Treating Anemia in Patients With HIV Reduces TB Risk

Teresa Santos (in collaboration with Ilana Polistchuck, MD)

August 16, 2023

Simple markers of anemia and systemic inflammation may be important tools for identifying patients with human immunodeficiency virus (HIV) infection who are at higher risk for active tuberculosis (TB) and death, according to a study published in June in eClinicalMedicine, which is part of the journal The Lancet Discovery Science.

The article affirms that, based on World Health Organization estimates, 700,000 patients were living with HIV and active TB worldwide in 2021. Since TB is associated with a higher mortality rate in patients with HIV, the possibility of early risk stratification is highly relevant.

The research is a case-cohort study from participants enrolled in the REMEMBER clinical trial and was designed as an international, open-label study. Researchers studied patients with HIV who had not yet begun antiretroviral therapy (ART). All participants had a low CD4+ T lymphocyte count (< 50 cells/μL). After collecting data on anemia and systemic inflammation, the researchers randomly assigned participants to receive either intermittent preventive therapy against TB (isoniazid) or empiric TB therapy with four medications.

The analysis was led by Mariana Araújo Pereira, PhD, a biotechnologist and doctoral student in human pathology at the Federal University of Bahia, Salvador, Brazil, in partnership with the Oswaldo Cruz Foundation, under the guidance of Bruno de Bezerril Andrade, MD, PhD. The study included 269 participants from the initial cohort who were recruited at 18 clinical research sites in the following 10 low‑ to middle-income countries: Malawi, South Africa, Haiti, Kenya, Zambia, India, Brazil, Zimbabwe, Peru, and Uganda.

Anemia Highly Prevalent

An analysis of the blood samples collected at recruitment indicated that 76.2% (n = 205) of participants had some level of anemia, defined as hemoglobin (Hb) levels < 13 g/dL (for men) or < 12 g/dL (for women). Of these participants, 31.2% (n = 84) had moderate or severe anemia (Hb < 10 g/dL for both sexes).

Pereira and Andrade, who are professors in the medical program of the School of Technology and Science in Salvador, Bahia, spoke to Medscape's Portuguese edition. Both are also part of the MONSTER Initiative, a multinational translational medicine project of the Regional Prospective Observational Research for Tuberculosis (RePORT) International, and the Brazilian arm of the association, RePORT‑Brazil.

According to the researchers, the percent of anemia cases found (76.2%) was higher than the prevalence observed worldwide in people living with HIV but was still within the expected level for individuals with low CD4+ T lymphocyte counts. "In people living with HIV who have higher CD4+ T cell counts, the number of individuals with anemia is lower: approximately 20% to 30% lower in those with greater than 200 cells/μL," they explained.

In addition to identifying the presence and severity of anemia, the authors also assessed participants' inflammatory profiles. They found that individuals with moderate or severe anemia had higher plasma interleukin‑6 (IL-6) concentrations.

Tuberculosis Risk Tripled

The team followed the participants for a minimum of 48 weeks. During this period, 68% of patients did not present with TB. Moreover, the researchers noticed that the incidence of TB was 7.8% in nonanemic participants and 19.0% and 22.6% in the mild and moderate or severe anemia groups, respectively.

The same analysis was performed for death. Mortality was 10.9% in the nonanemic group, compared with 16.5% and 29.8% in patients with mild and moderate or severe anemia, respectively.

Moderate or severe anemia and higher levels of IL-6 at the beginning of the study were associated with a higher incidence of TB and death in patients with HIV.

"Some measures that healthcare professionals can adopt to decrease the risks of TB and death in these patients include investigating for anemia before starting ART, closer follow-up, and stricter monitoring of TB symptoms in anemic patients, in addition to a more detailed and systematic investigation of hemoglobin levels during ART," said Pereira and Andrade.

Based on these findings, these criteria are valid for different countries. The reason is that although the authors observed different prevalence rates in the various groups, the logistic regression analysis showed that the impact of moderate or severe anemia on the risk of TB and death occurred regardless of the participant's geographic location. "This shows that the results found in this study can serve as a basis for investigations and decision‑making in countries in different regions, as long as conditions such as access to healthcare, TB burden, and HIV viral load are similar," they said.

This article was translated from Medscape's Portuguese edition.


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