NR: not reported; PLWH: people living with HIV
The three studies respectively found 2/80 (2.5%)37,
56/357 (16%)46, and 15/116
(13%)49,50 deaths were ADR-related.
The proportion of deaths attributed to preventable ADRs was reported in
two studies: 28/357 (7.8%) in South Africa46 and
14/116 (12%) in Ethiopia49,50 respectively.
These two studies also reported the proportion of ADR-related deaths in
which decedents were people living with HIV (PLWH): 31/56
(55%)46 and 7/15 (47%)49,50respectively. In both studies, renal failure and drug-induced liver
injury were the most common ADRs resulting in death, and both studies
listed antiretrovirals and antituberculosis drugs as the drugs most
commonly implicated in ADR-related deaths.
Multivariable logistic regression in one study46identified HIV-infection with antiretroviral treatment, higher drug
count, and higher comorbidity score as independent risk factors for
ADR-related death. Unadjusted bivariate analyses in the
other49,50 also showed associations between
ADR-related death and exposure to antiretroviral treatment, higher drug
count, and higher comorbidity score, as well as pre-existing liver
disease, a history of prior ADR, low body-mass index, and exposure to
antituberculosis drugs.
In addition to the three studies included in this group, fatal ADR
outcomes were reported by nine other studies included in this
review36,38-40,42,44,45,48,51-53. However, these nine
studies did not report the proportion of ADR-related deaths against a
denominator of all in-hospital deaths.
A Nigerian study52 reported seven deaths attributed to
ADRs among 67 adults with serious and non-serious ADRs. These included
three cases of Stevens Johnson Syndrome or toxic epidermal necrolysis
with co-trimoxazole and phenytoin, two cases of haemorrhage with heparin
and diclofenac, and two cases of hepatotoxicity with anti-tuberculosis
therapy and herbal medicine. Two of the deaths occurred in PLWH. Among
other adult studies, the Malawian study42 reported one
fatal outcome (hyperlactatemia with stavudine) among their three
patients with serious ADRs; the Malian study38,39reported three fatal outcomes (hypoglycaemia, and “colchicine-induced
vomiting”) among 39 patients with 47 serious and non-serious ADRs; and
the spontaneous reporting study44,45 reported no fatal
outcomes among 30 patients with serious ADRs.
Paediatric studies generally reported low absolute numbers of
fatalities. However, fatal outcomes were reported to occur in a
relatively high proportion of serious ADRs: 2/17 serious ADRs were fatal
(Stevens-Johnson syndrome and hepatotoxicity) in one Nigerian
study36, 2/12 (Stevens-Johnson syndrome) in the
other40, and 1/40 in a South African
study53. No fatal outcomes were reported among 61
serious and non-serious ADRs in the other South African paediatric
study51.
In the country-wide Eritrean survey 48 fatal ADRs were reported among
5,848 patients admitted48. The two most common ADRs
resulting in death were anaemia (attributed to various drugs, including
zidovudine) and hepatotoxicity (mostly attributed to antituberculosis
therapy). Drugs used in the management of HIV, TB, and opportunistic
infections appear to have been implicated in 17 deaths.