ヒト免疫不全ウイルス感染者における 日和見感染症の予防ガイドライン2001 米国公衆衛生局・米国感染症学会 モジュール 1: 予防 のコア AETC National Resource Centerによる トレーニングスライドセット December 2001 OI Guidelines 11/28/01

声明文 これらのスライドは最新の治療ガイドラインが作成された時点の情報を用いて作られている。　しかしながら急速に変わるHIV医療の分野においては、この情報も急速に時代遅れとなる。このスライドを使用する場合は最も新しいガイドラインと比較することを推奨する。 また、 これらのスライドは内容や属性を変更せずに使用されることを目的としている。 使用者はこれらの意図に留意されるようお願いしたい。 AETC National Resource Center December 2001 OI Guidelines 11/28/01

予防が推奨される日和見感染症のまとめ 一次予防 ニューモシスチス・カリニ* 結核* トキソプラズマ・ゴンディ* マイコバクテリウム・アヴィウム* 水痘帯状疱疹ウイルス* 肺炎球菌† A 型およびB型肝炎ウイルス† インフルエンザ † 二次予防 ニューモシスチス・カリニ* トキソプラズマ・ゴンディ* マイコバクテリウム・アヴィウム* クリプトコッカス症* ヒストプラズマ症* コクシディオマイコーシス* サイトメガロウイルス* サルモネラ 菌血症 * 治療標準 † 一般的推奨 December 2001 OI Guidelines 11/28/01

日常的予防が推奨されない日和見感染症 一次予防 細菌感染症 (好中球減少) † クリプトコッカス症† ヒストプラズマ症† サイトメガロウイルス感染症 † 二次予防 単純ヘルペス感染症 § カンジダ症 § § 引き続き起こるエピソードが頻繁であったり重症である場合にのみ推奨される † 有効性の証明はあるが日常的には推奨されない December 2001 OI Guidelines 11/28/01

日和見感染症ガイドライン 2001年11月 一次予防と二次予防の中止指針の比較 日和見感染症ガイドライン　2001年11月 一次予防と二次予防の中止指針の比較 原因 推奨 カリニ 一次 CD4 > 200 X 3 ヶ月 二次 CD4 > 200 X 3 ヶ月 トキソプラズマ 二次 CD4 > 200 X 6 ヶ月+ 初期治療 + 無症状 MAC 一次 CD4 > 100 X 3 ヶ月 二次 CD4 > 100 X 6 ヶ月+ 12 ヶ月治療 + 無症状 December 2001 OI Guidelines 11/28/01

一次予防と二次予防が推奨される日和見感染症 日和見感染症ガイドライン　2001年11月 一次予防と二次予防が推奨される日和見感染症 December 2001 OI Guidelines 11/28/01

ニューモシスチス・カリニ肺炎 一次予防 適応: CD4 200未満 または鵞口瘡 いつ中止するか: CD4 200以上が 3 ヶ月以上 二次予防 一次予防に同じ Aults and addolescents who have HIV infection (including pregnant women and those on HAART) should receive chemoprophylaxis against PCP if they have a CD4+ count of less than 200/µL (AI) or a history of oropharyngeal candidiasis (AII). Persons who have a CD4+ percentage of less than 14% or history of an AIDS-defining illness but do not otherwise qualify should be considered for prophylaxis (BII). When monitoring the CD4+ count at least every 3 months is not possible, initiation of chemoprophylaxis at a CD4+ count of greater than 200 but less than 250 cells/µL also should be considered (BII). Primary pneumocystis prophylaxis should be discontinued in adult and adolescent patients who have responded to HAART with an increase in CD4+ counts to >200 cells/µL for at least 3 months (AI). Prophylaxis should be reintroduced if the CD4+ count decreases to <200 cells/µL (AIII).  Patients who have a history of PCP should be administered chemoprophylaxis (i.e., secondary prophylaxis or chronic maintenance therapy) for life (AI) unless immune reconstitution occurs as a consequence of HAART. Secondary prophylaxis should be discontinued for adult and adolescent patients whose CD4+ T cell count has increased from <200 cells µL to >200 cells/µL for at least 3 months due to HAART (BII). If the episode of PCP (leading to secondary prophylaxis) occurred at a CD4+ count >200 cells/µL, it is probably prudent to continue PCP prophylaxis for life regardless of how high the CD4+ count rises as a consequence of HAART (CIII). Prophylaxis should be reintroduced if the CD4+ count decreases to < 200 cells/µL (AIII), or if PCP recurred at a CD4+ count >200 cells/µL December 2001 OI Guidelines 11/28/01

