Community-based accompaniment for adolescents transitioning to adult HIV care in urban Peru: a pilot study.

We piloted a community-based intervention to improve outcomes among adolescents living with HIV who were transitioning to adult-oriented care in Lima, Peru. We assessed feasibility and potential effectiveness, including within-person changes in self-reported adherence, psychosocial metrics (NIH Toolbox), and transition readiness ("Am I on TRAC" questionnaire, "Got Transition" checklist). From October 2019 to January 2020, we enrolled 30 adolescents (15-21 years). The nine-month intervention consisted of logistical, adherence and social support delivered by entry-level health workers and group sessions to improve health-related knowledge and skills and social support. In transition readiness, we observed within-person improvements relative to baseline. We also observed strong evidence of improvements in adherence, social support, self-efficacy, and stress, which were generally sustained three months post-intervention. All participants remained in treatment after 12 months. The intervention was feasible and potentially effective for bridging the transition to adult HIV care. A large-scale evaluation, including biological endpoints, is warranted.

RESUMEN: Piloteamos una intervención comunitaria para mejorar los resultados de adolescentes viviendo con el VIH que se encontraban en transición a la atención de VIH orientada a adultos en Lima, Perú. Evaluamos la viabilidad y la eficacia potencial, incluidos los cambios personales en la adherencia auto-reportada, criterios psicosociales (NIH Toolbox), y preparación para la transición (cuestionario "Estoy en el TRAC", lista de verificación "Got Transition"). Desde octubre de 2019 hasta enero de 2020, enrolamos a 30 adolescentes (15 a 21 años). La intervención de nueve meses consistió en apoyo logístico, de adherencia y social brindado por técnicos de enfermería y sesiones grupales para mejorar tanto el conocimiento y las habilidades relacionados con la salud, como el apoyo social. En cuanto a la preparación para la transición, observamos mejoras comparada con el basal. También observamos una fuerte evidencia de mejoras en la adherencia, apoyo social, autoeficacia y estrés, que se mantuvieron, generalmente, tres meses después del fin de la intervención. Todos los participantes seguían en tratamiento después de 12 meses. La intervención fue factible y potencialmente efectiva para tender un puente en la transición a la atención del VIH para adultos. Esto amerita una evaluación a mayor escala y que incluya criterios clínicos.

Feasibility and Acceptability of an Adolescent-Friendly Rap Video to Improve Health Literacy Among HIV-Positive Youth in Urban Peru.

Clinical outcomes among adolescents living with HIV (ALHIV) might be improved by interventions aimed at addressing limited health literacy. We developed a Spanish-language rap video on HIV concepts and examined its acceptability and feasibility as a learning tool among ALHIV in Lima, Peru. Twenty-eight ALHIV receiving care at an urban pediatric hospital and ten stakeholders engaged in the care of adolescents watched the video. Adolescents completed a pre- and post-video questionnaire. We conducted focus groups with ALHIV and in-depth interviews with stakeholders and analyzed transcripts to identify themes. ALHIV described concepts of CD4 cell count and viral load as they were portrayed. Participants reported the video was relatable, accessible, and provided hope that ALHIV could lead healthy lives and advocated for future videos to address topics such as transmission and sexual health. Questionnaires indicated some improvement in viral load knowledge. An HIV health literacy music video intervention was feasible to implement and accepted by ALHIV and their healthcare providers. Communicating HIV knowledge via music videos may be promising; further study is needed to optimize implementation.

