Renal function of MDR-TB patients treated with kanamycin regimens or concomitantly with antiretroviral agents

SETTING: To compare renal insufficiency among mul-tidrug-resistant tuberculosis (MDR-TB) patients treated with kanamycin (KM) based regimens and those treated concomitantly with tenofovir disoproxil fumarate (TDF) or other antiretroviral therapy (ART) regimens in Namibia. DESIGN: Retrospective review of the treatment records and laboratory tests of patients initiated on MDR-TB treatment (January–December 2014). The glomerular filtration rates (eGFR) estimated pre- and post-treatment were compared using the analysis of variance test. Renal insufficiency was defined as an eGFR of,60 ml/ min/1.73 m2. Use of KM or TDF and association with renal insufficiency was assessed using Kaplan-Meier plots and Cox proportional hazards analysis. RESULTS: The baseline mean eGFR for the three groups was similar (P ¼ 0.24): 139.3 6 25.6 ml/min for the KM group (n ¼ 68), 131.1 6 25.7 ml/min for the KMþTDF group (n ¼ 44) and 134.2634.4 ml/min for the KMþOther group (n ¼ 23). After 8 months, the values had declined significantly to respectively 104.8 6 37.5 ml/min (P, 0.001), 101.5 6 38.3 ml/min (P, 0.001) and 111.5 6 41.7 ml/min (P ¼ 0.01). Co-treatment with KMþART was associated with an increased risk of renal insufficiency (hazard ratio [HR] 1.8, 95%CI 0.7–4.1, P ¼ 0.20 for KMþTDF, and HR 3.5, 95%CI 1.4–8.2, P ¼ 0.005 for KMþOther ART). CONCLUSION: Renal function declined at a similar rate in MDR-TB patients treated with KM-based regimens compared with patients treated concomitantly with TDF-based or other ART. The risk of renal insufficiency was greater for patients on ART

Track E Implementation Science, Health Systems and Economics

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138412/1/jia218443.pd

Adverse events and patients' perceived health-related quality of life at the end of multidrug-resistant tuberculosis treatment in Namibia

PURPOSE:The health-related quality of life (HRQoL) of patients completing multidrug-resistant tuberculosis (MDR-TB) treatment in Namibia and whether the occurrence of adverse events influenced patients' rating of their HRQoL was evaluated.PATIENTS AND METHODS:A cross-sectional analytic survey of patients completing or who recently completed MDR-TB treatment was conducted. The patients rated their HRQoL using the simplified Short Form-™ (SF-8) questionnaire consisting of eight Likert-type questions. Three supplemental questions on the adverse events that the patients may have experienced during their MDR-TB treatment were also included. Scoring of HRQoL ratings was norm-based (mean =50, standard deviation =10) ranging from 20 (worst health) to 80 (best health), rather than the conventional 0-100 scores. We evaluated the internal consistency of the scale items using the Cronbach's alpha, performed descriptive analyses, and analyzed the association between the patients' HRQoL scores and adverse events.RESULTS:Overall, 36 patients (20 males, 56%) aged 17-54 years (median =40 years) responded to the questionnaire. The median (range) HRQoL score for the physical component summary was 58.6 (35.3-60.5), while the median score for the mental component summary was 59.3 (26.6-61.9), indicating not-so-high self-rating of health. There was good internal consistency of the scale scores, with a Cronbach's alpha value of >0.80. In all, 32 (89%) of the 36 patients experienced at least one adverse drug event of any severity during their treatment (median events =3, range 1-6), of which none was life-threatening. The occurrence of adverse events was not related to HRQoL scores. For patients reporting zero to two events, the median (range) HRQoL score was 56.8 (44.4-56.8), while for those reporting three or more events, the median score was 55.2 (38.6-56.8); P=0.34 for difference between these scores.CONCLUSION:Patients completing treatment for MDR-TB in Namibia tended to score moderately low on their HRQoL, using the generic SF-8 questionnaire. The occurrence of adverse events did not lead to lower HRQoL scores upon treatment completion

Adverse Drug Reactions and Clinical Outcomes in Patients Initiated on Antiretroviral Therapy: A Prospective Cohort Study From Ethiopia

