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

48-yr-old man with HIV for 12 years presented 1 year after his last visit with a history of methamphetamine use, inconsistent engagement in care, and a new diabetes diagnosis. He reported no recent ART and no meth use for about 8 months. On returning to care, his viral load was 250,000 copies/mL, the CD4 count was 230 cells/mm3, creatinine levels were elevated, and genotype testing found a K103N mutation. He was motivated to resume ART. Drs. Scully and Hoffmann evaluate the patient’s new ART options in light of his clinical viremia and comorbidities.

References Cited

• Andreatta K, D'Antoni ML, Chang S, et al. High efficacy of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in Black adults in the United States, including those with pre-existing HIV resistance and suboptimal adherence. J Med Virol. 2024;96(10):e29899. PMID: 39370775.
• Denyer R, Zemskova J, Benator DA. HIV treatment with dolutegravir and doravirine: rationale for selection and clinical outcomes in a highly treatment experienced population. Int J STD AIDS. 2022;33(12):1073-1077. PMID: 36113042
• Figueroa MI, Sued O, Cecchini D, et al. Dual therapy based on co-formulated darunavir/ritonavir plus lamivudine for initial therapy of HIV infection: The ANDES randomized controlled trial. Int J Antimicrob Agents. 2024;64(4):107301. PMID: 39151647
• Kabra M, Barber TJ, Allavena C, et al. Virologic Response to Dolutegravir Plus Lamivudine in People With Suppressed Human Immunodeficiency Virus Type 1 and Historical M184V/I: A Systematic Literature Review and Meta-analysis. Open Forum Infect Dis. 2023;10(11):ofad526. Published 2023 Oct 27. PMID: 38033982
• Paton NI, Musaazi J, Kityo C, et al. Dolutegravir or Darunavir in Combination with Zidovudine or Tenofovir to Treat HIV. N Engl J Med. 2021 Jul 22;385(4):330-341. PMID: 34289276.
• Rolle CP, Berhe M, Singh T, et al. Dolutegravir/lamivudine as a first-line regimen in a test-and-treat setting for newly diagnosed people living with HIV. AIDS. 2021;35(12):1957-1965. PMID: 34115650
• Rossotti R, D'Amico F, Bana NB, et al. Durability of doravirine with dolutegravir dual regimen compared with other dolutegravir-based dual combinations. HIV Med. 2024;25(6):675-683. PMID: 38263787
• Sax PE, Rockstroh JK, Luetkemeyer AF, et al. Switching to Bictegravir, Emtricitabine, and Tenofovir Alafenamide in Virologically Suppressed Adults With Human Immunodeficiency Virus. Clin Infect Dis. 2021;73(2):e485-e493. PMID: 32668455

Related Guidance and Guidelines
NYSDOH AI Clinical Guidelines Program:

• ChemSex: Questions and Answers
• HIV Resistance Assays
• Resource: ART Drug-Drug Interactions
• Stimulant Use Clinical Guidance
• Substance Use Harm Reduction in Medical Care
• Use of Injectable CAB/RPV LA as Replacement ART in Virally Suppressed Adults

Clinical Info HIV.gov:

• Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents With HIV
• Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents With HIV