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Background Medication adherence is known to challenge treatment of human immunodeficiency virus (HIV)/AIDS and multidrug-resistant tuberculosis (MDR-TB). We hypothesized that adherence using electronic dose monitoring (EDM) would identify an antiretroviral therapy (ART) adherence threshold for emergent ART resistance and predict treatment outcomes in patients with MDR-TB and HIV on ART and bedaquiline-containing TB regimens. Methods A prospective cohort of adults with MDR-TB and HIV on ART and initiating MDR-TB treatment with bedaquiline were enrolled at a public hospital in KwaZulu-Natal, South Africa (PRAXIS Study). Participants received separate EDM devices that measure adherence to bedaquiline and ART (nevirapine or lopinavir/ritonavir). Adherence was calculated cumulatively over 6 months. Participants were followed through completion of MDR-TB treatment. HIV genome sequencing was performed at baseline and 2 and 6 months on samples with HIV RNA ≥1000 copies/mL. Results From November 2016 through February 2018, 198 persons with MDR-TB and HIV were enrolled and followed (median, 17.2 months; interquartile range, 12.2–19.6). Eleven percent had baseline ART resistance mutations, and 7.5% developed emergent ART resistance at 6 months. ART adherence was independently associated with ART resistance and mortality. Modeling identified a significant (P <.001), linear association between ART adherence and emergent resistance, suggesting a strong association without a specific threshold. Conclusions Our findings highlight the need for ART resistance testing, especially in patients with MDR-TB and HIV, which is currently not the standard of care in resource-limited settings. Despite short follow-up duration, reduced ART adherence was significantly associated with emergent resistance and increased mortality. Clinical Trials Registration NCT03162107. [ABSTRACT FROM AUTHOR]

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Background New onset or worsening drug-induced liver injury challenges coinfected patients on antiretroviral therapy (ART) initiation during antituberculosis (TB) treatment. Methods Post hoc analysis within a randomized trial, the Starting Antiretroviral Therapy at Three Points in Tuberculosis trial, was conducted. Patients were randomized to initiate ART either early or late during TB treatment or after TB treatment completion. Liver enzymes were measured at baseline, 6-month intervals, and when clinically indicated. Results Among 642 patients enrolled, the median age was 34 years (standard deviation, 28–40), and 17.6% had baseline CD4+ cell counts <50 cells/mm3. Overall, 146/472 patients (52, 47, and 47: early, late, and sequential arms) developed new-onset liver injury following TB treatment initiation. The incidence of liver injury post-ART initiation in patients with CD4+ cell counts <200 cells/mm3 and ≥200 cells/ mm3 was 27.4 (95% confidence interval [CI], 18.0–39.8), 19.0 (95% CI, 10.9–30.9), and 18.4 (95% CI, 8.8–33.8) per 100 person-years, and 32.1 (95% CI, 20.1–48.5), 11.8 (95% CI, 4.3–25.7), and 28.2 (95% CI, 13.5–51.9) per 100 person-years in the early, late integrated, and sequential treatment arms, respectively. Severe and life-threatening liver injury occurred in 2, 7, and 3 early, late, and sequential treatment arm patients, respectively. Older age and hepatitis B positivity predicted liver injury. Conclusions High incidence rates of liver injury among cotreated human immunodeficiency virus (HIV)–TB coinfected patients were observed. Clinical guidelines and policies must provide guidance on frequency of liver function monitoring for HIV–TB coinfected patients. [ABSTRACT FROM AUTHOR]

Using an open-access spatiotemporal analytics program, we mapped spatiotemporal heterogeneity loci in tuberculosis (TB) cases (clusters) and dynamic changes, and characterized the drug-resistant TB clustering risk using routine microbiological data from KwaZulu-Natal, South Africa. The data may provide insight into transmission dynamics and support efficient deployment of public health resources. [ABSTRACT FROM AUTHOR]

Background: Extensively drug-resistant tuberculosis (XDR-TB)/HIV coinfection has been associated with high mortality and poor TB outcomes. We performed a prospective study to comprehensively characterize a cohort of patients with XDR-TB. Methods: Adult patients with XDR-TB were enrolled at treatment initiation at a TB referral hospital in KwaZulu-Natal Province, South Africa, and followed through the end of treatment. Clinical data, questionnaires, adherence data, and sputum were collected monthly. Whole genome sequencing was performed on baseline Mycobacterium tuberculosis (MTB) isolates. Treatment outcomes were defined using standard definitions. Results: One hundred five patients with XDR-TB (76.1% HIV-infected) were enrolled from August 2009 to July 2011. Among HIV-coinfected patients, 82.5% were on antiretroviral therapy initially and 93.8% cumulatively over the study period. At 24 months, 31.4% had a successful outcome and 68.6% had an unsuccessful outcome with 41% mortality. Antiretroviral therapy was associated with improved mortality in HIV-coinfected patients (P = 0.05), as was TB culture conversion (P < 0.0001). On whole genome sequencing, most strains were LAM4/KZN lineage (68%), with few single nucleotide polymorphism differences. Conclusions: Despite improved HIV care, treatment outcomes and mortality were only modestly improved compared with previous South African XDR-TB/HIV treatment cohorts. Of note, this study was completed before the introduction of new antimycobacterial agents (eg, bedaquiline and delamanid). As new TB drugs and regimens become available, it is important to monitor treatment to ensure that benefits seen in clinical trials are reproduced in high-burden, low-resource settings. [ABSTRACT FROM AUTHOR]

