Development and Pilot-Testing of an Optimized Conversational Agent or "Chatbot" for Peruvian Adolescents Living With HIV to Facilitate Mental Health Screening, Education, Self-Help, and Linkage to Care: Protocol for a Mixed Methods, Community-Engaged Study.

BACKGROUND: Adolescents living with HIV are disproportionally affected by depression, which worsens antiretroviral therapy adherence, increases viral load, and doubles the risk of mortality. Because most adolescents living with HIV live in low- and middle-income countries, few receive depression treatment due to a lack of mental health services and specialists in low-resource settings. Chatbot technology, used increasingly in health service delivery, is a promising approach for delivering low-intensity depression care to adolescents living with HIV in resource-constrained settings. OBJECTIVE: The goal of this study is to develop and pilot-test for the feasibility and acceptability of a prototype, optimized conversational agent (chatbot) to provide mental health education, self-help skills, and care linkage for adolescents living with HIV. METHODS: Chatbot development comprises 3 phases conducted over 2 years. In the first phase (year 1), formative research will be conducted to understand the views, opinions, and preferences of up to 48 youths aged 10-19 years (6 focus groups of up to 8 adolescents living with HIV per group), their caregivers (5 in-depth interviews), and HIV program personnel (5 in-depth interviews) regarding depression among adolescents living with HIV. We will also investigate the perceived acceptability of a mental health chatbot, including barriers and facilitators to accessing and using a chatbot for depression care by adolescents living with HIV. In the second phase (year 1), we will iteratively program a chatbot using the SmartBot360 software with successive versions (0.1, 0.2, and 0.3), meeting regularly with a Youth Advisory Board comprised of adolescents living with HIV who will guide and inform the chatbot development and content to arrive at a prototype version (version 1.0) for pilot-testing. In the third phase (year 2), we will pilot-test the prototype chatbot among 50 adolescents living with HIV naïve to its development. Participants will interact with the chatbot for up to 2 weeks, and data will be collected on the acceptability of the chatbot-delivered depression education and self-help strategies, depression knowledge changes, and intention to seek care linkage. RESULTS: The study was awarded in April 2022, received institutional review board approval in November 2022, received funding in December 2022, and commenced recruitment in March 2023. By the completion of study phases 1 and 2, we expect our chatbot to incorporate key needs and preferences gathered from focus groups and interviews to develop the chatbot. By the completion of study phase 3, we will have assessed the feasibility and acceptability of the prototype chatbot. Study phase 3 began in April 2024. Final results are expected by January 2025 and published thereafter. CONCLUSIONS: The study will produce a prototype mental health chatbot developed with and for adolescents living with HIV that will be ready for efficacy testing in a subsequent, larger study. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/55559.

Understanding linkage to biopsy and treatment for breast cancer after a high-risk telemammography result in Peru: a mixed-methods study.

OBJECTIVES: This mixed-method study aimed to understand the effectiveness of linkage to biopsy and treatment in women with a high-risk mammography result (Breast Imaging Reporting and Data System, BI-RADS 4 and 5) in the national telemammography programme and to explore women's experiences during this process. SETTING: Quantitative component: we collected and linked health data from the telemammography reading centre, the national public health insurance, the national centre for disease control and the national referral cancer centre. Qualitative component: we interviewed participants from different regions of the country representing diverse social and geographical backgrounds. PARTICIPANTS: Quantitative: women who underwent telemammography between July 2017 and September 2018 and had high-risk results (BI-RADS 4-5) were collected. Qualitative: women with a high-risk telemammography result, healthcare providers and administrators. OUTCOMES MEASURES: Quantitative: we determined biopsy and treatment linkage rates and delays. Qualitative: we explored barriers and facilitators for obtaining a biopsy and initiating treatment. RESULTS: Of 126 women with high-risk results, 48.4% had documentation of biopsy and 37.5% experienced a delay of >45 days to biopsy. Of 51 women diagnosed with breast cancer, 86.4% had evidence of treatment initiation, but 69.2% initiated treatment >45 days after biopsy. Travelling to major cities for care, administrative factors and breast cancer misconceptions, among other factors, impeded timely, continuous care for breast cancer. A multidisciplinary and culturally tailored patient education facilitated understanding of the disease and prompt decision making about subsequent medical care. CONCLUSIONS: Strengthened breast cancer care capacity outside the capital city, standardised referral pathways, ensured financial support for travel expenses, and enhanced patient education are required to secure linkage to the breast cancer care continuum. Robust information systems are needed to track patients and to evaluate the programme's performance.

