Proof of concept of the Universal Baby video innovation for early child development in Lima, Peru.

OBJECTIVE: Community-based video interventions offer an effective and potentially scalable early interaction coaching tool for caregivers living in low resource settings. We tested the Universal Baby (UB) video innovation; an early interaction coaching tool using video sourced and produced locally with early child development (ECD) expert supervision. METHODS: This proof-of-concept study enrolled 40 caregivers of children ages 10-18 months assigned to intervention and control groups by health establishments in Carabayllo, Lima, Peru. Mother/child dyads received 12 weekly group health education sessions with social support. Of those, 16 caregivers also received 6 UB videos featuring brain science education and local clips of responsive, reciprocal interaction, also known as "serve and return" interaction. Survey data assessed feasibility and acceptability of the intervention. We assessed improved quality of mother/child interaction using the Parenting Interactions with Children: Checklist of Observations Linked to Outcomes (PICCOLO). RESULTS: We found the program feasible. We successfully trained the local team to produce UB videos using locally-sourced footage and delivered the videos as part of a community-based intervention. We also found it to be acceptable in that participants enthusiastically received the UB videos, reporting they enjoyed being videotaped, and learned how to recognize and appropriately respond to their child's nuanced sounds and gestures. The median change in total PICCOLO scores favored the intervention group compared to the control group. CONCLUSIONS: UB offers great potential as a sustainable, potentially scalable, and culturally appropriate tool to promote equity for child development among young children living in low resource homes globally.

The complexities of selling fruits and vegetables in remote Navajo Nation retail outlets: perspectives from owners and managers of small stores.

OBJECTIVE: Navajo Nation residents experience extreme rates of poverty, food insecurity and diet-related diseases. While many residents travel far to shop at grocery stores, there are small stores closer to home that could provide more healthy options, like fruits and vegetables (F&V). Little is known from the perspective of store owners and managers regarding the barriers and facilitators to offering F&V; the present study contributes to filling that gap. DESIGN: Data were collected through structured interviews from a sampling frame of all store owners or managers in the setting (n 29). SETTING: Small stores in Navajo Nation, New Mexico, USA. Navajo Nation is predominantly rural and the largest federally recognized Native American tribe in the USA. PARTICIPANTS: Sixteen managers and six owners at twenty-two stores. RESULTS: When asked about the types of foods that were most commonly purchased at their stores, most participants reported snacks and drinks (82 and 68 %, respectively). Many participants reported they would like to offer more fresh F&V. However, barriers included varying perceived customer demand, limited F&V choices from distributors and (for some managers) limited authority over product selection. CONCLUSIONS: Findings contribute to the discussion on engaging store owners and managers in providing quality, healthy foods close to home in low-income, rural regions.

Implementation of the Navajo fruit and vegetable prescription programme to improve access to healthy foods in a rural food desert.

OBJECTIVE: To utilise a community-based participatory approach in the design and implementation of an intervention targeting diet-related health problems on Navajo Nation. DESIGN: A dual strategy approach of community needs/assets assessment and engagement of cross-sectorial partners in programme design with systematic cyclical feedback for programme modifications. SETTING: Navajo Nation, USA. PARTICIPANTS: Navajo families with individuals meeting criteria for programme enrolment. Participant enrolment increased with iterative cycles. RESULTS: The Navajo Fruit and Vegetable Prescription (FVRx) Programme. CONCLUSIONS: A broad, community-driven and culturally relevant programme design has resulted in a programme able to maintain core programmatic principles, while also allowing for flexible adaptation to changing needs.

Community Outreach for Navajo People Living with Diabetes: Who Benefits Most?

INTRODUCTION: The Community Outreach and Patient Empowerment (COPE) intervention provides integrated outreach through community health representatives (CHRs) to people living with diabetes in Navajo Nation. The aim of this study was to identify groups for whom the intervention had the greatest effect on glycated hemoglobin A1c (HbA1c). METHODS: We analyzed de-identified data extracted from routine health records dated from December 1, 2010, through August 31, 2014, to compare net change in HbA1c among COPE patients and non-COPE patients. We used linear mixed models to assess whether the intervention was modified by age, sex, preferred language, having a primary care provider, baseline HbA1c, or having a mental health condition. RESULTS: Age, having a primary care provider, and baseline HbA1c significantly modified HbA1c levels. Among patients aged 64 or younger, COPE participation was associated with a net decrease in HbA1c of 0.77%; among patients aged 65 or older, the net decrease was 0.49% (P = .03). COPE participation was associated with a steeper decrease in HbA1c among patients without a primary care physician (net decrease, 0.99%) than among patients with a primary care provider (net decrease, 0.57%) (P = .03). COPE patients with a baseline HbA1c >9% had a net decrease of 0.70%, while those with a baseline HbA1c ≤9% had a net decrease of 0.34% (P = .01). We found no significant differences based on sex, preferred language, or having a mental health condition. CONCLUSION: Findings suggest that the COPE intervention was robust and equitable, benefiting all groups living with diabetes in Navajo Nation, but conferring the greatest benefit on the most vulnerable.

