and were the most likely to have unfavorable HDL-C by National Cholesterol Education Program (NCEP) guidelines. PI HAART users had higher LDL-C than untreated HIV-infected women (107 vs. 100 mg/dL, P = 0.0006) and were the most likely to have unfavorable LDL-C and TGs by NCEP guidelines. HIV-negative women and non-PI HAART users had similar HDL-C levels (55 and 53 mg/dL, respectively), which were higher than those in untreated HIV-infected women and PI HAART users (42 and 49 mg/dL, respectively; P < 0.001 for all). Lamivudine, didanosine, nevirapine, and efavirenz were independently associated with higher HDL-C (P < 0.001 for all). Ritonavir, indinavir/ritonavir, and nelfinavir were associated with higher LDL-C (P < 0.01 for all). Stavudine, abacavir, and all ritonavir-containing regimens were associated with higher TGs (P < 0.05 for all), and tenofovir was associated with lower TGs (P = 0.009).
CONCLUSIONS: A dyslipidemic pattern was associated with HIV infection itself, was more severe in users of PI-containing HAART, but was not present in women taking non-PI HAART.

PMID 17460470  J Acquir Immune Defic Syndr. 2007 May 1;45(1):34-42. do・・・
著者: Sharon A Riddler, Ellen Smit, Stephen R Cole, Rui Li, Joan S Chmiel, Adrian Dobs, Frank Palella, Barbara Visscher, Rhobert Evans, Lawrence A Kingsley
雑誌名: JAMA. 2003 Jun 11;289(22):2978-82. doi: 10.1001/jama.289.22.2978.
Abstract/Text CONTEXT: Alterations in serum lipid values have been widely reported among persons infected with human immunodeficiency virus (HIV) type 1 treated with highly active antiretroviral therapy (HAART), but no data have yet been reported on changes from preseroconversion lipid values.
OBJECTIVE: To describe changes in serum cholesterol levels associated with HIV infection and antiretroviral medication exposure, and 1-time assessment of triglyceride levels post-HAART initiation.
DESIGN, SETTING, AND PARTICIPANTS: The Multicenter AIDS Cohort Study, a prospective study in which homosexual and bisexual men were enrolled and from which 50 of 517 HIV seroconverters were drawn for the analysis herein, who later initiated HAART, involving measurements of stored serum samples obtained between 1984 and 2002.
MAIN OUTCOME MEASURES: Changes in levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) at 6 time points during an average of 12 years; 1-time assessment of triglyceride levels from the third post-HAART clinic visit.
RESULTS: Among the 50 men, notable declines in mean serum TC (-30 mg/dL [-0.78 mmol/L]), HDL-C (-12 mg/dL [-0.31 mmol/L]), and LDL-C values (-22 mg/dL [-0.57 mmol/L]) were observed after HIV infection. Following HAART initiation, there were large increases in mean TC and LDL-C values (50 and 21 mg/dL [1.30 and 0.54 mmol/L], respectively); however, the mean changes from the preseroconversion values were 20 mg/dL (0.52 mmol/L) (95% confidence interval [CI], -1 to 41) and -1 mg/dL (-0.03 mmol/L) (95% CI, -25 to 22), respectively. Mean HDL-C remained below baseline levels throughout follow-up. The median value (interquartile range) of triglycerides was 225 mg/dL (2.54 mmol/L) (147-331 mg/dL).
CONCLUSIONS: Before treatment, HIV infection results in substantial decreases in serum TC, HDL-C, and LDL-C levels. Subsequent HAART initiation is associated with increases in TC and LDL-C but little change in HDL-C. Increases in TC and LDL-C observed after about 3 years of HAART possibly represent a return to preinfection serum lipid levels after accounting for expected age-related changes.

