Treatment Adherence Among Persons Receiving Concurrent Multidrug-Resistant Tuberculosis and HIV Treatment in KwaZulu-Natal, South Africa.
ABSTRACT: BACKGROUND:Success in multidrug-resistant tuberculosis (MDR-TB) and HIV treatment requires high medication adherence despite high pill burdens, frequent adverse events, and long treatment duration, which may jeopardize adherence. We prospectively compared MDR-TB/HIV-coinfected persons to those with MDR-TB alone to determine the impact of concurrent treatment on adherence and outcomes. METHODS:We assessed medication adherence monthly using 3-day recall, 30-day recall, and visual analog scale and examined adherence to monthly study visits (months 0-12). We determined the proportion of participants fully adherent (no reported missed doses) to MDR-TB vs. HIV treatment by each measure. We assessed the association of medication and clinic visit adherence with MDR-TB treatment success (cure or completion, 18-24 months) and HIV virologic suppression. RESULTS:Among 200 patients with MDR-TB, 63% were women, median age was 33 years, 144 (72%) were HIV-infected, and 81% were receiving antiretroviral therapy (ART) at baseline. Adherence to medications (81%-98% fully adherent across all measures) and clinic visits (80% missed ?1 visit) was high, irrespective of HIV status. Adherence to ART was significantly higher than to MDR-TB treatment by all self-reported measures (3-day recall: 92% vs. 84%, respectively; P = 0.003). In multivariable analysis, the adjusted risk ratio of unsuccessful MDR-TB treatment increased with every missed visit: 1.50, 2.25, and 3.37 for unsuccessful treatment, for 1, 2, and ?3 missed visits. CONCLUSIONS:Adherence to ART was higher than to MDR-TB treatment among persons with MDR-TB/HIV coinfection. Missed clinic visits may be a simple measure for identifying patients at risk of unsuccessful MDR-TB treatment outcome.
Project description:BACKGROUND:In India, a new care package consisting of (i) daily regimen with fixed-dose combination drugs, collected once-a-month and self-administered by the patient, (ii) 'one stop service' at antiretroviral treatment (ART) centre for both HIV and tuberculosis (TB) treatment and (iii) technology-enabled adherence support (99DOTS, which required patients to give a missed phone call after consuming drugs) was piloted for treatment of TB among HIV-infected TB patients. Conventional care included intermittent regimen (drugs consumed thrice-weekly) delivered under direct observation of treatment supporter and the patients needing to visit TB and HIV care facilities, separately for treatment. OBJECTIVE:To assess the effect of new care package on TB treatment outcomes among HIV-TB patients registered during January-December 2016, as compared to conventional care and explore the implementation challenges. METHODS:A mixed-methods study was conducted in four districts of Karnataka, India where new care package was piloted in few ART centres while the rest provided conventional care. Quantitative component involved a secondary cohort analysis of routine programme data. Adjusted relative risk(aRR) was calculated using Poisson regression to measure association between new care package and unsuccessful treatment outcome. We conducted in-depth interviews with healthcare providers and patients to understand the challenges. RESULTS:Unsuccessful TB treatment outcomes (death, loss to follow-up and failure) were higher in new care package (n = 871) compared to conventional care (n = 961) (30.5% vs 23.4%; P value<0.001) and aRR was 1.3(95% CI: 1.1-1.7). Key challenges included patients' inability to give missed call, increased work load for ART staff, reduced patient-provider interaction, deficiencies in training and lack of role clarity among providers and reduced involvement of TB program staff. CONCLUSION:With new care package, TB treatment outcomes did not improve as expected and conversely declined compared to conventional care. TB and HIV programs need to address the operational challenges to improve the outcomes.
