**6. Special Populations**

Current guidelines for special populations in HBV-infected patients include HIV-HBV coinfected patients, children, pregnant women, immunosuppressed patients and patients undergoing chemotherapy and dialysis. In most cases, practice points are well defined: HIV patients should follow a TAF/TAF based regimen; safety and efficacy profiles for interferon, TDF and entecavir in children are similar to adults, allowing for easy treatment when warranted; HBsAg-positive patients undergoing immunosuppressive therapy should undergo prophylaxis according to their reactivation risk; renal failure/dialysis patients should be administered entecavir or TAF as treatment/prophylaxis. Studies regarding new drugs, are, however, still missing. A search on clinicaltrial.gov reveals that active studies regarding bulevirtide either exclude special populations or do not plan sub-analysis for them. Similarly, Pubmed searches for "bulevirtide + HIV", "bulevirtide + pregnancy", "bulevirtide + children" and similar or related keywords yields no results. Lonafarnib has been more extensively studied (though evidence is still scarce) because of its potential activity in cancer patients and its proven efficacy in Hutchinson–Gilford progeria syndrome. Studies on solid tumors and hematological patients include the following pathologies: myelodysplastic syndrome, chronic myelomonocytic and myelogenous leukemia, lymphoma, breast, central nervous system, gastrointestinal, genitourinary, head and neck, lung and liver cancer and soft tissue sarcomas. Most of these studies are still ongoing with no published results; however, some phase II studies that used standard lonafarnib dosage (100 to 200 mg twice daily) reported mainly grade 1 and 2 side effects, with no excess of hematological side effects when compared to standard therapy [60–65]. A case report in three chronic myelomonocytic leukemia patients describes hyperleukocytosis associated with respiratory distress that has not been observed in other patients [27,66–71]. Thus, we can conclude that in terms of side effects, cancer patients and patients undergoing chemotherapy require no special attention. A few studies also examined potential drug–drug interactions, finding no interactions with gemcitabine, imatinib, paclitaxel. Concerning children, a phase I study on pediatric cancer patients determined an optimal body surface area-dependent dose (yielding good serum levels with grade 1 or 2 side effects) similar to adults, and higher doses resulted in the same side effects. It also noted that myelosuppression occurred only with higher doses, as it happened in adults [72]. This might also make this drug ideal for immunosuppressed patients. Studies on Hutchinson–Gilford progeria syndrome were obviously directed at children, and showed pharmacological properties and side effects profiles similar to the ones observed in adults [73,74]. Obviously, children with Hutchinson–Gilford progeria syndrome represent a nearly unique category given the rarity of the disease, and this, plus the minuscule number of participants involved in these studies, do not guarantee reliability of the findings on pharmacodynamics-kinetics and uncommon side effects. Other drugs in the pipeline for HBV treatment are still too new in their development phases to have data about special populations.