PMID 12799406  JAMA. 2003 Jun 11;289(22):2978-82. doi: 10.1001/jama.28・・・
著者: S K Gupta, B W Mamlin, C S Johnson, M D Dollins, J M Topf, M P Dubé
雑誌名: Clin Nephrol. 2004 Jan;61(1):1-6.
Abstract/Text AIMS: HIV-related renal diseases are increasingly prevalent and are associated with proteinuria and rapid progression to end-stage renal failure. Early treatment with highly active antiretroviral therapy (HAART) and ACE inhibition may prevent the development of chronic kidney disease (CKD), but studies evaluating the epidemiology of proteinuria and early CKD in HIV-infected patients are lacking.
METHODS: All consecutive patients at Wishard Memorial Hospital (Indiana University) whose initial HIV documentation occurred from 1990 to 1998, were retrospectively studied using a computerized medical record system. Clinical data were abstracted from time of first HIV documentation through 12/31/2000. The proportions of patients who developed CKD (doubling of serum creatinine from an initial level < or = 1.5 mg/dl) and who had proteinuria (> or = 1+ protein on the first urine dipstick after HIV documentation) were calculated. Case mix and laboratory variables at the time of HIV documentation were compared between those who did and did not develop CKD and between those who had and did not have initial proteinuria.
RESULTS: Of 487 subjects with initially normal renal function, 10 (2% (95% CI, 1-4%)) developed CKD. In univariable analysis, black race, a diagnosis of diabetes or hypertension and proteinuria were all significantly associated with the development of CKD; 89 (29% (95% CI, 24-35%)) of 289 evaluable subjects had > or = 1+ proteinuria on urine analysis. Multivariable regression revealed only older age (OR 1.08 per year increase; 95% CI, 1.03-1.14) to be associated with proteinuria.
CONCLUSIONS: A small, but potentially clinically meaningful proportion of HIV-infected patients develop CKD, and there appears to be a high prevalence of proteinuria on the first urine analysis obtained after HIV documentation.

PMID 14964451  Clin Nephrol. 2004 Jan;61(1):1-6.
著者: Marina Núñez, Massimo Puoti, Nuria Camino, Vincent Soriano
雑誌名: Clin Infect Dis. 2003 Dec 15;37(12):1678-85. doi: 10.1086/379774. Epub 2003 Oct 29.
Abstract/Text The management of chronic hepatitis B poses specific problems in the presence of human immunodeficiency virus (HIV) coinfection, because therapeutic approaches have to address both hepatitis B virus (HBV) and HIV infections. Response to interferon (IFN-alpha) is lower in HBV-HIV-coinfected than in HIV-negative subjects, especially in patients in advanced stages of immunosuppression. Thus far, there are no data on the performance of the new pegylated forms of IFN-alpha in HBV- and HIV-coinfected persons. After prolonged use of lamivudine, resistance develops in the majority of HBV-HIV-coinfected patients treated with the drug. The more recently approved tenofovir has shown excellent short-term results, and data from longer follow-up studies are eagerly awaited. Several drugs with combined anti-HIV and anti-HBV activity have recently been approved (emtricitabine) or are currently under development. Preliminary results with some of them are quite promising and probably will widen the therapeutic armamentarium against hepatitis B in patients with HIV infection.

PMID 14689351  Clin Infect Dis. 2003 Dec 15;37(12):1678-85. doi: 10.10・・・
著者: C S Graham, L R Baden, E Yu, J M Mrus, J Carnie, T Heeren, M J Koziel
雑誌名: Clin Infect Dis. 2001 Aug 15;33(4):562-9. doi: 10.1086/321909. Epub 2001 Jul 6.
Abstract/Text Studies have shown that rates of liver disease are higher in persons who are coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) than they are in persons with HCV alone, but estimates of risk vary widely and are based on data for dissimilar patient populations. We performed a meta-analysis to quantify the effect of HIV coinfection on progressive liver disease in persons with HCV. Eight studies were identified that included outcomes of histological cirrhosis or decompensated liver disease. These studies yielded a combined adjusted relative risk (RR) of 2.92 (95% confidence interval [CI], 1.70-5.01). Of note, studies that examined decompensated liver disease had a combined RR of 6.14 (95% CI, 2.86-13.20), whereas studies that examined histological cirrhosis had a pooled RR of 2.07 (95% CI, 1.40-3.07). There is a significantly elevated RR of severe liver disease in persons who are coinfected with HIV and HCV. This has important implications for timely diagnosis and consideration of treatment in coinfected persons.