Safety and Effectiveness Outcomes From a 14-Country Cohort of Patients With Multi-Drug Resistant Tuberculosis Treated Concomitantly With Bedaquiline, Delamanid, and Other Second-Line Drugs.

BACKGROUND: Concomitant use of bedaquiline (Bdq) and delamanid (Dlm) for multi-drug/rifampicin resistant tuberculosis (MDR/RR-TB) has raised concerns about a potentially poor risk-benefit ratio. Yet this combination is an important alternative for patients infected with strains of TB with complex drug resistance profiles or who cannot tolerate other therapies. We assessed safety and treatment outcomes of MDR/RR-TB patients receiving concomitant Bdq and Dlm, along with other second-line anti-TB drugs. METHODS: We conducted a multi-centric, prospective observational cohort study across 14 countries among patients receiving concomitant Bdq-Dlm treatment. Patients were recruited between April 2015 and September 2018 and were followed until the end of treatment. All serious adverse events and adverse events of special interest (AESI), leading to a treatment change, or judged significant by a clinician, were systematically monitored and documented. RESULTS: Overall, 472 patients received Bdq and Dlm concomitantly. A large majority also received linezolid (89.6%) and clofazimine (84.5%). Nearly all (90.3%) had extensive disease; most (74.2%) had resistance to fluoroquinolones. The most common AESI were peripheral neuropathy (134, 28.4%) and electrolyte depletion (94, 19.9%). Acute kidney injury and myelosuppression were seen in 40 (8.5%) and 24 (5.1%) of patients, respectively. QT prolongation occurred in 7 patients (1.5%). Overall, 78.0% (358/458) had successful treatment outcomes, 8.9% died, and 7.2% experienced treatment failure. CONCLUSIONS: Concomitant use of Bdq and Dlm, along with linezolid and clofazimine, is safe and effective for MDR/RR-TB patients with extensive disease. Using these drugs concomitantly is a good therapeutic option for patients with resistance to many anti-TB drugs.

Safety of Treatment Regimens Containing Bedaquiline and Delamanid in the endTB Cohort.

BACKGROUND: Safety of treatment for multidrug-resistant tuberculosis (MDR/RR-TB) can be an obstacle to treatment completion. Evaluate safety of longer MDR/RR-TB regimens containing bedaquiline and/or delamanid. METHODS: Multicentre (16 countries), prospective, observational study reporting incidence and frequency of clinically relevant adverse events of special interest (AESIs) among patients who received MDR/RR-TB treatment containing bedaquiline and/or delamanid. The AESIs were defined a priori as important events caused by bedaquiline, delamanid, linezolid, injectables, and other commonly used drugs. Occurrence of these events was also reported by exposure to the likely causative agent. RESULTS: Among 2296 patients, the most common clinically relevant AESIs were peripheral neuropathy (26.4%), electrolyte depletion (26.0%), and hearing loss (13.2%) with an incidence per 1000 person months of treatment, 1000 person-months of treatment 21.5 (95% confidence interval [CI]: 19.8-23.2), 20.7 (95% CI: 19.1-22.4), and 9.7 (95% CI: 8.6-10.8), respectively. QT interval was prolonged in 2.7% or 1.8 (95% CI: 1.4-2.3)/1000 person-months of treatment. Patients receiving injectables (N = 925) and linezolid (N = 1826) were most likely to experience events during exposure. Hearing loss, acute renal failure, or electrolyte depletion occurred in 36.8% or 72.8 (95% CI: 66.0-80.0) times/1000 person-months of injectable drug exposure. Peripheral neuropathy, optic neuritis, and/or myelosuppression occurred in 27.8% or 22.8 (95% CI: 20.9-24.8) times/1000 patient-months of linezolid exposure. CONCLUSIONS: AEs often related to linezolid and injectable drugs were more common than those frequently attributed to bedaquiline and delamanid. MDR-TB treatment monitoring and drug durations should reflect expected safety profiles of drug combinations. CLINICAL TRIALS REGISTRATION: NCT02754765.

