High Rate of Hypothyroidism in Multidrug-Resistant Tuberculosis Patients Co-Infected with HIV in Mumbai, India.

Adverse events (AEs) among HIV-infected patients with multidrug-resistant tuberculosis (MDR-TB) receiving anti-TB and antiretroviral treatments (ART) are under-researched and underreported. Hypothyroidism is a common AE associated with ethionamide, p-aminosalicylic acid (PAS), and stavudine. The aim of this study was to determine the frequency of and risk factors associated with hypothyroidism in HIV/MDR-TB co-infected patients

Poor outcomes in a cohort of HIV-infected adolescents undergoing treatment for multidrug-resistant tuberculosis in Mumbai, India.

BACKGROUND: Little is known about the treatment of multidrug-resistant tuberculosis (MDR-TB) in HIV-co-infected adolescents. This study aimed to present the intermediate outcomes of HIV-infected adolescents aged 10-19 years receiving second-line anti-TB treatment in a Médecins Sans Frontières (MSF) project in Mumbai, India. METHODS: A retrospective review of medical records of 11 adolescents enrolled between July 2007 and January 2013 was undertaken. Patients were initiated on either empirical or individualized second-line ambulatory anti-TB treatment under direct observation. RESULTS: The median age was 16 (IQR 14-18) years and 54% were female. Five (46%) adolescents had pulmonary TB (PTB), two (18%) extrapulmonary disease (EPTB) and four (36%) had both. Median CD4 count at the time of MDR-TB diagnosis was 162.7 cells/µl (IQR: 84.8-250.5). By January 2013, eight patients had final and 3 had interim outcomes. Favourable results were seen in four (36.5%) patients: one was cured and three were still on treatment with negative culture results. Seven patients (64%) had poor outcomes: four (36.5%) died and three (27%) defaulted. Three of the patients who died never started on antiretroviral and/or TB treatment and one died 16 days after treatment initiation. Two of the defaulted died soon after default. All patients (100%) on-treatment experienced adverse events (AEs): two required permanent discontinuation of the culprit drug and two were hospitalized due to AEs. No patient required permanent discontinuation of the entire second-line TB or antiretroviral regimens. CONCLUSIONS: Early mortality and mortality after default were the most common reasons for poor outcomes in this study. Early mortality suggests the need for rapid diagnosis and prompt treatment initiation, and adolescents might benefit from active contact-tracing and immediate referral. Default occurred at different times, suggesting the need for continuous, intensified and individualized psychosocial support for co-infected adolescents. Operational research among co-infected adolescents will be especially important in designing effective interventions for this vulnerable group

Correction: Ambulatory management of pre- and extensively drug resistant tuberculosis patients with imipenem delivered through port-a-cath: A mixed methods study on treatment outcomes and challenges.

[This corrects the article DOI: 10.1371/journal.pone.0234651.]

Ambulatory management of pre- and extensively drug resistant tuberculosis patients with imipenem delivered through port-a-cath: A mixed methods study on treatment outcomes and challenges.

