Stewardship / Resistance Scan for Dec 01, 2017

New TB molecular test
HIV drug resistance

Updated molecular TB test found to be more sensitive, less specific

An international team of researchers has found that a re-engineered rapid molecular test for detection of tuberculosis (TB) is more sensitive than the current test but less specific, according to a study yesterday in The Lancet Infectious Diseases.

The primary objectives of the prospective multicenter study were to estimate and compare the sensitivity and specificity of Xpert MTB/RIF Ultra (Xpert Ultra) with the original test (Xpert) for detection of smear-negative TB and rifampicin resistance. Xpert, an automated, cartridge-based molecular assay, is used in TB programs in more than 120 countries and has helped increase detection of TB and drug-resistant TB globally, but its sensitivity is inadequate when few bacilli are present in a clinical specimen, which limits its usefulness in children and patients with HIV. Xpert Ultra was developed to overcome this limitation.

Overall, 1,753 participants from eight high-incidence countries participated in the study, with 1,439 in the case detection group and 314 in the multidrug-resistance group. The results showed that the sensitivity of Xpert Ultra was superior to Xpert for TB detection in all patients with culture-positive TB (88% vs. 83%), with the difference being pronounced in patients with smear-negative sputum (63% vs. 46%) and in patients co-infected with HIV (90% vs. 77%).

But the specificity of Xpert Ultra was 2 percentage points lower than Xpert overall (96% vs. 98%) and 5 percentage points lower in patients who had a history of TB (93% vs. 98%), which means more false-positive results. The two assays performed similarly in detecting rifampicin resistance.

The authors of the study say that, in clinical practice, the high sensitivity of Xpert Ultra could facilitate diagnosis of TB at earlier stages of the disease, especially for patients with HIV, resulting in more evidence-based treatment decisions. Further research is needed, they add, to clarify the implications of the trade-off between increased sensitivity and decreased specificity.

Based on these findings, the World Health Organization (WHO) has concluded that Xpert Ultra can be used as an alternative to Xpert for initial testing in adults with signs or symptoms of TB, the authors said.
Nov 30 Lancet Infect Dis study


HIV drug-resistance on the rise, large meta-analysis finds

In another study yesterday in The Lancet Infectious Diseases, an international team of researchers report that the prevalence of pretreatment HIV drug resistance is rising in many lower- and middle-income countries (LMICs).

The study, a systematic review and meta-regression analysis of screened publications and unpublished datasets, aimed to assess the prevalence of pretreatment drug resistance in people starting or about to start antiretroviral therapy (ART) in LMICs. Although some degree of HIV drug resistance has been anticipated, the concern is that a substantial rise in resistance could endanger the WHO's efforts to end the AIDS epidemic. To achieve that goal, the WHO has set a milestone of ensuring treatment achieves virus suppression in 90% of all people with HIV infection by 2020.

The researchers identified 358 datasets from 2001 to 2016, representing 56,044 adults in 63 countries. They found substantial yearly increases in pretreatment resistance to non-nucleotide transcriptase inhibitors (NNRTIs)—a component of first-line ART—in all regions. The yearly increases in the odds of pretreatment NNRTI resistance were 23% in southern Africa, 17% in eastern Africa, 17% in western and central Africa, 11% in Latin America and the Caribbean, and 11% in Asia. Modelled prevalence estimates of pretreatment resistance in 2016 were 11% in southern Africa, 10.1% in eastern Africa, 7.2% in western and central Africa, 9.4% in Latin America and the Caribbean, and 3.2% in Asia.

The researchers also found that previous exposure to ART was found to be associated with substantially higher NNRTI resistance and significantly greater risk of treatment failure.

According to the study, modeling suggests that HIV drug resistance in excess of 10% could result in 890,000 AIDS deaths and 450,000 new infections in sub-Saharan Africa alone by 2030. The WHO's guidelines on pre-treatment HIV drug resistance recommend that countries switch their first-line treatment when resistance levels reach 10%.

"Our findings show the importance of improving how we monitor drug resistance, and suggest we should review which drugs are included in first-line therapies," lead author Ravindra Gupta, MPH, of University College London said in a university press release.
Nov 30 Lancet Infect Dis study
Nov 30 University College London news release

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