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Early Mortality After ART Initiation

In Uganda, 14% of those who started ART died within the first year, mostly from HIV-related causes; only 5% of those deaths were attributable to immune reconstitution inflammatory syndrome.

High rates of early mortality are a consistent feature of antiretroviral therapy (ART) rollout programs in Africa, despite otherwise impressive reductions in morbidity and mortality. Advanced HIV disease at treatment initiation (as reflected by low CD4-cell counts) is likely the cause of many of these deaths, but immune reconstitution inflammatory syndrome (IRIS) could also play a role.

In the present study, investigators evaluated mortality rates and causes of death among 559 patients in urban Uganda (69% women) who started ART between April 2004 and April 2005 (74% received nevirapine + d4T + 3TC; 26% received efavirenz + AZT + 3TC). About 90% of study participants had WHO stage 3 or 4 HIV disease; the median CD4 count was 98 cells/mm³, and the median viral load was 5.4 log copies/mL. Furthermore, 31% had a BMI <18 kg/m², 14% were receiving treatment for tuberculosis, and 5% had hemoglobin levels <8 g/dL.

Ninety-nine individuals (18%) died during 36 months of follow-up, including 80 during the first 12 months; of these, 58 died during the first 3 months. The mortality rate per 100 person-years was 17.9 for the first year, 2.3 for the second year, and 1.2 for the third year. Of the 80 deaths that occurred during the first year, 69 (86%) were HIV related; only 4 (5%) were attributable to IRIS. Mycobacterium tuberculosis and Cryptococcus neoformans were the two most common pathogens implicated in the deaths. In a multivariate analysis, independent risk factors for death were a CD4 count 25 cells/mm³, a BMI <18 kg/m², and a hemoglobin level <8 g/dL. The authors concluded that the high rate of early mortality in their cohort was due to low CD4-cell counts at ART initiation, with IRIS contributing only minimally.

Comment: The low rate of mortality attributable to IRIS in this study is surprising, given the low median CD4-cell count; however, data about the incidence of IRIS were not provided. The high rate of very early mortality (10% during the first 3 months of therapy), which is clearly linked to low initial CD4 counts (25 cells/mm³), makes a strong case for widespread HIV testing, along with clinical and laboratory follow-up of those with positive test results, to allow for earlier detection of infection and initiation of ART.

— Keith Henry, MD

Published in Journal Watch HIV/AIDS Clinical Care September 4, 2009

Citation(s):

Castelnuovo B et al. Cause-specific mortality and the contribution of immune reconstitution inflammatory syndrome in the first 3 years after antiretroviral therapy initiation in an urban African cohort. Clin Infect Dis 2009 Sep 15; 49:965.

• Original article (Subscription may be required)
• Medline abstract (Free)

Davies MA and Meintjes G. Assessing the contribution of immune reconstitution inflammatory syndrome to mortality in developing country antiretroviral therapy programs. Clin Infect Dis 2009 Sep 15; 49:973.

• Original article (Subscription may be required)
• Medline abstract (Free)

Reader Remarks:

Review and add to remarks on this article

• IRIS Vs Low CD4 at initiation
  kasule umar, MJAP, 21 Sep 2009 12:05 PM EST
  does it mean, if these pts werent initiated on ART, they would, according to the study, have died in the... [more]

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