The implementation of DRV/r as a preferred PI option for adults and adolescents has been demonstrated in several national HIV treatment programmes in LMICs, particularly with the development of generic formulations. However, its use can be limited or contraindicated in certain clinical situations or specific populations, and alternative PI options should be available. As observed with other PIs, the use of DRV/r in people with HIV-associated TB coinfection has limitations due to pharmacological drug interactions with rifampicin, which significantly reduce DRV/r levels. Increased doses of DRV/r (1600/200 mg once daily or 800/100 mg twice daily) could potentially overcome this drug level reduction but significantly elevate the risk of hepatotoxicity (108). The concomitant use of rifampicin and LPV/r with dose adjustment (800/200 mg twice daily or 400/400 mg twice daily) is also associated with a high incidence of hepatic adverse effects (109). More recently, a pharmacokinetic study with a small number of people living with HIV showed that a double dose of ATV/r (300/100 mg twice daily) was able to overcome the interaction with rifampicin given at a dose of 600 mg once daily without subsequent significant elevation of liver enzymes or rebound viraemia (110). Rifabutin can replace rifampicin when used with ATV/r or DRV/r, but it is more expensive, requires dose adjustments and toxicity monitoring, and has limited availability (111). DRV/r-based ART is widely considered safe and effective for use during pregnancy. However, pharmacokinetic studies have reported reduced drug exposure during the later stages of pregnancy, prompting ongoing discussion about the optimal dosing strategy – specifically, once-daily versus twice-daily administration (112). An analysis of observational data carried out by the WHO Pregnancy Therapeutics Working Group found that once-daily DRV/r 800/100 mg is effective in achieving viral suppression during pregnancy (113). Given the potential for reduced drug concentration with once-daily dosing during late pregnancy, routine viral load monitoring remains essential. DRV/r cannot be used in children under three years old or weighing less than 10 kg due to insufficient pharmacokinetic data and potential toxicity (114). For children older than three years, dose adjustments based on the child’s weight and age are necessary, and the availability of appropriate co-formulations of DRV/r for children remains a challenge. Liquid formulations may be available but are often unpalatable for children and require separate ritonavir for boosting. Tablet formulations are not feasible for younger children who cannot swallow pills, and current originator formulations require separate ritonavir for boosting effect. A heat-stable DRV/r 120/20 mg tablet for children is awaiting regulatory approval and has been recently reviewed and endorsed by the WHO Paediatric ARV Working Group (115).