Incidence, predictors and reasons for initial regimen modifications in patients on antiretroviral therapy in Witbank, South Africa, 2003-2017

Background Antiretroviral therapy (ART) is associated with unpleasant adverse effects that may require modification of regimens. ART modifications may lead to unpleasant treatment outcomes. We determined the incidence, reasons and predictors for modification of initial ART regimens. Methods We retrospectively analysed data from Witbank pharmacovigilance sentinel site, South Africa. Censoring targeted the first incident of ART modification from the initial regimen. We included human immunodeficiency virus (HIV)-infected patients on ART, aged more than 18 years. We used the Cox-proportional hazard model to identify predictors for changing initial ART regimens. Results Among 2, 045 eligible patients, 38% (n=783) had their initial ART regimens changed. The overall incidence rate of ART modification was 10.0 per 100 person-years within a follow-up period of 7 794.6 person-years (PYs). The most common reasons for changing were adverse drug reactions (ADRs) (60%), prescriber’s decisions (37%), drug toxicity (26%) and treatment failure (12%). The most commonly changed regimens were stavudine (68%) and zidovudine (44%) based regimens. Stavudine-based regimen had the highest changing rate of 13.6 per 100 PYs compared to zidovudine (8.0 per 100 PYs) and tenofovir (6.5 per 100 PYs). Using tenofovir as reference, stavudine (aHR 2.3; 95% CI 1.8-2.9; p<0.001) and zidovudine (aHR 1.5; 95% CI 1.0-2.2; p<0.001) based regimens were significantly associated with regimen modifications. The predictors for changing ART regimens included drug toxicity (aHR 2.6; 95% CI 2.1-3.1), ADRs (aHR 2.1; 95% CI 1.3-3.2), treatment failure (aHR 2.0; 95% CI 1.5-2.4), baseline cd4 count of ≥200 (aHR 1.7; 95% CI 1.3-2.1) and initiation regimens (stavudine and zidovudine). Conclusion The findings were suggestive of a moderate incidence of initial ART regimen changing. Patients on stavudine and zidovudine based regimens changed primarily due to ADRs and drug toxicity. We recommended that patients who are still on stavudine-based regimens be changed to avoid long-term toxicities.