Mid-50s-yr-old man with HIV since the early 1990s presented for evaluation of persistent low-level viremia, despite consistent engagement in care and ART. Genotypic testing found only a variety of minor mutations. The patient and his care provider were concerned about the health consequences, including the risk of inflammatory diseases in the future, and about implications for U=U. After a brief discussion of the good news on lenacapavir for HIV prevention and a reminder about mpox vaccination, Drs. Scully and Hoffmann delve into the patient’s history to uncover the source of his LLV and treatment options. References CitedBroyles LN, Luo R, Boeras D, Vojnov L. The risk of sexual transmission of HIV in individuals with low-level HIV viraemia: a systematic review. Lancet. 2023;402(10400):464-471. PMID: 37490935.Esber A, Polyak C, Kiweewa F, et al. Persistent Low-level Viremia Predicts Subsequent Virologic Failure: Is It Time to Change the Third 90? Clin Infect Dis. 2019;69(5):805-812. PMID: 30462188Fleming J, Mathews WC, Rutstein RM, et al. Low-level viremia and virologic failure in persons with HIV infection treated with antiretroviral therapy. AIDS. 2019 Nov 1;33(13):2005-2012. PMID: 31306175Hillus D, Le NH, Tober-Lau P, et al. Safety and effectiveness of MVA-BN vaccination against mpox in at-risk individuals in Germany (SEMVAc and TEMVAc): a combined prospective and retrospective cohort study. Lancet Infect Dis. Published online March 18, 2025. PMID: 40118087Jatt LP, Mgodi NM, Buchbinder SP, Gray GE, Kublin JG. An HIV Vaccine in the Era of Twice-Yearly Lenacapavir for PrEP - Essential or Irrelevant? N Engl J Med. 2025;392(16):1561-1563. PMID: 40260855White JA, Wu F, Yasin S, et al. Clonally expanded HIV-1 proviruses with 5'-leader defects can give rise to nonsuppressible residual viremia. J Clin Invest. 2023;133(6):e165245. Published 2023 Mar 15. PMID: 36602866.Related Guidelines NYSDOH AI Clinical Guidelines Program: Second-Line ART After Treatment Failure or for Regimen SimplificationClinical Info HIV.gov: Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents With HIV. Management of People With HIV and Antiretroviral Therapy Experience: Virologic Failure

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