Opportunities for cost reduction of current first-line WHO-recommended oral antiretroviral therapy: replacing tenofovir disoproxil fumarate with tenofovir alafenamide

Abstract

Introduction Dolutegravir-based first-line antiretroviral therapy (tenofovir disoproxil fumarate, lamivudine, and dolutegravir; TLD) has delivered substantial clinical and public health benefits. However, sharply decreasing funding for HIV programmes necessitates cost reduction within current treatment guidelines. We evaluated whether replacing tenofovir disoproxil fumarate with tenofovir alafenamide (TAFLD), a drug with equivalent effectiveness and side effect profile, could reduce HIV treatment costs in South Africa. Methods We conducted a budget-impact analysis over 2026-2030 from the provider-perspective. The cost of antiretroviral treatment (ART) provision with either TLD or TAFLD was estimated using ingredients-based costing, including the cost of drugs, laboratory monitoring, staff, consumables, equipment and overheads. Costs are reported in 2025 USD, are undiscounted and not inflated. Population estimates for adults on first-line therapy were derived from Thembisa 4.8. We modelled a phased transition from TLD to TAFLD over two years, and explored sensitivity to TAFLD price variation (+/-15%) and inclusion of creatinine monitoring. Results TAFLD reduced per-patient annual costs by 4-5% compared with TLD (from US$178 to US$169, and US$287 to US$277, for first and follow-up years, respectively). At full replacement, total programme savings were approximately US$54 million per year (-5%). Even with continued creatinine monitoring, TAFLD remained cost-saving, reducing annual costs by around 4%. Savings increased to 8% if TAFLD prices were 15% lower than base-case assumptions. Conclusions Replacing TDF with TAF in first-line antiretroviral therapy could generate meaningful cost savings for South Africa with minimal programme disruption. While long-term metabolic effects require consideration, TAFLD represents a feasible interim cost-reduction strategy while awaiting next-generation HIV therapies.