Integrating community health representatives with health care systems: clinical outcomes among individuals with diabetes in Navajo Nation.

BACKGROUND: We studied the impact of Community Outreach and Patient Empowerment (COPE) intervention to support Community Health Representatives (CHR) on the clinical outcomes of patients living with diabetes in the Navajo Nation extending into the States of Arizona, Utah, and New Mexico. The COPE intervention integrated CHRs into healthcare teams by providing a structured approach to referrals and home visits. METHODS: We abstracted routine clinical data from the Indian Health Service's information system on individuals with diabetes mellitus seen at participating clinical sites from 2010 to 2014. We matched 173 COPE participants to 2880 patients with similar demographic and clinical characteristics who had not participated in COPE. We compared the changes in clinical outcomes between the two groups using linear mixed models. RESULTS: Over the four years of the study, COPE patients had greater improvements in glycosylated hemoglobin (- 0.56%) than non-COPE participants (+ 0.07%) for a difference in differences of 0.63% (95% confidence interval (CI): 0.50, 0.76). Low-density lipoprotein fell more steeply in the COPE group (- 10.58 mg/dl) compared to the non-COPE group (- 3.18 mg/dl) for a difference in differences of 7.40 mg/dl (95%CI: 2.00, 12.80). Systolic blood pressure increased slightly more among COPE (2.06 mmHg) than non-COPE patients (0.61 mmHg). We noted no significant change for body mass index in either group. CONCLUSION: Structured outreach by Community Health Representatives as part of an integrated care team was associated with improved glycemic and lipid levels in the target Navajo population. TRIAL REGISTRATION: Trial registration: NCT03326206. Registered 31 October 2017 - Retrospectively registered, https://clinicaltrials.gov/ct2/show/study/NCT03326206.

Aggressive Regimens Reduce Risk of Recurrence After Successful Treatment of MDR-TB.

BACKGROUND: We sought to determine whether treatment with a "long aggressive regimen" was associated with lower rates of relapse among patients successfully treated for pulmonary multidrug-resistant tuberculosis (MDR-TB) in Tomsk, Russia. METHODS: We conducted a retrospective cohort study of adult patients that initiated MDR-TB treatment with individualized regimens between September 2000 and November 2004, and were successfully treated. Patients were classified as having received "aggressive regimens" if their intensive phase consisted of at least 5 likely effective drugs (including a second-line injectable and a fluoroquinolone) used for at least 6 months post culture conversion, and their continuation phase included at least 4 likely effective drugs. Patients that were treated with aggressive regimens for a minimum duration of 18 months post culture conversion were classified as having received "long aggressive regimens." We used recurrence as a proxy for relapse because genotyping was not performed. After treatment, patients were classified as having disease recurrence if cultures grew MDR-TB or they re-initiated MDR-TB therapy. Data were analyzed using Cox proportional hazard regression. RESULTS: Of 408 successfully treated patients, 399 (97.5%) with at least 1 follow-up visit were included. Median duration of follow-up was 42.4 months (interquartile range: 20.5-59.5), and there were 27 recurrence episodes. In a multivariable complete case analysis (n = 371 [92.9%]) adjusting for potential confounders, long aggressive regimens were associated with a lower rate of recurrence (adjusted hazard ratio: 0.22, 95% confidence interval, .05-.92). CONCLUSIONS: Long aggressive regimens for MDR-TB treatment are associated with lower risk of disease recurrence.

Surgery as an Adjunctive Treatment for Multidrug-Resistant Tuberculosis: An Individual Patient Data Metaanalysis.