PMID 11462196  Clin Infect Dis. 2001 Aug 15;33(4):562-9. doi: 10.1086/・・・
著者: Chloe L Thio, Eric C Seaberg, Richard Skolasky, John Phair, Barbara Visscher, Alvaro Muñoz, David L Thomas, Multicenter AIDS Cohort Study
雑誌名: Lancet. 2002 Dec 14;360(9349):1921-6.
Abstract/Text BACKGROUND: Although coinfection with HIV-1 and hepatitis B virus (HBV) is common, few long-term studies on liver-disease mortality in coinfected people have been undertaken. Our aim was to examine liver-related mortality among people at risk for HIV-1 and HBV infections.
METHODS: We used data from a multicentre, prospective cohort study to classify 5293 men who had sex with men, according to their HIV-1 antibody status, ascertained semiannually, and their hepatitis-B surface antigen status (HBsAg), which we ascertained at baseline. Mortality rates were estimated in terms of person-years and Poisson regression methods were used to test for significance of relative risks.
FINDINGS: 326 (6%) men were HBsAg positive, of whom 213 (65%) were HIV-1 positive. Of the 4967 HBsAg negative men, 2346 (47%) were infected with HIV-1. The liver-related mortality rate was 1.1/1000 person years, and was higher in men with HIV-1 and HBsAg (14.2/1000) than in those with only HIV-1 infection (1.7/1000, p<0.001) or only HBsAg (0.8/1000, p<0.001). In coinfected individuals, the liver-related mortality rate was highest with lower nadir CD4+ cell counts and was twice as high after 1996, when highly active antiretroviral therapy (HAART) was introduced.
INTERPRETATION: Individuals coinfected with HIV-1 and HBV, especially those with low CD4+ nadir counts, are at increased risk for liver-related mortality, underscoring the importance of prevention, identification, and comprehensive management of hepatitis B in people infected with HIV-1.

PMID 12493258  Lancet. 2002 Dec 14;360(9349):1921-6.
著者: B Wong, J W Gold, A E Brown, M Lange, R Fried, M Grieco, D Mildvan, J Giron, M L Tapper, C W Lerner
雑誌名: Ann Intern Med. 1984 Jan;100(1):36-42.
Abstract/Text Central-nervous-system toxoplasmosis developed in 7 of 269 patients with the acquired immunodeficiency syndrome reported to the New York City Health Department through July 1982. Focal neurologic abnormalities, mass lesions on computed-tomographic brain scans, lymphocytic cerebrospinal fluid pleocytosis, and detectable IgG antibody to Toxoplasma gondii were common; but IgG titers of 1:1024 or more, IgM antibody to T. gondii, and positive open brain biopsies were uncommon. Serologic findings suggested that the disease resulted from recrudescent rather than primary infection. Four of five patients improved when treated with sulfonamides and pyrimethamine, but 2 had relapses. An aggressive diagnostic approach and sometimes even empiric therapy are warranted when central-nervous-system toxoplasmosis is suspected in a seropositive patient with the acquired immunodeficiency syndrome.

PMID 6691657  Ann Intern Med. 1984 Jan;100(1):36-42.
著者: Pam Sonnenberg, Judith R Glynn, Katherine Fielding, Jill Murray, Peter Godfrey-Faussett, Stuart Shearer
雑誌名: J Infect Dis. 2005 Jan 15;191(2):150-8. doi: 10.1086/426827. Epub 2004 Dec 13.
Abstract/Text BACKGROUND: Infection with human immunodeficiency virus (HIV) increases the risk of tuberculosis (TB), but no study has assessed how this risk changes with time since HIV seroconversion.
METHODS: The incidence of pulmonary TB was estimated in miners with and those without HIV infection in a retrospective cohort study. HIV test results were linked to routinely collected TB, demographic, and occupational data. The rate ratio (RR) for the association between HIV status and TB was estimated by time since HIV seroconversion, calendar period, and age.
RESULTS: Of the 23,874 miners in the cohort, 17,766 were HIV negative on entry, 3371 were HIV positive on entry, and 2737 seroconverted during follow-up (1962 had a seroconversion interval of < or =2 years). A total of 740 cases of TB were analyzed. The incidence of TB increased with time since seroconversion, calendar period, and age. TB incidence was 2.90 cases/100 person-years at risk (pyar) in HIV-positive miners and was 0.80 cases/100 pyar in HIV-negative miners (adjusted RR, 2.9 [95% confidence interval {CI}, 2.5-3.4]). TB incidence doubled within the first year of HIV infection (adjusted RR, 2.1 [95% CI, 1.4-3.1]), with a further slight increase in HIV-positive miners for longer periods, up to 7 years.
CONCLUSION: The increase in the risk of TB so soon after infection with HIV was unexpected. Current predictive models of TB incidence underestimate the effect of HIV infection in areas where TB is endemic.

