There are no significant interactions between the nucleoside analogue class and the rifamycin class and these can be used together without dose adjustment. Tenofovir alafenamide serum concentrations are reduced with rifampin but intracellular concentrations of the active form of the drug appear adequate.40
All the other antiretroviral drug classes, including protease inhibitors (PI), non-nucleoside reverse transcriptase inhibitors (NNRTI), integrase inhibitors (INI) and CCR5 receptor blockers, demonstrate major interactions with the rifamycins and caution is required.
Dolutegravir and raltegravir may be used with rifampin, provided doses are increased to account for the enhanced metabolism (see Table 1).41–44 It should be noted, however, that twice-daily dosing of some components of an ART regimen adds significant complexity and pill-burden and that this can challenge consistent adherence to ART. In a recent randomized controlled trial involving people with HIV and TB receiving rifampin-based treatment, twice-daily raltegravir was less effective at controlling HIV than an efavirenz-based, once-daily regimen.41 The difference was largely attributed to reduced adherence to the more complicated ART regimen in the raltegravir arm.41 Although a single, small phase-one study suggests that dolutegravir can be given once daily with rifabutin, there is less published clinical experience with this regimen.45 Other members of the integrase-inhibitor class — bictegravir and elvitegravir — cannot be used with the rifamycins.23
Extensive experience and a controlled trial has shown that the NNRTI efavirenz at standard dosing of 600 mg/day remains effective when used with rifampin, despite variable reduction in efavirenz serum concentrations.46 An increase in dose of efavirenz to 800 mg has been used in patients with larger body mass or suboptimal viral suppression. Rilpivirine and doravirine are not compatible with rifampin but with dosage adjustment can be co-administered with rifabutin.23
No PI dosing regimen has been found to be safe and effective in combination with rifampin. Rifabutin can be substituted for rifampin in TB treatment to permit the use of PIs but is associated with higher rates of hematologic and ocular toxicity.20,47 This is because rifabutin concentrations are increased by concomitant therapy with PIs. There is greater experience with ritonavir than cobicistat “boosting” of PIs.
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