BACKGROUND: Medical treatment for multidrug-resistant (MDR)-tuberculosis is complex, toxic, and associated with poor outcomes. Surgical lung resection may be used as an adjunct to medical therapy, with the intent of reducing bacterial burden and improving cure rates. We conducted an individual patient data metaanalysis to evaluate the effectiveness of surgery as adjunctive therapy for MDR-tuberculosis. METHODS: Individual patient data, was obtained from the authors of 26 cohort studies, identified from 3 systematic reviews of MDR-tuberculosis treatment. Data included the clinical characteristics and medical and surgical therapy of each patient. Primary analyses compared treatment success (cure and completion) to a combined outcome of failure, relapse, or death. The effects of all forms of resection surgery, pneumonectomy, and partial lung resection were evaluated. RESULTS: A total of 4238 patients from 18 surgical studies and 2193 patients from 8 nonsurgical studies were included. Pulmonary resection surgery was performed on 478 patients. Partial lung resection surgery was associated with improved treatment success (adjusted odds ratio [aOR], 3.0; 95% confidence interval [CI], 1.5-5.9; I(2)R, 11.8%), but pneumonectomy was not (aOR, 1.1; 95% CI, .6-2.3; I(2)R, 13.2%). Treatment success was more likely when surgery was performed after culture conversion than before conversion (aOR, 2.6; 95% CI, 0.9-7.1; I(2)R, 0.2%). CONCLUSIONS: Partial lung resection, but not pneumonectomy, was associated with improved treatment success among patients with MDR-tuberculosis. Although improved outcomes may reflect patient selection, partial lung resection surgery after culture conversion may improve treatment outcomes in patients who receive optimal medical therapy.

Multidrug-resistant tuberculosis treatment failure detection depends on monitoring interval and microbiological method.

Debate persists about monitoring method (culture or smear) and interval (monthly or less frequently) during treatment for multidrug-resistant tuberculosis (MDR-TB). We analysed existing data and estimated the effect of monitoring strategies on timing of failure detection.We identified studies reporting microbiological response to MDR-TB treatment and solicited individual patient data from authors. Frailty survival models were used to estimate pooled relative risk of failure detection in the last 12 months of treatment; hazard of failure using monthly culture was the reference.Data were obtained for 5410 patients across 12 observational studies. During the last 12 months of treatment, failure detection occurred in a median of 3 months by monthly culture; failure detection was delayed by 2, 7, and 9 months relying on bimonthly culture, monthly smear and bimonthly smear, respectively. Risk (95% CI) of failure detection delay resulting from monthly smear relative to culture is 0.38 (0.34-0.42) for all patients and 0.33 (0.25-0.42) for HIV-co-infected patients.Failure detection is delayed by reducing the sensitivity and frequency of the monitoring method. Monthly monitoring of sputum cultures from patients receiving MDR-TB treatment is recommended. Expanded laboratory capacity is needed for high-quality culture, and for smear microscopy and rapid molecular tests.

Impact of HIV on mortality among patients treated for tuberculosis in Lima, Peru: a prospective cohort study.

BACKGROUND: Human immunodeficiency virus (HIV)-associated tuberculosis deaths have decreased worldwide over the past decade. We sought to evaluate the effect of HIV status on tuberculosis mortality among patients undergoing treatment for tuberculosis in Lima, Peru, a low HIV prevalence setting. METHODS: We conducted a prospective cohort study of patients treated for tuberculosis between 2005 and 2008 in two adjacent health regions in Lima, Peru (Lima Ciudad and Lima Este). We constructed a multivariate Cox proportional hazards model to evaluate the effect of HIV status on mortality during tuberculosis treatment. RESULTS: Of 1701 participants treated for tuberculosis, 136 (8.0%) died during tuberculosis treatment. HIV-positive patients constituted 11.0% of the cohort and contributed to 34.6% of all deaths. HIV-positive patients were significantly more likely to die (25.1 vs. 5.9%, P < 0.001) and less likely to be cured (28.3 vs. 39.4%, P = 0.003). On multivariate analysis, positive HIV status (hazard ratio [HR] = 6.06; 95% confidence interval [CI], 3.96-9.27), unemployment (HR = 2.24; 95% CI, 1.55-3.25), and sputum acid-fast bacilli smear positivity (HR = 1.91; 95% CI, 1.10-3.31) were significantly associated with a higher hazard of death. CONCLUSIONS: We demonstrate that positive HIV status was a strong predictor of mortality among patients treated for tuberculosis in the early years after Peru started providing free antiretroviral therapy. As HIV diagnosis and antiretroviral therapy provision are more widely implemented for tuberculosis patients in Peru, future operational research should document the changing profile of HIV-associated tuberculosis mortality.

