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A Trial of Itraconazole or Amphotericin B for HIV-Associated Talaromycosis.

Abstract Talaromyces marneffei infection is a major cause of human immunodeficiency virus (HIV)-related death in South and Southeast Asia. Guidelines recommend initial treatment with amphotericin B deoxycholate, but this drug has substantial side effects, a high cost, and limited availability. Itraconazole is available in oral form, is associated with fewer unacceptable side effects than amphotericin, and is widely used in place of amphotericin; however, clinical trials comparing these two treatments are lacking.
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Authors

Mayor MeshTerms

Talaromyces

Keywords
Journal Title the new england journal of medicine
Publication Year Start




PMID- 28614691
OWN - NLM
STAT- MEDLINE
DA  - 20170614
DCOM- 20170621
LR  - 20170622
IS  - 1533-4406 (Electronic)
IS  - 0028-4793 (Linking)
VI  - 376
IP  - 24
DP  - 2017 Jun 15
TI  - A Trial of Itraconazole or Amphotericin B for HIV-Associated Talaromycosis.
PG  - 2329-2340
LID - 10.1056/NEJMoa1613306 [doi]
AB  - BACKGROUND: Talaromyces marneffei infection is a major cause of human
      immunodeficiency virus (HIV)-related death in South and Southeast Asia.
      Guidelines recommend initial treatment with amphotericin B deoxycholate, but this
      drug has substantial side effects, a high cost, and limited availability.
      Itraconazole is available in oral form, is associated with fewer unacceptable
      side effects than amphotericin, and is widely used in place of amphotericin;
      however, clinical trials comparing these two treatments are lacking. METHODS: In 
      this open-label, noninferiority trial, we randomly assigned 440 HIV-infected
      adults who had talaromycosis, confirmed by either microscopy or culture, to
      receive either intravenous amphotericin B deoxycholate (amphotericin) (219
      patients), at a dose of 0.7 to 1.0 mg per kilogram of body weight per day, or
      itraconazole capsules (221 patients), at a dose of 600 mg per day for 3 days,
      followed by 400 mg per day, for 11 days; thereafter, all the patients received
      maintenance therapy with itraconazole. The primary outcome was all-cause
      mortality at week 2. Secondary outcomes included all-cause mortality at week 24, 
      the time to clinical resolution of talaromycosis, early fungicidal activity,
      relapse of talaromycosis, development of the immune reconstitution inflammatory
      syndrome (IRIS), and the side-effect profile. RESULTS: The risk of death at week 
      2 was 6.5% in the amphotericin group and 7.4% in the itraconazole group (absolute
      risk difference, 0.9 percentage points; 95% confidence interval [CI], -3.9 to
      5.6; P<0.001 for noninferiority); however, the risk of death at week 24 was 11.3%
      in the amphotericin group and 21.0% in the itraconazole group (absolute risk
      difference, 9.7 percentage points; 95% CI, 2.8 to 16.6; P=0.006). Treatment with 
      amphotericin was associated with significantly faster clinical resolution and
      fungal clearance and significantly lower rates of relapse and IRIS than
      itraconazole. The patients who received amphotericin had significantly higher
      rates of infusion-related reactions, renal failure, hypokalemia, hypomagnesemia, 
      and anemia than patients in the itraconazole group. CONCLUSIONS: Amphotericin was
      superior to itraconazole as initial treatment for talaromycosis with respect to
      6-month mortality, clinical response, and fungicidal activity. (Funded by the
      Medical Research Council and others; IVAP Current Controlled Trials number,
      ISRCTN59144167 .).
FAU - Le, Thuy
AU  - Le T
AD  - From Wellcome Trust Major Overseas Programme, Oxford University Clinical Research
      Unit (T.L., N.T.T., T.P.T., N.T.H., H.B.L., H.T.N., H.F.L.W., J.N.D., J.F., G.T.,
      M.W.), and the Hospital for Tropical Diseases (N.T.K.C., N.L.N.T., N.V.V.C.), Ho 
      Chi Minh City, the National Hospital for Tropical Diseases (N.V.K., N.T.L.) and
      Bach Mai Hospital (P.T.T.T., D.D.C.), Hanoi, Viet Tiep Hospital, Hai Phong
      (P.T.H.P., V.H.V.), and Vietnam-Sweden Uong Bi Hospital, Quang Ninh (D.T.H.H.,
      V.V.T.) - all in Vietnam; the Centre for Tropical Medicine and Global Health
      (T.L., J.N.D., G.T., M.W.), and the Worldwide Antimalarial Resistance Network
      (L.M.), University of Oxford, Oxford, United Kingdom; the Department of Medical
      Microbiology, Radboudumc, Nijmegen, the Netherlands (H.F.L.W.); and the Hawaii
      Center for AIDS, University of Hawaii at Manoa, Honolulu (T.L., C.S.).
