How ART Affects HIV Patients with Cryptococcal Meningitis

*Updated on 10/03/2017 at 1:24 PM EST

Cryptococcal meningitis (CM) is a fungal infection known to significantly impact HIV-positive populations, causing an estimated 15% to 20% of deaths from AIDS.

Because few studies have been done on the correlation between the death rate from CM and the time of administration of antiretroviral therapy (ART) to HIV-infected individuals in Latin America (the majority of this work has been done in sub-Saharan Africa), a team of researchers at the Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran in Mexico City and the Vanderbilt University School of Medicine in Nashville set out to discover what effect, if any, the timing of ART has on CM mortality rates.

The team studied data on 340 HIV-positive adults who received care at various locations in the Caribbean, Central and South America (285), and at the Vanderbilt Comprehensive Care Clinic (55), from 1985 to 2014. Death rates were compared between patients who were already on ART when they were diagnosed with CM and those who were not on ART at diagnosis. In the latter group, the scientists also looked at the risk of death when ART was initiated within 2 weeks of CM diagnosis compared with the risk of death when ART wasn’t started until 2 to 8 weeks post-diagnosis, and they found that beginning ART soon after a CM diagnosis did carry a slightly higher risk of death than delaying ART initiation for at least two weeks—however, the numbers were not statistically significant. Fifty-six patients, or 37%, of the 151 who received ART at any point after being diagnosed with CM died.

"The lack of statistical significance in the adjusted analysis could indicate that the unadjusted associations may have been due to differences between patients diagnosed prior to versus after ART initiation," Anna Person, MD, an assistant professor of medicine at Vanderbilt University Medical Center and an author of the study, told Contagion^®. "Or it may be due to insufficient statistical power due to the limited numbers of events."

However, the University of Minnesota’s Cryptococcal Optimal ART Timing (COAT) Trial found that the death rate for patients initiating ART within a week or two of CM diagnosis was significantly higher (45%) than the death rate for patients who delayed ART until 5 weeks post-diagnosis (30%).

Why would ART, which is a life-saving regimen, have a deleterious effect on patients newly diagnosed with CM? “[It’s] most likely due to increased intracranial pressure from inflammatory responses,” Dr. Person said. “We also know that in some of our regions, the ability to place VP (ventriculoperitoneal) shunts for persistently elevated intracranial pressure in the setting of CM, the ability to obtain amphotericin or flucytosine (drugs normally prescribed to treat CM), and other diagnostic or treatment modalities may be limited."

Because the correct timing of ART is so crucial to the health of patients with CM, the standard of care now is to wait 5 weeks after a CM diagnosis to begin ART, according to Dr. Person. She also noted that her team’s study found a significant number of patients who developed CM long after beginning ART, probably due to noncompliance or virologic failure. “I think this highlights the importance of virologic suppression and ongoing adherence in the role of preventing opportunistic infections months to years after ART start,” she said.

Laurie Saloman, MS, is a health writer with more than 20 years of experience working for both consumer and physician-focused publications. She is a graduate of Brandeis University and the Medill School of Journalism at Northwestern University. She lives in New Jersey with her family.

Feature Picture: A photomicrograph of C. neoformans stained with India ink. Feature Picture Source: Centers for Disease Control and Prevention.