Dataset Information

The Impact of Concurrent Antiretroviral Therapy and MDR-TB Treatment on Adverse Events.

ABSTRACT:

Background

South Africa has among the highest incidence of multidrug-resistant tuberculosis (MDR-TB) and more than 70% of patients are HIV co-infected. MDR-TB treatment is associated with frequent adverse events (AEs). Although guidelines recommend concurrent treatment of MDR-TB and HIV, safety data on concurrent therapy are limited.

Methods

We conducted a prospective observational study of MDR-TB patients with and without HIV-coinfection in South Africa between 2011 and 2015. Participants received standardized MDR-TB and HIV regimens. Participants were followed monthly for the duration of MDR-TB therapy and screened for clinical and laboratory AEs. Audiometry was performed monthly during the intensive phase; color discrimination testing was performed every 2 months.

Results

We enrolled 150 HIV-infected and 56 HIV-uninfected participants. Nearly all experienced at least one clinical (93%) or laboratory (96%) AE. The most common clinical AEs were peripheral neuropathy (50%) and difficulty sleeping (48%); the most common laboratory AEs were hypokalemia (47%) and decreased creatinine clearance (46%). Among 19 clinical and lab AEs examined, there were no differences by HIV status, except for diarrhea (27% HIV-infected vs. 13% HIV-uninfected, P = 0.03). Hearing loss was experienced by 72% of participants (8% severe loss). Fourteen percent experienced color discrimination loss (4% severe loss). There were no differences in frequency or severity of hearing or vision loss by HIV status.

Conclusions

AEs were common, but not more frequent or severe among MDR-TB/HIV co-infected participants receiving concurrent antiretroviral therapy. Given the favorable treatment outcomes associated with concurrent treatment, antiretroviral therapy initiation should not be delayed in MDR-TB patients with HIV-coinfection.

SUBMITTER: Smith JP

PROVIDER: S-EPMC6903405 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Publications

The Impact of Concurrent Antiretroviral Therapy and MDR-TB Treatment on Adverse Events.

Smith Jonathan P JP Gandhi Neel R NR Shah N Sarita NS Mlisana Koleka K Moodley Pravi P Johnson Brent A BA Allana Salim S Campbell Angela A Nelson Kristin N KN Master Iqbal I Brust James C M JCM

Journal of acquired immune deficiency syndromes (1999) 20200101 1

<h4>Background</h4>South Africa has among the highest incidence of multidrug-resistant tuberculosis (MDR-TB) and more than 70% of patients are HIV co-infected. MDR-TB treatment is associated with frequent adverse events (AEs). Although guidelines recommend concurrent treatment of MDR-TB and HIV, safety data on concurrent therapy are limited.<h4>Methods</h4>We conducted a prospective observational study of MDR-TB patients with and without HIV-coinfection in South Africa between 2011 and 2015. Par ...[more]

PMID: 31809360

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Project description:BACKGROUND: Significant adverse events (AE) have been reported in patients receiving medications for multidrug- and extensively-drug-resistant tuberculosis (MDR-TB & XDR-TB). However, there is little prospective data on AE in MDR- or XDR-TB/HIV co-infected patients on antituberculosis and antiretroviral therapy (ART) in programmatic settings. METHODS: Médecins Sans Frontières (MSF) is supporting a community-based treatment program for drug-resistant tuberculosis in HIV-infected patients in a slum setting in Mumbai, India since 2007. Patients are being treated for both diseases and the management of AE is done on an outpatient basis whenever possible. Prospective data were analysed to determine the occurrence and nature of AE. RESULTS: Between May 2007 and September 2011, 67 HIV/MDR-TB co-infected patients were being treated with anti-TB treatment and ART; 43.3% were female, median age was 35.5 years (Interquartile Range: 30.5-42) and the median duration of anti-TB treatment was 10 months (range 0.5-30). Overall, AE were common in this cohort: 71%, 63% and 40% of patients experienced one or more mild, moderate or severe AE, respectively. However, they were rarely life-threatening or debilitating. AE occurring most frequently included gastrointestinal symptoms (45% of patients), peripheral neuropathy (38%), hypothyroidism (32%), psychiatric symptoms (29%) and hypokalaemia (23%). Eleven patients were hospitalized for AE and one or more suspect drugs had to be permanently discontinued in 27 (40%). No AE led to indefinite suspension of an entire MDR-TB or ART regimen. CONCLUSIONS: AE occurred frequently in this Mumbai HIV/MDR-TB cohort but not more frequently than in non-HIV patients on similar anti-TB treatment. Most AE can be successfully managed on an outpatient basis through a community-based treatment program, even in a resource-limited setting. Concerns about severe AE in the management of co-infected patients are justified, however, they should not cause delays in the urgently needed rapid scale-up of antiretroviral therapy and second-line anti-TB treatment.

