SUMMARY BACKGROUND Despite renewed focus on molecular tuberculosis (TB) diagnostics and new antimycobacterial agents, treatment outcomes for patients co-infected with drug-resistant TB and human immunodeficiency virus (HIV) remain dismal, in part due to lack of focus on medication adherence as part of a patient-centered continuum of care. OBJECTIVE To review current barriers to drug-resistant TB-HIV treatment and propose an alternative model to conventional approaches to treatment support. DISCUSSION Current national TB control programs rely heavily on directly observed therapy (DOT) as the centerpiece of treatment delivery and adherence support. Medication adherence and care for drug-resistant TB-HIV could be improved by fully implementing team-based patient-centered care, empowering patients through counseling and support, maintaining a rights-based approach while acknowledging the responsibility of health care systems in providing comprehensive care, and prioritizing critical research gaps. CONCLUSION It is time to re-invent our understanding of adherence in drug-resistant TB and HIV by focusing attention on the complex clinical, behavioral, social, and structural needs of affected patients and communities.

Tuberculosis (TB) remains an enormous public health concern globally. India and South Africa rank among the top 10 high TB burden countries with the highest absolute burden of TB, and the second highest rate of TB incidence, respectively. Although the primary drivers of TB transmission vary considerably between these two countries, they do indeed share common themes. In 2017, only 64% of the global estimated incident cases of TB were reported, the remaining 36% of ‘missing’ cases were either undiagnosed, untreated or unreported. These ‘missing TB cases’ have generated much hype for the challenges they present in achieving the End TB Strategy. Although India and South Africa have indeed made significant strides in TB control, analysis of the patient cascade of care clearly suggests that these ‘missed’ patients are not really missing—most are actively engaging the health system—the system, however, is failing to appropriately manage them. In short, quality of TB care is suboptimal and must urgently be addressed, merely focusing on coverage of TB services is no longer sufficient. While the world awaits revolutionary vaccines, drugs and diagnostics, programmatic data indicate that much can be done to accelerate the decline of TB. In this perspective, we compare and contrast these two national epidemics, and explore barriers, with a particular focus on the role of health systems in finding the missing millions.

BACKGROUND: Bedaquiline (BDQ) has not been extensively studied among patients co-infected with HIV drug-resistant tuberculosis (DR-TB). We compared treatment outcomes in DR-TB patients treated with BDQ- and linezolid (LZD) containing regimens to historic controls treated with second-line injectable-containing regimens.METHODS: Retrospective cohort study of consecutive DR-TB patients initiated on BDQ- and LZD-containing regimens at a TB referral hospital in KwaZulu-Natal, South Africa. Participants were prospectively followed through 24 months for treatment outcome and adverse events. Outcomes were compared to a historic control cohort of DR-TB HIV patients enrolled at the same facility prior to BDQ introduction.RESULTS: Adult DR-TB patients initiating BDQ between January 2014 and November 2015 were enrolled (n = 151). The majority of patients were female (52%), HIV co-infected (77%) and on antiretroviral therapy (100%). End of treatment outcomes included cure (63%), TB culture conversion (83%), completion (0.7%), loss to follow-up (15%), treatment failure (5%), and death (17%). Compared to historic controls (n = 105), patients treated with BDQ experienced significantly higher TB culture conversion and cure, with significantly lower mortality. Adverse effects were common (92%), and most frequently attributed to LZD (24.1%). QT segment prolongation was common but without clinical sequelae.CONCLUSION: Treatment with BDQ- and LZD-containing regimens was associated with improved treatment outcomes and survival in DR-TB HIV patients.