Clinical utility of a commercial LAM-ELISA assay for TB diagnosis in HIV-infected patients using urine and sputum samples

Background: The accurate diagnosis of TB in HIV-infected patients, particularly with advanced immunosuppression, is
difficult. Recent studies indicate that a lipoarabinomannan (LAM) assay (Clearview-TBH-ELISA) may have some utility for the
diagnosis of TB in HIV-infected patients; however, the precise subgroup that may benefit from this technology requires
clarification. The utility of LAM in sputum samples has, hitherto, not been evaluated.
Methods: LAM was measured in sputum and urine samples obtained from 500 consecutively recruited ambulant patients,
with suspected TB, from 2 primary care clinics in South Africa. Culture positivity for M. tuberculosis was used as the reference
standard for TB diagnosis.
Results: Of 440 evaluable patients 120/387 (31%) were HIV-infected. Urine-LAM positivity was associated with HIV positivity
(p = 0.007) and test sensitivity, although low, was significantly higher in HIV-infected compared to uninfected patients (21%
versus 6%; p,0.001), and also in HIV-infected participants with a CD4 ,200 versus .200 cells/mm3 (37% versus 0%;
p = 0.003). Urine-LAM remained highly specific in all 3 subgroups (95%–100%). 25% of smear-negative but culture-positive
HIV-infected patients with a CD4 ,200 cells/mm3 were positive for urine-LAM. Sputum-LAM had good sensitivity (86%) but
poor specificity (15%) likely due to test cross-reactivity with several mouth-residing organisms including actinomycetes and
nocardia species.
Conclusions: These preliminary data indicate that in a high burden primary care setting the diagnostic usefulness of urine-
LAM is limited, as a rule-in test, to a specific patient subgroup i.e. smear-negative HIV-infected TB patients with a CD4 count
,200 cells/mm3, who would otherwise have required further investigation. However, even in this group sensitivity was
modest. Future and adequately powered studies in a primary care setting should now specifically target patients with
suspected TB who have advanced HIV infection.