Virologic outcomes for tenofovir disoproxil fumarate antiretroviral therapy based regimens in Swaziland 2013-2015

Abstract

Introduction: The scale up of antiretroviral therapy (ART) in sub-Saharan Africa has seen a great reduction in morbidity and mortality related to human immuno-deficiency virus (HIV). Recent advances in ART has seen the introduction of more efficacious and safer regimens. As a result, the use of tenofovir disoproxil fumarate (TDF) based regimens have increased exponentially in the last ten years. However, few studies in the sub-Saharan Africa setting have sought to evaluate the comparative virologic efficacy and durability of the two first line TDF based regimens used in Eswatini (Swaziland), namely TDF + lamivudine (3TC) + efavirenz (EFV) and TDF + 3TC + nevirapine (NVP), (TDE and TDN respectively). Methods: A retrospective cohort analysis was conducted of routinely collected patient data enrolled onto ART from three health facilities of the Shiselweni region, Eswatini between 2013 and 2015. The primary outcomes were viral non-suppression at 12 months and regimen modification, for any reason, during the follow-up period. Modified Poisson regression models with robust error variance were used to estimate relative risks (RR) and 95% Confidence Intervals (CI) of the association between potential risk factors and viral non-suppression at 12 months. Cox proportional hazard models were applied to estimate the hazard ratios (HR) and 95% CIs of the association between potential risk factors and regimen change during follow-up. Results: Out of 1442 patients, 10.5% failed to achieve viral suppression by 12 months on ART. Patients on NVP based TDF regimens (NVP-TDF-3TC / TDN) had a 2-fold risk for viral non-suppression compared to those on EFV-TDF-3TC / TDE (adjusted RR: 2.03, 95% CI 1.31-3.15). Advanced disease (WHO stage III and IV) and poor adherence (<95%) were significantly associated with viral non-suppression (adjusted RR: 1.89, 95% CI 1.39-2.57 and adjusted RR: 3.87, 95%CI 2.83-5.29 respectively). Over a median follow-up time of 2.2 years, incidence of regimen change was 24.4 per 1 000 person-years (95% CI 19.5 - 30.5). Patients on a TDN had an approximately 6-fold risk of regimen modification compared to those on TDE combination, adjusted HR: 5.67, 95%CI 3.23 - 9.58. Conclusions: Among adult patients on first line ART regimens, those on an NVP-based TDF regimen (TDN) had poorer virologic outcomes at 12 months and had higher risk of regimen modification compared to patients that were on an EFV-based regimen (TDE). Even in the advent of more durable and safer TDF based first line ART regimens, these data suggest EFV should remain the preferred non-nucleoside reverse transcriptase inhibitor.