PMID 15609223  J Infect Dis. 2005 Jan 15;191(2):150-8. doi: 10.1086/42・・・
著者: C Robert Horsburgh
雑誌名: N Engl J Med. 2004 May 13;350(20):2060-7. doi: 10.1056/NEJMsa031667.
Abstract/Text BACKGROUND: The prevention of active tuberculosis through the treatment of latent tuberculosis infection is a major element of the national strategy for eliminating tuberculosis in the United States. Targeted treatment for persons who are at the highest risk for reactivation tuberculosis will be needed to achieve this goal. A more precise assessment of the lifetime risk of reactivation tuberculosis, usually estimated at 5 to 10 percent, could help to identify patients who are at the highest risk and motivate them to complete treatment. Currently, the rate of completion of treatment is low.
METHODS: Published reports were reviewed to obtain estimates of the risk of tuberculosis among persons with a positive tuberculin skin test. Using these data, I constructed a model to estimate the lifetime risk of tuberculosis among persons with specific medical conditions.
RESULTS: The lifetime risk of reactivation tuberculosis is 20 percent or more among most persons with induration of 10 mm or more on a tuberculin skin test and either human immunodeficiency virus infection or evidence of old, healed tuberculosis. The lifetime risk is 10 to 20 percent among persons with recent conversion of a tuberculin skin test and among most persons younger than 35 years of age who are receiving infliximab therapy and have induration of 15 mm or more on a tuberculin skin test. The risk is also 10 to 20 percent among children five years of age or younger who have induration of 10 mm or more on a tuberculin skin test.
CONCLUSIONS: Persons with these characteristics should be targeted for intensive efforts to ensure full treatment of latent tuberculosis. Improved rates of completion of treatment among such persons could help to eliminate tuberculosis in the United States.

Copyright 2004 Massachusetts Medical Society
PMID 15141044  N Engl J Med. 2004 May 13;350(20):2060-7. doi: 10.1056/・・・
著者: D C Perlman, W M el-Sadr, E T Nelson, J P Matts, E E Telzak, N Salomon, K Chirgwin, R Hafner
雑誌名: Clin Infect Dis. 1997 Aug;25(2):242-6.
Abstract/Text Our aim was to evaluate the effect of human immunodeficiency virus (HIV) disease stage on chest radiographic (CXR) findings among patients with HIV-related pulmonary tuberculosis (TB). Data are from a prospective multicenter treatment trial for HIV-related TB. Baseline CXR findings and CD4+ lymphocyte counts were compared among patients with HIV-related TB. Data from published studies describing CXR findings in HIV-infected patients were reviewed and a pooled-data analysis was conducted. Of 135 patients with culture-confirmed HIV-related TB, 128 had both CXR and CD4+ lymphocyte data. CD4+ lymphocyte counts of < 200/mm3 (n = 98) were significantly associated with hilar/mediastinal adenopathy on CXR (30%, vs. 7% with counts > or = 200/mm3; P = .01); counts of > or = 200/mm3 (n = 30) more frequently were associated with cavitation (20% vs. 7%; P = .08). Analyses of these results, pooled with other published data, confirmed these findings. This study demonstrates associations of certain CXR findings with HIV disease stage. Knowledge of the degree of immunosuppression is important when evaluating CXR findings in HIV-infected patients.

