Special considerations Careful consideration should be given to the selection of TPT regimen for people living with HIV. Rifamycins induce certain cytochrome P-450 enzymes and may therefore accelerate the elimination of medicines that depend on this metabolic pathway, including several antiretroviral drugs (ARVs) (22). These regimens should not be administered to people receiving protease inhibitors or nevirapine, including for HIV-exposed infants on TPT. Rifampicin can decrease the concentrations of other antiviral agents: atazanavir, darunavir, fosamprenavir, lopinavir, saquinavir and tipranavir. It should not be used with saquinavir/ritonavir. No dose adjustment is required when rifampicin is co-administered with efavirenz. The dose of dolutegravir (DTG) however needs to be increased to 50 mg twice daily when given together with rifampicin, a dose that is usually well tolerated and gives equivalent efficacy in viral suppression and recovery of CD4 cell count compared with efavirenz (22). The 3HP regimen can be administered to individuals receiving efavirenz-based antiretroviral regimens without dose adjustment, according to a study of pharmacokinetics (84). Administration of rifapentine with raltegravir was found to be safe and well tolerated (85). A drug interaction study in healthy volunteers of DTG with once weekly HP reported toxicities in two of four participants (86). However results released more recently from a Phase 1/2 trial of 3HP and DTG in adults with HIV reported good tolerance and viral load suppression, no adverse events of Grade > 3 related to 3HP, and did not indicate that rifapentine reduced DTG levels sufficiently to require dose adjustment (87). Pregnant women living with HIV are at risk for TB, which can have severe consequences for both the mother and the fetus, with increased risk of maternal and infant death (54). Pregnancy should not disqualify women living with HIV from receiving preventive treatment with medicines commonly used to treat TB that are generally considered safe for use in pregnancy, such as isoniazid and rifampicin (classified as Pregnancy Category C by the United States FDA (55, 56). There are limited data on the efficacy and safety of rifapentine during pregnancy. WHO currently recommends six months of isoniazid regimen as TPT for pregnant women living with HIV. A systematic review in 2019 identified one RCT and three non-randomized comparative observational studies that provided data on adverse pregnancy outcomes associated with the use of IPT among pregnant women living with HIV. While the RCT showed a higher risk of adverse pregnancy outcomes among those who initiated IPT during pregnancy (Mantel-Haenszel OR stratified by gestational age, 1.51; 95% CI: 1.09–2.10), all three other studies reported an overall OR < 1 suggesting the opposite (I2=80%, p=0.002). A meta-analysis from two observational studies that cited adjusted estimates and whose data could be pooled suggested lower risk for composite adverse pregnancy outcomes (OR 0.40; 95% CI: 0.20–0.74) (88). Based upon these findings the GDG concluded that there were insufficient grounds to change previous guidance or to develop a separate recommendation for the use of IPT in pregnant women living with HIV. The GDG considered that systematic deferral of IPT to the postpartum period would deprive people from its protective effect at a point when they are more vulnerable to TB. Concurrent use of alcohol should be avoided with TPT.