Impacto de la pandemia por SARS-CoV-2 en adolescentes que viven con el VIH en Lima, Perú / Impact of SARS-CoV-2 pandemic on adolescents living with HIV in Lima, Peru

RESUMEN Los adolescentes que viven con el VIH (AVVIH) tienen tasas más bajas de supresión virológica y tasas más altas de deterioro inmunológico en comparación con sus contrapartes mayores, colocándolos potencialmente en alto riesgo de enfermedad severa por SARS-CoV-2. Los AVVIH que están transicionando hacia el cuidado de adultos enfrentan dificultades adicionales para permanecer en el cuidado y adherirse al tratamiento antirretroviral. En esta sección especial reportamos el impacto observado en AVVIH transicionando al servicio de VIH para adultos durante la pandemia por SARS-CoV-2. En primer lugar, el acceso a la atención del VIH se ha visto perjudicado por la restricción del transporte público, la falta de antirretrovirales, y la suspensión de citas médicas y laboratoriales. Adicionalmente, dificultades financieras, incertidumbre sobre el futuro, estresores emocionales, alteración del estilo de vida y el temor de divulgar el diagnóstico involuntariamente han desafiado aún más la continuidad en la atención de esta población adolescente.

ABSTRACT Adolescents living with HIV (ALWH) have lower rates of virologic suppression and higher rates of immunologic decline compared to their older counterparts, potentially placing them at high-risk for developing severe SARS-CoV-2 disease. ALWH who are transitioning to adult care face additional challenges to remaining in care and adhering to treatment. In this special section we report the experiences of ALWH in the process of transitioning to adult HIV services during the COVID-19 pandemic. In first place, the government-mandated stay-at-home order has substantially limited access to full HIV care by restricting public transportation, HIV medication stock-outs, and the suspension of routine medical and laboratory appointments. In addition, financial hardship, uncertainty about their future plans, emotional stressors, lifestyle disruptions, and concerns of involuntary disclosure have further challenged continuity in care for this adolescent population.

Impacto de la pandemia por SARS-CoV-2 en adolescentes que viven con el VIH en Lima, Perú / Impact of SARS-CoV-2 pandemic on adolescents living with HIV in Lima, Peru

RESUMEN Los adolescentes que viven con el VIH (AVVIH) tienen tasas más bajas de supresión virológica y tasas más altas de deterioro inmunológico en comparación con sus contrapartes mayores, colocándolos potencialmente en alto riesgo de enfermedad severa por SARS-CoV-2. Los AVVIH que están transicionando hacia el cuidado de adultos enfrentan dificultades adicionales para permanecer en el cuidado y adherirse al tratamiento antirretroviral. En esta sección especial reportamos el impacto observado en AVVIH transicionando al servicio de VIH para adultos durante la pandemia por SARS-CoV-2. En primer lugar, el acceso a la atención del VIH se ha visto perjudicado por la restricción del transporte público, la falta de antirretrovirales, y la suspensión de citas médicas y laboratoriales. Adicionalmente, dificultades financieras, incertidumbre sobre el futuro, estresores emocionales, alteración del estilo de vida y el temor de divulgar el diagnóstico involuntariamente han desafiado aún más la continuidad en la atención de esta población adolescente.

