PMID- 23094059
OWN - NLM
STAT- MEDLINE
DCOM- 20130401
LR  - 20220408
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 7
IP  - 10
DP  - 2012
TI  - Causes of death on antiretroviral therapy: a post-mortem study from South Africa.
PG  - e47542
LID - 10.1371/journal.pone.0047542 [doi]
LID - e47542
AB  - BACKGROUND: Mortality in the first months of antiretroviral therapy (ART) is a 
      significant clinical problem in sub-Saharan Africa. To date, no post-mortem study 
      has investigated the causes of mortality in these patients. METHODS: HIV-positive 
      adults who died as in-patients at a Johannesburg academic hospital underwent 
      chart-review and ultrasound-guided needle autopsy for histological and 
      microbiological examination of lung, liver, spleen, kidney, bone marrow, lymph 
      node, skin and cerebrospinal fluid. A clinico-pathologic committee considered all 
      available data and adjudicated immediate and contributing causes of death. 
      RESULTS: Thirty-nine adults were enrolled: 14 pre-ART, 15 early-ART (7-90 days), 
      and 10 late-ART (>90 days). Needle sampling yielded adequate specimen in 100% of 
      kidney, skin, heart and cerebrospinal fluid samples, 97% of livers and lungs, 92% 
      of bone marrows, 87% of spleens and 68% of lymph nodes. Mycobacterial infections 
      were implicated in 69% of deaths (26 of 27 of these due to M. tuberculosis), 
      bacterial infections in 33%, fungal infections in 21%, neoplasm in 26%, and 
      non-infectious organ failure in 26%. Immune reconstitution inflammatory syndrome 
      (IRIS) was implicated in 73% of early-ART deaths. Post-mortem investigations 
      revealed previously undiagnosed causes of death in 49% of cases. Multiple 
      pathologies were common with 62% of subjects with mycobacterial infection also 
      having at least one other infectious or neoplastic cause of death. CONCLUSIONS: 
      Needle biopsy was efficient and yielded excellent pathology. The large majority 
      of deaths in all three groups were caused by M. tuberculosis suggesting an urgent 
      need for improved diagnosis and expedited treatment prior to and throughout the 
      course of antiretroviral therapy. Complex, unrecognized co-morbidities pose an 
      additional challenge.
FAU - Wong, Emily B
AU  - Wong EB
AD  - Wits Reproductive Health and HIV Institute, University of the Witwatersrand, 
      Johannesburg, South Africa. emily.wong@k-rith.org
FAU - Omar, Tanvier
AU  - Omar T
FAU - Setlhako, Gosetsemang J
AU  - Setlhako GJ
FAU - Osih, Regina
AU  - Osih R
FAU - Feldman, Charles
AU  - Feldman C
FAU - Murdoch, David M
AU  - Murdoch DM
FAU - Martinson, Neil A
AU  - Martinson NA
FAU - Bangsberg, David R
AU  - Bangsberg DR
FAU - Venter, W D F
AU  - Venter WD
LA  - eng
GR  - T32 AI007387/AI/NIAID NIH HHS/United States
GR  - K24 MH087227/MH/NIMH NIH HHS/United States
GR  - 674-A-00-08-00005-00/PHS HHS/United States
GR  - D43TW000010-21S1/TW/FIC NIH HHS/United States
GR  - PEPFAR/PEPFAR/United States
GR  - P30 AI060354/AI/NIAID NIH HHS/United States
GR  - RTW007373/0/PHS HHS/United States
GR  - K01 TW008005/TW/FIC NIH HHS/United States
GR  - U2R TW007373/TW/FIC NIH HHS/United States
GR  - R24 TW007988/TW/FIC NIH HHS/United States
GR  - D43 TW000010/TW/FIC NIH HHS/United States
GR  - R24TW007988/TW/FIC NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20121016
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
SB  - IM
MH  - Adult
MH  - *Antiretroviral Therapy, Highly Active
MH  - Autopsy
MH  - Bacterial Infections/drug therapy/microbiology/*mortality/pathology/virology
MH  - Biopsy, Needle
MH  - Bone Marrow/drug effects/pathology/virology
MH  - Cause of Death
MH  - Female
MH  - HIV/drug effects/growth & development
MH  - HIV Infections/drug therapy/*mortality/pathology/virology
MH  - Humans
MH  - Immune Reconstitution Inflammatory Syndrome/drug 
      therapy/*mortality/pathology/virology
MH  - Kidney/drug effects/pathology/virology
MH  - Liver/drug effects/pathology/virology
MH  - Lung/drug effects/pathology/virology
MH  - Lymph Nodes/drug effects/pathology/virology
MH  - Male
MH  - Middle Aged
MH  - Mycobacterium tuberculosis/drug effects/growth & development
MH  - Skin/drug effects/pathology/virology
MH  - South Africa/epidemiology
MH  - Tuberculosis, Pulmonary/drug therapy/microbiology/*mortality/pathology/virology
PMC - PMC3472995
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2012/10/25 06:00
MHDA- 2013/04/02 06:00
PMCR- 2012/10/16
CRDT- 2012/10/25 06:00
PHST- 2012/06/18 00:00 [received]
PHST- 2012/09/12 00:00 [accepted]
PHST- 2012/10/25 06:00 [entrez]
PHST- 2012/10/25 06:00 [pubmed]
PHST- 2013/04/02 06:00 [medline]
PHST- 2012/10/16 00:00 [pmc-release]
AID - PONE-D-12-17319 [pii]
AID - 10.1371/journal.pone.0047542 [doi]
PST - ppublish
SO  - PLoS One. 2012;7(10):e47542. doi: 10.1371/journal.pone.0047542. Epub 2012 Oct 16.