RESUMEN: Los resultados clínicos entre los adolescentes que viven con el VIH (AVVIH) podrían mejorarse mediante intervenciones dirigidas a abordar la limitada alfabetización sanitaria. Desarrollamos un video de rap en español sobre los conceptos del VIH y examinamos su aceptabilidad y viabilidad como herramienta de aprendizaje entre los AVVIH en Lima, Perú. Veintiocho AVVIH que reciben atención en un hospital pediátrico urbano y diez interesados involucrados en la atención de adolescentes vieron el video. Los adolescentes completaron un cuestionario previo y posterior al video. Realizamos grupos focales con AVVIH y entrevistas a profundidad a los interesados y analizamos las transcripciones para identificar los temas. Los AVVIH describieron conceptos de recuento de células CD4 y carga viral tal como se retrataron. Los participantes informaron que el video era identificable, accesible y brindaba la esperanza de que los AVVIH pudiera llevar una vida saludable y abogaron por videos futuros para abordar temas como la transmisión y la salud sexual. Los cuestionarios indicaron cierta mejora en el conocimiento de la carga viral. Una intervención de video musical para educación en salud sobre el VIH fue factible de implementar y fue aceptada por los AVVIH y sus proveedores de atención médica. La comunicación de conocimientos sobre el VIH a través de videos musicales puede ser prometedora; se necesitan más estudios para optimizar la implementación.

Treatment outcomes among children, adolescents, and adults on treatment for tuberculosis in two metropolitan municipalities in Gauteng Province, South Africa.

BACKGROUND: Gauteng Province has the second lowest tuberculosis (TB) incidence rate in South Africa but the greatest proportion of TB/HIV co-infection, with 68% of TB patients estimated to have HIV. TB treatment outcomes are well documented at the national and provincial level; however, knowledge gaps remain on how outcomes differ across detailed age groups. METHODS: Using data from South Africa's National Electronic TB Register (ETR), we assessed all-cause mortality and loss to follow-up (LTFU) among patients initiating treatment for TB between 01/2010 and 12/2015 in the metropolitan municipalities of Ekurhuleni Metropolitan Municipality and the City of Johannesburg in Gauteng Province. We excluded patients who were missing age, had known drug-resistance, or transferred into TB care from sites outside the two metropolitan municipalities. Among patients assigned a treatment outcome, we investigated the association between age group at treatment initiation and mortality or LTFU (treatment interruption of ≥2 months) within 10 months after treatment initiation using Cox proportional hazard models and present hazard ratios and Kaplan-Meier survival curves. RESULTS: We identified 182,890 children (<10 years), young adolescent (10-14), older adolescent (15-19), young adult (20-24), adult (25-49), and older adult (≥50) TB cases without known drug-resistance. ART coverage among HIV co-infected patients was highest for young adolescents (64.3%) and lowest for young adults (54.0%) compared to other age groups (all over 60%). Treatment success exceeded 80% in all age groups (n = 170,017). All-cause mortality increased with age. Compared to adults, young adults had an increased hazard of LTFU (20-24 vs 25-49 years; aHR 1.43 95% CI: 1.33, 1.54) while children, young adolescents, and older adults had lower hazard of LTFU. Patients with HIV on ART had a lower risk of LTFU, but greater risk of death when compared to patients without HIV. CONCLUSIONS: Young adults in urban areas of Gauteng Province experience a disproportionate burden of LTFU and low coverage of ART among co-infected patients. This group should be targeted for interventions aimed at improving clinical outcomes and retention in both TB and HIV care.

Understanding health-related behavior among adolescents living with HIV in Lima, Peru.

BACKGROUND: The global HIV burden among adolescents ages 10-19 is growing. This population concurrently confronts the multifaceted challenges of adolescence and living with HIV. With the goal of informing future interventions tailored to this group, we assessed sexual activity, HIV diagnosis disclosure, combination antiretroviral therapy (cART) adherence, and drug use among adolescents living with HIV (ALHIV) in Lima, Peru. METHODS: Adolescents at risk or with a history of suboptimal cART adherence completed a self-administered, health behaviors survey and participated in support group sessions, which were audio recorded and used as a qualitative data source. Additionally, we conducted in-depth interviews with caregivers and care providers of ALHIV. Thematic content analysis was performed on the group transcripts and in-depth interviews and integrated with data from the survey to describe adolescents' health related behaviors. RESULTS: We enrolled 34 ALHIV, of which 32 (14 male, 18 female, median age 14.5 years) completed the health behavior survey. Nine (28%) adolescents reported prior sexual intercourse, a minority of whom (44%) reported using a condom. cART adherence was highest in the 10-12 age group with 89% reporting ≤2 missed doses in the last month, compared to 36% in adolescents 13 years or older. Over 80% of adolescents had never disclosed their HIV status to a friend or romantic partner. Adolescents, caregivers, and health service providers described sexual health misinformation and difficulty having conversations about sexual health and HIV. CONCLUSIONS: In this group of ALHIV, adherence to cART declined with age and condom use among sexually active adolescents was low. Multifactorial interventions addressing sexual health, gaps in HIV-related knowledge, and management of disclosure and romantic relationships are urgently needed for this population.