ABSTRACT Adolescents living with HIV (ALWH) have lower rates of virologic suppression and higher rates of immunologic decline compared to their older counterparts, potentially placing them at high-risk for developing severe SARS-CoV-2 disease. ALWH who are transitioning to adult care face additional challenges to remaining in care and adhering to treatment. In this special section we report the experiences of ALWH in the process of transitioning to adult HIV services during the COVID-19 pandemic. In first place, the government-mandated stay-at-home order has substantially limited access to full HIV care by restricting public transportation, HIV medication stock-outs, and the suspension of routine medical and laboratory appointments. In addition, financial hardship, uncertainty about their future plans, emotional stressors, lifestyle disruptions, and concerns of involuntary disclosure have further challenged continuity in care for this adolescent population.

Lifetime Changes in CD4 T-cell count, Viral Load Suppression and Adherence Among Adolescents Living With HIV in Urban Peru.

We quantified longitudinal changes in CD4 T-cell count, viral load suppression and combined antiretroviral therapy adherence from childhood to adolescence among patients living with HIV in urban Peru. Mean CD4 count and viral load suppression decreased dramatically in early adolescence (13 years of age) in tandem with increases in nonadherence.

The Impact of a Community-Based Intervention Including a Monthly Food Ration on Food Insecurity Among HIV-Positive Adults During the First Year of Antiretroviral Therapy.

The objective of this study was to examine how food insecurity changed among HIV-positive adults during the first 12 months of combination antiretroviral therapy (cART) and whether any change differed according to the receipt of food support, which was provided in the context of a comprehensive community-based intervention. We conducted secondary data analyses of data from a prospective cohort study of the effectiveness of a community-based cART delivery model when added to clinic-based cART delivery in Rwanda. We included patients from four health centers that implemented a clinic-based cART delivery model alone and five health centers that additionally implemented the intervention, which included 10 months of food support. We compared food insecurity at 3, 6, and 12 months, relative to baseline, and stratified by receipt of the intervention. Relative to baseline, median food insecurity score decreased after 3, 6, and 12 months (p value <0.0001 for all) for patients receiving a food ration through the community-based model for cART delivery. Among patients receiving care under the clinic-based cART model, food insecurity scores remained unchanged at 3 and 12 months and were significantly higher after 6 months. In adjusted analyses, participants enrolled in the community-based intervention with a food ration had a lower risk of severe food insecurity and a lower risk of moderate or severe food insecurity after 12 months. A comprehensive community-based HIV program including a food ration likely contributes to an alleviation of food insecurity among adults newly initiating cART.

Community-Based Accompaniment Mitigates Predictors of Negative Outcomes for Adults on Antiretroviral Therapy in Rural Rwanda.

Clinical, socioeconomic, and access barriers remain a critical problem to antiretroviral (ART) programs in sub-Saharan Africa. Community-based accompaniment (CBA), including daily home visits and psychosocial and socioeconomic support, has been associated with improved patient outcomes at 1 year. We conducted a prospective observational cohort study of 578 HIV-infected adults initiating ART in 2007-2008 with or without CBA in rural Rwanda. Among patients without CBA, those with advanced HIV disease, low CD4 cell counts, lower social support, and transport costs had significantly higher odds of negative outcomes at 1 year; amongst patients who received CBA, only those with low CD4 cell counts had significantly higher odds of negative outcomes at 1 year. CBA also significantly mitigated the effect of transport costs and inaccessibility of services on the likelihood of negative outcome. CBA may be one approach to mitigating known risk factors for negative outcomes for patients on ART in resource-poor settings.

Partner testing, linkage to care, and HIV-free survival in a program to prevent parent-to-child transmission of HIV in the Highlands of Papua New Guinea.

