{"doi":"10.1093/cid/ciad726","title":"Daily Second-generation Integrase Strand Inhibitors and Short-course Tuberculosis Preventive Therapy: What More Do We Need to Know?","abstract":"Tuberculosis (TB) is the leading cause of death among persons with human immunodeficiency virus (HIV) (PWH), and before the coronavirus disease 2019 pandemic, was the leading cause of death from a single infectious pathogen globally [1]. With an estimated 25% of the world's population latently infected with TB, the use of TB preventive therapy (TPT) to reduce the risk of progression from latent infection to active TB disease is crucial for global TB control. Over the past several years, clinical trials have demonstrated that “short-course” TPT regimens, including 3 months of weekly isoniazid and rifapentine (3HP), and 1 month of daily isoniazid and rifapentine (1HP), are efficacious and noninferior to a traditional 9-month course of isoniazid for TPT among PWH [2,3]. Short-course TPT offers advantages, including significantly higher completion rates and lower rates of hepatotoxicity compared with a 9-month course of isoniazid. However, 1 factor that has slowed implementation of short-course TPT, all of which include rifamycins, has been drug–drug interactions with antiretrovirals in PWH, particularly interactions between rifapentine and the second-generation integrase strand inhibitors (INSTIs) dolutegravir (DTG) and bictegravir (BIC), which are recommended as part of first-line antiretroviral therapy (ART) in World Health Organization (DTG) and US (DTG and BIC) guidelines. Rifamycins, including rifapentine, are potent cytochrome P450 3A4 and uridine diphosphate glucuronosyltransferase 1A1 inducers that increase the metabolism of DTG and BIC, thus lowering DTG and BIC levels. To date, studies of DTG administration with rifapentine have been reassuring. In the DOLPHIN study, a single-arm trial of 3HP use among 60 PWH with baseline HIV viral suppression (<40 copies/mL) on once-daily DTG-based ART (with tenofovir disoproxil fumarate and lamivudine), all participants maintained viral suppression, despite a modest increase in DTG clearance while receiving weekly rifapentine at 900 mg/week [4]. Data from an ongoing clinical trial, ACTG A5372, have found that daily rifapentine (at 600 mg/day) during 1HP can be safely coadministered with twice-daily DTG, with DTG trough concentrations remaining higher than daily DTG without rifapentine [5]: additional evidence from a subsequent phase of this trial evaluating daily DTG with 1HP are anticipated. A Thai study randomized 403 PWH currently on or initiating daily DTG (in combination with tenofovir disoproxil fumarate and lamivudine) to 1HP versus 3HP. At week 24, 91.8% on 1HP and 94.7% on 3HP were virally suppressed (<50 copies/mL); week 48 data and drug resistance testing for those with viremia is under way [6]. In contrast, our understanding of the safety of bictegravir (a mixed cytochrome P450 3A4 and uridine diphosphate glucuronosyltransferase 1A1 substrate) and rifapentine coadministration is incomplete. One study of 48 PWH who received 1HP with daily BIC/emtricitabine (FTC)/tenofovir alafenamide (TAF), found that the proportion of participants with BIC trough concentrations above 95% effective concentrations dropped to 56.2% and 37.0% at days 15 and 29 of 1HP, respectively [7]. As such, current US Department of Health and Human Services HIV treatment guidelines do not recommend the use of bictegravir with rifamycins, including rifapentine, and caution against TAF coadministration with rifamycins given the potential for decreased TAF concentrations [8]. In this issue of CID, Lin et al present observational data on virologic outcomes among 479 PWH who tested positive or indeterminate for latent TB infection by interferon gamma release assay in Taiwan and were then provided short-course TPT with 3HP or 1HP, primarily while receiving second-generation INSTIs: 92% of participants were on daily BIC/FTC/TAF or daily DTG-containing regimens [9]. These regimens were administered according to Taiwan Centers for Disease Control guidelines following informed discussion with patients regarding the","journal":"Clinical Infectious Diseases","year":2023,"id":414653,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9549,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":104971,"name":"Anne F. Luetkemeyer","orcid":"0000-0003-0911-1578","position":1,"is_corresponding":false},{"id":255283,"name":"Gabriel Chamie","orcid":"0000-0002-5860-8081","position":0,"is_corresponding":true}],"reference_count":6,"raw_metadata":null,"created_at":"2026-07-19T01:22:05.177070Z","pmid":"38051645","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":[]}