PMID 9332519  Clin Infect Dis. 1997 Aug;25(2):242-6.
著者: J Batungwanayo, H Taelman, R Dhote, J Bogaerts, S Allen, P Van de Perre
雑誌名: Am Rev Respir Dis. 1992 Jul;146(1):53-6. doi: 10.1164/ajrccm/146.1.53.
Abstract/Text The aim of the present study was to compare the clinical and radiographic presentation as well as the therapeutic outcome of pulmonary tuberculosis (PT) in adult patients with and without human immunodeficiency virus type 1 (HIV-1) infection in Kigali, Rwanda. Over a 17-month period 59 consecutive patients with bacteriologically and/or histopathologically documented PT were enrolled. Of these, 48 (81%) patients were HIV seropositive. Among these, 35 fit the WHO clinical criteria for AIDS (WHOCCA) at the time of admission. Significant differences were found between the HIV-seropositive and HIV-seronegative groups of patients: fever (85 versus 36%; p less than 0.001), tuberculin skin test anergy (69 versus 0%; p less than 0.01), mediastinal and/or hilar adenopathies (31 versus 0%; p = 0.05), and pleural effusion (43 versus 9%; p less than 0.05) were more frequently encountered in the HIV-seropositive group, and upper lobe infiltrates (55 versus 16%; p less than 0.02) and cavitation (91 versus 39%; p less than 0.003) were more often seen in the HIV-seronegative group. However, HIV-seropositive patients not meeting WHOCCA were less frequently anergic (0 versus 100%; p less than 0.001) and feverish (53 versus 97%; p less than 0.01) and more often had cavitation (69 versus 28%; p less than 0.02) and less often mediastinal and/or hilar adenopathies (7 versus 40%; p less than 0.04) compared with HIV-seropositive patients meeting WHOCCA. Under antituberculosis treatment, clearance of fever was slower in HIV-seropositive compared with HIV-seronegative patients, and among the HIV-seropositive group it was slower in those fitting WHOCCA.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID 1626814  Am Rev Respir Dis. 1992 Jul;146(1):53-6. doi: 10.1164/a・・・
著者: J Phair, A Muñoz, R Detels, R Kaslow, C Rinaldo, A Saah
雑誌名: N Engl J Med. 1990 Jan 18;322(3):161-5. doi: 10.1056/NEJM199001183220304.
Abstract/Text We assessed the risk of pneumonia due to Pneumocystis carinii in 1665 participants in the Multicenter AIDS Cohort Study who were seropositive for human immunodeficiency virus type 1 (HIV-1) but did not have the acquired immunodeficiency syndrome (AIDS) and were not receiving prophylaxis against P. carinii. During 48 months of follow-up, 168 participants (10.1 percent) had a first episode of P. carinii pneumonia. The risk was greatly increased in participants with CD4+ cell counts at base line of 200 per cubic millimeter or less (relative risk, 4.9; 95 percent confidence interval, 3.1 to 8.0). Although most participants (60.7 percent) described no HIV-1-related symptoms at the clinic visit at which a CD4+ cell count of 200 per cubic millimeter or less was first noted, this finding during follow-up was also associated with an increased risk of P. carinii pneumonia. The development of thrush or fever significantly and independently increased the risk of P. carinii pneumonia in these patients (adjusted relative risks, 1.86 and 2.15 for thrush and fever, respectively). Most participants with CD4+ cell counts above 200 per cubic millimeter who had P. carinii pneumonia within six months were symptomatic. We conclude that P. carinii pneumonia is unlikely to develop in HIV-1-infected patients unless their CD4+ cells are depleted to 200 per cubic millimeter or below or the patients are symptomatic, and therefore that prophylaxis should be reserved for such patients.

PMID 1967190  N Engl J Med. 1990 Jan 18;322(3):161-5. doi: 10.1056/NE・・・
著者: J D Stansell, D H Osmond, E Charlebois, L LaVange, J M Wallace, B V Alexander, J Glassroth, P A Kvale, M J Rosen, L B Reichman, J R Turner, P C Hopewell
雑誌名: Am J Respir Crit Care Med. 1997 Jan;155(1):60-6. doi: 10.1164/ajrccm.155.1.9001290.
Abstract/Text The Pulmonary Complications of HIV Infection Study is a prospective, multicenter, observational study evaluating pulmonary disease among HIV-infected persons. For approximately 52 mo, 1,182 HIV-infected subjects were followed. All participants were evaluated for pulmonary disease on a predetermined schedule. There were 145 episodes of Pneumocystis carinii pneumonia (PCP). Low CD4 count correlated with risk of PCP (p < 0.0001); 79% had CD4 counts less than 100/microl and 95% had CD4 counts less than 200/microl. Subtle changes in diffusing capacity for carbon monoxide (DLCO) were associated with PCP. Univariate analysis identified recurrent undiagnosed fevers, night sweats, oropharyngeal thrush, and unintentional weight loss to be associated with risk among persons with CD4 counts above 200/microl. Subjects in whom CD4 counts declined to below 200/microl and who were not receiving preventive therapy were nine times more likely to develop PCP within 6 mo compared with subjects who received such therapy. A strong trend toward differences between the sexes was detected. Black subjects had less than one third the risk of developing PCP as did white subjects (p < 0.0001). There was no significant difference in risk by HIV transmission category, study site, frequency of follow-up, age, education, smoking history, or use of antiretroviral therapy. Multivariable analysis revealed low CD4 lymphocyte count (p < 0.0001), use of prophylaxis (p < 0.0001), racial differences (p < 0.0001), and declining DLCO (p = 0.015) to influence risk. Constitutional signs and symptoms indicate increased risk for PCP among HIV-infected persons with CD4 counts above 200/microl.