ニューモシスチス・カリニ肺炎 推奨レジメ: ＳＴ合剤（TMP-SMX DS ＝バクタ２Ｔ） 1回/日* ＳＴ合剤（TMP-SMX SS ＝バクタ１Ｔ ） 1回/日 代替レジメ: ダプソン （プロトゲン、レクチゾール）100 mg/日 ダプソン50 mg/日 + ピリメサミン 50 mg/週 + ロイコボリン 25 mg /週* ダプソン200 mg/週 + ピリメサミン75 mg/週 + ロイコボリン 25 mg/週* アトヴァクオン1500 mg/日* ペンタミジン吸入 300 mg/月 ＳＴ合剤（TMP-SMX DS ＝バクタ２Ｔ） 3回/週 Trimethoprim-sulfamethoxazole (TMP-SMZ) is the recommended prophylactic agent (AI). One double strength (DS) tablet per day is preferred (AI). However, one single-strength (SS) tablet per day is also effective and might be better tolerated. (AI). One DS tablet three times per week is also effective (BI). TMP-SMZ ,one DS tablet per day confers cross protection against toxoplasmosis and some common respiratory bacterial infections. Lower doses of TMPSMZ also might confer such protection. For patients who have an adverse reaction that is not life-threatening, treatment with TMP-SMZ should be continued if clinically feasible; for those who have discontinued such therapy because of an adverse reaction, reinstitution of TMP-SMZ should be strongly considered after the adverse event has resolved (AII). Patients who have experienced adverse events, especially fever and rash, might better tolerate reintroduction of the drug with a gradual increase in dose (desensitization) as per published regimens (BI) or reintroduction of TMP-SMZ at a reduced dose or frequency (CIII); up to 70% of patients can tolerate such reinstitution of therapy. If TMP-SMZ cannot be tolerated, prophylactic regimens that can be recommended as alternatives include Dapsone (BI), dapsone plus pyrimethamine plus leucovorin (BI), aerosolized pentamidine administered by the Respirgard IITM nebulizer (Marquest, Englewood, Colorado) (BI), and atovaquone (BI). Atovaquone appears to be as effective as aerosolized pentamidine or dapsone (BI) but is substantially more expensive than the other regimens. For patients seropositive for Toxoplasma gondii who cannot tolerate TMP-SMZ, recommended alternatives to TMP-SMZ for prophylaxis against both PCP and toxoplasmosis include dapsone plus pyrimethamine (BI) or atovaquone with or without pyrimethamine (CIII). The following regimens generally cannot be recommended as alternatives because of insufficient data on efficacy: aerosolized pentamidine administered by other nebulization devices, intermittently administered parenteral pentamidine, oral pyrimethamine plus sulfadoxine, oral clindamycin plus primaquine, and intravenous trimetrexate. However, clinicians may consider using these agents in unusual situations in which the recommended agents cannot be administered (CIII).  * トキソプラズマ症に対して有効 (CD4 <100 + 血清検査陽性) December 2001 OI Guidelines 11/28/01

トキソプラズマ症: 一次予防 適応: トキソプラズマ lgG 抗体陽性 + CD4 100未満 トキソプラズマ症: 一次予防 適応: トキソプラズマ lgG 抗体陽性 + CD4 100未満 いつ中止するか: CD4 200以上で 3 ヶ月 いつ再開するか: CD4 が 100-200以下 Toxoplasma-seropositive patients who have a CD4+ T-lymphocyte count of less than 100/µL should be administered prophylaxis against toxoplasmic encephalitis (TE) (AII).  Toxoplasma-seronegative persons who are not taking a PCP prophylactic regimen known to be active against TE should be retested for IgG antibody to Toxoplasma when their CD4+ T-lymphocyte count declines below 100/µL to determine whether they have seroconverted and are therefore at risk for TE (CIII). Patients who have seroconverted should be administered prophylaxis for TE as described above (AII). Prophylaxis against TE should be discontinued in adult and adolescent patients who have responded to HAART with an increase in CD4+ T-lymphocyte counts to > 200 cells/µL for at least 3 months (AI). Prophylaxis should be reintroduced if the CD4+ T lymphocyte count decreases to <100-200 cells/µL (AIII).   December 2001 OI Guidelines 11/28/01

トキソプラズマ症: 一次予防 推奨レジメ: ＳＴ合剤（ TMP - SMX DS ＝バクタ２Ｔ ） 1回/日 経口 代替レジメ: トキソプラズマ症: 一次予防 推奨レジメ: ＳＴ合剤（ TMP - SMX DS ＝バクタ２Ｔ ） 1回/日 経口 代替レジメ: ＳＴ合剤（TMP-SMX SS＝バクタ１Ｔ ） 1回/日 ダプソン 50 mg/日 + ピリメサミン50 mg/週 + ロイコボリン25mg /週 ダプソン 200 mg/週 + ピリメサミン75 mg/週 + ロイコボリン25mg/週 アトヴァクオン1500 mg/日 + ピリメサミン25 mg/日 + ロイコボリン10mg/日 The double-strength tablet daily dose of TMP-SMZ recommended as the preferred regimen for PCP prophylaxis appears to be effective against TE as well and is therefore recommended (AII). If patients cannot tolerate TMP-SMZ, the recommended alternative is dapsone-pyrimethamine, which is also effective against PCP (BI). Atovaquone with or without pyrimethamine also may be considered (CIII). Prophylactic monotherapy with dapsone, pyrimethamine, azithromycin, or clarithromycin cannot be recommended on the basis of current data (DII). Aerosolized pentamidine does not protect against TE and is not recommended (EI). December 2001 OI Guidelines 11/28/01

トキソプラズマ症: 二次予防 適応: HAARTより免疫再構築が起こらない限りトキソプラズマ症に対する治療を行う. いつ中止するか: 　CD4 200以上で 6 ヶ月 + 初期治療完了 + 無症状 いつ再開するか: 　CD4 200以下に低下 Patients who have completed initial therapy for TE should be administered lifelong suppressive therapy (secondary prophylaxis or chronic maintenance therapy) (AI) unless immune reconstitution occurs as a consequence of HAART. Adult and adolescent patients receiving secondary prophylaxis (chronic maintenance therapy) for TE appear to be at low risk for recurrence of TE when they have successfully completed initial therapy for TE, remain asymptomatic with respect to signs and symptoms of TE, and have a sustained increase in their CD4+ Tlymphocyte counts to >200 cells/µL following HAART (e.g., 6 months). While the numbers of patients who have been evaluated remain small and occasional recurrences have been seen, based on these observations and on inference from more extensive cumulative data suggesting the safety of discontinuation of secondary prophylaxis for other OIs during advanced HIV disease, it is reasonable to consider discontinuation of chronic maintenance therapy in such patients (CIII). Some experts would obtain a magnetic resonance image of the brain as part of their evaluation to determine whether or not discontinuation of therapy is appropriate.   Secondary prophylaxis (chronic maintenance therapy) should be reintroduced if the CD4+ T lymphocyte count decreases to <200 cells/µL (AIII). December 2001 OI Guidelines 11/28/01