Improving outcomes for multidrug-resistant tuberculosis: aggressive regimens prevent treatment failure and death.

BACKGROUND: Evidence is sparse regarding the optimal construction of regimens to treat multidrug-resistant (MDR) tuberculosis disease due to strains of Mycobacterium tuberculosis resistant to at least both isoniazid and rifampin. Given the low potency of many second-line antituberculous drugs, we hypothesized that an aggressive regimen of at least 5 likely effective drugs during the intensive phase, including a fluoroquinolone and a parenteral agent, would be associated with a reduced risk of death or treatment failure. METHODS: We conducted a retrospective cohort study of patients initiating MDR tuberculosis treatment between 2000 and 2004 in Tomsk, Russian Federation. We used a multivariate Cox proportional hazards model to assess whether monthly exposure to an aggressive regimen was associated with the risk of death or treatment failure. RESULTS: Six hundred fourteen individuals with confirmed MDR tuberculosis were eligible for analysis. On multivariable analysis that adjusted for extensively drug-resistant (XDR) tuberculosis-MDR tuberculosis isolates resistant to fluoroquinolones and parenteral agents-we found that monthly exposure to an aggressive regimen was significantly associated with a lower risk of death or treatment failure (hazard ratio, 0.52 [95% confidence interval, .29-.94]; P = .030). CONCLUSIONS: Receipt of an aggressive treatment regimen was a robust predictor of decreased risk of death or failure during MDR tuberculosis treatment. These findings further support the use of this regimen definition as the benchmark for the standard of care of MDR tuberculosis patients and should be used as the basis for evaluating novel therapies.

Retention and Viral Suppression Among Adolescents Newly Initiating Antiretroviral Therapy in Adult HIV Care in Lima, Peru: A Retrospective Cohort Study.

PURPOSE: Published data on outcomes among adolescents newly initiating antiretroviral treatment in the Latin American context are sparse. We estimated the frequency of sustained retention with viral load suppression (i.e., successful transition) and identified predictors of successful transition into adult care among youth (aged 14-21 years) with recently acquired HIV in Lima, Peru. METHODS: A retrospective cohort study was conducted among 184 adolescents and young adults who initiated antiretroviral therapy in an adult public sector HIV clinic between June 2014 and June 2019. Sustained retention (no loss-to-follow-up or death) with viral suppression was calculated for the first 12 and 24 months following treatment initiation. We conducted regression analyses to assess factors associated with successful transition to adult HIV care, including gender, age, occupation, nationality, pregnancy, same-sex sexual behavior, presence of treatment supporter, number of living parents, and social risk factors that may adversely influence health (e.g., lack of social support, economic deprivation). RESULTS: Patients were predominantly male (n = 167, 90.8%). Median age was 19 years (interquartile range: 18-21). Frequency of sustained retention with viral load suppression was 42.4% (78/184) and 35.3% (30/85) at 12 and 24 months following treatment initiation. In multivariable analyses, working and/or studying was inversely associated with successful transition into adult care at 12 months; number of known living parents (relative risk: 2.20; 95% confidence interval: 1.12, 4.34) and absence of social risk factors (relative risk: 1.68; 95% confidence interval: 0.91, 3.11) were positively associated with successful transition at 24 months. DISCUSSION: Sustained retention in HIV care was uncommon. Parental support and interventions targeting social risk factors may contribute to successful transition into adult HIV care in this group.

Water Is K'é: Learning from the Navajo Community to Promote Early Child Health.

BACKGROUND: Drinking water instead of sugary drinks is key to reducing health disparities. Since beverage habits are shaped by complex personal, community, and environmental factors, community input is critical to design any intervention promoting water. OBJECTIVES: We worked with community partners to design a program to promote healthy beverage habits among young Navajo children. METHODS: The socioecological model, community-based participatory methods, and strengths-based principles shaped our process. In Phase 1, multigenerational feedback taught us about the cultural importance of water and how water quality concerns influence beverage choices. In Phase 2, our Water is K'é Community Advisory Group played a leading role to design the intervention centered around cultural connection, health literacy, and water access. LESSONS LEARNED: Water is K'é was created through community partnership. Community listening and mini-pilots take time but allows the program to meet community's needs and interests. CONCLUSIONS: The solutions to health disparities lie within the community itself.

Training and fidelity monitoring of alcohol treatment interventions integrated into routine tuberculosis care in Tomsk, Russia: the IMPACT Effectiveness Trial.

