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May '25 Infectious Diseases Update

Posted by Doug Black, PharmD., Ann Lloyd, PharmD. on May 15th 2025

Article of the Month (Editors' Choice)

Cellular HIV DNA Resistance Testing

By Michael S. Saag, MD

  • In a recent Viewpoint article in Clinical Infectious Diseases (Clin Infect Dis 2025;Apr 3:ciaf161 [online ahead of print]; click here for PDF), Wensing and colleagues review the benefits and limitations of using cellular HIV DNA resistance testing in clinical practice.* The ability using PCR to amplify and sequence HIV DNA from integrated cellular DNA has been available commercially for over a decade, and has been more frequently used since the introduction of long-acting injectable antiretroviral (LA-ARV) drugs into clinical practice. The formal indications for use of LA-ARV require suppression of plasma HIV RNA prior to initiation of LA-ARV treatment. Presence of a known NNRTI (or INSTI) resistance-conferring mutation from prior HIV RNA resistance tests would deter use of LA-ARV.
  • In many cases, previous plasma HIV RNA resistance test results are not readily available and, in the setting of undetectable plasma HIV RNA levels, standard plasma resistance testing would not yield results. Therefore, it is attractive to order the HIV DNA test to determine the presence or absence of NNRTI or INSTI resistance-conferring mutations from "archived," integrated, HIV prior to initiation of the injectable LA-ARV regimen. If a resistance-conferring mutation is present, the regimen will not be prescribed; if there is no mutation detected, the clinician has confidence the regimen will work.
  • However, as Lee Corso would say on ESPN College Game Day, "Not so fast, my friend!"
  • In the Viewpoint article in CID, Wensing and colleagues clearly point out the pitfalls and limitations of HIV DNA resistance testing and how the results of the test are often misleading or misinterpreted. The technical aspects of DNA sequencing generate many limitations of the test. First, the testing may not amplify (read: miss) archived HIV-resistant viruses in the cellular DNA, leading to a false-negative result. Conversely, the PCR process may amplify a fragment of HIV, not part of a full-length viral genome, leading to the interpretation that a resistant virus is present. Finally, even if the amplified fragment originated from a full-length viral product, this does not mean that the virus is replication competent. As the authors point out, host DNA editing gene products, such as APOBEC3, can alter the HIV DNA in a fashion that generates drug resistance mutations that were not in the original HIV virion. Simply put, it's complicated.
  • In Table 1 in the Viewpoint, the authors discriminate in what clinical settings cellular DNA testing is useful. The test is most valuable in determining the HIV-1 subtype. It is potentially useful in estimating whether the virus is CCR5 or CXCR4 tropic. However, the use of the test to determine the presence or absence of drug-related mutations is at best "potentially useful" or of uncertain meaning (read: not terribly useful).
  • My take: The routine use of cellular DNA resistance testing is not useful as a routine practice for determination of the presence of drug-resistance mutations in PWH who are suppressed on their current ARV regimen. When such testing is strongly desired, I suggest partnering with a virology lab that can amplify low levels of HIV RNA, can determine if the amplified viral gene product came from a full-length virus, and can better determine whether mutations may have been generated by APOBEC3. However, it is not easy to connect with these labs, and they generally are research labs that are not certified to produce findings that are approved for use in clinical practice.
  • In short: Caveat Emptor.

*The authors are members of the International Antiviral Society-USA (IAS-USA) resistance guideline panel who have published guidance on the use of HIV resistance testing since the mid-1990s. Click on the hyperlink for their most recent iteration of the Guidelines and the Mutations Chart.

New Practice Guidelines

Vaccine Updates

  • FDA/CDC Safety Communication (9 May 2025): Do not use Ixchiq* (Chikungunya Vaccine, Live) in persons >60 years of age pending further investigation of 17 severe adverse events (including encephalopathy and cardiac events) and 2 deaths in the US and in the current Reunion Island outbreak. Click here for full communication.
  • New approvals (February)
    • Penmenvy* (Meningococcal Groups A, B, C, W, and Y Vaccine)
    • Vimkunya* (Chikungunya Vaccine, Recombinant).
  • ACIP voted to approve the following at its April 15-16 meeting. However, these will not be official until signed off on by CDC/HHS (still pending).
    • Penmenvy to have the same indications as Penbraya.
    • Vimkunya for all persons ≥12 years of age traveling to areas with chikungunya outbreaks as listed by CDC, and persons with expected long stays (e.g., six months) in areas where one or more American travelers have acquired confirmed chikungunya in the last five years.
    • RSV vaccine* recommended for persons ≥50 years of age (previously ≥60) with significant comorbidities.