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.

The Dynamics of Intimate Partner Violence and Its Impact on HIV Care: A Cross-Sectional Study of People of Mixed Gender and Sexual Preference in Lima, Peru.

Intimate partner violence (IPV) is associated with a higher risk of contracting HIV and developing worse HIV outcomes. This cross-sectional, mixed methods study presents data on IPV using the Conflicts Tactics Scale (CTS2-S) among 180 persons with HIV in Lima, Peru, as well as qualitative interviews with 7 of them and 18 of their community caregivers. This study used data collected for a randomized controlled trial (RCT), CASAommunity Based Accompaniment with Supervised Antiretrovirals (CASA) Community-based Accompaniment with Supervised Antiretrovirals (CASA). Physical or sexual IPV was self-reported in 82 (45.6%) of participants reporting having been in a relationship in the last year and 59,8% of those were involved in bidirectional violence. Coping subscales, social support, and stigma were associated with IPV. Intimate partner violence negatively impacted patient adherence to medication and care, particularly during times of severe conflict. In conclusion, profound psychosocial vulnerability-including low social support, substance use as coping, and HIV stigma-contextualize IPV among people with HIV. Bidirectional violence often evolved over time as victims negotiated inter-personal strategies for survival, including retaliation. Interventions should focus on a deeper understanding IPV and facilitating of coping mechanisms to help people with HIV stay in care.

Comparative effectiveness of adding delamanid to a multidrug-resistant tuberculosis regimen comprised of three drugs likely to be effective.

Clarity about the role of delamanid in longer regimens for multidrug-resistant TB is needed after discordant Phase IIb and Phase III randomized controlled trial results. The Phase IIb trial found that the addition of delamanid to a background regimen hastened culture conversion; the results of the Phase III trial were equivocal. We evaluated the effect of adding delamanid for 24 weeks to three-drug MDR/RR-TB regimens on two- and six-month culture conversion in the endTB observational study. We used pooled logistic regression to estimate the observational analogue of the intention-to-treat effect (aITT) adjusting for baseline confounders and to estimate the observational analogue of the per-protocol effect (aPP) using inverse probability of censoring weighting to control for time-varying confounding. At treatment initiation, 362 patients received three likely effective drugs (delamanid-free) or three likely effective drugs plus delamanid (delamanid-containing). Over 80% of patients received two to three Group A drugs (bedaquiline, linezolid, moxifloxacin/levofloxacin) in their regimen. We found no evidence the addition of delamanid to a three-drug regimen increased two-month (aITT relative risk: 0.90 (95% CI: 0.73-1.11), aPP relative risk: 0.89 (95% CI: 0.66-1.21)) or six-month culture conversion (aITT relative risk: 0.94 (95% CI: 0.84, 1.02), aPP relative risk: 0.93 (95% CI: 0.83, 1.04)). In regimens containing combinations of three likely effective, highly active anti-TB drugs the addition of delamanid had no discernible effect on culture conversion at two or six months. As the standard of care for MDR/RR-TB treatment becomes more potent, it may become increasingly difficult to detect the benefit of adding a single agent to standard of care MDR/RR-TB regimens. Novel approaches like those implemented may help account for background regimens and establish effectiveness of new chemical entities.

Selection bias in multidrug-resistant tuberculosis cohort studies assessing sputum culture conversion.