BackgroundImipenem, an intravenous antibiotic is recommended for use in drug resistant tuberculosis (DR-TB) when an effective regimen with combination of other second line drugs is not possible. Though the treatment success rates with carbapenems are promising, the twice daily injection of Imipenem usually requires patients to be hospitalized. The Médecins Sans Frontières independent clinic in Mumbai, India implemented ambulatory and home based management of patients receiving Imipenem through the use of port-a-cath.ObjectiveWe aimed to describe the adverse events and treatment outcomes of ambulatory pre- and XDR-TB patients initiated on imipenem through port-a-cath between January 2015 and June 2018 and to explore the challenges with this regimen as perceived by healthcare providers and patients.MethodsA convergent mixed methods study with quantitative (longitudinal descriptive study using the routine data) and qualitative (descriptive study) part conducted concurrently. For the quantitative component, all XDR-TB and pre-XDR-TB initiated on imipenem containing regimen during January 2015-June 2018 were included. For qualitative component, interviews were carried out including patients who initiated on imipenem (n = 5) and healthcare providers (n = 7) involved in providing treatment. Treatment outcomes, culture conversion and adverse events during treatment were described. Thematic analysis was carried out for qualitative component.ResultsOf the 70 patients included, the mean age was 28.1 (standard deviation: 11.2) years and 36 (51.4%) were females. Fifty one (72.9%) had XDR-TB. All patients were resistant to fluoroquinilone, levofloxacin. Vomiting was reported by 55 (78.6%) patients and at least one episode of QTC prolongation (more than 500 msec by Fredrecia method) was detected in 25 (35.7%). Port-a-cath block and infection was seen in 11 (15.7%) and 20 (28.6%) patients respectively. Favourable outcomes were seen in 43 (61.4%) patients. Mortality was seen in 22 (31.4%) patients, 2 (2.9%) were lost-to-follow-up and 3 (4.3%) were declared as treatment failure. The overarching theme of the qualitative analysis was: Challenges in delivering Imipenem via port-a-cath device in ambulatory care. Major challenges identified were difficulties in adhering to drug dose timelines, vomiting, restricted mobility due to port-a-cath, paucity of infection control and space constraints at patients' home for optimal care.ConclusionAdministration of imipenem was feasible through port-a-cath. Though outcomes with ambulatory based imipenem containing regimens were promising, there were several challenges in providing care. The feasibility of infusion at day care facilities needs to explored to overcome challenges in infusion at patients home

Flowchart of the Mumbai HIV/MDR-TB co-infected adolescent cohort, 2007–2013.

<p>Flowchart of the Mumbai HIV/MDR-TB co-infected adolescent cohort, 2007–2013.</p

Outcomes of the Mumbai HIV/MDR-TB co-infected adolescent cohort, 2007–2013.

<p>Outcomes of the Mumbai HIV/MDR-TB co-infected adolescent cohort, 2007–2013.</p

Treatment-related adverse events in the Mumbai HIV/MDR-TB co-infected adolescent cohort, 2007–2013.

<p>M: male; F: female; S: streptomycin; Cm: capreomycin; Km: kanamycin; Lfx: levofloxacin; Eto: ethionamide; CS: cycloserine; Amcl: amoxicillin/clavulanic acid; Mfx: moxifloxacin; PAS: para-aminosalicylic acid; Z: pyrazinamide; H: isoniazid; Hh: high dose isoniazid; E; ethambutol, Cfz: clofazimine; GI: gastrointestinal; CrCl: creatinine clearanc.</p

Clinical Characteristics of the Mumbai HIV/MDR-TB co-infected adolescent cohort, 2007–2013.

<p>M: male; F: female; D4T: stavudine; 3TC: lamivudine; EFV: efavirenz; TDF: tenofovir; AZT: zidovudine; ABC: abacavir; NVP: nevirapine; ATV/r: atazanavir/ritonavir; LPV: lopinavir; PTB: pulmonary tuberculosis; EPTB: extra-pulmonary tuberculosis; Abd; abdominal; Cereb; cerebral, LN: lymph node; NEG: negative; POS: positive; S: streptomycin; Cm: capreomycin; Km: kanamycin; Lfx: levofloxacin; Eto: ethionamide; CS: cycloserine; Amcl: amoxicillin/clavulanic acid; Mfx: moxifloxacin; Ofx; ofloxacin; PAS; para-aminosalicylic acid; Z: pyrazinamide; H: isoniazid; Hh: high dose isoniazid; E: ethambutol; Cfz: clofazimine; XDR: extensively drug-resistant; MDR: multidrug-resistant.</p>*<p>at time of MDR-TB diagnosis.</p

Time-to-Hypothyroidism following initiation of MDR-TB treatment using Kaplan-Meier analysis.

<p>Time-to-Hypothyroidism following initiation of MDR-TB treatment using Kaplan-Meier analysis.</p