トキソプラズマ症: 二次予防 推奨レジメ : スルファジアジン 500-1000 mg ×４回/日 + ピリメサミン25-50 mg/日 + ロイコボリン 10-25 mg/日 代替レジメ : クリンダマイシン 300-450 mg 6-8時間毎 + ピリメサミン25-50 mg/日 + ロイコボリン10-25 mg/日 アトヴァクオン750 mg 6-12 時間毎 + ピリメサミン25 mg/日 + ロイコボリン10 mg/日 The combination of pyrimethamine plus sulfadiazine plus leucovorin is highly effective for this purpose (AI). A commonly used regimen for patients who cannot tolerate sulfa drugs is pyrimethamine plus clindamycin plus leucovorin (BI). Atovaquone with or without Pyrimethamine plus leukovorin is also used. However, only the combination of pyrimethamine plus sulfadiazine appears to provide protection against PCP as well (AII). December 2001 OI Guidelines 11/28/01

マイコバクテリウム・アヴィウム・コンプレックス（MAC）: 一次予防 適応:　　　　　　　　CD4 50未満 いつ中止するか: CD4 100以上 が 3 ヶ月以上 いつ再開するか: CD4 が50-100以下に低下 Adults and adolescents who have HIV infection should receive chemoprophylaxis against disseminated MAC disease if they have a CD4+ T-lymphocyte count of less than 50 cells/µL (AI). Primary MAC prophylaxis should be discontinued in adult and adolescent patients who have responded to HAART with an increase in CD4+ T lymphocyte count to >100 cells/µL for at least 3 months (AI). Primary prophylaxis should be reintroduced if the CD4+ T lymphocyte count decreases to < 50-100 cells/µL (AIII).   December 2001 OI Guidelines 11/28/01

TMP-SMX DS ： 日本のバクタ、バクトラミン（S 400mg, T80mg）の倍量含有 訳注 TMP-SMX DS　：　日本のバクタ、バクトラミン（S 400mg, T80mg）の倍量含有 ピリメサミン　：　日本ではスルファドキシン・ピリメサミン合剤（ファンシダール錠－ロシュ） アトヴァクオン　：　海外ではアトヴァクオン／プログアニル合剤（Malarone） スルファジアジン　：日本ではテラジアパスタ、ゲーベンなど外用のみ アジスロマイシン　：日本ではジスロマック December 2001 OI Guidelines 11/28/01

マイコバクテリウム・アヴィウム・コンプレックス（MAC）: 一次予防 推奨レジメ: アジスロマイシン 1200 mg/週 または クラリスロマイシン 500 mg ×２回/日 代替レジメ: リファブチン* 300 mg/日 または アジスロマイシン 1200 mg/週 + リファブチン* 300 mg/日 Clarithromycin or azithromycin are the preferred prophylactic agents (AI). The combination of clarithromycin and rifabutin is no more effective than clarithromycin alone for chemoprophylaxis and is associated with a higher rate of adverse effects than either drug alone; this combination should not be used (EI). The combination of azithromycin with rifabutin is more effective than azithromycin alone; however, the additional cost, increased occurrence of adverse effects, potential for drug interactions, and absence of a difference in survival when compared with azithromycin alone do not warrant a routine recommendation for this regimen (CI). In addition to their preventive activity for MAC disease, clarithromycin and azithromycin each confer protection against respiratory bacterial infections (BII). If clarithromycin or Azithromycin cannot be tolerated, rifabutin is an alternative prophylactic agent for MAC disease although rifabutin-associated drug interactions make this agent difficult to use (BI). Tolerance, cost, and drug interactions are among the issues that should be considered in decisions regarding the choice of prophylactic agents for MAC disease. Particular attention to interactions with antiretroviral protease inhibitors and nonnucleoside reverse transcriptase inhibitors is warranted. Before prophylaxis is initiated, disseminated MAC disease should be ruled out by clinical assessment, which might include obtaining a blood culture for MAC if warranted. Because treatment with rifabutin could result in the development of resistance to rifampin in persons who have active tuberculosis, active tuberculosis should also be excluded before rifabutin is used for prophylaxis. * 同時投与の PI または NNRTIに調整した投与量 December 2001 OI Guidelines 11/28/01

マイコバクテリウム・アヴィウム・コンプレックス（MAC）: 二次予防 いつ中止するか: CD4 100以上が 6ヶ月以上 かつ 治療 12 ヶ月 かつ 無症状 いつ再開するか: CD4 が100未満に低下 Adult and adolescent patients with disseminated MAC should receive lifelong therapy (i.e., secondary prophylaxis or maintenance therapy) (AII), unless immune reconstitution occurs as a consequence of HAART. Patients appear to be at low risk for recurrence of MAC when they have completed a course of at least 12 months of treatment for MAC, remain asymptomatic with respect to MAC signs and symptoms, and have a sustained increase , e.g., 6 months, in their CD4+ T-lymphocyte counts to >100cells/µL following HAART (CIII). Some experts would obtain a blood culture for MAC, even in asymptomatic patients, prior to discontinuation of therapy, to substantiate that disease is no longer active.  Secondary prophylaxis should be reintroduced if the CD4+ T lymphocyte count decreases to <100 cells/µL (AIII).   December 2001 OI Guidelines 11/28/01

