Improved Survival with Multiple Antimicrobial Prophylaxis in Severely Immunosuppressed Patients Initiating ART

July 24, 2017

Improved Survival with Multiple Antimicrobial Prophylaxis in Severely Immunosuppressed Patients Initiating ART

  1. Salim S. Abdool Karim, MD, PhD

Chemoprophylaxis for tuberculosis, cryptococcal disease, pneumonia, and sepsis, added to antiretroviral therapy, led to lower mortality among this population in an open-label trial.

  1. Salim S. Abdool Karim, MD, PhD

In HIV positive patients, mortality is highest in those who have low CD4 cell counts. The open-label REALITY (Reduction of Early Mortality in HIV Infected Adults and Children Starting Antiretroviral Therapy) trial, conducted from 2013 to 2015 in 1805 patients ≥5 years old from Uganda, Zimbabwe, Malawi, and Kenya assessed whether enhanced antimicrobial prophylaxis, started when initiating antiretroviral therapy (ART), would reduce mortality. The enhanced antimicrobial prophylaxis regimen included trimethoprim-sulfamethoxazole plus 12 weeks of isoniazid-pyridoxine, 12 weeks of fluconazole, 5 days of azithromycin, and a single dose of albendazole. Standard prophylaxis was trimethoprim-sulfamethoxazole for 12 weeks.

At baseline, the median CD4 cell count was 37 cells/mm3; 74% had HIV viral loads ≥100,000 copies/mL. After 24 weeks, 80 patients in the enhanced-prophylaxis group and 108 patients in the standard-prophylaxis group had died. The death rate was a significant 27% lower in the enhanced-prophylaxis group. The survival benefit was still significant (24%) at 48 weeks.

Despite similar viral suppression and ART adherence rates in the treatment groups, the enhanced-prophylaxis group was less likely than the standard-prophylaxis group to die of cryptococcal infection or unknown causes or to have tuberculosis or oral/esophageal candidiasis. Serious adverse events were marginally, but not statistically, lower in the enhanced-prophylaxis group. The cost of the enhanced-prophylaxis regimen ranged from $8 to $34 across the four trial countries.

Comment

Even though the number of HIV patients presenting with severe immunosuppression has been steadily declining, up to 25% of HIV patients in sub-Saharan Africa still present late for care. Hence, implementation of this enhanced prophylaxis regimen could have a substantial impact on deaths in this group. The costs for the intervention were principally for the prophylactic medications and could readily be offset by the reduced number of hospitalizations in patients with advanced HIV disease.

Editor Disclosures at Time of Publication

  • Disclosures for Salim S. Abdool Karim, MD, PhD at time of publication Consultant / Advisory board UNAIDS; World Health Organization; Bill and Melinda Gates Foundation, Population Council Grant / Research support National Institutes of Health; National Institute of Allergy and Infectious Diseases; Tides Foundation/MAC AIDS Fund; USAID; South African National Research Foundation; European Union; South African Medical Research Council Editorial boards HIV and Infectious Diseases; The Lancet Global Health; AIDS Reviews; New England Journal of Medicine; AIDS Research and Human Retroviruses; The Lancet HIV; mBio; Indian Journal of Medical Research; JAIDS: Journal of Acquired Immune Deficiency Syndromes

Citation(s):

Your Comment

(will not be published)

Filtered HTML

  • Allowed HTML tags: <a> <em> <strong> <cite> <blockquote> <code> <ul> <ol> <li> <dl> <dt> <dd>
  • Web page addresses and e-mail addresses turn into links automatically.
  • Lines and paragraphs break automatically.

Plain text

  • No HTML tags allowed.
  • Web page addresses and e-mail addresses turn into links automatically.
  • Lines and paragraphs break automatically.
Do you have any conflict of interest to disclose?
CAPTCHA
This question is for testing whether you are a human visitor and to prevent automated spam submissions.

Vertical Tabs

* Required

Reader comments are intended to encourage lively discussion of clinical topics with your peers in the medical community. We ask that you keep your remarks to a reasonable length, and we reserve the right to withhold publication of remarks that do not meet this standard.

PRIVACY: We will not use your email address, submitted for a comment, for any other purpose nor sell, rent, or share your e-mail address with any third parties. Please see our Privacy Policy.