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.