マイコバクテリウム・アヴィウム・コンプレックス（MAC）: 二次予防 推奨レジメ: クラリスロマイシン 500 mg ×２回/日 + エタンブトール 15 mg/kg/日 ± リファブチン* † 300 mg/日 代替レジメ: アジズロマイシン 1200 mg/週 + エタンブトール 15 mg/kg/日 ± リファブチン* 300 mg/日 Unless good clinical or laboratory evidence of macrolide resistance exists, the use of a macrolide (clarithromycin or, alternatively, azithromycin) is recommended in combination with ethambutol (AII) with or without rifabutin (CI). Treatment of MAC disease with clarithromycin in a dose of 1,000 mg twice a day is associated with a higher mortality rate than has been observed with clarithromycin administered at 500 mg twice a day; thus, the higher dose should not be used (EI). Clofazimine has been associated with adverse clinical outcomes in the treatment of MAC disease and should not be used (DII). *同時投与の PI または NNRTIに調整した投与量 † リファブチン は クラリスロマイシン 濃度を50%まで減少させる December 2001 OI Guidelines 11/28/01

通常は一次予防のみが推奨される日和見感染症 日和見感染症ガイドライン2001年11月 通常は一次予防のみが推奨される日和見感染症 December 2001 OI Guidelines 11/28/01

結核: 潜伏感染 スクリーニング: マントウ法によるツベルクリン反応 HIV 感染が初めて認識されたとき. スクリーニング: 　マントウ法によるツベルクリン反応 HIV 感染が初めて認識されたとき. 初期評価のツベルクリン反応陰性でリスクが持続しているならば年１回のテスト. アネルギーの定期的評価は推奨されない. When HIV infection is first recognized, the patient should receive a tuberculin skin test (TST) by administration of intermediate-strength (5-TU) purified protein derivative (PPD) by the Mantoux method (AI). Routine evaluation for anergy is not recommended. However, there are selected situations in which anergy evaluation might assist in guiding individual decisions about preventive therapy. Although the reliability of the TST might diminish as the CD4+ T-lymphocyte count declines, annual repeat testing should be considered for HIV-infected persons who are TST-negative on initial evaluation and who belong to populations in which there is a substantial risk for exposure to M. tuberculosis (BIII). Clinicians should consider repeating the TST for persons whose initial skin test was negative and whose immune function has improved in response to HAART (i.e., those whose CD4+ T-lymphocyte count has increased to greater than 200 cells/µL) (BIII). In addition to confirming tuberculous infection, TST conversion in an HIV-infected person should alert health-care providers to the possibility of recent M. tuberculosis transmission and should prompt notification of public health officials for investigation to identify a possible source case. The administration of bacille Calmette-Guerin (BCG) vaccine to HIV-infected persons is contraindicated because of its potential to cause disseminated disease (EII). December 2001 OI Guidelines 11/28/01

結核: 潜伏感染の治療 適応: 48-72時間めのツベルクリン反応膨隆 5 mm以上 ツベルクリン反応陽性既往 + 治療なし 結核接触 (ツベルクリン反応が12 週時点で陰性の場合は中止) 全てのツベルクリン反応陽性者は活動性結核について胸部レ線を含む検査を行うべきである. All HIV-infected persons who have a positive TST result (greater than or equal to 5 mm of induration) should undergo chest radiography and clinical evaluation to rule out active tuberculosis. HIV-infected persons who have symptoms suggestive of tuberculosis should promptly undergo chest radiography and clinical evaluation regardless of their TST status (AII). All HIV-infected persons, regardless of age, who have a positive TST result yet have no evidence of active tuberculosis and no history of treatment for active or latent tuberculosis should be treated for latent TB infection. Additionally, HIV-infected persons who are close contacts of persons who have infectious tuberculosis should be treated for latent TB infection -- regardless of their TST results, age, or prior courses of treatment -- after the diagnosis of active tuberculosis has been excluded (AII). In addition to household contacts, such persons might also include contacts in the same drug-treatment or health-care facility, coworkers, and other contacts if transmission of TB is demonstrated. December 2001 OI Guidelines 11/28/01

結核: 潜伏感染の治療: CDC/ATS ガイドライン, 2001年８月* 推奨レジメ: 非HIV　: 　イソニアジド を 9 ヶ月間. HIV　:　イソニアジドを 9ヶ月間. (もしコンプライアンスが確実ならば) リファンピシン-ピラジナミド を2 ヶ月間. 代替　　リファンピシン　/　リファブチン 単独を 4 ヶ月間. * Am J Resp Crit Care 2001; 164:1319 December 2001 OI Guidelines 11/28/01

結核: 潜伏感染の治療: CDC/ATS ガイドライン, 2001年８月* HIV 同時感染におけるリファンピシン-ピラジナミドの理論的根拠 : コンプライアンス & 活動性疾患のリスク. HIV 同時感染においてイソニアジド に伴う ALT上昇のリスクはリファンピシン-ピラジナミド に比較して大きい. リファンピシン-ピラジナミドの重症肝障害21例の報告, HIV感染者なし. HIV 同時感染患者において良く耐えうる. * Am J Resp Crit Care 2001; 164:1319 December 2001 OI Guidelines 11/28/01

結核: 潜伏感染の治療: CDC/ATS ガイドライン, 2001年８月* リファンピシン-ピラジナミド のレジメ: HAART: リファブチンを使用し投与量を調節 警告: 推奨されない: 肝疾患またはイソニアジド肝障害の既往 注意: 他の肝毒性薬またはエタノール 処方: ２週間のみ供給 * Am J Resp Crit Care 2001; 164:1319 December 2001 OI Guidelines 11/28/01

結核: 潜伏感染の治療: CDC/ATS ガイドライン, 2001年８月* リファンピシン-ピラジナミド のレジメ: 観察: 臨床的: 2,4,6,と 8 週目. 検査: ALTと ビリルビンを開始前, 2,4,と 6 週目. 中止: 1) 症状 + ALT上昇 2) ALT > 正常上限の5倍以上, または 3) ビリルビン上昇. * Am J Resp Crit Care 2001; 164:1319 December 2001 OI Guidelines 11/28/01

