Characteristics and early outcomes of patients with Xpert MTB/RIF-negative pulmonary tuberculosis diagnosed during screening before antiretroviral therapy.
BACKGROUND
A proportion of patients with tuberculosis diagnosed by sputum culture during screening before antiretroviral therapy (ART) have false-negative Xpert MTB/RIF assay results (Xpert-negative tuberculosis). We determined the characteristics and early ART program outcomes of such patients.


METHODS
Adult patients who enrolled in a South African township ART service were systematically screened for pulmonary tuberculosis regardless of symptoms by testing paired sputum samples with Xpert MTB/RIF and liquid culture. The ART service provided follow-up for all patients, and early (90-day) programmatic outcomes were determined.


RESULTS
Among 602 patients screened, 523 had ≥1 Xpert and culture result, yielding 89 culture-positive tuberculosis diagnoses. Of these, 37 (42%) of the patients with tuberculosis were Xpert-negative when a single sputum sample was tested, compared with 25 (28%) when 2 samples were tested. Compared with patients with Xpert-positive tuberculosis, those with Xpert-negative tuberculosis (using either definition) had substantially higher CD4 cell counts, lower plasma viral loads, higher hemoglobin concentrations, and higher body mass index. Their tuberculosis was also less advanced, with a lower frequency of prolonged cough (≥2 weeks), less extensive radiographic abnormalities, and a lower frequency of detectable lipoarabinomannan antigenuria and mycobacteriuria. Xpert-negative cases were all sputum smear negative with prolonged time to culture positivity (median, 21 days). Despite greater delays in starting tuberculosis treatment, Xpert-negative patients were less likely to die during follow-up.


CONCLUSIONS
Compared to patients with Xpert-positive tuberculosis diagnosed during pre-ART screening, Xpert-negative cases had less advanced immunosuppression and less advanced tuberculosis and did not have adverse outcomes despite substantial delays in starting tuberculosis treatment.
The Desmond Tutu HIV Centre, Institute for Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Anzio Rd, Observatory 7925, Cape Town, South Africa. stevelawn@yahoo.co.uk
Stephen D
SD
Lawn
Andrew D
AD
Kerkhoff
Monica
M
Vogt
Yonas
Y
Ghebrekristos
Andrew
A
Whitelaw
Robin
R
Wood
D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D000995:Antitubercular Agents / Q000008:administration & dosage; D019411:Clinical Laboratory Techniques / Q000379:methods; D005188:False Negative Reactions; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy; D006801:Humans; D008297:Male; D008403:Mass Screening / Q000379:methods; D013019:South Africa; D016896:Treatment Outcome; D014397:Tuberculosis, Pulmonary / Q000175:diagnosis* / Q000188:drug therapy*
D000995:Antitubercular Agents