Journal Club

In this feature, a panel of IDSA members identifies and critiques important new studies in the current literature that have a significant impact on the practice of infectious diseases medicine.

• Perinatal Hepatitis C Virus Exposure: An Increasing Public Health Concern
• Ibalizumab: A New Medicine, with a New Mechanism, to Treat HIV

Click here for the previous edition of Journal Club. For a review of other recent research in the infectious diseases literature, see “In the Literature,”  by Stanley Deresinski, MD, FIDSA, in each issue of Clinical Infectious Diseases.

Perinatal Hepatitis C Virus Exposure: An Increasing Public Health Concern

Reviewed by Terri Stillwell, MD

Hepatitis C virus (HCV) infections continue to have significant impact on the U.S. population. With rising prevalence in young adults, perinatal HCV exposure is an increasing public health concern. 

In a recent article in The Journal of Pediatrics, the authors assessed HCV care at a specialized program that provides perinatal care to pregnant women with known substance use disorders. In this study, the authors queried electronic health records and registry data to determine the frequency of HCV testing and follow-up care in pregnant women and, subsequently, their infants.

Over a 10-year time period (2006 to 2015), 879 pregnant women with known substance use disorders were included in this study. Of those women, 744 (85 percent) were tested for HCV during pregnancy, of which 510 (68 percent) were found to be HCV antibody positive. Of the seropositive women, 369 (72 percent) had virologic testing during pregnancy, of whom 261 (71 percent) were noted to be viremic. Despite viremia, only 107 (41 percent) had evidence of follow-up HCV medical care. Those women who delivered in the most recent year of the study were more likely to have follow-up when compared to those who delivered in earlier years.

Regarding infant testing, of the 404 infants born, 273 (68 percent) had some form of HCV testing; however, only 180 (45 percent) had complete testing performed. Of the 180 infants with complete testing, only five (2.8 percent) were diagnosed with HCV, all of whom had follow-up HCV care.

This study reveals that even in clinical settings dedicated to high-risk patient populations there is still significant room for improvement in HCV care. If we aim to eliminate HCV mother-to-infant transmission, we need to optimize care of these high-risk populations.

(Epstein et al. J Pediatr. 2018;203:34-40.)

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Ibalizumab: A New Medicine, with a New Mechanism, to Treat HIV

Reviewed by Lauren Richey, MD, MPH, FIDSA

Ibalizumab is a humanized IgG4 monoclonal antibody that binds to the extracellular domain of the CD4 cell, preventing the conformational change in the envelope protein gp120 that is required for HIV to enter the cell. As a result, this medicine is active against both CCR5 and CXCR4-tropic strains and does not have any cross resistance with other HIV drugs. A recent article by Emu et al. in the New England Journal of Medicine reports the results of an open-label phase III study of the drug, which was approved in March 2018 in the U.S. for HIV patients with limited treatment options. 

Forty eligible adult patients were enrolled, with a viral load over 1,000 despite antiretroviral therapy and with resistance to at least one drug in at least three drug classes. Patients had to have an optimized background regimen, selected based on genotypes, phenotypes, and treatment history, and the regimen needed to include one fully active medicine (which could be another investigational agent). The primary end point was the proportion of patients with a 0.5 log drop from baseline to day 14. Thirty-two of the 40 patients received all the scheduled doses, which started with a 2,000 mg infusion, followed by 800 mg intravenously every 14 days. Eighty-three percent of the patients met the primary end point and 43 percent had a viral load less than 50 at week 25.

Adverse events were common (83 percent) but mostly mild to moderate, including diarrhea (20 percent), nausea (13 percent), and rash (13 percent), among others. A serious immune reconstitution event was reported in one patient. Eighteen percent of the patients had virologic failure at week 25. Limitations included the small size, lack of a control group, and the fact that 43 percent of the patients required another investigational drug (fostemsavir) to create the background regimen, which could confound the results.

Overall ibalizumab, a new medicine to treat HIV, does provide a salvage therapy option for patients with multidrug-resistant HIV, despite its complicated dosing (intravenous infusion every 2 weeks).

(Emu et al. N Engl J Med. 2018;379:645-54.)

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