FAU - Kinh, Nguyen Van
AU  - Kinh NV
AD  - From Wellcome Trust Major Overseas Programme, Oxford University Clinical Research
      Unit (T.L., N.T.T., T.P.T., N.T.H., H.B.L., H.T.N., H.F.L.W., J.N.D., J.F., G.T.,
      M.W.), and the Hospital for Tropical Diseases (N.T.K.C., N.L.N.T., N.V.V.C.), Ho 
      Chi Minh City, the National Hospital for Tropical Diseases (N.V.K., N.T.L.) and
      Bach Mai Hospital (P.T.T.T., D.D.C.), Hanoi, Viet Tiep Hospital, Hai Phong
      (P.T.H.P., V.H.V.), and Vietnam-Sweden Uong Bi Hospital, Quang Ninh (D.T.H.H.,
      V.V.T.) - all in Vietnam; the Centre for Tropical Medicine and Global Health
      (T.L., J.N.D., G.T., M.W.), and the Worldwide Antimalarial Resistance Network
      (L.M.), University of Oxford, Oxford, United Kingdom; the Department of Medical
      Microbiology, Radboudumc, Nijmegen, the Netherlands (H.F.L.W.); and the Hawaii
      Center for AIDS, University of Hawaii at Manoa, Honolulu (T.L., C.S.).
FAU - Cuc, Ngo T K
AU  - Cuc NTK
AD  - From Wellcome Trust Major Overseas Programme, Oxford University Clinical Research
      Unit (T.L., N.T.T., T.P.T., N.T.H., H.B.L., H.T.N., H.F.L.W., J.N.D., J.F., G.T.,
      M.W.), and the Hospital for Tropical Diseases (N.T.K.C., N.L.N.T., N.V.V.C.), Ho 
      Chi Minh City, the National Hospital for Tropical Diseases (N.V.K., N.T.L.) and
      Bach Mai Hospital (P.T.T.T., D.D.C.), Hanoi, Viet Tiep Hospital, Hai Phong
      (P.T.H.P., V.H.V.), and Vietnam-Sweden Uong Bi Hospital, Quang Ninh (D.T.H.H.,
      V.V.T.) - all in Vietnam; the Centre for Tropical Medicine and Global Health
      (T.L., J.N.D., G.T., M.W.), and the Worldwide Antimalarial Resistance Network
      (L.M.), University of Oxford, Oxford, United Kingdom; the Department of Medical
      Microbiology, Radboudumc, Nijmegen, the Netherlands (H.F.L.W.); and the Hawaii
      Center for AIDS, University of Hawaii at Manoa, Honolulu (T.L., C.S.).
FAU - Tung, Nguyen L N
AU  - Tung NLN
AD  - From Wellcome Trust Major Overseas Programme, Oxford University Clinical Research
      Unit (T.L., N.T.T., T.P.T., N.T.H., H.B.L., H.T.N., H.F.L.W., J.N.D., J.F., G.T.,
      M.W.), and the Hospital for Tropical Diseases (N.T.K.C., N.L.N.T., N.V.V.C.), Ho 
      Chi Minh City, the National Hospital for Tropical Diseases (N.V.K., N.T.L.) and
      Bach Mai Hospital (P.T.T.T., D.D.C.), Hanoi, Viet Tiep Hospital, Hai Phong
      (P.T.H.P., V.H.V.), and Vietnam-Sweden Uong Bi Hospital, Quang Ninh (D.T.H.H.,
      V.V.T.) - all in Vietnam; the Centre for Tropical Medicine and Global Health
      (T.L., J.N.D., G.T., M.W.), and the Worldwide Antimalarial Resistance Network
      (L.M.), University of Oxford, Oxford, United Kingdom; the Department of Medical
      Microbiology, Radboudumc, Nijmegen, the Netherlands (H.F.L.W.); and the Hawaii
      Center for AIDS, University of Hawaii at Manoa, Honolulu (T.L., C.S.).
FAU - Lam, Nguyen T
AU  - Lam NT
AD  - From Wellcome Trust Major Overseas Programme, Oxford University Clinical Research
      Unit (T.L., N.T.T., T.P.T., N.T.H., H.B.L., H.T.N., H.F.L.W., J.N.D., J.F., G.T.,
      M.W.), and the Hospital for Tropical Diseases (N.T.K.C., N.L.N.T., N.V.V.C.), Ho 
      Chi Minh City, the National Hospital for Tropical Diseases (N.V.K., N.T.L.) and
      Bach Mai Hospital (P.T.T.T., D.D.C.), Hanoi, Viet Tiep Hospital, Hai Phong
      (P.T.H.P., V.H.V.), and Vietnam-Sweden Uong Bi Hospital, Quang Ninh (D.T.H.H.,
      V.V.T.) - all in Vietnam; the Centre for Tropical Medicine and Global Health
      (T.L., J.N.D., G.T., M.W.), and the Worldwide Antimalarial Resistance Network
      (L.M.), University of Oxford, Oxford, United Kingdom; the Department of Medical
      Microbiology, Radboudumc, Nijmegen, the Netherlands (H.F.L.W.); and the Hawaii
      Center for AIDS, University of Hawaii at Manoa, Honolulu (T.L., C.S.).
