(Table 3.2 Preferred and alternative initial regimens in adults, adolescents, children and neonates and Table 3.3 Preferred and alternative subsequent ART regimens for adults, adolescents, children and infants in the full guideline) Recycling tenofovir or abacavir in subsequent antiretroviral regimens may affect the demand for these NRTIs. Procurement and supply chain processes should be adjusted accordingly by anticipating an increased need for tenofovir and abacavir while decreasing the need for AZT formulations. Effective monitoring and management of adherence issues are required to sustain the population health benefits of this strategy. TAF-containing regimens have been used as alternative options for specific situations where TDF should not be used and represent up to 10–20% of procurement demand for tenofovir-containing formulations in a majority of HIV treatment programmes in LMICs that have incorporated them in their drug portfolio (62). Some countries have recently adopted TAF as the preferred tenofovir prodrug option and procurement demand is expected to increase (63). A large and unplanned switch from TDF to TAF regimens as a preferred option may introduce important programmatic challenges in some settings such as increasing drug costs and supply chain demands (e.g. different strength formulations for boosted and unboosted regimens), without significant clinical benefits outside the specific situations where their use is currently recommended. Weighing the benefits and risks of these two options and setting the right procurement plan for both TDF and TAF should be based on a clear clinical and public health rationale. In individuals with pre-existing mild-to-moderate chronic renal disease, use of TAF may be a preferred option to reduce the impact of tenofovir on renal function. Patients with a clinical history of osteoporosis, chronic use of corticosteroids or medications that may worsen bone density, or a history of fragility fractures may benefit from the use of TAF over TDF. Rifamycins (including rifampicin, rifabutin and rifapentine) and certain anticonvulsants (such as carbamazepine, phenytoin and phenobarbital) are strong inducers of cytochrome P450 3A4 enzyme and P-glycoproteins, which can significantly lower plasma levels of TAF. However, pharmacokinetic studies have demonstrated that intracellular levels of tenofovir diphosphate are four to five times higher than those achieved with the standard dose of TDF when concomitantly used with rifampicin (64,65). This suggests that the use of TAF 25 mg once daily with rifampicin may be acceptable. There is no significant drug interaction between TDF and rifampicin (66). In older populations, where renal, bone and cardiovascular comorbidities are common, a balanced risk assessment is recommended for a more appropriate choice between both drug options. Ritonavir and other pharmacological boosting agents (e.g. cobicistat) may increase plasma levels of tenofovir, which can lead to a higher risk of renal and bone adverse events (67). TAF should therefore be reduced to a 10 mg dose (68). However, a dose-adjusted version of TDF is not available in current formulations: compared to dose-adjusted TAF this has led to an increased risk of treatment discontinuation due to renal events when TDF has been used together with boosting agents (69). The risk of bone and renal adverse events is not significantly different between TDF and TAF when used without booster drugs