AMS Pearl: Penicillin Allergy Delabeling in a Pediatric Clinic

  • This retrospective pilot study describes a pharmacist-driven group amoxicillin challenge in a pediatric primary care clinic for patients with a penicillin allergy label.
  • Patients without a history of severe cutaneous adverse reactions to penicillin were invited to attend an amoxicillin challenge group visit. A two-step graded amoxicillin challenge was performed by a pharmacist trained in the procedure. A total of 61 challenges were completed with 95% of patients tolerating with no reaction. These 58 patients were delabeled and subsequently had no penicillin allergy documented after a mean follow up of nearly 20 months. Three patients had positive reactions which were mild, isolated to cutaneous symptoms, and resolved with oral antihistamines.
  • Antimicrobial stewardship programs could use this study to aid in the development of a penicillin allergy delabeling program in the outpatient setting .  Open Forum Infect Dis. 2025;ofaf236, https://doi.org/10.1093/ofid/ofaf236.

Antimicrobial Shortages (US)

  • Recent shortages:
  • Recently resolved shortages:
    • Ampicillin injection (24 Feb 2025)
    • Ofloxacin 0.3% ophthalmic solution (3 Feb 2025)
  • Antimicrobial drugs or vaccines in continued reduced supply or unavailable due to increased demand, manufacturing delays, product discontinuation by a specific manufacturer, or unspecified reasons: 
    • Antibacterial drugs:
      • Aminoglycosides:
        • Gentamicin injection (22 Feb 2021)
      • Azithromycin oral suspension, 1 gm packets (20 Nov 2024)
      • Bacitracin ophthalmic ointment 500 units/gm (12 Sep 2024)
      • Cephalosporins:
        • Cefazolin injection (4 Jun 2018)
        • Cefdinir 300 mg capsules (29 Jun 2023)
        • Cefdinir 125 mg/5 mL, 250 mg/5 mL oral suspension (29 Jun 2023)
        • Cefotaxime injection (10 Jun 2015)
          • FDA is allowing temporary importation of product from SteriMax in Canada, in conjunction with Provepharm Life Solutions and its distributor Direct Success. Click here for details.
      • Chloramphenicol injection (9 Oct 2023)
      • Clindamycin phosphate injection (25 Jun 2015)
      • Fluoroquinolones:
        • Ciprofloxacin injection (13 Jan 2023)
        • Levofloxacin injection in D5W (29 May 2024)
        • Levofloxacin oral solution, 25 mg/mL (15 Sep 2023)
        • Moxifloxacin 400 mg tablets (6 Dec 2023)
      • Glycopeptides, glycolipopeptides, lipopeptides:
        • Vancomycin injection (1 Jun 2015)
      • Metronidazole injection (20 Oct 2021)
      • Neomycin and Polymyxin B Sulfates GU Irrigant (25 Jun 2023)
      • Nitrofurantoin oral suspension (5 Jun 2018)
      • Oxazolidinones:
        • Linezolid injection (16 Oct 2024)
      • Penicillins:
        • Amoxicillin, all oral formulations (18 Oct 2022)
        • Amoxicillin-clavulanate, all oral formulations (17 Nov 2022)
        • Dicloxacillin 250 mg, 500 mg capsules (18 Aug 2021)
        • Nafcillin injection (20 Mar 2024)
        • Penicillin G benzathine injection (1 Feb 2023) Availability update here
          • Temporary importation of Extencilline from France: click here
          • Temporary importation of Lentocilin from Portugal: click here
        • Penicillin G benzathine/Penicillin G procaine (31 Mar 2023) Availability update here
        • Penicillin VK oral solution 250 mg/5 mL (17 May 2023)
        • Penicillin VK 250 mg, 500 mg tablets (17 May 2023)
      • Rifaximin 200 mg tablets (11 Apr 2024)
    • Antifungal drugs: 
      • Amphotericin B Lipid Complex (5 Aug 2022)
      • Fluconazole injection (9 Aug 2024)
      • Ibrexafungerp 150 mg tablets (3 Dec 2024)
      • Nystatin oral suspension (21 June 2024)
    • Antimycobacterial drugs: 
      • Isoniazid 100 mg, 300 mg tablets (1 Sep 2022)
      • Rifapentine 150 mg tablets (25 Feb 2025)
    • Antiparasitic drugs:
      • Mefloquine 250 mg tablets (14 May 2024)
      • Nitazoxanide oral susp 100 mg/5 mL (15 Feb 2024)
    • Antiviral drugs: 
      • Cidofovir injection (01 Nov 2024)
      • Oseltamivir 30 mg, 45 mg, 75 mg capsules (1 Nov 2022)
      • Oseltamivir powder for oral suspension (1 Nov 2022)
      • Peginterferon alfa-2a (Pegasys) (8 Jan 2025)
      • Ribavirin for inhalation solution (23 May 2023)
  • Antimicrobial drugs recently discontinued: 
    • Bezlotoxumab injection (31 Jan 2025, by Merck)
    • Posaconazole oral susp 40 mg/mL (Dec 2023, by Merck)
    • Sulfacetamide 10%/Prednisolone acetate 0.2% oph ointment (Aug 2023 by Allergan, sole supplier)
    • Penicillin G procaine 600,000 units/mL IM injection (Jun 2023)
    • Ritonavir oral solution 80 mg/mL (Jan 2023)
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