PMID 9001290  Am J Respir Crit Care Med. 1997 Jan;155(1):60-6. doi: 1・・・
著者: F O Richards, J A Kovacs, B J Luft
雑誌名: Clin Infect Dis. 1995 Aug;21 Suppl 1:S49-56.
Abstract/Text Toxoplasmic encephalitis (TE) is the second most common AIDS-related opportunistic infection of the CNS. It occurs in 10%-50% of patients with AIDS who are seropositive for antibodies to Toxoplasma gondii and have CD4+ T lymphocyte counts of < 100/mm3. Primary toxoplasmic infection usually is acquired by ingestion of T. gondii oocysts from soil contaminated by cat feces or by ingestion of tissue cysts present in undercooked red meats. In patients with AIDS, TE probably results from the reactivation of Toxoplasma tissue cysts that remained latent after the primary infection. Detection of IgG antibodies to Toxoplasma indicates prior infection and the possible presence of tissue cysts and, thus, risk for developing TE. A regimen of trimethoprim-sulfamethoxazole or dapsone plus pyrimethamine with leucovorin is recommended for persons infected with the human immunodeficiency virus (HIV) and who are seropositive for IgG to Toxoplasma after their CD4+ T lymphocyte counts fall to < 100/mm3. HIV-infected persons who are seronegative for IgG to Toxoplasma should be counseled to protect themselves from primary toxoplasmic infection by eating only well-cooked meats and washing their hands after outdoor activities involving soil contact; if they have a cat, they should feed it only commercial or well-cooked foods, keep it indoors, and make sure that the litter box is changed daily. HIV-infected persons who are Toxoplasma seropositive may also be advised about these preventive behavioral practices.

PMID 8547512  Clin Infect Dis. 1995 Aug;21 Suppl 1:S49-56.
著者: A Carr, B Tindall, B J Brew, D J Marriott, J L Harkness, R Penny, D A Cooper
雑誌名: Ann Intern Med. 1992 Jul 15;117(2):106-11.
Abstract/Text OBJECTIVE: To determine the efficacy of low-dose trimethoprim-sulfamethoxazole (trimethoprim, 160 mg plus sulfamethoxazole, 800 mg; one tablet twice daily, 2 days per week) as primary prophylaxis against toxoplasmic encephalitis in patients with human immunodeficiency virus (HIV) infection and previous Pneumocystis carinii pneumonia.
DESIGN: A retrospective study.
SETTING: Tertiary referral teaching hospital.
PATIENTS: During a 3-year period after primary episodes of P. carinii pneumonia, 60 patients received trimethoprim-sulfamethoxazole, and 95 patients received pentamidine (aerosolized in 78 patients and intravenous in 17 patients) as secondary prophylaxis.
RESULTS: No patient in the trimethoprim-sulfamethoxazole group and no patient seronegative for Toxoplasma gondii developed toxoplasmic encephalitis, compared with 12 of 36 (33%; 95% Cl, 19% to 51%) seropositive patients in the pentamidine group (trimethoprim-sulfamethoxazole compared with pentamidine, P = 0.008). A significant difference was seen in the time to development of toxoplasmic encephalitis between the trimethoprim-sulfamethoxazole group (no case at 1153 days) and the pentamidine group (median time, 460 days) (P = 0.004). Neither the CD4+ lymphocyte count at the start of prophylaxis nor zidovudine therapy during the period of prophylaxis influenced the rate of toxoplasmic encephalitis in any group.
CONCLUSIONS: Low-dose trimethoprim-sulfamethoxazole (four tablets per week) appears to be effective prophylaxis against toxoplasmic encephalitis in HIV-infected patients with previous P. carinii pneumonia. A prospective, randomized, controlled study is needed to further evaluate these findings.