FAU - Thuy, Pham T T
AU  - Thuy PTT
AD  - From Wellcome Trust Major Overseas Programme, Oxford University Clinical Research
      Unit (T.L., N.T.T., T.P.T., N.T.H., H.B.L., H.T.N., H.F.L.W., J.N.D., J.F., G.T.,
      M.W.), and the Hospital for Tropical Diseases (N.T.K.C., N.L.N.T., N.V.V.C.), Ho 
      Chi Minh City, the National Hospital for Tropical Diseases (N.V.K., N.T.L.) and
      Bach Mai Hospital (P.T.T.T., D.D.C.), Hanoi, Viet Tiep Hospital, Hai Phong
      (P.T.H.P., V.H.V.), and Vietnam-Sweden Uong Bi Hospital, Quang Ninh (D.T.H.H.,
      V.V.T.) - all in Vietnam; the Centre for Tropical Medicine and Global Health
      (T.L., J.N.D., G.T., M.W.), and the Worldwide Antimalarial Resistance Network
      (L.M.), University of Oxford, Oxford, United Kingdom; the Department of Medical
      Microbiology, Radboudumc, Nijmegen, the Netherlands (H.F.L.W.); and the Hawaii
      Center for AIDS, University of Hawaii at Manoa, Honolulu (T.L., C.S.).
FAU - Cuong, Do D
AU  - Cuong DD
AD  - From Wellcome Trust Major Overseas Programme, Oxford University Clinical Research
      Unit (T.L., N.T.T., T.P.T., N.T.H., H.B.L., H.T.N., H.F.L.W., J.N.D., J.F., G.T.,
      M.W.), and the Hospital for Tropical Diseases (N.T.K.C., N.L.N.T., N.V.V.C.), Ho 
      Chi Minh City, the National Hospital for Tropical Diseases (N.V.K., N.T.L.) and
      Bach Mai Hospital (P.T.T.T., D.D.C.), Hanoi, Viet Tiep Hospital, Hai Phong
      (P.T.H.P., V.H.V.), and Vietnam-Sweden Uong Bi Hospital, Quang Ninh (D.T.H.H.,
      V.V.T.) - all in Vietnam; the Centre for Tropical Medicine and Global Health
      (T.L., J.N.D., G.T., M.W.), and the Worldwide Antimalarial Resistance Network
      (L.M.), University of Oxford, Oxford, United Kingdom; the Department of Medical
      Microbiology, Radboudumc, Nijmegen, the Netherlands (H.F.L.W.); and the Hawaii
      Center for AIDS, University of Hawaii at Manoa, Honolulu (T.L., C.S.).
FAU - Phuc, Pham T H
AU  - Phuc PTH
AD  - From Wellcome Trust Major Overseas Programme, Oxford University Clinical Research
      Unit (T.L., N.T.T., T.P.T., N.T.H., H.B.L., H.T.N., H.F.L.W., J.N.D., J.F., G.T.,
      M.W.), and the Hospital for Tropical Diseases (N.T.K.C., N.L.N.T., N.V.V.C.), Ho 
      Chi Minh City, the National Hospital for Tropical Diseases (N.V.K., N.T.L.) and
      Bach Mai Hospital (P.T.T.T., D.D.C.), Hanoi, Viet Tiep Hospital, Hai Phong
      (P.T.H.P., V.H.V.), and Vietnam-Sweden Uong Bi Hospital, Quang Ninh (D.T.H.H.,
      V.V.T.) - all in Vietnam; the Centre for Tropical Medicine and Global Health
      (T.L., J.N.D., G.T., M.W.), and the Worldwide Antimalarial Resistance Network
      (L.M.), University of Oxford, Oxford, United Kingdom; the Department of Medical
      Microbiology, Radboudumc, Nijmegen, the Netherlands (H.F.L.W.); and the Hawaii
      Center for AIDS, University of Hawaii at Manoa, Honolulu (T.L., C.S.).
FAU - Vinh, Vu H
AU  - Vinh VH
AD  - From Wellcome Trust Major Overseas Programme, Oxford University Clinical Research
      Unit (T.L., N.T.T., T.P.T., N.T.H., H.B.L., H.T.N., H.F.L.W., J.N.D., J.F., G.T.,
      M.W.), and the Hospital for Tropical Diseases (N.T.K.C., N.L.N.T., N.V.V.C.), Ho 
      Chi Minh City, the National Hospital for Tropical Diseases (N.V.K., N.T.L.) and
      Bach Mai Hospital (P.T.T.T., D.D.C.), Hanoi, Viet Tiep Hospital, Hai Phong
      (P.T.H.P., V.H.V.), and Vietnam-Sweden Uong Bi Hospital, Quang Ninh (D.T.H.H.,
      V.V.T.) - all in Vietnam; the Centre for Tropical Medicine and Global Health
      (T.L., J.N.D., G.T., M.W.), and the Worldwide Antimalarial Resistance Network
      (L.M.), University of Oxford, Oxford, United Kingdom; the Department of Medical
      Microbiology, Radboudumc, Nijmegen, the Netherlands (H.F.L.W.); and the Hawaii
      Center for AIDS, University of Hawaii at Manoa, Honolulu (T.L., C.S.).