IMPACT (Integrated Management of Physician-Delivered Alcohol Care for Tuberculosis patients) is a randomized, controlled effectiveness trial based in Tomsk, Russia, that assesses the effect of oral naltrexone and brief behavioral counseling on tuberculosis outcomes and alcohol use in 200 patients. Tuberculosis physicians without addiction experience delivered interventions as part of routine care over a 6-month period, focusing on alcohol intake reduction to support successful tuberculosis treatment. We describe design, training, and fidelity monitoring using a Russian and American team of physicians, bilingual coders, and supervisors. Culturally appropriate adaptations, limitations, and implications for future trials are discussed. The clinical trial identification number is NCT00675961. Funding came from the National Institutes of Health and National Institute on Drug Abuse.

Teacher and Caregiver Perspectives on Water Is K'é: An Early Child Education Program to Promote Healthy Beverages among Navajo Children.

The Water is K'é program was developed to increase water consumption and decrease consumption of sugar-sweetened beverages for young children and caregivers. The pilot program was successfully delivered by three Family and Child Education (FACE) programs on the Navajo Nation using a culturally centered curriculum between 2020 to 2022. The purpose of this research was to understand teacher and caregiver perspectives of program feasibility, acceptability, impact, and other factors influencing beverage behaviors due to the pilot program. Nine caregivers and teachers were interviewed between June 2022 and December 2022, and a study team of four, including three who self-identified as Navajo, analyzed the data using inductive thematic analysis and consensus building to agree on codes. Five themes emerged, including feasibility, acceptability, impact, suggestions for future use of the program, and external factors that influenced water consumption. The analysis showed stakeholders' strong approval for continuing the program based on impact and acceptability, and identified factors that promote the program and barriers that can be addressed to make the program sustainable. Overall, the Water is K'é program and staff overcame many challenges during the COVID-19 pandemic to support healthy behavior change that had a rippled influence among children, caregivers, teachers, and many others.

Global Learning for Health Equity: A Survey of Five Global Learning Sites in the United States.

Global learning is the practice of adopting and adapting global ideas to local challenges. To advance the field of global learning, we performed a case study of five communities that had implemented global health models to advance health equity in a U.S. setting. Surveys were developed using a Consolidated Framework for Implementation Research (CFIR) framework, and each site completed surveys to characterize their global learning experience with respect to community context, the learning and implementation process, implementation science considerations, and health equity. The immense diversity of sites and their experiences underscored the heterogenous nature of global learning. Nonetheless, all cases highlighted core themes of addressing social determinants of health through strong community engagement. Cross-sector participation and implementation science evaluation were strategies applied by many but not all sites. We advocate for continued global learning that advances health equity and fosters equitable partnerships with mutual benefits to origination and destination sites.

Use of spatial information to predict multidrug resistance in tuberculosis patients, Peru.

To determine whether spatiotemporal information could help predict multidrug resistance at the time of tuberculosis diagnosis, we investigated tuberculosis patients who underwent drug susceptibility testing in Lima, Peru, during 2005-2007. We found that crude representation of spatial location at the level of the health center improved prediction of multidrug resistance.

Targeted drug-resistance testing strategy for multidrug-resistant tuberculosis detection, Lima, Peru, 2005-2008.

The Peruvian National Tuberculosis Control Program issued guidelines in 2006 specifying criteria for culture and drug-susceptibility testing (DST), including district-level rapid DST. All patients referred for culture and DST in 2 districts of Lima, Peru, during January 2005-November 2008 were monitored prospectively. Of 1,846 patients, 1,241 (67.2%) had complete DST results for isoniazid and rifampin; 419 (33.8%) patients had multidrug-resistant (MDR) TB at the time of referral. Among patients with new smear-positive TB, household contact and suspected category I failure were associated with MDR TB, compared with concurrent regional surveillance data. Among previously treated patients with smear-positive TB, adult household contact, suspected category II failure, early relapse after category I, and multiple previous TB treatments were associated with MDR TB, compared with concurrent regional surveillance data. The proportion of MDR TB detected by using guidelines was higher than that detected by a concurrent national drug-resistance survey, indicating that the strategy effectively identified patients for DST.

Comprehensive treatment of extensively drug-resistant tuberculosis.