BACKGROUND: To eliminate new pediatric HIV infections, interventions that facilitate adherence, including those that minimize stigma, enhance social support, and mitigate the influence of poverty, will likely be required in addition to combination antiretroviral therapy (ART). We examined the relationship between partner testing and infant outcome in a prevention of parent-to-child transmission of HIV program, which included a family-centered case management approach and a supportive environment for partner disclosure and testing. DESIGN: We analyzed routinely collected data for women and infants who enrolled in the parent-to-child transmission of HIV program at Goroka Family Clinic, Eastern Highlands Provincial Hospital, Papua New Guinea, from 2007 through 2011. RESULTS: Two hundred and sixty five women were included for analysis. Of these, 226 (85%) had a partner, 127 (56%) of whom had a documented HIV test. Of the 102 HIV-infected partners, 81 (79%) had been linked to care. In adjusted analyses, we found a significantly higher risk of infant death, infant HIV infection, or loss to follow-up among mother-infant pairs in which the mother reported having no partner or a partner who was not tested or had an unknown testing status. In a second multivariable analysis, infants born to women with more time on ART or who enrolled in the program in later years experienced greater HIV-free survival. CONCLUSIONS: In a program with a patient-oriented and family-centered approach to prevent vertical HIV transmission, the majority of women's partners had a documented HIV test and, if positive, linkage to care. Having a tested partner was associated with program retention and HIV-free survival for infants. Programs aiming to facilitate diagnosis disclosure, partner testing, and linkage to care may contribute importantly to the elimination of pediatric HIV.

Improved retention associated with community-based accompaniment for antiretroviral therapy delivery in rural Rwanda.

BACKGROUND: Minimizing death and ensuring high retention and good adherence remain ongoing challenges for human immunodeficiency virus (HIV) treatment programs. We examined whether the addition of community-based accompaniment (characterized by daily home visits from a community health worker, directly observed treatment, nutritional support, transportation stipends, and other support as needed) to the Rwanda national model for antiretroviral therapy (ART) delivery would improve retention in care, viral load suppression, and change in CD4 count, relative to the national model alone. METHODS: We conducted a prospective observational cohort study among 610 HIV-infected adults initiating ART in 1 of 2 programs in rural Rwanda. Psychosocial and clinical characteristics were recorded at ART initiation. Death, treatment retention, and plasma viral load were assessed at 1 year. CD4 count was evaluated at 6-month intervals. Multivariable regression models were used to adjust for baseline differences between the 2 populations. RESULTS: Eighty-five percent and 79% of participants in the community-based and clinic-based programs, respectively, were retained with viral load suppression at 1 year. After adjusting for CD4 count, depression, physical health quality of life, and food insecurity, community-based accompaniment was protective against death or loss to follow-up during the first year of ART (hazard ratio, 0.17; 95% confidence interval [CI], .09-.35; P < .0001). In a second multivariable analysis, individuals receiving accompaniment were more likely to be retained with a suppressed viral load at 1 year (risk ratio: 1.15; 95% CI, 1.03-1.27; P = .01). CONCLUSIONS: These findings indicate that community-based accompaniment is effective in improving retention, when added to a clinic-based program with fewer patient support mechanisms.

Excellent clinical outcomes and high retention in care among adults in a community-based HIV treatment program in rural Rwanda.

BACKGROUND: Access to antiretroviral therapy (ART) has rapidly expanded; as of the end of 2010, an estimated 6.6 million people are receiving ART in low-income and middle-income countries. Few reports have focused on the experiences of rural health centers or the use of community health workers. We report clinical and programatic outcomes at 24 months for a cohort of patients enrolled in a community-based ART program in southeastern Rwanda under collaboration between Partners In Health and the Rwandan Ministry of Health. METHODS AND FINDINGS: A retrospective medical record review was performed for a cohort of 1041 HIV+ adult patients initiating community-based ART between June 1, 2005, and April 30, 2006. Key programatic elements included free ART with direct observation by community health worker, tuberculosis screening and treatment, nutritional support, a transportation allowance, and social support. Among 1041 patients who initiated community-based ART, 961 (92.3%) were retained in care, 52 (5%) died and 28 (2.7%) were lost to follow-up. Median CD4 T-cell count increase was 336 cells per microliter [interquartile range: (IQR): 212-493] from median 190 cells per microliter (IQR: 116-270) at initiation. CONCLUSIONS: A program of intensive community-based treatment support for ART in rural Rwanda had excellent outcomes in 24-month retention in care. Having committed to improving access to HIV treatment in sub-Saharan Africa, the international community, including country HIV programs, should set high programmatic outcome benchmarks.

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.