BACKGROUND: Conversion of sputum culture from positive to negative for M. tuberculosis is a key indicator of treatment response. An initial positive culture is a pre-requisite to observe conversion. Consequently, patients with a missing or negative initial culture are excluded from analyses of conversion outcomes. To identify the initial, or "baseline" culture, researchers must define a sample collection interval. An interval extending past treatment initiation can increase sample size but may introduce selection bias because patients without a positive pre-treatment culture must survive and remain in care to have a culture in the post-treatment interval. METHODS: We used simulated data and data from the endTB observational cohort to investigate the potential for bias when extending baseline culture intervals past treatment initiation. We evaluated bias in the proportion with six-month conversion. RESULTS: In simulation studies, the potential for bias depended on the proportion of patients missing a pre-treatment culture, proportion with conversion, proportion culture positive at treatment initiation, and proportion of patients missing a pre-treatment culture who would have been observed to be culture positive, had they had a culture. In observational data, the maximum potential for bias when reporting the proportion with conversion reached five percentage points in some sites. CONCLUSION: Extending the allowable baseline interval past treatment initiation may introduce selection bias. If investigators choose to extend the baseline collection interval past treatment initiation, the proportion missing a pre-treatment culture and the number of deaths and losses to follow up during the post-treatment allowable interval should be clearly enumerated.

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.

Barriers and facilitators influencing facility-based childbirth in rural Haiti: a mixed method study with a convergent design.

INTRODUCTION: Haiti has the highest maternal mortality rate in the Western Hemisphere. Facility-based childbirth is promoted as the standard of care for reducing maternal and neonatal mortality. We conducted a convergent, mixed methods study to assess barriers and facilitators to facility-based childbirth at Hôpital Universitaire de Mirebalais (HUM) in Mirebalais, Haiti. METHODS: We conducted secondary analyses of a prospective cohort of pregnant women seeking antenatal care at HUM and quantitatively assessed predictors of not having a facility-based childbirth at HUM. We prospectively enrolled 30 pregnant women and interviewed them about their experiences delivering at home or at HUM. RESULTS: Of 1105 pregnant women seeking antenatal care at the hospital between May and December 2017, 773 (70%) returned to the hospital for facility-based childbirth. In multivariable analyses, living farther from the hospital (adjusted OR (AOR)=0.73; 95% CI 0.56 to 0.96), poverty (AOR=0.93; 95% CI 0.88 to 0.99) and household hunger (AOR=0.45; 95% CI 0.26 to 0.79) were associated with not having a facility-based childbirth. Primigravid women were more likely to have a facility-based childbirth (AOR=1.34, 95% CI 1.02 to 1.76). Qualitative data provided insight into the value women place on traditional birth attendants ('matrons') during home-based childbirths. While women perceived facility-based childbirths as better equipped to handle birth complications, barriers such as distance, costs of transportation and supplies, discomfort of facility birthing practices and mistreatment by medical staff resulted in negative perceptions of facility-based childbirths. CONCLUSION: Pregnant women in rural Haiti must overcome substantial structural barriers and forfeit valued support from traditional birth attendants when they pursue facility-based childbirths. If traditional birth attendants could be involved in care alongside midwives at facilities, women may be more inclined to deliver there. While complex structural barriers remain, the inclusion of matrons at facilities may increase uptake of facility-based childbirths, and ultimately improve maternal and neonatal outcomes.

Mortality in children diagnosed with tuberculosis: a systematic review and meta-analysis.