FAU - Hanh, Doan T H
AU  - Hanh DTH
AD  - From Wellcome Trust Major Overseas Programme, Oxford University Clinical Research
      Unit (T.L., N.T.T., T.P.T., N.T.H., H.B.L., H.T.N., H.F.L.W., J.N.D., J.F., G.T.,
      M.W.), and the Hospital for Tropical Diseases (N.T.K.C., N.L.N.T., N.V.V.C.), Ho 
      Chi Minh City, the National Hospital for Tropical Diseases (N.V.K., N.T.L.) and
      Bach Mai Hospital (P.T.T.T., D.D.C.), Hanoi, Viet Tiep Hospital, Hai Phong
      (P.T.H.P., V.H.V.), and Vietnam-Sweden Uong Bi Hospital, Quang Ninh (D.T.H.H.,
      V.V.T.) - all in Vietnam; the Centre for Tropical Medicine and Global Health
      (T.L., J.N.D., G.T., M.W.), and the Worldwide Antimalarial Resistance Network
      (L.M.), University of Oxford, Oxford, United Kingdom; the Department of Medical
      Microbiology, Radboudumc, Nijmegen, the Netherlands (H.F.L.W.); and the Hawaii
      Center for AIDS, University of Hawaii at Manoa, Honolulu (T.L., C.S.).
FAU - Tam, Vu Van
AU  - Tam VV
AD  - From Wellcome Trust Major Overseas Programme, Oxford University Clinical Research
      Unit (T.L., N.T.T., T.P.T., N.T.H., H.B.L., H.T.N., H.F.L.W., J.N.D., J.F., G.T.,
      M.W.), and the Hospital for Tropical Diseases (N.T.K.C., N.L.N.T., N.V.V.C.), Ho 
      Chi Minh City, the National Hospital for Tropical Diseases (N.V.K., N.T.L.) and
      Bach Mai Hospital (P.T.T.T., D.D.C.), Hanoi, Viet Tiep Hospital, Hai Phong
      (P.T.H.P., V.H.V.), and Vietnam-Sweden Uong Bi Hospital, Quang Ninh (D.T.H.H.,
      V.V.T.) - all in Vietnam; the Centre for Tropical Medicine and Global Health
      (T.L., J.N.D., G.T., M.W.), and the Worldwide Antimalarial Resistance Network
      (L.M.), University of Oxford, Oxford, United Kingdom; the Department of Medical
      Microbiology, Radboudumc, Nijmegen, the Netherlands (H.F.L.W.); and the Hawaii
      Center for AIDS, University of Hawaii at Manoa, Honolulu (T.L., C.S.).
FAU - Thanh, Nguyen T
AU  - Thanh NT
AD  - From Wellcome Trust Major Overseas Programme, Oxford University Clinical Research
      Unit (T.L., N.T.T., T.P.T., N.T.H., H.B.L., H.T.N., H.F.L.W., J.N.D., J.F., G.T.,
      M.W.), and the Hospital for Tropical Diseases (N.T.K.C., N.L.N.T., N.V.V.C.), Ho 
      Chi Minh City, the National Hospital for Tropical Diseases (N.V.K., N.T.L.) and
      Bach Mai Hospital (P.T.T.T., D.D.C.), Hanoi, Viet Tiep Hospital, Hai Phong
      (P.T.H.P., V.H.V.), and Vietnam-Sweden Uong Bi Hospital, Quang Ninh (D.T.H.H.,
      V.V.T.) - all in Vietnam; the Centre for Tropical Medicine and Global Health
      (T.L., J.N.D., G.T., M.W.), and the Worldwide Antimalarial Resistance Network
      (L.M.), University of Oxford, Oxford, United Kingdom; the Department of Medical
      Microbiology, Radboudumc, Nijmegen, the Netherlands (H.F.L.W.); and the Hawaii
      Center for AIDS, University of Hawaii at Manoa, Honolulu (T.L., C.S.).
FAU - Thuy, Tran P
AU  - Thuy TP
AD  - From Wellcome Trust Major Overseas Programme, Oxford University Clinical Research
      Unit (T.L., N.T.T., T.P.T., N.T.H., H.B.L., H.T.N., H.F.L.W., J.N.D., J.F., G.T.,
      M.W.), and the Hospital for Tropical Diseases (N.T.K.C., N.L.N.T., N.V.V.C.), Ho 
      Chi Minh City, the National Hospital for Tropical Diseases (N.V.K., N.T.L.) and
      Bach Mai Hospital (P.T.T.T., D.D.C.), Hanoi, Viet Tiep Hospital, Hai Phong
      (P.T.H.P., V.H.V.), and Vietnam-Sweden Uong Bi Hospital, Quang Ninh (D.T.H.H.,
      V.V.T.) - all in Vietnam; the Centre for Tropical Medicine and Global Health
      (T.L., J.N.D., G.T., M.W.), and the Worldwide Antimalarial Resistance Network
      (L.M.), University of Oxford, Oxford, United Kingdom; the Department of Medical
      Microbiology, Radboudumc, Nijmegen, the Netherlands (H.F.L.W.); and the Hawaii
      Center for AIDS, University of Hawaii at Manoa, Honolulu (T.L., C.S.).
