Xpert MTB/RIF as a measure of sputum bacillary burden. Variation by HIV status and immunosuppression.
BACKGROUND
Xpert MTB/RIF cycle threshold values are a measure of sputum mycobacterial burden. Data on the impact of HIV infection and immunosuppression on this measure are limited.


OBJECTIVE
Examine the impact of HIV status and level of immunosuppression on the distribution of mean cycle threshold values, and the correlation of cycle threshold values and smear microscopy grade with time to culture positivity.


METHODS
Paired sputum samples from 2,406 individuals with suspected pulmonary tuberculosis in South Africa were tested by Xpert MTB/RIF, concentrated smear microscopy, and liquid culture to quantify bacterial burden using cycle threshold values, smear grading, and time to culture positivity.


RESULTS
Cycle threshold values were lower in HIV-uninfected versus HIV-infected individuals (22.9 vs. 26.6; P < 0.001). Among HIV-infected, CD4 count was an independent predictor of cycle threshold value, with an average increase of 1.50 cycles for CD4 count greater than or equal to 200 (P 0.071) and 3.66 cycles for CD4 count less than 200 (P < 0.001) compared with HIV-uninfected individuals. Correlation between cycle threshold value and time to culture positivity was similar to that between smear status and time to culture positivity (both Spearman ρ 0.58). The strength of correlation between measures decreased as the level of immunosuppression increased. A cycle threshold value cutoff of 28 had good predictive value for smear positivity.


CONCLUSIONS
We observed decreasing bacillary burden with increasing level of immunosuppression as measured by Xpert MTB/RIF cycle threshold values. A cycle threshold value of 28 can be used as a measure of bacterial burden and smear status in a high HIV burden setting.
1 Department of Epidemiology, University of North Carolina Gillings School of Global Public Health, Chapel Hill, North Carolina.
Colleen F
CF
Hanrahan
Grant
G
Theron
Jean
J
Bassett
Keertan
K
Dheda
Lesley
L
Scott
Wendy
W
Stevens
Ian
I
Sanne
Annelies
A
Van Rie
D000328:Adult; D018791:CD4 Lymphocyte Count; D003430:Cross-Sectional Studies; D005260:Female; D015658:HIV Infections / Q000150:complications*; D006801:Humans; D016867:Immunocompromised Host; D008297:Male; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000302:isolation & purification*; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests; D012680:Sensitivity and Specificity; D013019:South Africa; D013183:Sputum / Q000382:microbiology*; D014397:Tuberculosis, Pulmonary / Q000150:complications / Q000175:diagnosis*