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 Cited

• Broyles 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: 30462188
• Fleming 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: 31306175
• Hillus 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: 40118087
• Jatt 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: 40260855
• White 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 Simplification
• Clinical 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