Should Urine-LAM Tests Be Used in TB Symptomatic HIV-Positive Patients When No CD4 Count Is Available? A Prospective Observational Cohort Study From Malawi

J Acquir Immune Defic Syndr. 2020 Jan 1;83(1):24-30. doi: 10.1097/QAI.0000000000002206.

Abstract

Background: Current eligibility criteria for urine lateral-flow lipoarabinomannan assay (LF-LAM) in ambulatory, HIV-positive patients rely on the CD4 count. We investigated the diagnostic yield of LF-LAM and the 6-month mortality in ambulatory, TB symptomatic, HIV-positive patients regardless of their CD4 count.

Methods: We conducted a prospective, observational study that included all ambulatory, ≥15-year-old, TB symptomatic (cough, weight loss, fever, or night sweats) HIV-positive patients presenting at 4 health facilities in Malawi. Patients received a clinical examination and were requested urine LF-LAM, sputum microscopy, and Xpert MTB/RIF. TB was defined as bacteriologically confirmed if Xpert was positive.

Results: Of 485 patients included, 171 (35.3%) had a CD4 <200 and 32 (7.2%) were seriously ill. Median CD4 count was 341 cells/µL (interquartile range: 129-546). LAM was positive in 24.9% patients with CD4 < 200 (50% LAM grades 2-4) and 12.5% with CD4 ≥ 200 (12.8% LAM grades 2-4). Xpert was positive in 14.1% (44/312). Among Xpert-positive patients, LAM positivity was 56.7% (CD4 < 200) and 42.9% (CD4 ≥ 200), P = 0.393. Of the patients without an Xpert result, 13.4% (23/172) were LAM positive (ie, potentially missed patients). Overall, mortality was 9.2% (44/478). More pronounced LAM-positive patients had higher mortality than LAM-negative (grades 2-4: 36.0%; grade 1: 9.1%; negative: 7.4%; P < 0.001). LAM-positive patients with CD4 <200 cells/µL had higher risk of mortality than LAM negatives (adjusted hazard ratio: 3.2, 95% confidence interval: 1.4 to 7.2, P = 0.006), particularly those with LAM grades 2-4 (adjusted hazard ratio: 4.9, 95% confidence interval: 1.8 to 13.3, P = 0.002).

Conclusions: Urine-LAM testing can be useful for TB diagnosis in HIV-positive TB-symptomatic patients with no CD4 cell count. LAM grade can identify patients at higher risk of death in this situation.

Publication types

  • Observational Study

MeSH terms

  • Adult
  • CD4 Lymphocyte Count
  • Female
  • HIV Seropositivity / complications
  • HIV Seropositivity / urine*
  • Humans
  • Lipopolysaccharides / urine*
  • Malawi
  • Male
  • Prospective Studies
  • Tuberculosis / complications
  • Tuberculosis / urine*

Substances

  • Lipopolysaccharides
  • lipoarabinomannan