Clinic-Based Urinary Lipoarabinomannan as a Biomarker of Clinical Disease Severity and Mortality Among Antiretroviral Therapy-Naive Human Immunodeficiency Virus-Infected Adults in South Africa
Drain, Paul K.
Coleman, Sharon M
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CitationDrain, Paul K., Elena Losina, Sharon M Coleman, Janet Giddy, Douglas Ross, Jeffrey N Katz, Kenneth A Freedberg, and Ingrid V Bassett. 2017. “Clinic-Based Urinary Lipoarabinomannan as a Biomarker of Clinical Disease Severity and Mortality Among Antiretroviral Therapy-Naive Human Immunodeficiency Virus-Infected Adults in South Africa.” Open Forum Infectious Diseases 4 (3): ofx167. doi:10.1093/ofid/ofx167. http://dx.doi.org/10.1093/ofid/ofx167.
AbstractAbstract Background: Urinary lipoarabinomannan (LAM) has limited sensitivity for diagnosing active human immunodeficiency virus (HIV)-associated tuberculosis (TB) disease, but LAM screening at HIV diagnosis might identify adults with more severe clinical disease or greater risk of mortality. Methods: We enrolled antiretroviral therapy-naive HIV-infected adults from 4 clinics in Durban. Nurses performed urine LAM testing using a rapid assay (Determine TB LAM) graded from low (1+) to high (≥3+) intensity. Urine LAM results were not used to guide anti-TB therapy. We assessed TB-related symptoms and obtained sputum for mycobacterial smear and culture. Participants were observed for 12 months, and we used multivariable Cox proportional hazard models to determine hazard ratios for all-cause mortality. Results: Among 726 HIV-infected adults with median CD4 of 205 cells/mm3 (interquartile range, 79–350 cells/mm3), 93 (13%) were LAM positive and 89 (12%) participants died during the follow-up period. In multivariable analyses, urine LAM-positive participants had a mortality hazard ratio (MHR) of 3.58 (95% confidence interval [CI], 2.20–5.81) for all-cause mortality. Among participants with mycobacterial-confirmed TB, urine LAM-positivity had a 2.91 (95% CI, 1.26–6.73) MHR for all participants and a 4.55 (95% CI, 1.71–12.1) MHR for participants with CD4 ≤100 cell/mm3. Participants with LAM-positive TB had significantly more clinical signs and symptoms of disease, compared with participants with LAM-negative TB disease. Conclusions: Among HIV-infected adults, urinary LAM-positive patients had more clinical disease severity and a 3-fold increase in 12-month mortality compared with those who were LAM negative.
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