Poor Outcomes in a Cohort of HIV-Infected Adolescents Undergoing Treatment for Multidrug-Resistant Tuberculosis in Mumbai, India

Abstract

BackgroundLittle 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.MethodsA 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.ResultsThe 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.ConclusionsEarly 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.

Outcomes in Adolescents Undergoing Treatment for Drug-resistant Tuberculosis in Cape Town, South Africa, 2008-2013

“…However we observed much lower mortality in a larger cohort of patients with final treatment outcomes 15. Our loss from treatment proportion of 43% was 1.6 times that seen in the Mumbai cohort (15). It is possible that the high proportion of those lost from treatment masked some deaths in our cohort (only one of these is known to have died); therefore overall mortality is likely to be higher than presented here.…”

“…Two adolescents refused treatment, an observation previously reported in TB patients (15,34). In this population this can be attributed to a myriad of reasons including the physical and emotional changes, and the pressures associated with life during this period.…”

“…These patients who had resistance to second line drugs and were HIV negative demonstrate very poor outcomes and early mortality in extensive resistance. They could however also be disease that presented and was diagnosed and treated late in its course as has been described in other settings (15,37). In the Indian adolescent cohort, three of the four reported deaths occurred prior to treatment initiation and one within three weeks of initiation, and were ascribed to delayed diagnosis and treatment rather than treatment failure (15).…”

“…The outcomes for the entire cohort have been reported elsewhere in the literature (22). The adolescent outcomes are presented separately here given the poor treatment outcomes seen in the Mumbai cohort (15) and since this is to our knowledge one of the largest cohorts of adolescent patients reported in the literature.…”

“…The period of adolescence defined by the WHO as between the ages of 10-19 years (12) may pose significant challenges to the management of DR-TB (13,14). One of the only studies of DR-TB in adolescents was of HIV co-infected adolescents in Mumbai which found that poor treatment outcomes were common, with 64% experiencing death, treatment failure, or default (15).…”