The transition to Xpert MTB/RIF ultra: diagnostic accuracy for pulmonary tuberculosis in Kampala, Uganda.

BACKGROUND: The World Health Organization (WHO) has endorsed the next-generation Xpert MTB/RIF Ultra (Ultra) cartridge, and Uganda is currently transitioning from the older generation Xpert MTB/RIF (Xpert) cartridge to Ultra as the initial diagnostic test for pulmonary tuberculosis (TB). We assessed the diagnostic accuracy of Ultra for pulmonary TB among adults in Kampala, Uganda. METHODS: We sampled adults referred for Xpert testing at two hospitals and a health center over a 12-month period. We enrolled adults with positive Xpert and a random 1:1 sample with negative Xpert results. Expectorated sputum was collected for Ultra, and for solid and liquid culture testing for Xpert-negative patients. We measured sensitivity and specificity of Ultra overall and by HIV status, prior history of TB, and hospitalization, in reference to Xpert and culture results. We also assessed how classification of results in the new "trace" category affects Ultra accuracy. RESULTS: Among 698 participants included, 211 (30%) were HIV-positive and 336 (48%) had TB. The sensitivity of Ultra was 90.5% (95% CI 86.8-93.4) and specificity was 98.1% (95% CI 96.1-99.2). There were no significant differences in sensitivity and specificity by HIV status, prior history of TB or hospitalization. Xpert and Ultra results were concordant in 670 (96%) participants, with Ultra having a small reduction in specificity (difference 1.9, 95% CI 0.2 to 3.6, p=0.01). When "trace" results were considered positive for all patients, sensitivity increased by 2.1% (95% CI 0.3 to 3.9, p=0.01) without a significant reduction in specificity (- 0.8, 95% CI - 0.3 to 2.0, p=0.08). CONCLUSIONS: After 1 year of implementation, Ultra had similar performance to Xpert. Considering "trace" results to be positive in all patients increased case detection without significant loss of specificity. Longitudinal studies are needed to compare the benefit of greater diagnoses to the cost of overtreatment.

Hepatotoxicity from first line antiretroviral therapy: an experience from a resource limited setting.

BACKGROUND: Highly active antiretroviral therapy (HAART) has been associated with liver toxicity. The role of monitoring for liver toxicity has not been well studied in resource-limited settings (RLS). OBJECTIVES: To determine the background prevalence and incidence of liver injury and describe the associated signs and symptoms of acute hepatitis after initiating HAART; and to determine the role of liver enzyme tests in monitoring hepatotoxicity. METHODS: In this prospective study, in Mulago Hospital AIDS Clinics, we consecutively enrolled adult patients initiated on one of three first line HAART regimens [Stavudine (d4T)-Lamivudine (3TC) and nevirapine (NVP); Zidovudine (AZT)-3TC and Efavirenz (EFV) or d4T-3TC-EFV]. We monitored ALT (alanine aminotransferase) and clinical evidence of acute hepatitis at baseline, 2(nd), 6(th), 10(th) and 14(th) week of therapy. RESULTS: Two hundred and forty HIV-positive HAART- naïve patients were enrolled in the study. The baseline prevalence of transaminitis was 1.7% with an incidence of 4.2% at 14 weeks. Grade 3-4 hepatotoxicity was documented in 1.3%. Jaundice was seen in grade 2-4 ALT elevations. Being on concurrent HAART and antituberculous drugs was associated with grade 2-4 toxicity compared to those who were only on HAART [OR; 16.0 (95% CI; 2.4-104.2)]. CONCLUSIONS: Incidence of severe hepatotoxicity within three months of first-line antiretroviral therapy was low, suggesting that routine measurement of transaminases may not be necessary in all patients initiating HAART in RLS. Routine measurement may be important in following patients on HAART and concurrent TB treatment as well as those with jaundice to avoid missing hepatotoxicity.