結核: 潜伏感染の治療: レジメ HAART/非HAART: イソニアジド 300 mg/日 + ピリドキシン 50 mg/日 を9 ヶ月 (270 回) † イソニアジド900 mg + ピリドキシン 100 mg 2 X週 を9 ヶ月 (76 回) † The generally accepted treatment options for HIV-infected patients regardless of concomitant HAART are isoniazid daily (AII) or twice weekly (BII) for 9 months. For these HIV-infected persons completion of treatment must be assured. Because HIV-infected persons are at risk for peripheral neuropathy, those receiving isoniazid should also receive pyridoxine (BIII). Directly observed therapy should be used with intermittent dosing regimens (AI) and when otherwise operationally feasible (BIII). † 治療完了が確認されたとして December 2001 OI Guidelines 11/28/01

結核: 潜伏感染の治療: レジメ HAARTの場合: リファブチン* 毎日 4 ヶ月間 結核: 潜伏感染の治療: レジメ HAARTの場合: リファブチン* 毎日 　4 ヶ月間 リファブチン* + ピラジナミド 20 mg/kg/日 を2 ヶ月 (60 回) HAARTでない場合: リファンピシン 600 mg/日 X 4 ヶ月 リファンピシン 600 mg/日 + ピラジナミド20 mg/kg/日 を2 ヶ月 (60 回) Other treatment options include 4 months of therapy daily with either rifampin (BIII) or rifabutin (CIII); or 2 months of therapy with either rifampin and pyrazinamide (BI) or rifabutin and pyrazinamide (CIII). There have been reports of fatal and severe liver injury associated with the treatment of latent TB infection in HIV-uninfected persons treated with the 2 month regimen of daily rifampin and pyrazinamide; therefore it may be prudent to use regimens that do not contain pyrazinamide in HIV-infected persons whose completion of treatment can be assured. A decision to use a regimen containing either rifampin or rifabutin should be made after careful consideration of potential drug interactions, especially those related to protease inhibitors and nonnucleoside reverse transcriptase inhibitors. Dose adjustments for these drugs may have to be made. *PI または NNRTIに対して調整した投与量 December 2001 OI Guidelines 11/28/01

結核: 潜伏感染の治療 いつ再開するか: 結核感染または結核症に対する治療の既往がある患者では、免疫機能が低下しているとの理由のみからでは治療を要しない. 既知の曝露または獲得性結核感染の疑われる場合は治療が必要である.これらの事例では専門医への紹介が強く推奨される. December 2001 OI Guidelines 11/28/01

抗ウイルス剤療法中のリファブチン至適投与量 プロテアーゼ阻害剤 / 非核酸系逆転写酵素阻害剤 リファブチン 毎日 週 2-3回 インジナビル 1000 mg ×8時間毎 150 300 ネルフィナビル 1250 mg ×２回/日 アンプレナビル1200 mg ×２回/日 リトナビル/サキナビル 400/400 mg - ロピナビル/リトナビル 400/100 mg 150 １回/２日 ネビラピン200 mg ×２回/日 エファビレンツ 600 mg 450 600 December 2001 OI Guidelines 11/28/01

結核予防 治療的モニタリング Drug 臨床的 検査室 介入 イソニアジド 肝炎の症状につき毎月観察 治療前と3 ヶ月目に肝機能検査 結核予防　治療的モニタリング Drug 臨床的 検査室 介入 イソニアジド 肝炎の症状につき毎月観察 治療前と3 ヶ月目に肝機能検査 ALT > 正常上限の5倍の時は中止 リファンピシン/ ピラジナミド 臨床的評価を 2, 4, 6 と 8週目に行う ALT と Bili を 2, 4 と 6 週 または　有症状時に行う 症状 + 異常値 ALT/ AST, または ALT/AST > 正常上限の5倍, または ビリルビン上昇 December 2001 OI Guidelines 11/28/01

水痘・帯状疱疹ウイルスによる疾患 成人HIV感染者には水痘ワクチンは禁忌. 感受性のあるHIV感染成人または小児に対する水痘帯状疱疹免疫グロブリン(VZIG). 水痘または帯状疱疹患者と濃厚接触後96 時間以内にできるだけ早く投与. 帯状疱疹に対する予防法は現在のところない. Varicella-Zoster Virus Disease Prevention of Disease. Very little data regarding the safety and efficacy of varicella vaccine in HIV-infected adults are available, and no recommendation for its use can be made for this population. (See Special Considerations/Children, below, for information about the use of varicella vaccine in children.) For the prophylaxis of chickenpox, HIV-infected children and adults who are susceptible to VZV (i.e., those who have no history of chickenpox or shingles or who have no detectable antibody against VZV) should be administered varicella zoster immune globulin (VZIG) as soon as possible but within 96 hours after close contact with a patient who has chickenpox or shingles (AIII). Data are lacking on the effectiveness of acyclovir for preventing chickenpox in susceptible HIV-infected children or adults. No preventive measures are currently available for shingles. December 2001 OI Guidelines 11/28/01