Project description:BackgroundThe Union in collaboration with national TB programme (NTP) started the community-based MDR-TB care (CBMDR-TBC) project in 33 townships of upper Myanmar to improve treatment initiation and treatment adherence. Patients with MDR-TB diagnosed/registered under NTP received support through the project staff, in addition to the routine domiciliary care provided by NTP staff. Each township had a project nurse exclusively for MDR-TB and 30 USD per month (max. for 4 months) were provided to the patient as a pre-treatment support.ObjectivesTo assess whether CBMDR-TBC project's support improved treatment initiation.MethodsIn this cohort study (involving record review) of all diagnosed MDR-TB between January 2015 and June 2016 in project townships, CBMDR-TBC status was categorized as "receiving support" if date of project initiation in patient's township was before the date of diagnosis and "not receiving support", if otherwise. Cox proportional hazards regression (censored on 31 Dec 2016) was done to identify predictors of treatment initiation.ResultsOf 456 patients, 57% initiated treatment: 64% and 56% among patients "receiving support (n = 208)" and "not receiving support (n = 228)" respectively (CBMDR-TBC status was not known in 20 (4%) patients due to missing diagnosis dates). Among those initiated on treatment (n = 261), median (IQR) time to initiate treatment was 38 (20, 76) days: 31 (18, 50) among patients "receiving support" and 50 (26,101) among patients "not receiving support". After adjusting other potential confounders (age, sex, region, HIV, past history of TB treatment), patients "receiving support" had 80% higher chance of initiating treatment [aHR (0.95 CI): 1.8 (1.3, 2.3)] when compared to patients "not receiving support". In addition, age 15-54 years, previous history of TB and being HIV negative were independent predictors of treatment initiation.ConclusionReceiving support under CBMDR-TBC project improved treatment initiation: it not only improved the proportion initiated but also reduced time to treatment initiation. We also recommend improved tracking of all diagnosed patients as early as possible.

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Project description:BackgroundIn 2013, approximately 480,000 people developed active multidrug-resistant tuberculosis (MDR-TB), while only 97,000 started MDR-TB treatment. We sought to estimate the impact of improving access to MDR-TB diagnosis and treatment, under multiple diagnostic algorithm and treatment regimen scenarios, on ten-year projections of MDR-TB incidence and mortality.MethodsWe constructed a dynamic transmission model of an MDR-TB epidemic in an illustrative East/Southeast Asian setting. Using approximate Bayesian computation, we investigated a wide array of potential epidemic trajectories consistent with current notification data and known TB epidemiology.ResultsDespite an overall projected decline in TB incidence, data-consistent simulations suggested that MDR-TB incidence is likely to rise between 2015 and 2025 under continued 2013 treatment practices, although with considerable uncertainty (median 17% increase, 95% Uncertainty Range [UR] -38% to +137%). But if, by 2017, all identified active TB patients with previously-treated TB could be tested for drug susceptibility, and 85% of those with MDR-TB could initiate MDR-appropriate treatment, then MDR-TB incidence in 2025 could be reduced by 26% (95% UR 4-52%) relative to projections under continued current practice. Also expanding this drug-susceptibility testing and appropriate MDR-TB treatment to treatment-naïve as well as previously-treated TB cases, by 2020, could reduce MDR-TB incidence in 2025 by 29% (95% UR 6-55%) compared to continued current practice. If this diagnosis and treatment of all MDR-TB in known active TB cases by 2020 could be implemented via a novel second-line regimen with similar effectiveness and tolerability as current first-line therapy, a 54% (95% UR 20-74%) reduction in MDR-TB incidence compared to current-practice projections could be achieved by 2025.ConclusionsExpansion of diagnosis and treatment of MDR-TB, even using current sub-optimal second-line regimens, is expected to significantly decrease MDR-TB incidence at the population level. Focusing MDR diagnostic efforts on previously-treated cases is an efficient first-step approach.

Dataset Information

The Impact of Concurrent Antiretroviral Therapy and MDR-TB Treatment on Adverse Events.

Background

Methods

Results

Conclusions

Publications

The Impact of Concurrent Antiretroviral Therapy and MDR-TB Treatment on Adverse Events.

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