title: Causes of death on antiretroviral therapy: a post-mortem study from South Africa.
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.
authors.affiliation: Wits Reproductive Health and HIV Institute, University of the Witwatersrand, Johannesburg, South Africa. emily.wong@k-rith.org
authors.forename: Emily B
authors.initials: EB
authors.lastname: Wong
authors.forename: Tanvier
authors.initials: T
authors.lastname: Omar
authors.forename: Gosetsemang J
authors.initials: GJ
authors.lastname: Setlhako
authors.forename: Regina
authors.initials: R
authors.lastname: Osih
authors.forename: Charles
authors.initials: C
authors.lastname: Feldman
authors.forename: David M
authors.initials: DM
authors.lastname: Murdoch
authors.forename: Neil A
authors.initials: NA
authors.lastname: Martinson
authors.forename: David R
authors.initials: DR
authors.lastname: Bangsberg
authors.forename: W D F
authors.initials: WD
authors.lastname: Venter
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D001344:Autopsy; D001424:Bacterial Infections / Q000188:drug therapy / Q000382:microbiology / Q000401:mortality* / Q000473:pathology / Q000821:virology; D001707:Biopsy, Needle; D001853:Bone Marrow / Q000187:drug effects / Q000473:pathology / Q000821:virology; D002423:Cause of Death; D005260:Female; D006678:HIV / Q000187:drug effects / Q000254:growth & development; D015658:HIV Infections / Q000188:drug therapy / Q000401:mortality* / Q000473:pathology / Q000821:virology; D006801:Humans; D054019:Immune Reconstitution Inflammatory Syndrome / Q000188:drug therapy / Q000401:mortality* / Q000473:pathology / Q000821:virology; D007668:Kidney / Q000187:drug effects / Q000473:pathology / Q000821:virology; D008099:Liver / Q000187:drug effects / Q000473:pathology / Q000821:virology; D008168:Lung / Q000187:drug effects / Q000473:pathology / Q000821:virology; D008198:Lymph Nodes / Q000187:drug effects / Q000473:pathology / Q000821:virology; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000254:growth & development; D012867:Skin / Q000187:drug effects / Q000473:pathology / Q000821:virology; D013019:South Africa / Q000453:epidemiology; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy / Q000382:microbiology / Q000401:mortality* / Q000473:pathology / Q000821:virology