FAU - Hang, Nguyen T
AU  - Hang NT
AD  - From Wellcome Trust Major Overseas Programme, Oxford University Clinical Research
      Unit (T.L., N.T.T., T.P.T., N.T.H., H.B.L., H.T.N., H.F.L.W., J.N.D., J.F., G.T.,
      M.W.), and the Hospital for Tropical Diseases (N.T.K.C., N.L.N.T., N.V.V.C.), Ho 
      Chi Minh City, the National Hospital for Tropical Diseases (N.V.K., N.T.L.) and
      Bach Mai Hospital (P.T.T.T., D.D.C.), Hanoi, Viet Tiep Hospital, Hai Phong
      (P.T.H.P., V.H.V.), and Vietnam-Sweden Uong Bi Hospital, Quang Ninh (D.T.H.H.,
      V.V.T.) - all in Vietnam; the Centre for Tropical Medicine and Global Health
      (T.L., J.N.D., G.T., M.W.), and the Worldwide Antimalarial Resistance Network
      (L.M.), University of Oxford, Oxford, United Kingdom; the Department of Medical
      Microbiology, Radboudumc, Nijmegen, the Netherlands (H.F.L.W.); and the Hawaii
      Center for AIDS, University of Hawaii at Manoa, Honolulu (T.L., C.S.).
FAU - Long, Hoang B
AU  - Long HB
AD  - From Wellcome Trust Major Overseas Programme, Oxford University Clinical Research
      Unit (T.L., N.T.T., T.P.T., N.T.H., H.B.L., H.T.N., H.F.L.W., J.N.D., J.F., G.T.,
      M.W.), and the Hospital for Tropical Diseases (N.T.K.C., N.L.N.T., N.V.V.C.), Ho 
      Chi Minh City, the National Hospital for Tropical Diseases (N.V.K., N.T.L.) and
      Bach Mai Hospital (P.T.T.T., D.D.C.), Hanoi, Viet Tiep Hospital, Hai Phong
      (P.T.H.P., V.H.V.), and Vietnam-Sweden Uong Bi Hospital, Quang Ninh (D.T.H.H.,
      V.V.T.) - all in Vietnam; the Centre for Tropical Medicine and Global Health
      (T.L., J.N.D., G.T., M.W.), and the Worldwide Antimalarial Resistance Network
      (L.M.), University of Oxford, Oxford, United Kingdom; the Department of Medical
      Microbiology, Radboudumc, Nijmegen, the Netherlands (H.F.L.W.); and the Hawaii
      Center for AIDS, University of Hawaii at Manoa, Honolulu (T.L., C.S.).
FAU - Nhan, Ho T
AU  - Nhan HT
AD  - From Wellcome Trust Major Overseas Programme, Oxford University Clinical Research
      Unit (T.L., N.T.T., T.P.T., N.T.H., H.B.L., H.T.N., H.F.L.W., J.N.D., J.F., G.T.,
      M.W.), and the Hospital for Tropical Diseases (N.T.K.C., N.L.N.T., N.V.V.C.), Ho 
      Chi Minh City, the National Hospital for Tropical Diseases (N.V.K., N.T.L.) and
      Bach Mai Hospital (P.T.T.T., D.D.C.), Hanoi, Viet Tiep Hospital, Hai Phong
      (P.T.H.P., V.H.V.), and Vietnam-Sweden Uong Bi Hospital, Quang Ninh (D.T.H.H.,
      V.V.T.) - all in Vietnam; the Centre for Tropical Medicine and Global Health
      (T.L., J.N.D., G.T., M.W.), and the Worldwide Antimalarial Resistance Network
      (L.M.), University of Oxford, Oxford, United Kingdom; the Department of Medical
      Microbiology, Radboudumc, Nijmegen, the Netherlands (H.F.L.W.); and the Hawaii
      Center for AIDS, University of Hawaii at Manoa, Honolulu (T.L., C.S.).
FAU - Wertheim, Heiman F L
AU  - Wertheim HFL
AD  - From Wellcome Trust Major Overseas Programme, Oxford University Clinical Research
      Unit (T.L., N.T.T., T.P.T., N.T.H., H.B.L., H.T.N., H.F.L.W., J.N.D., J.F., G.T.,
      M.W.), and the Hospital for Tropical Diseases (N.T.K.C., N.L.N.T., N.V.V.C.), Ho 
      Chi Minh City, the National Hospital for Tropical Diseases (N.V.K., N.T.L.) and
      Bach Mai Hospital (P.T.T.T., D.D.C.), Hanoi, Viet Tiep Hospital, Hai Phong
      (P.T.H.P., V.H.V.), and Vietnam-Sweden Uong Bi Hospital, Quang Ninh (D.T.H.H.,
      V.V.T.) - all in Vietnam; the Centre for Tropical Medicine and Global Health
      (T.L., J.N.D., G.T., M.W.), and the Worldwide Antimalarial Resistance Network
      (L.M.), University of Oxford, Oxford, United Kingdom; the Department of Medical
      Microbiology, Radboudumc, Nijmegen, the Netherlands (H.F.L.W.); and the Hawaii
      Center for AIDS, University of Hawaii at Manoa, Honolulu (T.L., C.S.).
