Compared with twice-daily dosing, once-daily dosing offers the benefits of reduced pill burden and better side-effect profile.  

As with ATV, DRV cannot be co-prescribed with RIF-based TB treatment. 

Initiation of third-line therapy 

There should be documented PI or dolutegravir (DTG) resistance before switching to a third-line regimen. Resistance tests should be interpreted by an expert in conjunction with a full antiretroviral treatment (ART) history. In many patients failing second-line regimens, there are no PI (or DTG) mutations. In these patients, improved adherence is required rather than switching to a third-line regimen. If side effects interfere with adherence, then consideration should be given to switching to a more tolerable regimen, provided that this regimen is predicted to be effective based on the treatment history. 

In a patient who has been on a second-line regimen for >2 years, if there are two or three VL measurements >50 copies/mL in a six-month period despite adherence interventions, and adherence is assessed to be satisfactory (eg 100% pharmacy claims over six months), then a resistance test should be performed (resistance test can only be done if VL >500 copies/mL). 

If a patient who has been on second-line therapy for <2 years is found to have a detectable VL, then a resistance test should not be performed; rather, the same regimen should be continued, and adherence counselling and support intensified. The regimen may be switched if there are significant side effects. It is unlikely that significant resistance to the PI or DTG will have developed within two years. Exceptions include: a patient who in error was not prescribed LPV/r double dosing with concurrent RIF use, and subsequently demonstrates a detectable VL; and a patient who has been taking an incorrectly low dose of medication. Such patients should be eligible for resistance testing even if they have been on second-line therapy for <2 years. Specific adherence counselling should be provided for patients preparing to start third-line ART, with a clear discussion that this regimen is likely to be their last option for the foreseeable future. 

A third-line regimen including a combination of DRV/r and other drugs decided upon based on resistance testing, results in virological suppression in most patients, provided that adherence is optimal.  

Third-line regimen recommended for most patients failing protease inhibitor-based second-line therapy: tenofovir disoproxil fumarate (TDF) 300mg daily, lamivudine (3TC) 300mg daily, DTG 50mg daily (given as tenofovir disoproxil fumarate [TLD] plus ritonavir-boosted darunavir (DRV/r) 600mg/100mg twice daily. 

For patients with mutations that confer any degree of resistance to DRV (eg I50V, L76V, I84V), the dose should be DRV/r 600mg/100 mg twice daily. For patients without any DRV mutations, the drug can be taken at a dose of DRV/r 800mg/100mg once daily.  

There is evidence, however, that DRV/r 400mg/100mg once daily may be sufficient in this scenario, especially for patients with suppressed VLs at the time of the switch.  

REFERENCES:  

Source: Nel J, Dlamini S, Meintjes G, et al; for the South African HIV Clinicians Society. Southern African HIV Clinicians Society guidelines for antiretroviral therapy in adults: 2020 update. Southern African Journal of HIV Medicine 2020;21(1), a1115. https://sahivsoc.org/ARTGuidelines.