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The Lower the CD4+ Count, the Higher the CDI Risk, Study Shows


A new retrospective analysis looks at the incidence of infection with common scourge Clostridium difficile in the specific context of HIV infection.

Clostridium difficile is today a common pathogen, and the bacterial infections it causes are routine in hospitals and other health care settings. Beyond diarrhea, C difficile infection (CDI) can also lead to pseudomembranous colitis, toxic megacolon, and even death. Its incidence has steadily increased and as bacteria become progressively resistant to current treatment, morbidity and mortality also have increased.1 The profound immunosuppression experienced by HIV-infected patients has recently been characterized as an independent risk factor for development of CDI.

The largest study of CDI in a HIV-infected population in the modern antiretroviral therapy era was published online in the journal AIDS.2 Study authors conducted a retrospective cohort analysis of HIV-infected patients receiving HIV primary care in the Johns Hopkins Hospital outpatient HIV clinic between 2003 and 2010. A total of 4217 individuals were included, with a median follow-up of 4.1 years and a total follow-up time of 18,525 person-years. Analysis identified 154 incident cases of CDI, for an overall incidence of 8.3 cases per 1000 person-years. Of the incident cases, 152 were matched with 602 case controls (HIV-infected patients without known CDI). CDI patients overall had lower CD4+ cell counts and higher viral loads, and were less likely to be receiving antiretroviral therapy at the time of CDI diagnosis. The risk of CDI inversely correlated with CD4+ cell count in the univariate analysis. In the multivariate model, there was an increase in CDI risk as CD4+ cell count category decreased from 51 to 200/µL to 50/µL or less (adjusted OR = 5.2; 95% CI, 1.3–21.5). This effect was independent of antibiotic use, gastric acid suppression, immunosuppressant use, chronic kidney disease, and health care exposure.

The study is notable not only for its size but also for the absolute incidence of CDI, which was twice that reported in another cohort of HIV-infected patients followed from 1992 to 2002.3

Although these results are not surprising, they do underscore the extreme vulnerability of the HIV-infected population and should serve as a reminder to all clinicians who treat these patients to avoid exposing them whenever possible to additional risks such as hospitalization, antibiotics, immunosuppression, or gastric acid suppression.       


  • Freeman J, Bauer MP, Baines SD, et al. The changing epidemiology of Clostridium difficile infections. Clin Microbiol Rev. 2010;23:529–549. (FULL TEXT)
  •  Haines CF, Moore RD, Bartlett JG, et al. Clostridium difficile in a HIV-infected cohort: incidence, risk factors, and clinical outcomes. AIDS. 2013;27:2799. (ABSTRACT)
  •  Sanchez TH, Brooks JT, Sullivan PS, et al. Bacterial diarrhea in persons with HIV infection, United States, 1992-2002. Clin Infect Dis. 2005;41:1621–1627. (FULL TEXT)
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