FAU - Merson, Laura
AU  - Merson L
AD  - From Wellcome Trust Major Overseas Programme, Oxford University Clinical Research
      Unit (T.L., N.T.T., T.P.T., N.T.H., H.B.L., H.T.N., H.F.L.W., J.N.D., J.F., G.T.,
      M.W.), and the Hospital for Tropical Diseases (N.T.K.C., N.L.N.T., N.V.V.C.), Ho 
      Chi Minh City, the National Hospital for Tropical Diseases (N.V.K., N.T.L.) and
      Bach Mai Hospital (P.T.T.T., D.D.C.), Hanoi, Viet Tiep Hospital, Hai Phong
      (P.T.H.P., V.H.V.), and Vietnam-Sweden Uong Bi Hospital, Quang Ninh (D.T.H.H.,
      V.V.T.) - all in Vietnam; the Centre for Tropical Medicine and Global Health
      (T.L., J.N.D., G.T., M.W.), and the Worldwide Antimalarial Resistance Network
      (L.M.), University of Oxford, Oxford, United Kingdom; the Department of Medical
      Microbiology, Radboudumc, Nijmegen, the Netherlands (H.F.L.W.); and the Hawaii
      Center for AIDS, University of Hawaii at Manoa, Honolulu (T.L., C.S.).
FAU - Shikuma, Cecilia
AU  - Shikuma C
AD  - From Wellcome Trust Major Overseas Programme, Oxford University Clinical Research
      Unit (T.L., N.T.T., T.P.T., N.T.H., H.B.L., H.T.N., H.F.L.W., J.N.D., J.F., G.T.,
      M.W.), and the Hospital for Tropical Diseases (N.T.K.C., N.L.N.T., N.V.V.C.), Ho 
      Chi Minh City, the National Hospital for Tropical Diseases (N.V.K., N.T.L.) and
      Bach Mai Hospital (P.T.T.T., D.D.C.), Hanoi, Viet Tiep Hospital, Hai Phong
      (P.T.H.P., V.H.V.), and Vietnam-Sweden Uong Bi Hospital, Quang Ninh (D.T.H.H.,
      V.V.T.) - all in Vietnam; the Centre for Tropical Medicine and Global Health
      (T.L., J.N.D., G.T., M.W.), and the Worldwide Antimalarial Resistance Network
      (L.M.), University of Oxford, Oxford, United Kingdom; the Department of Medical
      Microbiology, Radboudumc, Nijmegen, the Netherlands (H.F.L.W.); and the Hawaii
      Center for AIDS, University of Hawaii at Manoa, Honolulu (T.L., C.S.).
FAU - Day, Jeremy N
AU  - Day JN
AD  - From Wellcome Trust Major Overseas Programme, Oxford University Clinical Research
      Unit (T.L., N.T.T., T.P.T., N.T.H., H.B.L., H.T.N., H.F.L.W., J.N.D., J.F., G.T.,
      M.W.), and the Hospital for Tropical Diseases (N.T.K.C., N.L.N.T., N.V.V.C.), Ho 
      Chi Minh City, the National Hospital for Tropical Diseases (N.V.K., N.T.L.) and
      Bach Mai Hospital (P.T.T.T., D.D.C.), Hanoi, Viet Tiep Hospital, Hai Phong
      (P.T.H.P., V.H.V.), and Vietnam-Sweden Uong Bi Hospital, Quang Ninh (D.T.H.H.,
      V.V.T.) - all in Vietnam; the Centre for Tropical Medicine and Global Health
      (T.L., J.N.D., G.T., M.W.), and the Worldwide Antimalarial Resistance Network
      (L.M.), University of Oxford, Oxford, United Kingdom; the Department of Medical
      Microbiology, Radboudumc, Nijmegen, the Netherlands (H.F.L.W.); and the Hawaii
      Center for AIDS, University of Hawaii at Manoa, Honolulu (T.L., C.S.).
FAU - Chau, Nguyen V V
AU  - Chau NVV
AD  - From Wellcome Trust Major Overseas Programme, Oxford University Clinical Research
      Unit (T.L., N.T.T., T.P.T., N.T.H., H.B.L., H.T.N., H.F.L.W., J.N.D., J.F., G.T.,
      M.W.), and the Hospital for Tropical Diseases (N.T.K.C., N.L.N.T., N.V.V.C.), Ho 
      Chi Minh City, the National Hospital for Tropical Diseases (N.V.K., N.T.L.) and
      Bach Mai Hospital (P.T.T.T., D.D.C.), Hanoi, Viet Tiep Hospital, Hai Phong
      (P.T.H.P., V.H.V.), and Vietnam-Sweden Uong Bi Hospital, Quang Ninh (D.T.H.H.,
      V.V.T.) - all in Vietnam; the Centre for Tropical Medicine and Global Health
      (T.L., J.N.D., G.T., M.W.), and the Worldwide Antimalarial Resistance Network
      (L.M.), University of Oxford, Oxford, United Kingdom; the Department of Medical
      Microbiology, Radboudumc, Nijmegen, the Netherlands (H.F.L.W.); and the Hawaii
      Center for AIDS, University of Hawaii at Manoa, Honolulu (T.L., C.S.).