PMID 1351371  Ann Intern Med. 1992 Jul 15;117(2):106-11.
著者: S D Nightingale, L T Byrd, P M Southern, J D Jockusch, S X Cal, B A Wynne
雑誌名: J Infect Dis. 1992 Jun;165(6):1082-5.
Abstract/Text The product-limit incidence of Mycobacterium avium-intracellulare complex (MAC) bacteremia in 1006 human immunodeficiency virus (HIV)-positive patients followed at one institution over a 3-year period from the day of AIDS diagnosis with monthly lysis-centrifugation blood cultures was 21% +/- 2% SE at 1 year and 43% +/- 3% at 2 years. The product-limit incidence of MAC bacteremia at 1 year after the patients' first CD4 cell count was related to both the CD4 cell count and to whether they had an AIDS diagnosis (both P less than .0001) but not to age, sex, or race. This incidence was 39% +/- 6% for CD4 cell counts of less than 10/mm3, 30% +/- 5% for 10-19/mm3, 20% +/- 4% for 20-39/mm3, 15% +/- 4% for 40-59/mm3, 8% +/- 3% for 60-99/mm3, and 3% +/- 1% for 100-199/mm3. MAC may eventually infect most if not all HIV-positive patients who do not die from another HIV-related event.

PMID 1349906  J Infect Dis. 1992 Jun;165(6):1082-5.
著者: M Pierce, S Crampton, D Henry, L Heifets, A LaMarca, M Montecalvo, G P Wormser, H Jablonowski, J Jemsek, M Cynamon, B G Yangco, G Notario, J C Craft
雑誌名: N Engl J Med. 1996 Aug 8;335(6):384-91. doi: 10.1056/NEJM199608083350603.
Abstract/Text BACKGROUND: Disseminated infection with Mycobacterium avium complex is the most common opportunistic infection in patients with advanced stages of the acquired immunodeficiency syndrome (AIDS). We studied the efficacy and safety of prophylactic treatment with clarithromycin, a macrolide antibiotic.
METHODS: We conducted a randomized, placebo-controlled, double-blind study of clarithromycin in patients with AIDS in the United States and Europe. Entry criteria included blood cultures that were negative for M. avium complex, a Karnofsky performance score of 50 or higher, a CD4 cell count of 100 or less per cubic millimeter, and a life expectancy of at least six months.
RESULTS: After the first interim analysis, the study was stopped. M. avium complex infection developed in 19 of the 333 patients (6 percent) assigned to clarithromycin and in 53 of the 334 (16 percent) assigned to placebo (adjusted hazard ratio, 0.31; 95 percent confidence interval, 0.18 to 0.53; P<0.001). During the follow-up period of about 10 months, 32 percent of the patients in the clarithromycin group died and 41 percent of those in the placebo group died (hazard ratio, 0.75; P=0.026). In the clarithromycin group, isolates from 11 of the 19 patients with M. avium complex infection were resistant to clarithromycin. Prophylaxis with clarithromycin was associated with an increased incidence of taste perversion (11 percent in the clarithromycin group vs. 2 percent in the placebo group, P<0.001) and rectal disorders (8 percent vs. 3 percent, P = 0.007); however, the frequency of more severe adverse events was similar in the two groups (7 percent and 6 percent, respectively).
CONCLUSIONS: In patients with advanced AIDS, the prophylactic administration of clarithromycin is well tolerated, prevents M. avium complex infection, and reduces mortality.