BACKGROUND: Case fatality ratios in children with tuberculosis are poorly understood-particularly those among children with HIV and children not receiving tuberculosis treatment. We did a systematic review of published work to identify studies of population-representative samples of paediatric (ie, <15 years) tuberculosis cases. METHODS: We searched PubMed and Embase for reports published in English, French, Portuguese, or Spanish before Aug 12, 2016, that included terms related to tuberculosis, children, mortality, and population representativeness. We also reviewed our own files and reference lists of articles identified by this search. We screened titles and abstracts for inclusion, excluding studies in which outcomes were unknown for 10% or more of the children and publications detailing non-representative samples. We used random-effects meta-analysis to produce pooled estimates of case fatality ratios from the included studies, which we divided into three eras: the pre-treatment era (ie, studies before 1946), the middle era (1946-80), and the recent era (after 1980). We stratified our analyses by whether or not children received tuberculosis treatment, age (0-4 years, 5-14 years), and HIV status. FINDINGS: We identified 31 papers comprising 35 datasets representing 82 436 children with tuberculosis disease, of whom 9274 died. Among children with tuberculosis included in studies in the pre-treatment era, the pooled case fatality ratio was 21·9% (95% CI 18·1-26·4) overall. The pooled case fatality ratio was significantly higher in children aged 0-4 years (43·6%, 95% CI 36·8-50·6) than in those aged 5-14 years (14·9%, 11·5-19·1). In studies in the recent era, when most children had tuberculosis treatment, the pooled case fatality ratio was 0·9% (95% CI 0·5-1·6). US surveillance data suggest that the case fatality ratio is substantially higher in children with HIV receiving treatment for tuberculosis (especially without antiretroviral therapy) than in those without HIV. INTERPRETATION: Without adequate treatment, children with tuberculosis, especially those younger than 5 years, are at high risk of death. Children with HIV have an increased mortality risk, even when receiving tuberculosis treatment. FUNDING: US National Institutes of Health, Janssen Global Public Health.

Development and Validation of a Food Frequency Questionnaire to Estimate Intake among Children and Adolescents in Urban Peru.

Tools to assess intake among children in Latin America are limited. We developed and assessed the reproducibility and validity of a semi-quantitative food frequency questionnaire (FFQ) administered to children, adolescents, and their caregivers in Lima, Peru. We conducted 24-h diet recalls (DRs) and focus groups to develop a locally-tailored FFQ prototype for children aged 0-14 years. To validate the FFQ, we administered two FFQs and three DRs to children and/or their caregivers (N = 120) over six months. We examined FFQ reproducibility by quartile agreement and Pearson correlation coefficients, and validity by quartile agreement and correlation with DRs. For reproducibility, quartile agreement ranged from 60-77% with correlations highest for vitamins A and C (0.31). Age-adjusted correlations for the mean DR and the second-administered FFQ were highest in the 0-7 age group, in which the majority of caregivers completed the FFQ on behalf of the child (total fat; 0.67) and in the 8-14 age group, in which both the child and caregiver completed the FFQ together (calcium, niacin; 0.54); correlations were <0.10 for most nutrients in the 8-14 age group in which the caregiver completed the FFQ on the child's behalf. The FFQ was reproducible and the first developed and validated to assess various nutrients in children and adolescents in Peru.

Discordant Treatment Responses to Combination Antiretroviral Therapy in Rwanda: A Prospective Cohort Study.

INTRODUCTION: Some antiretroviral therapy naïve patients starting combination antiretroviral therapy (cART) experience a limited CD4 count rise despite virological suppression, or vice versa. We assessed the prevalence and determinants of discordant treatment responses in a Rwandan cohort. METHODS: A discordant immunological cART response was defined as an increase of <100 CD4 cells/mm3 at 12 months compared to baseline despite virological suppression (viral load [VL] <40 copies/mL). A discordant virological cART response was defined as detectable VL at 12 months with an increase in CD4 count ≥100 cells/mm3. The prevalence of, and independent predictors for these two types of discordant responses were analysed in two cohorts nested in a 12-month prospective study of cART-naïve HIV patients treated at nine rural health facilities in two regions in Rwanda. RESULTS: Among 382 patients with an undetectable VL at 12 months, 112 (29%) had a CD4 rise of <100 cells/mm3. Age ≥35 years and longer travel to the clinic were independent determinants of an immunological discordant response, but sex, baseline CD4 count, body mass index and WHO HIV clinical stage were not. Among 326 patients with a CD4 rise of ≥100 cells/mm3, 56 (17%) had a detectable viral load at 12 months. Male sex was associated with a virological discordant treatment response (P = 0.05), but age, baseline CD4 count, BMI, WHO HIV clinical stage, and travel time to the clinic were not. CONCLUSIONS: Discordant treatment responses were common in cART-naïve HIV patients in Rwanda. Small CD4 increases could be misinterpreted as a (virological) treatment failure and lead to unnecessary treatment changes.