ワクチン: ルーチン使用 原因 適応 B型肝炎 HBc 抗体陰性者 A型肝炎 リスク * + HAV抗体陰性患者 肺炎球菌 ワクチン: ルーチン使用 原因 適応 B型肝炎 HBc 抗体陰性者 A型肝炎 リスク * + HAV抗体陰性患者 肺炎球菌 CD4 200未満 インフルエンザ 毎年, 10月 – 11月 Hepatitis B vaccine ( 3 doses) is generally recommended for all susceptible (anti-HBc-negative) patients. Hepatitis A vaccine is generally recommended for all susceptible (anti-HAV-negative) (BIII) patients at increased risk for HAV infection (e.g., illicit drug users, men who have sex with men, hemophiliacs) or with chronic liver disease, including chronic hepatitis B or hepatitis C. Adults and adolescents who have a CD4+ T-lymphocyte  200 cells/ L should be administered a single dose of 23-valent polysaccharide pneumococcal vaccine if they have not received this vaccine during the previous five years (BII). Immunization should also be considered for patients with CD4+ T lymphocyte counts < 200 cells/µL, although there is no clinical evidence for efficacy (CIII). Revaccination may be considered for patients who were initially immunized when their CD4+ T lymphocyte count was <200 cells/µL and whose CD4+ count has increased to > 200 cells/µL in response to HAART (CIII). The recommendation to vaccinate is increasingly pertinent because of the increasing incidence of invasive infections with drug-resistant (including TMP-SMZ-, macrolide-, and beta-lactam-resistant) strains of S. pneumoniae. The duration of the protective effect of primary pneumococcal vaccination is unknown. Periodic revaccination may be considered; an interval of 5 years has been recommended for persons not infected with HIV and also might be appropriate for persons infected with HIV (CIII). There is, however, no evidence for clinical benefit from revaccination. The incidence of H. influenzae type B infection in adults is low. Therefore, H. influenzae type B vaccine is not generally recommended for adult use (DIII). Influenza vaccine is recommended (1 dose) prior to the onset of the influenza season. Alternatives: Oseltamivir, 75 mgpo q.d. (influenza A or B) (CIII); rimantadine, 100 mgpo b.i.d. (CIII), or amantadine, 100 mg po b.i.d. (CIII) (influenza A only) * リスク = 静脈内薬物使用, 男性同性愛, 血友病, 慢性BまたはC型肝炎 December 2001 OI Guidelines 11/28/01

適応ならば投与: コレラ、日本脳炎、ライム病、破傷風・ジフテリア、 不活化チフス (Typhim V1) ワクチン: その他 適応ならば投与: コレラ、日本脳炎、ライム病、破傷風・ジフテリア、 不活化チフス (Typhim V1) December 2001 OI Guidelines 11/28/01

禁忌 (生ウイルス): 水痘、 黄熱病、生チフス (Ty21a)、 麻疹、 ワクシニア（牛痘） ワクチン: その他 禁忌 (生ウイルス): 水痘、 黄熱病、生チフス (Ty21a)、 麻疹、 ワクシニア（牛痘） Live virus vaccines are contraindicated in HIV positive patients. December 2001 OI Guidelines 11/28/01

通常は二次予防のみが推奨される日和見感染症 日和見感染症ガイドライン2001年11月 通常は二次予防のみが推奨される日和見感染症 December 2001 OI Guidelines 11/28/01

サイトメガロウイルス感染症 初期治療に続く慢性維持療法 フォミビルセン (VitraveneTM：CMV複製アンチセンス阻害剤)の硝子体注射 推奨レジメ: ガンシクロビル静注 または 経口 フォスカルネット静注 ガンシクロビル埋め込み + 経口 (網膜症に対して) 代替レジメ: シドフォビル 静注 + プロベネシド経口 フォミビルセン (VitraveneTM：CMV複製アンチセンス阻害剤)の硝子体注射 ヴァルガンシクロビル(ValcyteＴＭ） 経口 いつ中止するか: CD4 >100-150 X 6 ヶ月 + 非活動性 + 眼科的検査正常. いつ再開するか: CD4 < 100-150 Prevention of Recurrence CMV disease is not cured with the currently available antiviral agents. Following induction therapy, chronic maintenance therapy is recommended for life (AI), unless there is immune reconstitution as a consequence of HAART. Regimens demonstrated to be effective for chronic suppression include parenteral or oral ganciclovir, parenteral foscarnet, combined parenteral ganciclovir and foscarnet, parenteral cidofovir, and (for retinitis only) ganciclovir administration via intraocular implant or repetitive intravitreous injections of fomivirsen (AI). Oral valganciclovir has been approved by the FDA for both acute induction therapy and for maintenance therapy. Repetitive intravitreous injections of ganciclovir, foscarnet, and cidofovir have been reported to be effective for secondary prophylaxis of CMV retinitis in uncontrolled case series. Intraocular therapy alone does not provide protection to the contralateral eye or to other organ systems and typically is combined with oral ganciclovir. The choice of a chronic maintenance regimen for patients treated for CMV disease should be made in consultation with an expert. For patients with retinitis, this decision should be made in consultation with an ophthalmologist and should take into consideration the anatomic location of the retinal lesion, vision in the contralateral eye, the immunologic and virologic status of the patient, and the patient's response to HAART (BIII). Discontinuation of Chronic Maintenance Therapy should be considered in patients with a sustained, (e.g., 6 months) increase in CD4+ count to >100-150 cells/ L in response to HAART (BII). Such decisions should be made in consultation with an ophthalmologist and should take into account such factors as magnitude and duration of CD4+ increase, anatomic location of the retinal lesion, vision in the contralateral eye, and the feasibility of regular ophthalmologic monitoring (BII). All patients who have had anti-CMV maintenance therapy discontinued should have regular ophthalmologic monitoring for early detection of CMV relapse (as well as for immune reconstitution uveitis) (AIII). CMV viral load or other markers of CMV infection, .g., antigenemia, or viral DNA tests are not well standardized; their role in predicting relapse remains to be defined. Relapses have been reported rarely in patients with CD4+ count >100-150 cells/µL. Restarting Secondary Prophylaxis . Relapse of CMV retinitis occurs in patients whose anti-CMV maintenance therapy has been discontinued and whose CD4+ T-lymphocyte count has decreased to 50 cells/ L . Therefore, reinstitution of secondary prophylaxis should be reinstituted when the CD4+ count has decreased to 100-150 cells/ L (AIII). Relapse has been reported in patients whose CD4+ counts are higher then 100 cells/µL, but such reports are rare to date. December 2001 OI Guidelines 11/28/01