Project description:BACKGROUND:Despite the predictive role of body weight variation in treatment outcome in multidrug-resistant tuberculosis (MDR-TB), few corroborating data are available. We studied weight variation in patients with MDR-TB to identify groups of weight change and to determine factors that influence these changes. METHODS:We analyzed patients with rifampicin resistance who were treated with an MDR-TB treatment regimen between June 07, 2016 and June 22, 2018 at three major drug-resistant TB centers in Guinea. Patients were seen monthly until the end of treatment. Clinical outcome was the body mass index (BMI). We used a linear mixed model to analyze trajectories of BMI and a latent class mixed model to identify groups of BMI trajectories. RESULTS:Of 232 patients treated for MDR-TB during the study period, 165 were analyzed. These patients had a total of 1387 visits, with a median of 5 visits (interquartile range, 3-8 visits). Monthly BMI increase was 0.24 (SE 0.02) per kg/m2. Factors associated with faster BMI progression were success of MDR-TB treatment (0.24 [SE 0.09] per kg/m2; p?=?0.0205) and absence of lung cavities on X-ray (0.18 [0.06] per kg/m2; p?=?0.0068). Two groups of BMI change were identified: rapid BMI increase (n?=?121; 85%) and slow BMI increase (n?=?22; 15%). Patients in the slow BMI increase group were mostly female (68%) had no history of TB treatment (41%), had a positive HIV infection (59%), and had a more severe clinical condition at baseline, characterized by a higher frequency of symptoms including depression (18%), dyspnea (68%), poor adherence to MDR-TB treatment (64%), lower platelet count, and higher SGOT. These patients also had a longer time to initial culture conversion (log-rank test: p?=?0.0218). CONCLUSION:Quantitative BMI data on patients with MDR-TB treated with a short regimen allowed the identification of subgroups of patients with different trajectories of BMI and emphasized the usefulness of BMI as a biomarker for the monitoring of MDR-TB treatment outcome.
Project description:Interim treatment outcomes at 6-months for multidrug-resistant tuberculosis (MDR-TB) treatment are among the most basic performance monitoring and key evaluation indicators in the Stop and End TB strategy of the World Health Organization (WHO). Therefore, this study was conducted to evaluate the interim treatment outcomes of MDR-TB patients in Pakistan.This study was conducted at the Programmatic Management Unit for Drug-resistance TB (PMDT) site of the National Tuberculosis Program (NTP), Pakistan. It is located in the Chest Disease Unit (CDU) of the Bahawal Victoria Hospital (BVH), Bahawalpur, Punjab, Pakistan. Data was collected between April 1, 2014 and December 31, 2015. The medical records, Electronic Nominal Recording Reporting System (ENRS) data and MRD-TB notification forms of the MDR-TB patients registered at the PMDT site were reviewed to obtain data. For reporting and calculation of interim treatment outcomes, standardized WHO methodology was adopted. Simple logistic regression analysis was used to examine the possible association between the dependent variable (i.e. unsuccessful interim treatment outcome) and selected socio-demographic and clinical variables.A total of 100 drug-resistant TB (DR-TB) patients (all types) were registered during the study period. Out of these, 80 were MDR-TB patients for whom interim results were available. Out of the 80 MDR-TB cases, 48 (60%) were classified under the successful interim treatment outcome category. The remaining 40% had unsuccessful 6-month treatment outcomes and 12 (15%) patients died, while nine (11.3%) were lost to follow-up by six months. The final predictors of unsuccessful interim treatment outcomes were; being resistant to ofloxacin (AOR 3.23, 95% CI 0.96-10.89; p-value = 0.04), having above normal baseline serum creatinine levels (AOR 6.49, 95% CI 1.39-30.27; p-value = 0.02), and being culture positive at the second month of treatment (AOR 6.94, 95% CI 2-24.12; p-value = 0.01).Despite free treatment and programmatic efforts to ensure patient adherence, the high rate of unsuccessful interim treatment outcomes is concerning. The identified risk factors for unsuccessful interim treatment outcomes in the current study provides clinicians an opportunity to identify high-risk patients and ensure enhanced clinical management and greater treatment success rates.