FAU - Farrar, Jeremy
AU  - Farrar J
AD  - From Wellcome Trust Major Overseas Programme, Oxford University Clinical Research
      Unit (T.L., N.T.T., T.P.T., N.T.H., H.B.L., H.T.N., H.F.L.W., J.N.D., J.F., G.T.,
      M.W.), and the Hospital for Tropical Diseases (N.T.K.C., N.L.N.T., N.V.V.C.), Ho 
      Chi Minh City, the National Hospital for Tropical Diseases (N.V.K., N.T.L.) and
      Bach Mai Hospital (P.T.T.T., D.D.C.), Hanoi, Viet Tiep Hospital, Hai Phong
      (P.T.H.P., V.H.V.), and Vietnam-Sweden Uong Bi Hospital, Quang Ninh (D.T.H.H.,
      V.V.T.) - all in Vietnam; the Centre for Tropical Medicine and Global Health
      (T.L., J.N.D., G.T., M.W.), and the Worldwide Antimalarial Resistance Network
      (L.M.), University of Oxford, Oxford, United Kingdom; the Department of Medical
      Microbiology, Radboudumc, Nijmegen, the Netherlands (H.F.L.W.); and the Hawaii
      Center for AIDS, University of Hawaii at Manoa, Honolulu (T.L., C.S.).
FAU - Thwaites, Guy
AU  - Thwaites G
AD  - From Wellcome Trust Major Overseas Programme, Oxford University Clinical Research
      Unit (T.L., N.T.T., T.P.T., N.T.H., H.B.L., H.T.N., H.F.L.W., J.N.D., J.F., G.T.,
      M.W.), and the Hospital for Tropical Diseases (N.T.K.C., N.L.N.T., N.V.V.C.), Ho 
      Chi Minh City, the National Hospital for Tropical Diseases (N.V.K., N.T.L.) and
      Bach Mai Hospital (P.T.T.T., D.D.C.), Hanoi, Viet Tiep Hospital, Hai Phong
      (P.T.H.P., V.H.V.), and Vietnam-Sweden Uong Bi Hospital, Quang Ninh (D.T.H.H.,
      V.V.T.) - all in Vietnam; the Centre for Tropical Medicine and Global Health
      (T.L., J.N.D., G.T., M.W.), and the Worldwide Antimalarial Resistance Network
      (L.M.), University of Oxford, Oxford, United Kingdom; the Department of Medical
      Microbiology, Radboudumc, Nijmegen, the Netherlands (H.F.L.W.); and the Hawaii
      Center for AIDS, University of Hawaii at Manoa, Honolulu (T.L., C.S.).
FAU - Wolbers, Marcel
AU  - Wolbers M
AD  - From Wellcome Trust Major Overseas Programme, Oxford University Clinical Research
      Unit (T.L., N.T.T., T.P.T., N.T.H., H.B.L., H.T.N., H.F.L.W., J.N.D., J.F., G.T.,
      M.W.), and the Hospital for Tropical Diseases (N.T.K.C., N.L.N.T., N.V.V.C.), Ho 
      Chi Minh City, the National Hospital for Tropical Diseases (N.V.K., N.T.L.) and
      Bach Mai Hospital (P.T.T.T., D.D.C.), Hanoi, Viet Tiep Hospital, Hai Phong
      (P.T.H.P., V.H.V.), and Vietnam-Sweden Uong Bi Hospital, Quang Ninh (D.T.H.H.,
      V.V.T.) - all in Vietnam; the Centre for Tropical Medicine and Global Health
      (T.L., J.N.D., G.T., M.W.), and the Worldwide Antimalarial Resistance Network
      (L.M.), University of Oxford, Oxford, United Kingdom; the Department of Medical
      Microbiology, Radboudumc, Nijmegen, the Netherlands (H.F.L.W.); and the Hawaii
      Center for AIDS, University of Hawaii at Manoa, Honolulu (T.L., C.S.).