BACKGROUND: Extensively drug-resistant tuberculosis has been reported in 45 countries, including countries with limited resources and a high burden of tuberculosis. We describe the management of extensively drug-resistant tuberculosis and treatment outcomes among patients who were referred for individualized outpatient therapy in Peru. METHODS: A total of 810 patients were referred for free individualized therapy, including drug treatment, resective surgery, adverse-event management, and nutritional and psychosocial support. We tested isolates from 651 patients for extensively drug-resistant tuberculosis and developed regimens that included five or more drugs to which the infecting isolate was not resistant. RESULTS: Of the 651 patients tested, 48 (7.4%) had extensively drug-resistant tuberculosis; the remaining 603 patients had multidrug-resistant tuberculosis. The patients with extensively drug-resistant tuberculosis had undergone more treatment than the other patients (mean [+/-SD] number of regimens, 4.2+/-1.9 vs. 3.2+/-1.6; P<0.001) and had isolates that were resistant to more drugs (number of drugs, 8.4+/-1.1 vs. 5.3+/-1.5; P<0.001). None of the patients with extensively drug-resistant tuberculosis were coinfected with the human immunodeficiency virus (HIV). Patients with extensively drug-resistant tuberculosis received daily, supervised therapy with an average of 5.3+/-1.3 drugs, including cycloserine, an injectable drug, and a fluoroquinolone. Twenty-nine of these patients (60.4%) completed treatment or were cured, as compared with 400 patients (66.3%) with multidrug-resistant tuberculosis (P=0.36). CONCLUSIONS: Extensively drug-resistant tuberculosis can be cured in HIV-negative patients through outpatient treatment, even in those who have received multiple prior courses of therapy for tuberculosis.

Food insufficiency is a risk factor for suboptimal antiretroviral therapy adherence among HIV-infected adults in urban Peru.

We examined the relationship between food insufficiency and antiretroviral therapy (ART) adherence. A cohort of HIV-infected adults in urban Peru was followed for a two-year period after ART initiation. ART adherence was measured using a 30-day self-report tool and classified as suboptimal if <95% adherence was reported. We conducted a repeated measures cohort analysis to examine whether food insufficiency was more common during months of suboptimal adherence relative to months with optimal adherence. 1,264 adherence interviews were conducted for 134 individuals. Participants who reported food insufficiency in the month prior to interview were more likely to experience suboptimal adherence than those who did not (odds ratio [O.R.]:2.4; 95% confidence interval [C.I.]:1.4, 4.1), even after adjusting for baseline social support score (O.R. per 5 point increase:0.91; C.I.:[0.85, 0.98]) and good baseline adherence self-efficacy (O.R.:0.25; C.I.:[0.09, 0.69]). Interventions that ensure food security for HIV-infected individuals may help sustain high levels of adherence.

Development of extensively drug-resistant tuberculosis during multidrug-resistant tuberculosis treatment.

RATIONALE: Extensively drug-resistant (XDR) tuberculosis (TB) may arise in individuals on treatment for multidrug-resistant (MDR) TB. Preventing this amplification of resistance will likely improve clinical outcomes and delay the secondary spread of XDR-TB. OBJECTIVES: To measure the proportion of individuals that develops XDR-TB during the course of MDR-TB treatment, and to identify those factors associated with the development of XDR. METHODS: We performed a retrospective analysis of 608 consecutive patients with documented MDR-TB who were started on MDR-TB treatment between September 10, 2000 and November 1, 2004 in the Tomsk Oblast TB Treatment Services in Western Siberia, Russian Federation. MEASUREMENTS AND MAIN RESULTS: A total of 6% of patients were observed to develop XDR-TB while on MDR-TB treatment. These patients were significantly less likely to be cured or to complete treatment. Using Cox proportional hazard models, we found that the presence of bilateral and cavitary lesions was associated with a greater than threefold increase in hazard (adjusted hazard ratio [HR], 3.47; 95% confidence interval [CI], 1.32-9.14). Prior exposure to a second-line injectable antibiotic was associated with a greater than threefold increase in hazard (adjusted HR, 3.65; 95% CI, 1.81-7.37), and each additional month in which a patient failed to take at least 80% of their prescribed drugs was associated with nearly an additional 20% hazard of developing XDR-TB (adjusted HR, 1.17; 95% CI, 1.01-1.35). CONCLUSIONS: Early and rapid diagnosis, timely initiation of appropriate therapy, and programmatic efforts to optimize treatment adherence during MDR-TB therapy are crucial to avoiding the generation of excess XDR-TB in MDR-TB treatment programs.