RESUMO
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.
Assuntos
Coinfecção , Infecções por HIV , Tuberculose Resistente a Múltiplos Medicamentos , Adulto , Antituberculosos/uso terapêutico , Coinfecção/tratamento farmacológico , Diarilquinolinas , Feminino , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Humanos , Linezolida , Masculino , Estudos Retrospectivos , África do Sul , Resultado do Tratamento , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológicoRESUMO
Assuntos
Tuberculose Extensivamente Resistente a Medicamentos/epidemiologia , Tuberculose Pulmonar/epidemiologia , Adulto , Cidades , Estudos Transversais , Demografia , Tuberculose Extensivamente Resistente a Medicamentos/etiologia , Feminino , Sistemas de Informação Geográfica , Humanos , Incidência , Masculino , Fatores Socioeconômicos , África do Sul/epidemiologia , Tuberculose Pulmonar/etiologiaRESUMO
SETTING: Referral hospital for drug-resistant tuberculosis (DR-TB) in KwaZulu-Natal Province, South Africa. OBJECTIVE: To review the clinical outcomes of patients (age î¶ 14 years) with a laboratory-confirmed diagnosis of DR-TB who had minimal symptoms and/or did not have chest radiographic evidence of active disease at referral. These patients were not started on treatment, but were enrolled in an observation programme with follow-up at 2, 6 and 12 months. RESULTS: Of 3345 referred patients diagnosed with DR-TB, 192 (6%) were enrolled in the observation programme. The median duration from initial sputum collection in primary care to examination at our hospital was 92 days (IQR 64-124). After 12 months, 120 (62%) patients were well, 36 (19%) were lost to follow-up, 30 (16%) had deteriorated and were started on second-line anti-tuberculosis treatment and 6 (3%) had died. Bilateral disease (OR 4.25, 95%CI 1.14-15.77, P = 0.030) and previous TB (OR 2.14, 95%CI 1.10-4.19, P = 0.026) were independent predictors of an unfavourable end result in a multivariate model. CONCLUSION: In our high-burden setting, most patients diagnosed with DR-TB who had minimal symptoms at referral remained well without treatment. Longitudinal observation, coupled with symptom checking and chest radiograph, is a viable strategy.
Assuntos
Escarro/microbiologia , Tuberculose Resistente a Múltiplos Medicamentos/terapia , Conduta Expectante/métodos , Adulto , Feminino , Seguimentos , Humanos , Estudos Longitudinais , Perda de Seguimento , Masculino , Análise Multivariada , Atenção Primária à Saúde , Encaminhamento e Consulta , África do Sul , Fatores de TempoRESUMO
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.
Assuntos
Infecções por HIV/tratamento farmacológico , Adesão à Medicação , Assistência Centrada no Paciente/métodos , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Coinfecção/tratamento farmacológico , Terapia Diretamente Observada , Humanos , Educação de Pacientes como AssuntoRESUMO
SETTING: Treatment outcomes for multidrug-resistant tuberculosis (MDR-TB) in South Africa have suffered as centralized, in-patient treatment programs struggle to cope with rising prevalence and human immunodeficiency virus (HIV) co-infection rates. A new treatment model is needed to expand treatment capacity and improve MDR-TB and HIV outcomes. OBJECTIVE: To describe the design and preliminary results of an integrated, home-based MDR-TB-HIV treatment program created in rural KwaZulu-Natal. METHOD: In 2008, a decentralized center was established to provide out-patient MDR-TB and HIV treatment. Nurses, community health workers and family supporters have been trained to administer injections, provide adherence support and monitor adverse reactions in patients' homes. Physicians assess clinical response, adherence and the severity of adverse reactions to MDR-TB and HIV treatment at monthly follow-up visits. Treatment outcomes are assessed by monthly cultures and CD4 and viral load every 6 months. RESULTS: Of 80 patients initiating MDR-TB treatment from February 2008 to April 2010, 66 were HIV-co-infected. Retention has been high (only 5% defaults, 93% of visits attended), and preliminary outcomes have been favorable (77% cured/still on treatment, 82% undetectable viral load). Few patients have required escalation of care (9%), had severe adverse events (8%) or died (6%). CONCLUSION: Integrated, home-based treatment for MDR-TB and HIV is a promising treatment model to expand capacity and achieve improved outcomes in rural, resource-poor and high HIV prevalent settings.