予防のまとめ: 抗真菌剤 * CD4 < 100 + 流行地域 (>10 例/100患者・年)ならば考慮する 静注 一次 二次 二次予防中止 二次予防再開 カンジダ しない 重症/頻回 ? - ヒストプラズマ しない * する クリプトコッカス する ** CD4 <100 コクシディオイデス * CD4 < 100 + 流行地域 (>10 例/100患者・年)ならば考慮する ** CD4 > 100-200 X 6 ヶ月 + 初期治療完結 + 無症状　の場合 December 2001 OI Guidelines 11/28/01

クリプトコッカス症 慢性維持療法 レジメ: 推奨: フルコナゾール. 代替: アムホテリシンB, イトラコナゾール いつ中止するか: 初期治療完結 + 無症状 + HAARTにより CD4 >100 - 200 X 6 ヶ月 いつ再開するか: CD4 が < 100 - 200 に低下したとき Prevention of Recurrence Patients who have completed initial therapy for cryptococcosis should be administered lifelong suppressive treatment, (i.e., secondary prophylaxis or chronic maintenance therapy) (AI) unless immune reconstitution occurs as a consequence of HAART. Fluconazole is superior to itraconazole in preventing relapse of cryptococcal disease and is the preferred drug (AI).   Discontinuation of Secondary Prophylaxis (Chronic Maintenance Therapy) Adult and adolescent patients appear to be at low risk for recurrence of cryptococcosis when they have successfully completed a course of initial therapy for cryptococcosis, remain asymptomatic with respect to signs and symptoms of cryptococcosis, and have a sustained increase (e.g., 6 months) in their CD4+ T-lymphocyte counts to >100-200 cells/µL following HAART. The numbers of patients who have been evaluated remain small. Based on these observations and on inference from more extensive data suggesting the safety of discontinuation of secondary prophylaxis for other OIs during advanced HIV disease, and while recurrences could occur it may be reasonable to consider discontinuation of chronic maintenance therapy in such patients (CIII). Some experts would perform a lumbar puncture to determine if the CSF is culture negative before stopping therapy even if patients have been asymptomatic; other experts do not believe this is necessary. Restarting Secondary Prophylaxis Maintenance therapy should be reinitiated if the CD4+ T-lymphocyte count decreases to < 100-200 cells/ L (AIII). December 2001 OI Guidelines 11/28/01

ヒストプラズマ症 生涯にわたる抑制治療 適応: ヒストプラズマ症の治療完了 薬剤: イトラコナゾール (200 mg １日２回). いつ中止するか: データ不足 (? CD4+ >100 cells/µL) Prevention of Recurrence Patients who complete initial therapy for histoplasmosis should be administered lifelong suppressive treatment (i.e., secondary prophylaxis or chronic maintenance therapy) with itraconazole (200 mg twice a day) (AI).   Discontinuation of Secondary Prophylaxis (Chronic Maintenance Therapy) Although patients receiving secondary prophylaxis (chronic maintenance therapy) might be at low risk for recurrence of systemic mycosis when their CD4+ T-lymphocyte counts increase to greater than 100 cells/µL, in response to HAART, the numbers of patients who have been evaluated are insufficient to warrant a recommendation to discontinue prophylaxis. December 2001 OI Guidelines 11/28/01

コクシディオマイコーシス 生涯にわたる抑制治療 適応: コクシディオマイコーシスの治療完了後 レジメ: フルコナゾール経口 または イトラコナゾール. 髄膜病変を有する患者は専門医へのコンサルテーションを必要とする. いつ中止するか: データ不足 (? CD4+ >100 cells/µL ) Prevention of Recurrence Patients who complete initial therapy for coccidioidomycosis should be dministered lifelong suppressive therapy (i.e., secondary prophylaxis or chronic maintenance therapy) (AII) using either 400 mg of fluconazole by mouth each day or 200 mg of itraconazole twice a day (95). Patients with meningeal disease require consultation with an expert.   Discontinuation of Secondary Prophylaxis (Chronic Maintenance Therapy) Although patients receiving secondary prophylaxis (chronic maintenance therapy) might be at low risk for recurrence of systemic mycosis when their CD4+ T-lymphocyte counts increase to greater than 100 cells/µL, in response to HAART, the numbers of patients who have been evaluated are insufficient to warrant a recommendation to discontinue prophylaxis. December 2001 OI Guidelines 11/28/01

サルモネラ 再発の予防: 適応: サルモネラ菌血症 レジメ: 推奨: 感受性菌にはフルオロキノロン (シプロフロキサシン). その他の管理: 家庭内接触は衛生的方法と抗菌療法が可能かどうか、また反復感染を予防可能かどうかを評価すべきである. (随意) HIV-infected persons who have Salmonella septicemia require long-term therapy (i.e., secondary prophylaxis or chronic maintenance therapy) to prevent recurrence. Fluoroquinolones, primarily ciprofloxacin, are usually the drugs of choice for susceptible organisms (BII). Household contacts of HIV-infected persons who have salmonellosis or shigellosis should be evaluated for persistent asymptomatic carriage of Salmonella or Shigella so that strict hygienic measures and/or antimicrobial therapy can be instituted and recurrent transmission to the HIV-infected person can be prevented (CIII). December 2001 OI Guidelines 11/28/01

