Adverse Drug Reactions Reported to a National HIV & Tuberculosis Health Care Worker Hotline in South Africa: Description and Prospective Follow-Up of Reports

Abstract

Introduction The National HIV & Tuberculosis Health Care Worker (HCW) Hotline provides advice on the management of suspected adverse drug reactions (ADRs). We describe suspected ADRs reported to the hotline by HCWs, concordance with advice, and patient outcomes. Methods We reviewed suspected ADRs in HIV-infected patients, patients taking antiretrovirals and patients taking anti-tuberculosis therapy reported from May 2013 to October 2014. We performed causality assessment using the World Health Organization Uppsala Monitoring Centre (WHO-UMC) criteria. We included suspected ADRs categorized as certain, probable or possible in further analysis. Results We received 772 ADR reports, of which 87/772 (11.3 %) were classified as certain, 176/772 (22.8 %) as probable, 361/772 (46.8 %) as possible, and 148/772 (19.2 %) as unlikely or unassessable. The most frequent ADRs were rash, drug-induced liver injury (DILI) and kidney injury, comprising 110/624 (17.6 %), 87/624 (13.9 %), and 77/624 (12.3 %), respectively. The ADR was severe in 27.3 % of rashes, 36.4 % of kidney injury reports and 88.5 % of DILI reports. Most frequently implicated drugs, either alone or in combination with other potentially causative drugs, were efavirenz (rashes), efavirenz and anti-tuberculosis drugs (DILI) and tenofovir (kidney injury). In 383 cases with HCW follow-up, 254 (66.3 %) improved, 9 (2.3 %) had complete resolution, 32 (8.4 %) remained unchanged, 6 (1.6 %) deteriorated, 10 (2.6 %) died and 72 (18.8 %) had unknown outcome. Advice provided was followed in 93.2 % of these cases. Of 223 ADRs with preventability data, 40 (17.9 %) were preventable. Conclusion Queries about rashes, DILIs and kidney injuries were common. Detection and management of these ADRs should be included in HCW training. In cases with follow-up, concordance with advice was high, and HCWs reported improvement in the majority.

Targeted ultra-deep sequencing of a South African Bantu-speaking cohort to comprehensively map and characterize common and novel variants in 65 pharmacologically-related genes

“…Coadministration of antiretrovirals and anti-TB drugs is associated with major complications, including immune reconstitution inflammatory response [61] and DILI. In South Africa, up to 8.3% of admissions and 2.9% of hospital deaths have been attributed to adverse reactions associated with TDF, rifampicin and co-trimoxazole coadministration [52,54,62]. Identification of valid genetic biomarkers that can guide treatment and prevent such outcomes has therefore become highly warranted.…”

Management of Antiretroviral Therapy with Boosted Protease Inhibitors—Darunavir/Ritonavir or Darunavir/Cobicistat

“…This viral resistance leads to aggravation of the patient’s condition, therefore, obtaining patient adherence is a major goal of therapy [ 15 ]. There are several causes that contribute to non-adherence, the main one being the occurrence of significant side effects or secondary mortality [ 2 , 74 , 75 ]. For example, in many HIV-infected patients who were given ARV drugs, liver failure was observed, and major complications were reported [ 76 , 77 , 78 ].…”

Mechanistic insights into antiretroviral drug‐induced liver injury

“…48,49,52 NVP and EFV have been reported to be the most common causes of skin rashes in patients taking first line ART regimens and have an incidence rate of 10%-17%. [53][54][55] NNRTIs induce a mild macular, maculopapular, or erythematous rash and a severe rash characterized with blistering, moist desquamation, and ulceration. 53 69 They also showed that CNS adverse effects were associated with CYP3A4 rs4646437 genotype.…”