People with HIV represented 19.5% of those enrolled in the ZeNix trial, 51% of those enrolled in the Nix-TB study and 26.7% of those enrolled in the TB-PRACTECAL trial. People with HIV were eligible to enrol in the ZeNix trial if they had a CD4 count of more than 100 cells/uL, and in TB-PRACTECAL regardless of CD4 count. Thus, patients can be enrolled in the BPaLM/BPaL regimen irrespective of the CD4 count; however, care should be taken when CD4 counts are below 100 cells/mm3.
In the ZeNix trial, enrolled participants had to be taking permitted antiretroviral medications.3 Although there was no such criterion in TB-PRACTECAL, it is important to consider drug–drug interactions when administering TB and HIV medications in combination. The antiretroviral drug efavirenz induces metabolism of bedaquiline, so its co-administration with bedaquiline may result in reduced bedaquiline exposure and loss of activity; therefore, co-administration is to be avoided. Efavirenz also reduces pretomanid exposures significantly (26); therefore, an alternative antiretroviral agent (potentially dolutegravir, although there is currently insufficient evidence for this) should be used if pretomanid or the BPaLM/BPaL regimen is considered. Ritonavir may increase bedaquiline exposure, which could potentially increase the risk of bedaquiline-related adverse reactions (27); however, increased risk has not been noted in studies administering both drugs concurrently (27–29), including in the current ZeNix trial. Individuals who are prescribed both bedaquiline and ritonavir should be monitored closely for adverse events, including QTc prolongation. Finally, regimens including zidovudine should be avoided, if possible, because both zidovudine and linezolid may cause peripheral nerve toxicity and are known to have myelosuppression cross-toxicity.
3 These permitted antiretroviral treatments were nevirapine in combination with tenofovir/abacavir or emtricitabine/lamivudine; lopinavir/ ritonavir in combination with tenofovir/abacavir or emtricitabine/lamivudine; and integrase inhibitor in combination with tenofovir/ abacavir or emtricitabine/lamivudine. For patients on efavirenz, therapy could be changed to rilpivirine with tenofovir/abacavir or emtricitabine/lamivudine.