Project description:Background:Variation in healthcare delivery is increasingly recognized as an important metric of healthcare quality. Directly observed therapy (DOT) has been the standard of care for tuberculosis (TB) treatment supervision for decades based on World Health Organization (WHO) guidelines. However, variation in implementation of DOT and associated TB treatment supervision practices remains poorly defined. Methods:We collected individual patient data from TB treatment registers at 18?TB treatment units in Uganda including District Health Centers, District Hospitals, and Regional Referral Hospitals. We also administered a survey and did observations of TB treatment supervision practices by health workers at each site. We describe variation in TB treatment outcomes and TB treatment supervision practices. Results:Of 2767 patients treated for TB across the 18 clinical sites between January 1 and December 31, 2017, 1740 (62.9%) were men, most were of working age (median 35?years, interquartile range [IQR] 27 - 46), 2546 (92.0%) had a new TB diagnosis, and nearly half (45.9%, n?=?1283) were HIV positive. The pooled treatment success proportion was 69.4% (95% confidence interval [CI] 67.8 - 71.1) but there was substantial variation across sites (range 42.6 - 87.6%, I-squared 92.7%, p?<?0.001). The survey and observation of TB treatment practices revealed that the majority of sites practice community-based DOT (66.7%, n?=?12) and request a family member, who receives no additional training or supervision, to serve as a treatment supporter (77.8%, n?=?14). At TB medication refill visits, all sites screen for side effects and most assess adherence via self-report (83.3%, n?=?15). Only 7 (38.9%) sites followed-up patients who missed appointments using either phone calls (22.2%, n?=?4/7) or community health workers (16.7%, n?=?3/7). All 18 sites counseled patients at treatment initiation, but none provided additional counseling at refill visits other than addressing poor adherence or missed appointments. Conclusion:There was substantial variation in implementation of DOT, including observation and documentation of daily dosing, training and supervision of treatment supporters, and follow-up for missed clinic visits. Identifying best practices and reducing uncontrolled variation in the delivery of TB treatment is critical to improving treatment outcomes.
Project description:Missed HIV medical visits predict poor clinical outcomes. We sought to identify patients at high risk of missing visits. We analyzed 2002-2014 data from six large US HIV clinics. At each visit, we predicted the likelihood of missing the next scheduled visit using demographic, clinical, and patient-reported psychosocial variables. Overall, 10,374 participants contributed 105,628 HIV visits. For 17% of visits, the next scheduled appointment was missed. The strongest predictor of a future missed visit was past-year missed visits. A model with only this predictor had area under the receiver operator curve?=?0.65; defining "high risk" as those with any past-year missed visits had 73% sensitivity and 51% specificity in correctly identifying a future missed visit. Inclusion of other clinical and psychosocial predictors only slightly improved performance. Past visit attendance can identify those at increased risk for future missed visits, allowing for proactive allocation of resources to those at greatest risk.
Project description:BACKGROUND:The prevention of thromboembolism events remains challenging in cases of poor medication adherence. Unfortunately, clinical prediction of future adherence has been suboptimal. The objective of this study was to examine the correlation between 2 measures of real-time, self-reported adherence and anticoagulation control. METHODS:The IN-RANGE2 cohort recruited patients initiating warfarin therapy in 3 urban anticoagulation clinics. At each study visit, participants reported adherence using a 100-point visual analogue scale (VAS, marking percentage of pills taken since prior visit on a linear scale) and 7-day recall of pill-taking behavior. Anticoagulation control was measured by between-visit percent time in international normalized ratio range (BVTR), dichotomized at the cohort median. The longitudinal association between adherence and anticoagulation control was estimated using generalized estimating equations, controlling for clinical and demographic characteristics, prior BVTR, and warfarin dose changes. RESULTS:Among 598 participants with 3204 (median 4) visits, the median BVTR was 36.8% (interquartile range 0%-73.9%). Participants reported ?80% adherence in 182 visits (5.7%) and missed pills in the past 7 days in 377 visits (11.8%). Multivariable regression analysis found poorer anticoagulation control (BVTR <36.8%) in those with a VAS ?80% (odds ratio 1.89; 95% confidence interval, 1.12-3.18; P = .02) and self-reported change in adherence since last visit (odds ratio 1.55; 95% confidence interval, 1.20-2.01; P = .001). CONCLUSION:Self-reported VAS medication adherence at a clinic visit and changes in reported adherence since the last visit are independently associated with BVTR. Clinicians may gain additional insight into patients' medication adherence by incorporating this information into patient management.