日和見感染症ガイドライン2001年11月 その他の医学的管理戦略を要する感染症 December 2001 OI Guidelines 11/28/01

Ｃ型肝炎ウイルス感染症 疾患の予防 陽性であった場合の推奨されるスクリーニング: RIBA/ HCV PCRを行いその後: 過量のアルコール摂取を控える A型肝炎に対するワクチン接種 慢性肝疾患と治療の必要性に対する評価. HAART療法患者は肝機能検査をモニター. HIVと HCVが合併感染していても HAARTは通常は中止すべきでない. Prevention of Disease All patients with HIV infection should be screened for HCV infection (BIII) because some HIV-infected patients are at increased risk for HCV infection and HCV related disease. Also, knowledge of HCV status is important for management of all HIV-infected patients (e.g., to interpret and manage elevated liver related tests). Screening should be performed by using licensed enzyme immunoassays (EIAs) for anti-HCV (BIII). Positive anti-HCV results should be verified with additional testing (i.e., RIBA™ or reverse transcriptase PCR for HCV RNA). The presence of HCV RNA in blood might also be assessed in HIV-infected persons with undetectable antibody but other evidence of chronic liver disease (e.g., unexplained elevated liver-specific enzymes) or when acute HCV infection is suspected (CIII). Persons coinfected with HIV and HCV should be advised not to drink excessive amounts of alcohol (AII). Avoiding alcohol altogether might be prudent because it is unclear whether even occasional alcohol use increases the incidence of cirrhosis among HCV-infected persons (CIII). Patients with chronic hepatitis C should be vaccinated against hepatitis A because a) the risk for fulminant hepatitis associated with hepatitis A appears increased in such patients; b) hepatitis A vaccine is safe for HIV-infected persons; and c) more than two thirds of patients develop protective antibody responses (BIII). Prevaccination screening for total (IgG and IgM) antibody to hepatitis A virus is cost-effective and therefore recommended when greater than 30% prevalence of hepatitis A virus antibody is expected in the population being screened. Patients should also be immunized for HBV if they are susceptible (BIII). HIV-HCV-coinfected patients may develop HCV associated liver disease over a shorter time course than patients infected with HCV alone and should be evaluated for chronic liver disease and for the possible need for treatment. Limited data suggest that HCV treatment can be safely provided to patients coinfected with HIV and HCV. This care should occur in a clinical trial or be coordinated by providers with experience treating both HIV and HCV infections (BIII). In some studies, the incidence of antiretroviral-associated liver enzyme elevations has been increased in patients coinfected with HIV and HCV ; such increases might not require treatment modifications. Thus, although liver enzymes should be carefully monitored, HAART should not be routinely withheld from patients coinfected with HIV and HCV (DIII). However, coinfected patients initiating HAART might have an inflammatory reaction that mimics an exacerbation of underlying liver disease. In this situation, careful monitoring of liver function is required. December 2001 OI Guidelines 11/28/01

ヒトパピローマウイルス感染症 疾病の予防 HIV感染女性における陰部上皮癌 内診 + 子宮頚部パパニコロスメア(PAP) X 2回を 　初めてHIVと診断された年に行う. 正常ならば, 毎年PAPを繰り返す 異常ならば, 米国国立がん研究所のガイドライン“ Interim Guidelines for Management of Abnormal Cervical Cytology “に従う 再発予防 治療後は注意深い経過観察とモニタリング 推奨される特別な治療はない. HPV-associated Genital Epithelial Cancers in HIV-infected Women After a complete history of previous cervical disease has been obtained, HIV-infected women should have a pelvic examination and a Pap smear. In accordance with the recommendation of the Agency for Health Care Policy and Research, the Pap smear should be obtained twice in the first year after diagnosis of HIV infection and, if the results are normal, annually thereafter (AII). If the results of the Pap smear are abnormal, care should be provided according to the Interim Guidelines for Management of Abnormal Cervical Cytology published by a National Cancer Institute Consensus Panel. No data are available to suggest that these guidelines to prevent cervical disease should be modified for women on HAART. Prevention of Recurrence The risks for recurrence of squamous intraepithelial lesions and cervical cancer after conventional therapy are increased among HIV-infected women. The prevention of illness associated with recurrence depends on careful followup of patients after treatment. Patients should be monitored with frequent cytologic screening and, when indicated, with colposcopic examination for recurrent lesions (AI). December 2001 OI Guidelines 11/28/01

日和見感染症ガイドライン2001年11月 経費に関する考察 December 2001 OI Guidelines 11/28/01

カリニ肺炎予防の薬剤経費 薬剤 投与量 年間経費 ＳＴ合剤 1 DS/日 135ドル ダプソン 100 mg/日 72ドル ペンタミジン吸入 1,185ドル* アトヴァクノン 1500 mg/日 11,627ドル * 投与に費用を考慮する必要がある. December 2001 OI Guidelines 11/28/01

ワクチンの経費 * ワクチン 経費 インフルエンザ 3ドル 肺炎球菌 13ドル A型肝炎 (2回) 124ドル B型肝炎 (3回) 70ドル * 平均卸売り価格 December 2001 OI Guidelines 11/28/01

年間10,000ドル*を越える薬剤 薬剤 投与量 年間経費 1500 mg/日 11,627ドル 900 mg/日 21,582ドル アトヴァクノン 1500 mg/日 11,627ドル ヴァルガンシクロビル 900 mg/日 21,582ドル ガンシクロビル静注 5 mg/kg/日 13,093ドル フォスカルネット静注 90 mg/kg/日 27,770ドル シドフォビル 375 mg　１回/２週 20,904ドル フォミビルセン 1 バイアル4週毎 12,000ドル * 平均卸売り価格 December 2001 OI Guidelines 11/28/01

その他の追加情報のために: ガイドライン完全版の原典: AETC Resource Center: www.aids-ed.org AIDS Treatment Information Service: www.hivatis.org December 2001 OI Guidelines 11/28/01

日和見感染症ガイドラインスライド 2001年12月（日本語版） 執筆: John G. Bartlett, M.D. 編集: Richard W. Dunning, M.H.S. レビュー: Renslow Sherer, M.D. Caroline Teter, PAC, M.P.H. 翻訳：小田健司（社会保険広島市民病院内科） December 2001 OI Guidelines 11/28/01