Programmatic Management of Drug-Resistant Tuberculosis: An Updated Research Agenda.

INTRODUCTION: There are numerous challenges in delivering appropriate treatment for multidrug-resistant tuberculosis (MDR-TB) and the evidence base to guide those practices remains limited. We present the third updated Research Agenda for the programmatic management of drug-resistant TB (PMDT), assembled through a literature review and survey. METHODS: Publications citing the 2008 research agenda and normative documents were reviewed for evidence gaps. Gaps were formulated into questions and grouped as in the 2008 research agenda: Laboratory Support, Treatment Strategy, Programmatically Relevant Research, Epidemiology, and Management of Contacts. A survey was distributed through snowball sampling to identify research priorities. Respondent priority rankings were scored and summarized by mean. Sensitivity analyses explored weighting and handling of missing rankings. RESULTS: Thirty normative documents and publications were reviewed for stated research needs; these were collapsed into 56 research questions across 5 categories. Of more than 500 survey recipients, 133 ranked priorities within at least one category. Priorities within categories included new diagnostics and their effect on improving treatment outcomes, improved diagnosis of paucibacillary and extra pulmonary TB, and development of shorter, effective regimens. Interruption of nosocomial transmission and treatment for latent TB infection in contacts of known MDR-TB patients were also top priorities in their respective categories. Results were internally consistent and robust. DISCUSSION: Priorities retained from the 2008 research agenda include shorter MDR-TB regimens and averting transmission. Limitations of recent advances were implied in the continued quest for: shorter regimens containing new drugs, rapid diagnostics that improve treatment outcomes, and improved methods of estimating burden without representative data. CONCLUSION: There is continuity around the priorities for research in PMDT. Coordinated efforts to address questions regarding shorter treatment regimens, knowledge of disease burden without representative data, and treatment for LTBI in contacts of known DR-TB patients are essential to stem the epidemic of TB, including DR-TB.

Global and Regional Burden of Isoniazid-Resistant Tuberculosis.

BACKGROUND: Isoniazid has been the backbone of tuberculosis chemotherapy for 6 decades. Resistance to isoniazid threatens the efficacy of treatment of tuberculosis disease and infection. To inform policies around treatment of tuberculosis disease and infection in children, we sought to estimate both the proportion of child tuberculosis cases with isoniazid resistance and the number of incident isoniazid-resistant tuberculosis cases in children, by region. METHODS: We determined the relationship between rates of isoniazid resistance among child cases and among treatment-naive adult cases through a systematic literature review. We applied this relationship to regional isoniazid resistance estimates to estimate proportions of childhood tuberculosis cases with isoniazid resistance. We applied these proportions to childhood tuberculosis incidence estimates to estimate numbers of children with isoniazid-resistant tuberculosis. RESULTS: We estimated 12.1% (95% confidence interval [CI] 9.8% to 14.8%) of all children with tuberculosis had isoniazid-resistant disease, representing 120,872 (95% CI 96,628 to 149,059) incident cases of isoniazid-resistant tuberculosis in children in 2010. The majority of these occurred in the Western Pacific and Southeast Asia regions; the European region had the highest proportion of child tuberculosis cases with isoniazid resistance, 26.1% (95% CI: 20.0% to 33.6%). CONCLUSIONS: The burden of isoniazid-resistant tuberculosis in children is substantial, and risk varies considerably by setting. The large number of child cases signals extensive ongoing transmission from adults with isoniazid-resistant tuberculosis. The risk of isoniazid resistance must be considered when evaluating treatment options for children with disease or latent infection to avoid inadequate treatment and consequent poor outcomes.