There is a growing imperative to improve the coordination and collaboration of tuberculosis (TB) and HIV healthcare services in response to escalating rates of TB/HIV coinfection. Patient-specific challenges associated with the delivery of TB/HIV care have been minimally explored in this regard. As part of a larger study conducted in South Africa, this article highlights coinfected patients' experiences with TB and HIV healthcare in light of their broader social environments. Qualitative, in-depth interviews were conducted with 40 adult, coinfected patients (24 women and 16 men) and eight key-informant healthcare workers at three urban/peri-urban, ambulatory, public health clinics in the high-burden province of KwaZulu-Natal. Transcribed interviews were analyzed under a modified grounded theory approach to capture subjective meanings of healthcare experience subsequent to patients' codiagnosis with TB and HIV. Emerging analytic themes highlighted critical sociomedical constraints to TB/HIV care in relation to patients' income and employment, eligibility for social assistance and antiretroviral treatment, fears around illness disclosure, social and material support, and treatment adherence. Patients' healthcare experiences were bound by their poor access to essential resources, multiple life responsibilities, disparate gender roles, limits within the healthcare system, and the stigmatizing social symbolism of their illness. Overlapping social inequalities perpetuated coinfected patients' experiences with stigma and collectively mediated their health decisions around disclosure, adherence, and retention in medical care. The study urges a contextualized understanding of the social challenges associated with TB/HIV healthcare and helps inform more patient-sensitive and socially responsive interventions against the co-epidemic. [ABSTRACT FROM PUBLISHER]

Introduction: For people living with HIV/AIDS, care is commonly delivered through differentiated service delivery (DSD). Although people with multidrug-resistant tuberculosis (MDR-TB) and HIV/AIDS experience severe treatment-associated challenges, there is no DSD model to support their treatment. In this study, we defined patterns of medication adherence and characterized longitudinal barriers to inform development of an MDR-TB/HIV DSD framework. Methods: Adults with MDR-TB and HIV initiating bedaquiline (BDQ) and receiving antiretroviral therapy (ART) in KwaZulu-Natal, South Africa, were enrolled and followed through the end of MDR-TB treatment. Electronic dose monitoring devices measured BDQ and ART adherence. Longitudinal focus groups were conducted and transcripts analyzed thematically to describe discrete treatment stage-specific and cross-cutting treatment challenges. Results: Two hundred eighty-three participants were enrolled and followed through treatment completion (median 17.8 months [interquartile range 16.5–20.2]). Thirteen focus groups were conducted. Most participants (82.7%, 234/283) maintained high adherence (mean BDQ adherence 95.3%; mean ART adherence 85.5%), but an adherence-challenged subpopulation with <85% cumulative adherence (17.3%, 49/283) had significant declines in mean weekly BDQ adherence from 94.9% to 39.9% (P < 0.0001) and mean weekly ART adherence from 83.9% to 26.6% (P < 0.0001) over 6 months. Psychosocial, behavioral, and structural obstacles identified in qualitative data were associated with adherence deficits in discrete treatment stages and identified potential stage-specific interventions. Conclusions: A DSD framework for MDR-TB/HIV should intensify support for adherence-challenged subpopulations, provide multimodal support for adherence across the treatment course, and account for psychosocial, behavioral, and structural challenges linked to discrete treatment stages. [ABSTRACT FROM AUTHOR]

Although neurocognitive impairment (NCI) is a well-recognized challenge in human immunodeficiency virus (HIV), there is little evidence regarding it among individuals with multiple drug-resistant tuberculosis (MDR-TB) within HIV endemic sub-Saharan Africa. The extent of NCI risk, particularly HIV-associated neurocognitive disorders (HAND) risk, was investigated in 200 microbiologically confirmed inpatients with MDR-TB at a TB-specialist hospital in KwaZulu-Natal Province, South Africa. Within this population, the prevalence of HIV coinfection, major depressive episode, and substance use disorder was 89.50%, 10.50%, and 7.00%, respectively. After excluding individuals with major depressive episode/substance use disorder and monoinfection (i.e., MDR-TB without HIV), the prevalence of HAND risk was 43.5%. Older and low-income individuals had significantly greater odds of HAND risk, whereas those with family members/relatives who work(ed) in the health services had lower odds. The role of timely linkage to and retention of care in TB/HIV treatment to offset cognitive decline in MDR-TB/HIV coinfected individuals needs to be investigated further. [ABSTRACT FROM AUTHOR]