Project description:Little is known about the impact of comorbidities on multidrug resistant (MDR) and extensively drug resistant (XDR) tuberculosis (TB) treatment outcomes. We aimed to examine the effect of human immunodeficiency virus (HIV), diabetes, chronic kidney disease (CKD), alcohol misuse, and smoking on MDR/XDRTB treatment outcomes. We searched MEDLINE, EMBASE, Cochrane Central Registrar and Cochrane Database of Systematic Reviews as per PRISMA guidelines. Eligible studies were identified and treatment outcome data were extracted. We performed a meta-analysis to generate a pooled relative risk (RR) for unsuccessful outcome in MDR/XDRTB treatment by co-morbidity. From 2457 studies identified, 48 reported on 18,257 participants, which were included in the final analysis. Median study population was 235 (range 60-1768). Pooled RR of unsuccessful outcome was higher in people living with HIV (RR?=?1.41 [95%CI: 1.15-1.73]) and in people with alcohol misuse (RR?=?1.45 [95%CI: 1.21-1.74]). Outcomes were similar in people with diabetes or in people that smoked. Data was insufficient to examine outcomes in exclusive XDRTB or CKD cohorts. In this systematic review and meta-analysis, alcohol misuse and HIV were associated with higher pooled OR of an unsuccessful outcome in MDR/XDRTB treatment. Further research is required to understand the role of comorbidities in driving unsuccessful treatment outcomes.
Project description:BACKGROUND:Multidrug-resistant tuberculosis (MDR-TB) in HIV endemic settings is a major threat to public health. MDR-TB is a substantial and underreported problem in Sub-Saharan Africa (SSA), with recognised cases projected to increase with advancement in diagnostic technology. There is paucity of review evidence on treatment outcomes and antiretroviral (ART) uptake among MDR-TB patients with HIV in SSA. To address this gap a review of treatment outcomes in HIV patients co-infected with MDR-TB in the SSA region was undertaken. METHODS:Three databases (Medline, Web of Science, CINHAL), Union on Lung Heath conference proceedings and grey literature were searched for publications between January 2004 and May 2018. Records were assessed for eligibility and data extracted. Random effect meta-analysis was conducted using STATA and Cochrane's review manager. RESULTS:A total of 271 publications were identified of which nine fulfilled the inclusion criteria. Data was collected from 3368 MDR-TB and HIV co-infected patients from four SSA countries; South Africa (6), Lesotho (1), Botswana (1) and Ethiopia (1). The most common outcome was cure (34.9% cured in the pooled analysis), this was followed by death (18.1% in pooled analysis). ART uptake was high, at 83% in the pooled analysis. Cure ranged from 28.6 to 54.7% among patients on ART and from 22.2 to 57.7% among those not on ART medication. MDR-TB and HIV co-infected patients were less likely to be successfully treated than HIV negative MDR-TB patients (Risk Ratio = 0.87, 95% CI 0.97, 0.96). CONCLUSION:Treatment outcomes for MDR-TB and HIV co-infected patients do not vary widely from those reported globally. However, treatment success was lower among HIV positive MDR-TB patients compared to HIV negative MDR-TB patients. Prompt antiretroviral initiation and interventions to improve treatment adherence are necessary.
