Meeting News CoveragePerspective

Nurse-led empirical TB treatment for HIV patients does not reduce death, hospitalization

BOSTON — An empirical treatment strategy for HIV patients demonstrating risk factors for tuberculosis that involved nurses did not reduce mortality or hospitalizations among South Africans, according to data presented at CROI 2016.

“TB is the most common cause of death among HIV-positive people,” Alison Grant, MBBS, PhD, DTM&H, professor of international health at the London School of Hygiene & Tropical Medicine, said during a press conference. “Empirical TB treatment — treating without laboratory confirmation—is common practice, but usually it takes a doctor’s decision to do that. In this study, we aimed to test whether enabling nurses to give empirical TB treatment could save lives.”

Alison Grant

Grant and colleagues randomly assigned 24 South African primary care clinics to either conduct a risk-based TB management strategy, or act as a control. When engaging HIV patients with CD4 counts of 150 cells/μL or fewer who were not already taking ART or TB treatment, nurses at the intervention clinics were asked to categorize the patient as high probability (hemoglobin < 10 g/dL, BMI ≤ 18.5 or positive lateral flow assay for urinary lipoarabinomannan), medium probability (any TB symptom and no high probability criteria) or low probability (no TB symptoms or high probability criteria). Patients determined to be at high risk by nurses were immediately given TB treatment and received ART after 2 weeks. Those classified as medium risk underwent additional investigation for TB. The primary outcome was mortality at 6 months, with secondary outcomes examining a difference in hospitalization rates by the same cutoff, and time from study enrollment to the start of ART.

“We thought this would work in two ways,” Grant said. “Firstly, by getting people to take TB treatment earlier, but also by avoiding the need for TB tests, [which] we thought would reduce the time to starting ART.”

There were 1,507 patients enrolled in intervention clinics and 1,516 patients enrolled as controls. The patients had a median age of 38 years, and their median CD4 count was 74 cells/μL.

Among patients enrolled in the intervention arm, 46% were categorized as high probability, 32% as medium and 23% as low. By the second month, 96% of high-probability patients had started TB medication, and 61.6% of intervention patients vs. 11.3% of controls were receiving TB treatment.

Analysis of patients with known vital status revealed a mortality rate of 19 per 100 person-years among those receiving the intervention, an insignificant decrease over the 21.6 per 100 person-years reported among controls (adjusted RR = 0.87; 95% CI, 0.61-1.24). No difference was seen between the intervention and control arms for hospitalization at 6 months (13.3% vs. 10.4%; aRR = 1.11; 95% CI, 0.88-1.38), as was the case when examining the proportion who had started ART by 30 days (66.4% vs. 72.8%; aRR = 0.91; 95% CI, 0.79-1.05).

“Just increasing the number of people treated for TB alone is not enough to make a big difference on early mortality,” Grant said. “What we need is more refined care for these very high-risk people with advanced HIV disease.” – by Dave Muoio

Reference:

Grant A, et al. Abstract 155. Presented at: Conference on Retroviruses and Opportunistic Infections; Feb. 22-25, 2016; Boston.

Disclosure: Grant reports no relevant financial disclosures. Alere donated materials for quality control of the assays used in the study.

BOSTON — An empirical treatment strategy for HIV patients demonstrating risk factors for tuberculosis that involved nurses did not reduce mortality or hospitalizations among South Africans, according to data presented at CROI 2016.

“TB is the most common cause of death among HIV-positive people,” Alison Grant, MBBS, PhD, DTM&H, professor of international health at the London School of Hygiene & Tropical Medicine, said during a press conference. “Empirical TB treatment — treating without laboratory confirmation—is common practice, but usually it takes a doctor’s decision to do that. In this study, we aimed to test whether enabling nurses to give empirical TB treatment could save lives.”

Alison Grant

Grant and colleagues randomly assigned 24 South African primary care clinics to either conduct a risk-based TB management strategy, or act as a control. When engaging HIV patients with CD4 counts of 150 cells/μL or fewer who were not already taking ART or TB treatment, nurses at the intervention clinics were asked to categorize the patient as high probability (hemoglobin < 10 g/dL, BMI ≤ 18.5 or positive lateral flow assay for urinary lipoarabinomannan), medium probability (any TB symptom and no high probability criteria) or low probability (no TB symptoms or high probability criteria). Patients determined to be at high risk by nurses were immediately given TB treatment and received ART after 2 weeks. Those classified as medium risk underwent additional investigation for TB. The primary outcome was mortality at 6 months, with secondary outcomes examining a difference in hospitalization rates by the same cutoff, and time from study enrollment to the start of ART.

“We thought this would work in two ways,” Grant said. “Firstly, by getting people to take TB treatment earlier, but also by avoiding the need for TB tests, [which] we thought would reduce the time to starting ART.”

There were 1,507 patients enrolled in intervention clinics and 1,516 patients enrolled as controls. The patients had a median age of 38 years, and their median CD4 count was 74 cells/μL.

Among patients enrolled in the intervention arm, 46% were categorized as high probability, 32% as medium and 23% as low. By the second month, 96% of high-probability patients had started TB medication, and 61.6% of intervention patients vs. 11.3% of controls were receiving TB treatment.

Analysis of patients with known vital status revealed a mortality rate of 19 per 100 person-years among those receiving the intervention, an insignificant decrease over the 21.6 per 100 person-years reported among controls (adjusted RR = 0.87; 95% CI, 0.61-1.24). No difference was seen between the intervention and control arms for hospitalization at 6 months (13.3% vs. 10.4%; aRR = 1.11; 95% CI, 0.88-1.38), as was the case when examining the proportion who had started ART by 30 days (66.4% vs. 72.8%; aRR = 0.91; 95% CI, 0.79-1.05).

“Just increasing the number of people treated for TB alone is not enough to make a big difference on early mortality,” Grant said. “What we need is more refined care for these very high-risk people with advanced HIV disease.” – by Dave Muoio

Reference:

Grant A, et al. Abstract 155. Presented at: Conference on Retroviruses and Opportunistic Infections; Feb. 22-25, 2016; Boston.

Disclosure: Grant reports no relevant financial disclosures. Alere donated materials for quality control of the assays used in the study.

    Perspective
    Richard E. Chaisson

    Richard E. Chaisson

    The surprising result of this study was that there was no difference with empiric TB treatment for those people who had warning signs of TB vs. the standard of care.

    Now, there might be two explanations for why this intervention did not work. The investigators assumed that by starting the TB therapy earlier, the disease would be treated earlier in those who had it. Therefore, they would be less likely to die of TB. They also thought that people in the intervention arm would get their ART faster, and it turns out that in the control arm, where the standard of care was used, many patients ended up getting treated for TB without an evaluation and without a workup because the doctors were concerned about them. These people actually started their ART faster than the people in the intervention arm.

    Overall, the study is concordant with other studies showing that empiric TB treatment in people who have not had a diagnosis of TB is not superior or better than the standard of care. This is an important lesson.

    • Richard E. Chaisson, MD
    • Director of the Johns Hopkins Center for TB Research

    Disclosures: Chaisson reports no relevant financial disclosures.

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