Assuntos
Assistência Ambulatorial/organização & administração , Fármacos Anti-HIV/uso terapêutico , Antituberculosos/uso terapêutico , Coinfecção , Prestação Integrada de Cuidados de Saúde/organização & administração , Infecções por HIV/tratamento farmacológico , Serviços de Assistência Domiciliar/organização & administração , Serviços de Saúde Rural/organização & administração , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Adulto , Fármacos Anti-HIV/efeitos adversos , Antituberculosos/efeitos adversos , Atitude do Pessoal de Saúde , Contagem de Linfócito CD4 , Cuidadores , Estudos de Viabilidade , Feminino , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Adesão à Medicação , Objetivos Organizacionais , Equipe de Assistência ao Paciente/organização & administração , Desenvolvimento de Programas , Avaliação de Programas e Projetos de Saúde , Apoio Social , África do Sul/epidemiologia , Fatores de Tempo , Resultado do Tratamento , Tuberculose Resistente a Múltiplos Medicamentos/diagnóstico , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Carga ViralRESUMO
SETTING: Recent studies suggest that the prevalence of drug-resistant tuberculosis (TB) in sub-Saharan Africa may be rising. This is of concern, as human immunodeficiency virus (HIV) co-infection in multidrug-resistant (MDR) and extensively drug-resistant (XDR) TB has been associated with exceedingly high mortality rates. OBJECTIVE: To identify risk factors associated with mortality in MDR- and XDR-TB patients co-infected with HIV in South Africa. DESIGN: Case-control study of patients who died of all causes within 2 years of diagnosis with MDR- or XDR-TB. RESULTS: Among 123 MDR-TB patients, 78 (63%) died following diagnosis. CD4 count ≤ 50 (HR 4.64, P = 0.01) and 51-200 cells/mm(3) (HR 4.17, P = 0.008) were the strongest independent risk factors for mortality. Among 139 XDR-TB patients, 111 (80%) died. CD4 count ≤ 50 cells/mm(3) (HR 4.46, P = 0.01) and resistance to all six drugs tested (HR 2.54, P = 0.04) were the principal risk factors. Use of antiretroviral therapy (ART) was protective (HR 0.34, P = 0.009). CONCLUSIONS: Mortality due to MDR- and XDR-TB was associated with greater degree of immunosuppression and drug resistance. Efforts to reduce mortality must focus on preventing the amplification of resistance by strengthening TB treatment programs, as well as reducing the pool of immunosuppressed HIV-infected patients through aggressive HIV testing and ART initiation.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/mortalidade , Coinfecção/mortalidade , Farmacorresistência Bacteriana Múltipla , Tuberculose Extensivamente Resistente a Medicamentos/mortalidade , Infecções por HIV/mortalidade , Tuberculose Resistente a Múltiplos Medicamentos/mortalidade , Tuberculose Pulmonar/mortalidade , Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Adulto , Antirretrovirais/uso terapêutico , Antituberculosos/uso terapêutico , Contagem de Linfócito CD4 , Coinfecção/diagnóstico , Coinfecção/tratamento farmacológico , Tuberculose Extensivamente Resistente a Medicamentos/diagnóstico , Tuberculose Extensivamente Resistente a Medicamentos/tratamento farmacológico , Feminino , Infecções por HIV/diagnóstico , Infecções por HIV/tratamento farmacológico , Humanos , Masculino , Cadeias de Markov , Método de Monte Carlo , Prevalência , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , África do Sul/epidemiologia , Análise de Sobrevida , Fatores de Tempo , Tuberculose Resistente a Múltiplos Medicamentos/diagnóstico , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/tratamento farmacológicoRESUMO
SETTING: Multidrug-resistant tuberculosis (MDR-TB) has emerged as a significant public health threat in South Africa. OBJECTIVE: To describe treatment outcomes and determine risk factors associated with unfavorable outcomes among MDR-TB patients admitted to the provincial TB referral hospital in KwaZulu-Natal Province, South Africa. DESIGN: Retrospective observational study of MDR-TB patients admitted from 2000 to 2003. RESULTS: Of 1209 MDR-TB patients with documented treatment outcomes, 491 (41%) were cured, 35 (3%) completed treatment, 208 (17%) failed treatment, 223 (18%) died and 252 (21%) defaulted. Of the total number of patients with known human immunodeficiency virus (HIV) status, 52% were HIV-infected. Treatment failure, death and default each differed in their risk factors. Greater baseline resistance (aOR 2.3-3.0), prior TB (aOR 1.7), and diagnosis in 2001, 2002 or 2003 (aOR 1.9-2.3) were independent risk factors for treatment failure. HIV co-infection was a risk factor for death (aOR 5.6), and both HIV (aOR 2.0) and male sex (aOR 1.9) were risk factors for treatment default. CONCLUSION: MDR-TB treatment outcomes in KwaZulu-Natal were substantially worse than those published from other MDR-TB cohorts. Interventions such as concurrent antiretroviral therapy and decentralized MDR-TB treatment should be considered to improve MDR-TB outcomes in this high HIV prevalence setting.