{"doi":"10.1093/cid/ciae248","title":"People With Hepatitis B Virus/HIV Coinfection Should Be Prioritized in Hepatitis B Virus Cure Research","abstract":"To the Editor—As articulated in the letter from Sun et al, tenofovir-based antiretroviral therapy (ART) is highly effective for hepatitis B virus/human immunodeficiency virus (HBV/HIV) coinfection [1]. In addition to suppressing both HBV DNA and HIV RNA, in the context of coinfection ART may restore HBV-specific immunity, evidenced by 15.4% hepatitis B surface antigen seroclearance (marker of HBV “functional cure”) at 5 years of follow-up in Zambia [2]. While these data are encouraging, improving the health of the 3 million individuals with HBV/HIV worldwide will require better treatment options that achieve HBV cure at much higher rates. The HBV cure research agenda has accelerated in recent years, with more than 20 antiviral and/or immunomodulating agents in development [3, 4]. However, people with HBV/HIV are excluded from trials of most new cure drugs for safety and efficacy concerns. Among 70 current HBV cure trials listed at www.clinicaltrials.gov [5], at least 61 (87.1%) exclude HIV. Instead, HBV/HIV should be prioritized within the HBV cure research agenda to answer the many open questions, including those raised by Sun et al [1]. Ours and most other published data were based on blood sampling and imaging, which can miss ongoing HBV replication and HBV-related disease that is only detectable inside the liver [6]. Therefore, whether current ART indeed lowers the risk of liver disease with HBV/HIV down to levels seen in HBV alone, as purported by Sun et al, remains to be determined. Head-to-head comparisons to people with HBV alone will be needed and will require liver sampling as blood markers of the HBV viral life cycle, such as HBV RNA, are suboptimal for characterizing the status of the intrahepatic HBV profile. With regard to the host response, it is recognized that peripheral blood sampling also fails to capture important immune cells that are compartmentalized to the liver and that may be essential for HBV control [7]. Furthermore, the possibility that cure therapies will be less efficacious in people with HBV/HIV must be evaluated. Untreated HBV/HIV is associated with increased markers of HBV replication compared with HBV alone, suggesting less effective HBV-specific immunity and/or larger HBV reservoirs. However, this difference is primarily seen at low CD4 counts (ie, severe immunosuppression) [8]. HIV status in the context of HBV cure studies should not be viewed as a dichotomous variable but rather as a spectrum across a range of immune competence. A final reason for prioritization of people with HBV/HIV in HBV cure research is that HIV infection and treatment are associated with dynamic changes in immune function over a period of months or a few years. This contrasts with HBV alone where changes in viral–host interactions, which underpin HBV clinical phenotypes, typically occur over decades, making them very challenging to study [9]. In summary, current ART, especially when started early and adhered to long-term, can mitigate some of the negative effects of HIV on HBV natural history. However, many important questions about HBV disease in the setting of HIV await final answers, which may elucidate important mechanisms that are also relevant for HBV alone. The rationale to include people with HBV/HIV in HBV cure research remains strong. Financial support. The authors are funded by the National Institute of Allergy and Infectious Diseases (R01AI147727 and R37AI179640).","journal":"Clinical Infectious Diseases","year":2024,"id":451436,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9541,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":331565,"name":"Georg M. Lauer","orcid":"0000-0002-9792-4271","position":1,"is_corresponding":false},{"id":393581,"name":"Michael J. Vinikoor","orcid":"0000-0002-3862-7795","position":0,"is_corresponding":true}],"reference_count":8,"raw_metadata":null,"created_at":"2026-07-19T02:02:41.417944Z","pmid":"38711349","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}