HIV and Hepatitis.com Coverage of the
14th Annual Conference on Retroviruses
and Opportunistic Infections (14th CROI)
February 25 - 28, 2007, Los Angeles, CA
Specific AIDS-defining Conditions are Associated with Variable Rates of Death

By Liz Highleyman

“AIDS” was initially developed as a surveillance diagnosis to track the emerging epidemic, and AIDS‑defining illnesses were never intended for clinical staging or prognosis. Nevertheless, in clinical trials, the occurrence of “AIDS‑defining conditions” or “AIDS-defining events” (ADEs) is often used as a single endpoint.

Before the advent of effective antiretroviral therapy, all AIDS-defining conditions ultimately did have similar mortality rates. But mortality associated with ADEs in patients treated with antiretroviral therapy varies widely according to specific diagnoses, according to a study by Amanda Mocroft and colleagues with the Antiretroviral Therapy Cohort Collaboration, presented by Michael Saag at the 14th Conference on Retroviruses and Opportunistic Infections last month in Los Angeles.

The present analysis was based on combined data from 16 European and North American cohort studies, with a total of more than 32,000 participants. Patients were 15 years or older, antiretroviral-naive, and had no prior ADEs when they initiated combination antiretroviral therapy. Most (75%) were men, the median age was 37 years, the median CD4 cell count at the time of HAART initiation was 250 cells/mm3, and the median baseline HIV RNA level was 4.81 log copies/mL.

The investigators used Cox models to estimate mortality hazard ratios for each ADE that occurred in more than 50 patients, compared with mortality in the absence of any ADE. Recurrences or relapses of ADEs were excluded.

Results  

  • A total of 2469 patients were diagnosed with ADEs during a median follow-up of 42 months.

  • 975 patients died during follow-up.

  • The 5 most common ADEs were:
    • tuberculosis (n = 543);
    • Pneumocystis pneumonia (n = 509);
    • Kaposi’s sarcoma (n = 386);
    • esophageal candidiasis (n = 306);
    • wasting syndrome (n = 261).

  • Only herpes simplex virus infection was not associated with an increased mortality rate (HR 0.97).

  • ADEs associated with a 1- to 4-fold increased risk of death included:
    • cytomegalovirus (CMV) infection;
    • esophageal candidiasis;
    • Kaposi’s sarcoma;
    • bacterial pneumonia.

  • ADEs associated with a 5- to 10-fold increased risk of death included:
    • mycobacterial infections (e.g., MAC) (HR 5.07);
    • toxoplasmosis (HR 5.10);
    • cryptococcosis (HR 9.00);
    • progressive multifocal leukoencephalopathy (PML) (HR 9.56).

  • Non-Hodgkin’s lymphoma (NHL) had the highest hazard ratio (19.31), indicating about a 19-fold increased risk of death.

  • Specific ADE diagnosis was a better predictor of mortality than CD4 cell count.

Conclusion

In conclusion, Dr. Saag said, all AIDS-defining conditions are “not created equal,” and there are “clear and substantial differences” in the mortality rates associated with different ADEs.

The researchers noted that ranking ADE severity and associated mortality would be “useful in design of clinical endpoint trials and for patient management.”

A limitation of this analysis is that it was not possible to determine from the available data whether patients actually died due to the ADEs with which they were diagnosed.

Royal Free and University College, London Medical School, UK.

Link to full study abstract

03/20/07

Reference
A Mocroft, M Saag, and others (Antiretroviral Therapy Cohort Collaboration). Clinical Endpoints for Randomized Clinical Trials: All AIDS-defining Conditions Are Not Created Equal. 14th Conference on Retroviruses and Opportunistic Infections. Los Angeles, CA. February 25-28, 2007. Abstract 80 (oral).












































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