Causes of Death on Antiretroviral Therapy: A Post-Mortem Study from South Africa

Emily B. Wong, Tanvier Omar, Gosetsemang J. Setlhako, Regina Osih, Charles Feldman, David M. Murdoch, Neil A. Martinson, David Bangsberg, W. D F Venter

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Article numbere47542
JournalPLoS One
Volume7
Issue number10
DOIs
StatePublished - Oct 16 2012
Externally publishedYes

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South Africa
Needles
Cerebrospinal fluid
Cause of Death
Pathology
death
Liver
therapeutics
Skin
Bone
mycobacterial diseases
Secondary Prevention
Biopsy
cerebrospinal fluid
Cerebrospinal Fluid
tuberculosis
Tuberculosis
skin (animal)
Spleen
bone marrow

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Wong, E. B., Omar, T., Setlhako, G. J., Osih, R., Feldman, C., Murdoch, D. M., ... Venter, W. D. F. (2012). Causes of Death on Antiretroviral Therapy: A Post-Mortem Study from South Africa. PLoS One, 7(10), [e47542]. https://doi.org/10.1371/journal.pone.0047542

Causes of Death on Antiretroviral Therapy : A Post-Mortem Study from South Africa. / Wong, Emily B.; Omar, Tanvier; Setlhako, Gosetsemang J.; Osih, Regina; Feldman, Charles; Murdoch, David M.; Martinson, Neil A.; Bangsberg, David; Venter, W. D F.

In: PLoS One, Vol. 7, No. 10, e47542, 16.10.2012.

Research output: Contribution to journalArticle

Wong, EB, Omar, T, Setlhako, GJ, Osih, R, Feldman, C, Murdoch, DM, Martinson, NA, Bangsberg, D & Venter, WDF 2012, 'Causes of Death on Antiretroviral Therapy: A Post-Mortem Study from South Africa', PLoS One, vol. 7, no. 10, e47542. https://doi.org/10.1371/journal.pone.0047542
Wong EB, Omar T, Setlhako GJ, Osih R, Feldman C, Murdoch DM et al. Causes of Death on Antiretroviral Therapy: A Post-Mortem Study from South Africa. PLoS One. 2012 Oct 16;7(10). e47542. https://doi.org/10.1371/journal.pone.0047542
Wong, Emily B. ; Omar, Tanvier ; Setlhako, Gosetsemang J. ; Osih, Regina ; Feldman, Charles ; Murdoch, David M. ; Martinson, Neil A. ; Bangsberg, David ; Venter, W. D F. / Causes of Death on Antiretroviral Therapy : A Post-Mortem Study from South Africa. In: PLoS One. 2012 ; Vol. 7, No. 10.
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abstract = "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.",
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