Treatment decisions and mortality in HIV-positive presumptive smear-negative TB in the Xpert® MTB/RIF era: a cohort study

Abstract

BackgroundThe Xpert® MTB/RIF (XP) has a higher sensitivity than sputum smear microscopy (70% versus 35%) for TB diagnosis and has been endorsed by the WHO for TB high burden countries to increase case finding among HIV co-infected presumptive TB patients. Its impact on the diagnosis of smear-negative TB in a routine care setting is unclear. We determined the change in diagnosis, treatment and mortality of smear-negative presumptive TB with routine use of Xpert MTB/RIF (XP).MethodsProspective cohort study of HIV-positive smear-negative presumptive TB patients during a 12-month period after XP implementation in a well-staffed and trained integrated TB/HIV clinic in Kampala, Uganda. Prior to testing clinicians were asked to decide whether they would treat empirically prior to Xpert result; actual treatment was decided upon receipt of the XP result. We compared empirical and XP-informed treatment decisions and all-cause mortality in the first year.ResultsOf 411 smear-negative presumptive TB patients, 175 (43%) received an XP; their baseline characteristics did not differ. XP positivity was similar in patients with a pre-XP empirical diagnosis and those without (9/29 [17%] versus 14/142 [10%], P = 0.23). Despite XP testing high levels of empirical treatment prevailed (18%), although XP results did change who ultimately was treated for TB. When adjusted for CD4 count, empirical treatment was not associated with higher mortality compared to no or microbiologically confirmed treatment.ConclusionsXP usage was lower than expected. The lower sensitivity of XP in smear-negative HIV-positive patients led experienced clinicians to use XP as a “rule-in” rather than “rule-out” test, with the majority of patients still treated empirically.

Rational use of Xpert testing in patients with presumptive TB: clinicians should be encouraged to use the test-treat threshold

“…Figure 1 shows the different measures, using data provided by Hermans et al [ 1 ], and the sensitivity and specificity of Xpert testing in PLHIV with a negative sputum smear [ 3 ].…”

“…Interestingly, Hermans et al inform the reader that clinicians had to indicate, prior to ordering an Xpert test, if they already had enough arguments to start TB treatment. In other words, they indicated if they had surpassed the treatment threshold [ 1 ]. Given the 17% pre-test probability, empirical TB treatment seems justified in this patient population [ 8 ].…”

“…Most TB diagnoses were made without Xpert testing. The article doesn’t provide a lot of data on the arguments that informed the clinical decisions made [ 1 ]. Still, the authors mention that the chest X-rays (CXR) showed abnormalities in respectively 69% and 54% of patients with and without an Xpert result.…”

“…Still, the authors mention that the chest X-rays (CXR) showed abnormalities in respectively 69% and 54% of patients with and without an Xpert result. In addition, signs of extrapulmonary TB were present in respectively 17% and 50% of patients with and without an Xpert result [ 1 ].…”

“…With great interest we read the article by Hermans et al “Treatment decisions and mortality in HIV-positive presumptive smear-negative TB in the Xpert MTB/RIF era: a cohort study” [ 1 ]. The authors assessed if clinicians based their clinical decision-making on available Xpert MTB/RIF (Xpert) testing to diagnose tuberculosis (TB) in HIV-positive smear-negative presumptive TB patients.…”