Project description:Each year, 10%-20% of patients with tuberculosis (TB) in low- and middle-income countries present with previously treated TB and are empirically started on a World Health Organization (WHO)-recommended standardized retreatment regimen. The effectiveness of this retreatment regimen has not been systematically evaluated.From July 2003 to January 2007, we enrolled smear-positive, pulmonary TB patients into a prospective cohort to study treatment outcomes and mortality during and after treatment with the standardized retreatment regimen. Median time of follow-up was 21 months (interquartile range 12-33 months). A total of 29/148 (20%) HIV-uninfected and 37/140 (26%) HIV-infected patients had an unsuccessful treatment outcome. In a multiple logistic regression analysis to adjust for confounding, factors associated with an unsuccessful treatment outcome were poor adherence (adjusted odds ratio [aOR] associated with missing half or more of scheduled doses 2.39; 95% confidence interval (CI) 1.10-5.22), HIV infection (2.16; 1.01-4.61), age (aOR for 10-year increase 1.59; 1.13-2.25), and duration of TB symptoms (aOR for 1-month increase 1.12; 1.04-1.20). All patients with multidrug-resistant TB had an unsuccessful treatment outcome. HIV-infected individuals were more likely to die than HIV-uninfected individuals (p<0.0001). Multidrug-resistant TB at enrollment was the only common risk factor for death during follow-up for both HIV-infected (adjusted hazard ratio [aHR] 17.9; 6.0-53.4) and HIV-uninfected (14.7; 4.1-52.2) individuals. Other risk factors for death during follow-up among HIV-infected patients were CD4<50 cells/ml and no antiretroviral treatment (aHR 7.4, compared to patients with CD4?200; 3.0-18.8) and Karnofsky score <70 (2.1; 1.1-4.1); and among HIV-uninfected patients were poor adherence (missing half or more of doses) (3.5; 1.1-10.6) and duration of TB symptoms (aHR for a 1-month increase 1.9; 1.0-3.5).The recommended regimen for retreatment TB in Uganda yields an unacceptable proportion of unsuccessful outcomes. There is a need to evaluate new treatment strategies in these patients.
Project description:<h4>Background</h4>The World Health Organization's End TB Strategy envisions a world free of tuberculosis (TB)-free of deaths, disease, and suffering due to TB-by 2035. Nonadherence reduces cure rates, prolongs infectiousness, and contributes to the emergence of multidrug-resistant TB (MDR-TB). Moreover, MDR-TB is a growing, complex, and costly problem that presents a major obstacle to TB control. Directly observed therapy (DOT) for treatment adherence monitoring is the recommended standard; however, it is challenging to implement at scale because it is labor-intensive. Mobile health interventions can facilitate remote adherence monitoring and minimize the costs and inconveniences associated with standard DOT.<h4>Objective</h4>The study aims to evaluate the effectiveness of using video directly observed therapy (VDOT) plus incentives to improve medication adherence in TB treatment versus usual-care DOT in an African context.<h4>Methods</h4>The DOT Selfie study is an open-label, randomized controlled trial (RCT) with 2 parallel groups, in which 144 adult patients with TB aged 18-65 years will be randomly assigned to receive the usual-care DOT monitoring or VDOT as the intervention. The intervention will consist of a smartphone app, a weekly internet subscription, translated text message reminders, and incentives for those who adhere. The participant will use a smartphone to record and send time-stamped encrypted videos showing their daily medication ingestion. This video component will directly substitute the need for daily face-to-face meetings between the health provider and patients. We hypothesize that the VDOT intervention will be more effective because it allows patients to swallow their pills anywhere, anytime. Moreover, patients will receive mobile-phone-based "social bundle" incentives to motivate adherence to continued daily submission of videos to the health system. The health providers will log into a secured computer system to verify treatment adherence, document missed doses, investigate the reasons for missed doses, and follow prespecified protocol measures to re-establish medication adherence. The primary endpoint is the adherence level as measured by the fraction of expected doses observed over the treatment period. The main secondary outcome will be time-to-treatment completion in both groups.<h4>Results</h4>This study was funded in 2019. Enrollment began in July and is expected to be completed by November 2020. Data collection and follow-up are expected to be completed by June 2021. Results from the analyses based on the primary endpoint are expected to be submitted for publication by December 2021.<h4>Conclusions</h4>This random control trial will be among the first to evaluate the effectiveness of VDOT within an African setting. The results will provide robust scientific evidence on the implementation and adoption of mobile health (mHealth) tools, coupled with incentives to motivate TB medication adherence. If successful, VDOT will apply to other low-income settings and a range of chronic diseases with lifelong treatment, such as HIV/AIDs.<h4>Trial registration</h4>ClinicalTrials.gov NCT04134689; http://clinicaltrials.gov/ct2/show/NCT04134689.<h4>International registered report identifier (irrid)</h4>DERR1-10.2196/18029.