Risk of death very high in kids with untreated HIV and suspected TB

“Improved access to ART with early diagnosis and ART initiation before presentation with presumptive tuberculosis is needed to prevent many cases of tuberculosis and related mortality,” Dr. Olivier Marcy of the University of Bordeaux in France and his colleagues write in their report, online November 23 in The Lancet HIV.

Estimates suggest that 5% of children in countries with a high TB burden have HIV infection, while prevalence is above 25% for children with TB in South Africa and Zimbabwe, the authors note. World Health Organization (WHO) guidelines recommend that HIV-positive children with poor weight gain, fever, current cough or past contact with a TB patient be investigated for TB, they add, but it is rarely possible to confirm a TB diagnosis in these patients.

“Tuberculosis treatment decisions are generally based on clinical characteristics such as fever, asthenia, weight loss, chronic cough and radiological features, which show poor specificity in the context of advanced immunosuppression,” they explain. “In resource-constrained settings, chest CT and other elaborate tests or technologies are often unavailable.”

WHO guidelines, which are based on studies in adults, recommend starting ART two to eight weeks after anti-TB treatment begins, they add.

To better understand mortality in children with HIV and suspected TB, Dr. Marcy and colleagues looked at 266 children from Burkina Faso, Cambodia, Cameroon and Vietnam who were 13 or younger, ART-naive, and followed for up to six months.

The researchers retrospectively classified study participants into three groups: 40 with confirmed TB, 119 with unconfirmed TB, and 107 with unlikely TB. Fifty-eight percent started anti-TB treatment and 80% started ART. Fifty children (19%) died.

By six months, 14 children with confirmed TB had died, for a two-month survival rate of 65%. Two-month survival was 83.5% for both the unconfirmed and the unlikely TB groups. Children with either confirmed or unconfirmed TB who started anti-TB treatment had a lower mortality risk.

ART initiation during the first month of follow-up was independently associated with lower mortality risk (hazard ratio, 0.08). Higher mortality risk was associated with confirmed TB (HR, 6.33), age younger than 2 years (HR, 5.90), CD4 below 10% (HR, 2.63), miliary features (HR, 4.08) and elevated serum transaminases (HR, 4.40).

“Suspected tuberculosis remains a common and challenging situation in HIV-infected children,” the authors write. “Despite the relatively low proportion of bacteriological confirmation, same-day Xpert MTB/RIF testing could lead to immediate treatment initiation in children most at risk of dying. Optimized algorithms for empirical tuberculosis treatment decision in those without smear-positive or Xpert MTV/RIF confirmed tuberculosis are needed to reduce mortality and accelerate initiation with ART.”

For children at high risk of death, Dr. Marcy and his team conclude, “concomitant initiation of ART and anti-tuberculosis treatment under cautious monitoring should be considered.”

One of the main reasons for delaying ART in TB patients is to help prevent TB immune reconstitution syndrome (IRIS), Dr. Hafsah Deepa Tootla and Dr. Mark Patric Nicol of the National Health Laboratory Service in Cape Town, South Africa, note in an editorial accompanying the study.

However, they add, IRIS may occur less frequently in children. “If paradoxical tuberculosis IRIS in children is uncommon, early concomitant ART and tuberculosis therapy might be beneficial to reduce mortality,” they write.

Dr. Marcy was not available for an interview by press time.

SOURCES: http://bit.ly/2zQbaSI and http://bit.ly/2jwt

Lancet HIV 2017.

Source: Medscape