Darunavir 400 mg tablets were recently approved by the South African Health Products Regulatory Authority (SAHPRA) for the following indication:
PREZISTA, in combination with low dose ritonavir (DRV/r) and with other antiretroviral medicines, is indicated for the treatment of human immunodeficiency virus (HIV) infection in antiretroviral treatment experienced adult patients who are protease-inhibitor-naïve or after exclusion of darunavir resistance associated mutations (DRV-RAMs: V11I, V32I, L33F, I47V, I50V, I54M, I54L, T74P, L76V, I84V and L89V). Genotypic or phenotypic testing should guide the use of DRV/r. (Prezista package insert)
There is no information on the use of darunavir in combination with ritonavir in the paediatric population for the once-daily dose.
Southern African HIV Clinicians Society adult antiretroviral therapy (ART) guidelines currently recommend ritonavir-boosted atazanavir (ATV/r) 300/100 mg as preferred boosted protease inhibitor (PI/r) for second-line ART. It was noted in the guidelines that once a suitable tablet for DRV/r 800/100 mg dosing became available, DRV/r 800/100 mg would be a feasible option in second-line ART, with fewer side effects than the DRV/r 600/100 mg twice-daily dosing.
In patients failing first-line non-nucleoside reverse transcriptase inhibitor (NNRTI)- or integrase strand transfer inhibitor (InSTI)-based regimens, switch to DRV/r 800/100 mg daily with two nucleoside reverse transcriptase inhibitors (NRTIs). Sequence the NRTIs as per guidelines (see
Patients failing non-nucleoside reverse transcriptase inhibitor- or integrase inhibitor-based first-line antiretroviral therapy.
For those patients who are already on a second-line PI/r-based regimen, check the viral load (VL). If the VL is undetectable, then PI/r can be switched to DRV/r 800/100 mg daily, retaining the same NRTI backbone (see
Patients on protease inhibitor-based second-line antiretroviral therapy.
If the VL is detectable, intensify adherence interventions and repeat the VL in 2–3 months. If the VL is undetectable, the PI/r can then be switched to DRV/r 800/100 mg daily. If VL > 1000 copies/mL, resistance genotype is needed to determine if the patient is eligible for third-line ART (see
Currently, patients on DRV/r on third-line ART receive DRV/r 600/100 mg bid. However, a small proportion of third-line patients have no DRV resistance-associated mutations (RAMs), and in such patients it may be possible to use DRV/r 800/100 mg daily instead of DRV/r 600/100 mg bid to reduce pill burden, dosing frequency and side effects.
For patients initiating third-line ART, if the composite DRV score (Stanford) is zero on
Patients initiating third-line antiretroviral therapy.
For those patients who are already on a third-line regimen, their VL must be checked. If the VL is undetectable, and the composite DRV score (Stanford) on
Third-line patients on darunavir/ritonavir-based third-line antiretroviral therapy (600/100 mg bid).