Clofazimine for Treatment of Cryptosporidiosis in Human Immunodeficiency Virus Infected Adults: An Experimental Medicine, Randomized, Double-blind, Placebo-controlled Phase 2a Trial.
Clofazimine for Treatment of Cryptosporidiosis in Human Immunodeficiency Virus Infected Adults: An Experimental Medicine, Randomized, Double-blind, Placebo-controlled Phase 2a Trial.
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DOI：
10.1093/cid/ciaa421
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发表时间：
2021-07-15
期刊：
影响因子：
--
通讯作者：
Van Voorhis WC
中科院分区：
文献类型：
--
作者：
Iroh Tam P;Arnold SLM;Barrett LK;Chen CR;Conrad TM;Douglas E;Gordon MA;Hebert D;Henrion M;Hermann D;Hollingsworth B;Houpt E;Jere KC;Lindblad R;Love MS;Makhaza L;McNamara CW;Nedi W;Nyirenda J;Operario DJ;Phulusa J;Quinnan GV;Sawyer LA;Thole H;Toto N;Winter A;Van Voorhis WC
我们评估了氯法齐明（CFZ）在人类免疫缺陷病毒（HIV）伴隐孢子虫病患者中的疗效、药代动力学（PK）和安全性。我们进行了一项随机、双盲、安慰剂对照的研究。A部分的主要结果是隐孢子虫脱落减少、安全性和PK。根据方案（ATP）进行初步分析。研究的B部分比较了没有隐孢子虫病的HIV感染者的CFZ PK。20名A部分参与者和10名B部分参与者完成了研究ATP。几乎所有的A部分参与者都有高病毒载量和低CD4计数，这与抗逆转录病毒（ARV）治疗失败一致。在研究开始时，与安慰剂组相比，A部分CFZ组有更高的隐孢子虫脱落、粪便总重量和更多的腹泻发作。在住院期间，与安慰剂组相比，CFZ组每克粪便隐孢子虫数量增加2.17 log2(95%置信上限为3.82)，粪便总重量减少45.3 g (P = 0.37)，腹泻次数增加2.32次（P = 0.87）。最常见的不良反应是腹泻、腹痛和不适。一名安慰剂和3名CFZ参与者在研究期间死亡。隐孢子虫病患者血浆CFZ水平比B组对照组低2倍。我们的研究结果不支持CFZ在严重免疫低下的HIV人群中治疗隐孢子虫病的疗效。然而，该试验展示了一种评估隐孢子虫病治疗药物治疗潜力的途径。对艾滋病毒感染者进行腹泻筛查，特别是隐孢子虫感染，可能会发现那些抗逆转录病毒治疗失败的人。NCT03341767。我们评估氯法齐明治疗成人人类免疫缺陷病毒和隐孢子虫病。氯法齐明耐受性良好，但与安慰剂治疗的成人相比，并没有减少隐孢子虫的排泄或腹泻。该试验为未来隐孢子虫病治疗试验提供了蓝图。
We evaluated the efficacy, pharmacokinetics (PK), and safety of clofazimine (CFZ) in patients living with human immunodeficiency virus (HIV) with cryptosporidiosis. We performed a randomized, double-blind, placebo-controlled study. Primary outcomes in part A were reduction in Cryptosporidium shedding, safety, and PK. Primary analysis was according to protocol (ATP). Part B of the study compared CFZ PK in matched individuals living with HIV without cryptosporidiosis. Twenty part A and 10 part B participants completed the study ATP. Almost all part A participants had high viral loads and low CD4 counts, consistent with failure of antiretroviral (ARV) therapy. At study entry, the part A CFZ group had higher Cryptosporidium shedding, total stool weight, and more diarrheal episodes compared with the placebo group. Over the inpatient period, compared with those who received placebo, the CFZ group Cryptosporidium shedding increased by 2.17 log2 Cryptosporidium per gram stool (95% upper confidence limit, 3.82), total stool weight decreased by 45.3 g (P = .37), and number of diarrheal episodes increased by 2.32 (P = .87). The most frequent solicited adverse effects were diarrhea, abdominal pain, and malaise. One placebo and 3 CFZ participants died during the study. Plasma levels of CFZ in participants with cryptosporidiosis were 2-fold lower than in part B controls. Our findings do not support the efficacy of CFZ for the treatment of cryptosporidiosis in a severely immunocompromised HIV population. However, this trial demonstrates a pathway to assess the therapeutic potential of drugs for cryptosporidiosis treatment. Screening persons living with HIV for diarrhea, and especially Cryptosporidium infection, may identify those failing ARV therapy. NCT03341767. We evaluated clofazimine for treatment of adults living with human immunodeficiency virus and cryptosporidiosis. Clofazimine was well tolerated but did not reduce Cryptosporidium excretion or diarrhea compared with adults treated with placebo. This trial forms a blueprint for future cryptosporidiosis therapeutic trials.
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DOI：
10.1016/s0140-6736(18)31267-4
发表时间：
2018-07-28
期刊：
Lancet (London, England)
影响因子：
--
作者：
Gupta-Wright A;Corbett EL;van Oosterhout JJ;Wilson D;Grint D;Alufandika-Moyo M;Peters JA;Chiume L;Flach C;Lawn SD;Fielding K
通讯作者：
Fielding K
影响因子：
6.4
作者：
Rossignol, JFA;Ayoub, A;Ayers, MS
通讯作者：
Ayers, MS
影响因子：
168.9
作者：
Kotloff, Karen L.;Nataro, James P.;Levine, Myron M.
通讯作者：
Levine, Myron M.
撒哈拉以南非洲和南亚的中等/高死亡率地区儿童中隐孢子虫腹泻病的负担，利用来自全球企业多中心研究（GEMS）的数据。
影响因子：
3.8
作者：
Sow SO;Muhsen K;Nasrin D;Blackwelder WC;Wu Y;Farag TH;Panchalingam S;Sur D;Zaidi AK;Faruque AS;Saha D;Adegbola R;Alonso PL;Breiman RF;Bassat Q;Tamboura B;Sanogo D;Onwuchekwa U;Manna B;Ramamurthy T;Kanungo S;Ahmed S;Qureshi S;Quadri F;Hossain A;Das SK;Antonio M;Hossain MJ;Mandomando I;Nhampossa T;Acácio S;Omore R;Oundo JO;Ochieng JB;Mintz ED;O'Reilly CE;Berkeley LY;Livio S;Tennant SM;Sommerfelt H;Nataro JP;Ziv-Baran T;Robins-Browne RM;Mishcherkin V;Zhang J;Liu J;Houpt ER;Kotloff KL;Levine MM
通讯作者：
Levine MM
影响因子：
2.5
作者：
Nachipo P;Hermann D;Quinnan G;Gordon MA;Van Voorhis WC;Iroh Tam PY
通讯作者：
Iroh Tam PY