PMID 8663871  N Engl J Med. 1996 Aug 8;335(6):384-91. doi: 10.1056/NE・・・
著者: D V Havlir, M P Dubé, F R Sattler, D N Forthal, C A Kemper, M W Dunne, D M Parenti, J P Lavelle, A C White, M D Witt, S A Bozzette, J A McCutchan
雑誌名: N Engl J Med. 1996 Aug 8;335(6):392-8. doi: 10.1056/NEJM199608083350604.
Abstract/Text BACKGROUND: Azithromycin is active in treating Mycobacterium avium complex disease, but it has not been evaluated as primary prophylaxis in patients with human immunodeficiency virus (HIV) infection. Because the drug is concentrated in macrophages and has a long half-life in tissue, there is a rationale for once-weekly dosing.
METHODS: We compared three prophylactic regimens in a multicenter, double-blind, randomized trial involving 693 HIV-infected patients with fewer than 100 CD4 cells per cubic millimeter. The patients were assigned to receive rifabutin (300 mg daily), azithromycin (1200 mg weekly), or both drugs. They were monitored monthly with blood cultures for M. avium complex.
RESULTS: In an intention-to-treat analysis, the incidence of disseminated M. avium complex infection at one year was 15.3 percent with rifabutin, 7.6 percent with azithromycin, and 2.8 percent with both drugs. The risk of the infection in the azithromycin group was half that in the rifabutin group (hazard ratio, 0.53; P = 0.008). The risk was even lower when two-drug prophylaxis was compared with rifabutin alone (hazard ratio, 0.28; P<0.001) or azithromycin alone (hazard ratio, 0.53; P = 0.03). Among the patients in whom azithromycin prophylaxis was not successful, 11 percent of M. avium complex isolates were resistant to azithromycin. Dose-limiting toxic effects were more common with the two-drug combination than with azithromycin alone (hazard ratio, 1.67; P=0.03). Survival was similar in all three groups.
CONCLUSIONS: For protection against disseminated M. avium complex infection, once-weekly azithromycin is more effective than daily rifabutin and infrequently selects for resistant isolates. Rifabutin plus azithromycin is even more effective but is not as well tolerated.

PMID 8676932  N Engl J Med. 1996 Aug 8;335(6):392-8. doi: 10.1056/NEJ・・・
著者: Sanjay R Kedhar, Douglas A Jabs
雑誌名: Herpes. 2007 Dec;14(3):66-71.
Abstract/Text Cytomegalovirus (CMV) is a common opportunistic infection in individuals with AIDS. Moreover, CMV retinitis represents a significant portion of end-organ disease in patients with CMV and AIDS. Prior to the advent of highly active antiretroviral therapy (HAART), almost one-third of people with AIDS developed CMV retinitis during their lifetime. Although effective therapies for CMV infection had been developed, treatment was often life-long due to persistent immune deficiency. Despite chronic suppressive maintenance therapy, disease relapse was nearly universal, and development of drug resistance was not uncommon. Widespread use of HAART has reduced the incidence and complications of CMV retinitis. With sustained immune recovery, discontinuation of anti-CMV therapy has been possible in many patients. Still, immune recovery does not guarantee protection from recurrent disease. CMV retinitis and uveitis associated with immune recovery remain causes of vision loss in this population and demand vigilance on the part of physicians.

PMID 18371289  Herpes. 2007 Dec;14(3):66-71.
著者: J E Gallant, R D Moore, D D Richman, J Keruly, R E Chaisson
雑誌名: J Infect Dis. 1992 Dec;166(6):1223-7.
Abstract/Text Data were analyzed from a multicenter observational cohort study of 1002 persons with AIDS or AIDS-related complex (ARC) and total CD4 cell count < 0.25 x 10(9)/L treated with zidovudine between April 1987 and April 1988. Cytomegalovirus (CMV) disease developed in 109 patients (10.9%), with a 2-year actuarial risk of 15%. Manifestations included retinitis (93 patients), esophagitis (10), colitis (8), gastritis (1), hepatitis (1), and encephalitis (1). The probability of CMV disease at 2 years for patients with initial counts < 0.1 x 10(9)/L was 21.4%, compared with 10.3% for patients with initial counts > or = 0.1 x 10(9)/L (P < .001). By proportional hazards analysis, baseline CD4 cell count < 0.1 x 10(9)/L, enrollment diagnosis of AIDS, and homosexuality were significantly associated with subsequently developing CMV disease. Median survival after diagnosis of CMV disease was 173 days, and CMV was an independent predictor of death. CMV contributes to AIDS-related morbidity and mortality. As new anti-CMV drugs become available, prophylaxis should be targeted at individuals with CD4 cell counts < 0.1 x 10(9)/L.

PMID 1358986  J Infect Dis. 1992 Dec;166(6):1223-7.

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