Dolutegravir hypersensitivity reaction: the need for strengthening pharmacovigilance systems with optimization of antiretroviral therapy in HIV programs in resource-limited settings: case report

Abstract

The incidence of antiretroviral therapy-related adverse drug reaction among people living with HIV in Liberia is unknown. For PLWH, unexplained new symptoms or deaths are often attributed to advanced HIV disease itself or opportunistic infections like tuberculosis. Surveillance systems for monitoring newly introduced combination antiretroviral drug treatments within HIV programs are either suboptimal or non-existent. Furthermore, when adverse drug reactions occur or are suspected by clinicians, the laboratory capacity for monitoring, diagnosis and medical treatment may be lacking. A 44-year woman diagnosed with HIV infection 5 years previously and on a regimen of lamivudine/zidovudine (3TC/AZT) and nevirapine (NVP) with viral suppression developed fever, rash and facial swelling 2 days after being transitioned to dolutegravir (DTG) based combination antiretroviral therapy and a backbone of lamivudine/tenofovir (3TC/TDF) as part of the Liberia National strategy for antiretroviral therapy treatment optimization. She was found to be acutely ill looking with fever, hives and angioedema but no features of anaphylaxis. Investigation was limited because of absence of routine laboratory monitoring, but her blood work showed eosinophilia. Following evaluation, a diagnosis of dolutegravir induced hypersensitivity reaction with angioedema was made. She was managed as outpatients on antihistamines and steroids. Dolutegravir (DTG) was also discontinued and substituted with ritonavir-boosted lopinavir (LPV/r) while retaining the 3TC/TDF backbone and relevant health education was provided. Symptoms resolved completely, and she was doing well at follow up 4 weeks later. We present a first case of hypersensitivity reaction leading to drug discontinuity following roll-out of dolutegravir as a first line cART in Liberia to call to attention the challenges of detecting and managing ART adverse drug reactions in a resource-limited setting and review the relevant literature to highlight the need for strengthening pharmacovigilance and laboratory monitoring systems in HIV programs in developing countries through planning, health systems strengthening and collaboration.