CN  - IVAP Investigators
LA  - eng
SI  - ISRCTN/ISRCTN59144167
GR  - Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PL  - United States
TA  - N Engl J Med
JT  - The New England journal of medicine
JID - 0255562
RN  - 0 (Antifungal Agents)
RN  - 0 (Drug Combinations)
RN  - 005990WHZZ (Deoxycholic Acid)
RN  - 304NUG5GF4 (Itraconazole)
RN  - 7XU7A7DROE (Amphotericin B)
RN  - 87687-70-5 (amphotericin B, deoxycholate drug combination)
RN  - AYI8EX34EU (Creatinine)
SB  - AIM
SB  - IM
MH  - AIDS-Related Opportunistic Infections/*drug therapy/mortality
MH  - Administration, Oral
MH  - Adult
MH  - Amphotericin B/adverse effects/*therapeutic use
MH  - Antifungal Agents/adverse effects/*therapeutic use
MH  - Creatinine/metabolism
MH  - Deoxycholic Acid/adverse effects/*therapeutic use
MH  - Drug Combinations
MH  - Female
MH  - Humans
MH  - Induction Chemotherapy/adverse effects
MH  - Infusions, Intravenous/adverse effects
MH  - Itraconazole/adverse effects/*therapeutic use
MH  - Male
MH  - Mycoses/*drug therapy/mortality
MH  - *Talaromyces/isolation & purification
IR  - Chi NH
FIR - Chi, Nguyen Huu
IR  - Quang VM
FIR - Quang, Vo Minh
IR  - Chinh NT
FIR - Chinh, Nguyen Tran
IR  - Hung NQ
FIR - Hung, Nguyen Quoc
IR  - Vinh LD
FIR - Vinh, Le Duc
IR  - Liem NT
FIR - Liem, Nguyen Thanh
IR  - Cong LQ
FIR - Cong, Ly Quoc
IR  - Ly VT
FIR - Ly, Vo Trieu
IR  - Lan NPH
FIR - Lan, Nguyen Phu Huong
IR  - Man DNH
FIR - Man, Dinh Nguyen Huy
IR  - Nga NTQ
FIR - Nga, Nguyen Thi Quynh
IR  - Ngan TTD
FIR - Ngan, Ta Thi Dieu
IR  - Dung NTH
FIR - Dung, Nguyen Thi Hoai
IR  - Thu NK
FIR - Thu, Nguyen Kim
IR  - Khuong PT
FIR - Khuong, Pham Thi
IR  - Bich DT
FIR - Bich, Dang Thi
IR  - Long NV
FIR - Long, Nguyen Van
IR  - Hoang DM
FIR - Hoang, Do Minh
IR  - Tu HTT
FIR - Tu, Hoang Thi Thanh
IR  - Luat LX
FIR - Luat, Le Xuan
IR  - Dung NT
FIR - Dung, Nguyen Thi
IR  - Lan NT
FIR - Lan, Nguyen Thi
IR  - Huyen TB
FIR - Huyen, Tran Bang
IR  - Tuan NQ
FIR - Tuan, Nguyen Quang
IR  - Tra DT
FIR - Tra, Doan Thu
IR  - Hoa LT
FIR - Hoa, Le Thi
IR  - Hanh TM
FIR - Hanh, Tran Minh
IR  - Phuong NT
FIR - Phuong, Nguyen Thi
IR  - Lien TT
FIR - Lien, Tran Thi
IR  - Hoang DT
FIR - Hoang, Dao Trong
IR  - Sinh VT
FIR - Sinh, Vu Thi
IR  - Nga CT
FIR - Nga, Chu Thi
IR  - Quynh LT
FIR - Quynh, Lai Thi
IR  - Tiep TV
FIR - Tiep, Tran Viet
IR  - Hien HV
FIR - Hien, Ha Van
IR  - Hoan TT
FIR - Hoan, Trinh Thu
IR  - Ha NTT
FIR - Ha, Nguyen Thi Thu
IR  - Dong LQ
FIR - Dong, Le Quang
IR  - Anh NTK
FIR - Anh, Nguyen Thi Kim
IR  - Hien TT
FIR - Hien, Tran Tinh
IR  - Thu NTM
FIR - Thu, Nguyen Thi Mai
IR  - Hien HTA
FIR - Hien, Ha Thuc Ai
IR  - Nguyen A
FIR - Nguyen, Ashley
IR  - Thao VP
FIR - Thao, Vu Phuong
IR  - Dao PTH
FIR - Dao, Phan Thi Hong
IR  - Anh HSN
FIR - Anh, Hoang Suong Nguyet
IR  - Anh DV
FIR - Anh, Duong Van
IR  - Campbell J
FIR - Campbell, James
IR  - Thuy NTT
FIR - Thuy, Nguyen Thi Thanh
IR  - Dung NTP
FIR - Dung, Nguyen Thi Phuong
IR  - Hien HV
FIR - Hien, Ho Van
IR  - Tien NT
FIR - Tien, Nguyen Thanh
IR  - Van NT
FIR - Van, Nguyen Thu
IR  - Linh HD
FIR - Linh, Hoang Dieu
IR  - Huong TTK
FIR - Huong, Tran Thi Kieu
IR  - Bao NT
FIR - Bao, Ngo Thanh
IR  - Tran NB
FIR - Tran, Nguyen Bao
IR  - Nadjim B
FIR - Nadjim, Behzah
IR  - van Doorn R
FIR - van Doorn, Rogier
IR  - Gray A
FIR - Gray, Alastair
IR  - Hope W
FIR - Hope, William
IR  - Larsson M
FIR - Larsson, Mattias
IR  - Pouplin T
FIR - Pouplin, Thomas
EDAT- 2017/06/15 06:00
MHDA- 2017/06/22 06:00
CRDT- 2017/06/15 06:00
AID - 10.1056/NEJMoa1613306 [doi]
PST - ppublish
SO  - N Engl J Med. 2017 Jun 15;376(24):2329-2340. doi: 10.1056/NEJMoa1613306.