© 2015, Springer International Publishing Switzerland.Introduction: In Ethiopia, the use of antiretroviral therapy (ART) has been scaled up for HIV/AIDS over the past decade. Adverse drug reactions (ADRs) associated with ART pose a unique challenge in the treatment of the infection in this resource-limited setting. Objectives: The aims of this study were to examine the incidence and nature of ADRs, identify the risk factors associated with the development of ADRs, and assess their impact on treatment outcomes. Methods: A prospective cohort study was conducted in adult patients (=18 years of age) with HIV/AIDS who commenced ART. All ADRs in the first 12 months of therapy were recorded, and the severity, causality, and preventability assessed. The impact of severe ADRs on self-reported adherence, immunological, and body mass index (BMI) outcomes were assessed. Results: Of the 211 patients included in the analysis, 181 (85.7 %) experienced at least one ADR and 66 (31.3 %) experienced at least one severe ADR within 12 months of commencing ART (incidence rates for any ADR and severe ADR of 14.8 and 3.2 per 100 person-months, respectively). Logistic regression analysis indicated that taking zidovudine-containing regimens (odds ratio [OR] 4.2, 95 % confidence interval [CI] 2.1–8.4) or being unemployed (OR 2.2, 95 % CI 1.1–4.3) were independent predictors of experiencing severe ADRs. Patients who experienced a severe ADR were less likely (OR 0.4, 95 % CI 0.2–0.9) to be =90 % adherent to ART. The mean gain in BMI was significantly lower in patients with severe ADRs after 3 and 12 months of therapy. Conclusions: ADRs were common within the first 3 months in patients initiated on ART. Severe ADRs were negatively associated with self-reported adherence and gain in BMI. Measures need to be implemented to routinely monitor for severe ADRs to improve ART adherence and treatment outcomes

Enhanced infection prophylaxis reduces mortality in severely immunosuppressed HIV-infected adults and older children initiating antiretroviral therapy in Kenya, Malawi, Uganda and Zimbabwe: the REALITY trial

Meeting abstract FRAB0101LB from 21st International AIDS Conference 18–22 July 2016, Durban, South Africa. Introduction: Mortality from infections is high in the first 6 months of antiretroviral therapy (ART) among HIV‐infected adults and children with advanced disease in sub‐Saharan Africa. Whether an enhanced package of infection prophylaxis at ART initiation would reduce mortality is unknown. Methods: The REALITY 2×2×2 factorial open‐label trial (ISRCTN43622374) randomized ART‐naïve HIV‐infected adults and children >5 years with CD4 <100 cells/mm3. This randomization compared initiating ART with enhanced prophylaxis (continuous cotrimoxazole plus 12 weeks isoniazid/pyridoxine (anti‐tuberculosis) and fluconazole (anti‐cryptococcal/candida), 5 days azithromycin (anti‐bacterial/protozoal) and single‐dose albendazole (anti‐helminth)), versus standard‐of‐care cotrimoxazole. Isoniazid/pyridoxine/cotrimoxazole was formulated as a scored fixed‐dose combination. Two other randomizations investigated 12‐week adjunctive raltegravir or supplementary food. The primary endpoint was 24‐week mortality. Results: 1805 eligible adults (n = 1733; 96.0%) and children/adolescents (n = 72; 4.0%) (median 36 years; 53.2% male) were randomized to enhanced (n = 906) or standard prophylaxis (n = 899) and followed for 48 weeks (3.8% loss‐to‐follow‐up). Median baseline CD4 was 36 cells/mm3 (IQR: 16–62) but 47.3% were WHO Stage 1/2. 80 (8.9%) enhanced versus 108(12.2%) standard prophylaxis died before 24 weeks (adjusted hazard ratio (aHR) = 0.73 (95% CI: 0.54–0.97) p = 0.03; Figure 1) and 98(11.0%) versus 127(14.4%) respectively died before 48 weeks (aHR = 0.75 (0.58–0.98) p = 0.04), with no evidence of interaction with the two other randomizations (p > 0.8). Enhanced prophylaxis significantly reduced incidence of tuberculosis (p = 0.02), cryptococcal disease (p = 0.01), oral/oesophageal candidiasis (p = 0.02), deaths of unknown cause (p = 0.02) and (marginally) hospitalisations (p = 0.06) but not presumed severe bacterial infections (p = 0.38). Serious and grade 4 adverse events were marginally less common with enhanced prophylaxis (p = 0.06). CD4 increases and VL suppression were similar between groups (p > 0.2). Conclusions: Enhanced infection prophylaxis at ART initiation reduces early mortality by 25% among HIV‐infected adults and children with advanced disease. The pill burden did not adversely affect VL suppression. Policy makers should consider adopting and implementing this low‐cost broad infection prevention package which could save 3.3 lives for every 100 individuals treated