{"doi":"10.1093/cid/ciaa1620","title":"High Baseline Viremia: An Achilles Heel for Integrase Inhibitor–Based Antiretroviral Therapy?","abstract":"(See the Major Article by Pyngottu et al on pages e2134–41.) Integrase strand transfer inhibitors (INSTIs) are considered a key advancement in our efforts to achieve global human immunodeficiency virus (HIV) viral suppression targets. Rates of pretreatment and acquired drug resistance to nonnucleoside reverse transcriptase inhibitors (NNRTIs) have risen dramatically over the past decade [1]. In fact, in 2019, the World Health Organization reported that two-thirds of surveyed countries had >10% prevalence of pretreatment drug resistance to NNRTIs, calling into question their use in first-line antiretroviral therapy (ART) [2]. In contrast, the late-generation INSTIs dolutegravir (DTG) and bictegravir (BIC) have a high genetic barrier to resistance, and as such, are now included as part of preferred first-line ART regimens worldwide [3, 4]. In addition, a fixed-dose combination of tenofovir disoproxil fumarate, lamuvidine, and dolutegravir (TLD) was introduced in 2018 as first-line therapy for both ART-naive and ART-experienced patients. As millions of people with HIV are now receiving INSTI-containing ART, it is critical to understand the factors that may predict virologic failure on these regimens, even if it is a rare event. In this issue of Clinical Infectious Diseases, Pyngottu et al present an insightful retrospective analysis of the Swiss HIV Cohort Study, which provided a comprehensive assessment of the virologic outcomes for 1472 ART-naive adults who initiated ART with INSTI-containing regimens over a 12-year period from 2006 to 2018, prior to the introduction of BIC. This represents the first large observational study to describe the incidence and evaluate predictors of virologic failure on INSTI-based first-line regimens in a routine clinical setting. The majority of patients in the study (65%) were on DTG-containing ART. The authors evaluated predictors of both time to virologic failure and time to viral suppression. They importantly concluded that a pretreatment HIV-1 RNA viral load >100 000 copies/mL was associated with an increased risk of both virologic failure and longer time to viral suppression. In addition, imperfect adherence (missing at least 1 dose within the past month) and AIDS-defining events were associated with virologic failure, whereas a CD4 count >200 cells/μL was found to be protective. Time to viral suppression was similarly influenced by pretreatment CD4, choice of INSTI (DTG being favorable), and financial independence. Notably, pretreatment minor integrase mutations and polymorphisms (present in 16% of the cohort) did not influence virologic outcomes. We offer the following insights to consider when interpreting the study findings. First, data regarding single-tablet vs multiple-tablet regimens were not available to the investigators, which could also influence regimen efficacy due to differences in adherence and barrier to resistance. Currently, single-tablet regimens containing either DTG or BIC are more available globally than during the study period. In addition, the study defines virologic failure as either (1) confirmed viremia >50 copies/mL after at least 6 months on treatment; (2) a single episode of viremia >50 copies/mL after at least 6 months of treatment and followed by a regimen change off INSTIs; or (3) failure to achieve viral suppression within 6 months. Among 121 episodes of virologic failure in the study (<10%), only 23 occurred with HIV-1 RNA viral loads >1000 copies/mL. The majority of virologic failure events in the study would be classified as low-level viremia, which is reassuring. Although not specifically described in this study, viral resuppression rates, emergence of resistance, and long-term outcomes for individuals with low-level viremia while on INSTI-containing regimens could provide further insight into the impact of initial virologic failure. Regarding the study’s third virologic failure criterion, it is important to recognize that 27% of the cohort was classifi","journal":"Clinical Infectious Diseases","year":2020,"id":131342,"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":0.9486,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":104965,"name":"Vincent C. Marconi","orcid":"0000-0001-8409-4689","position":1,"is_corresponding":false},{"id":584834,"name":"Suzanne M. McCluskey","orcid":"0000-0001-8463-5430","position":0,"is_corresponding":true}],"reference_count":4,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:16:00.235845Z","pmid":"33091127","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":[]}