(P-383) Adverse Reactions to Dolutegravir Reported to the National HIV & Tuberculosis Health Care Worker Hotline in South Africa

Background: The National HIV & Tuberculosis Health Care Worker (HCW) Hotline in South Africa provides advice on the management of suspected adverse drug reactions (ADRs). In December 2019, South African public sector antiretroviral therapy (ART) guidelines changed to include dolutegravir in preferred first- and second-line regimens.

Objectives: We describe adverse reactions to dolutegravir reported to the hotline during the first year of dolutegravir rollout (Jan-Dec 2020).

Methods: All queries made to the hotline were prospectively entered into an Access database. We reviewed all ADR queries involving patients taking dolutegravir-containing ART. We used World Health Organization Uppsala Monitoring Centre criteria for causality assessment, and included ADRs categorised as certain, probable, or possible.

Results: There were 695 queries regarding suspected ADRs due to ART and/or antituberculosis medicines during 2020, of which 105 involved dolutegravir-containing ART. We identified 47 adverse reactions to dolutegravir (27 possible, 20 probable) involving 41 patients. In 34/41, dolutegravir was stopped due to an ADR. There were 14 dermatological ADRs (12 rashes of which 3 had associated angioedema and 1 had mucosal involvement, 2 cases of angioedema without rash); 13 neuropsychiatric ADRs (including 7 insomnia, 2 psychosis, 1 depression); 8 cases of liver injury; 5 cases of gastrointestinal symptoms; 3 cases of weight gain; 2 cases of musculoskeletal pain; 1 case of rhabdomyolysis; and 1 case of erectile dysfunction.

In addition, there were 9 reports of a marked increase in serum creatinine concentration on initiation of dolutegravir with tenofovir (range: 32-112%): 5 in adults on tenofovir throughout and switched from efavirenz to dolutegravir, and 4 in adolescents starting dolutegravir in combination with tenofovir. Dolutegravir was stopped in 5/9.

Conclusions: In the first year of dolutegravir rollout in South Africa, 15% of ADR queries to the hotline concerned patients taking dolutegravir. Review of these queries identified ADRs posing diagnostic and management challenges to HCWs. Diagnosis and management of commonly reported dolutegravir ADRs, including insomnia, rash, and liver injury should be included in HCW training. Guidance for HCWs regarding management of changes in creatinine concentration with concomitant use of tenofovir and dolutegravir is needed.