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BACKGROUND: Tuberculosis (TB) preventive therapy (TPT) reduces the risk of TB disease in people with human immunodeficiency virus (HIV), yet uptake has been suboptimal in many countries. We assessed whether QuantiFERON Gold In-Tube (QGIT) during routine HIV care increased TB infection (TBI) testing and TPT prescriptions. METHODS: This parallel-arm, 1:1 cluster-randomized controlled trial compared the standard-of-care tuberculin skin test to QGIT in South Africa. We enrolled consenting, TPT-eligible adults diagnosed with HIV ≤30 days prior and used intention-to-treat analyses for the outcomes: proportion of patients with documented TBI results, proportion with documented TPT, and time from enrollment to outcomes. FINDINGS: We enrolled 2232 patients across 14 clinics from November 2014 to May 2017 (58% in intervention clinics). At 24 months of follow-up, more participants in intervention clinics had TBI results (69% vs 2%, P < .001) and TPT prescriptions (45% vs 30%, P = .13) than control clinics. Controlling for baseline covariates, intervention clinics had 60% (95% confidence interval, 51-68; P < .001) more participants with TBI results and 12% (95% confidence interval, -6 to 31; P = .18) more with TPT prescriptions. Among participants with results, those in intervention clinics received results and TPT faster (intervention: median of 6 and 29 days after enrollment vs control: 21 and 54 days, respectively). INTERPRETATION: In this setting, QGIT in routine HIV care resulted in more patients with TBI results. Clinicians also initiated more people with HIV on TPT in QGIT intervention clinics, and did so more quickly, than the control arm. CLINICAL TRIALS REGISTRATION: NCT02119130.
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BACKGROUND: Both pregnancy and human immunodeficiency virus (HIV) increase the risk of tuberculosis disease, which results in poor maternal, pregnancy, and infant outcomes. Isoniazid preventive therapy (IPT) reduces mortality among individuals living with HIV in high-burden settings but has recently been associated with adverse pregnancy outcomes when initiated during pregnancy. METHODS: In this secondary analysis, we used multivariable logistic regression to evaluate the association between IPT exposure and adverse pregnancy outcomes (fetal demise, prematurity, low birth weight, congenital anomaly) in pregnant women living with HIV enrolled as controls in the Tshepiso study, a prospective observational cohort of pregnant women living with HIV with and without tuberculosis disease in Soweto, South Africa, from 2011-2014. RESULTS: There were 151 women enrolled with known pregnancy outcomes; 69 (46%) reported IPT initiation during pregnancy. Of the 69 IPT-exposed women, 11 (16%) had an adverse pregnancy outcome compared with 23 (28%) IPT-unexposed women. The adjusted odds of having an adverse pregnancy outcome was 2.5 (95% confidence interval, 1.0-6.5; P = .048) times higher in IPT-unexposed women compared with IPT-exposed women after controlling for maternal age, CD4 count, viral load, antiretroviral regimen, body mass index, and anemia. CONCLUSIONS: IPT exposure during pregnancy was not negatively associated with pregnancy outcomes after controlling for demographic, clinical, and HIV-related factors. These results provide some reassurance that IPT can be safely used in the second or third trimester of pregnancy. Additional research is needed to evaluate the safety of IPT and new short-course tuberculosis preventive therapies during pregnancy.
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Infecções por HIV , Isoniazida , Antituberculosos/uso terapêutico , Feminino , HIV , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Humanos , Lactente , Recém-Nascido , Isoniazida/uso terapêutico , Gravidez , Resultado da Gravidez , África do Sul/epidemiologiaRESUMO
BACKGROUND: Tuberculosis preventive therapy (TPT) is highly effective at preventing tuberculosis disease in household child contacts (<5 years), but is poorly implemented worldwide. In 2006, the World Health Organization recommended symptom-based screening as a replacement for tuberculin skin testing (TST) to simplify contact evaluation and improve implementation. We aimed to determine the effectiveness of this recommendation. METHODS: We conducted a pragmatic, cluster-randomized trial to determine whether contact evaluation using symptom screening improved the proportion of identified child contacts who initiated TPT, compared to TST-based screening, in Matlosana, South Africa. We randomized 16 clinics to either symptom-based or TST-based contact evaluations. Outcome data were abstracted from customized child contact management files. RESULTS: Contact tracing identified 550 and 467 child contacts in the symptom and TST arms, respectively (0.39 vs 0.32 per case, respectively; P = .27). There was no significant difference by arm in the adjusted proportion of identified child contacts who were screened (52% in symptom arm vs 60% in TST arm; P = .39). The adjusted proportion of identified child contacts who initiated TPT or tuberculosis treatment was 51.5% in the symptom clinics and 57.1% in the TST clinics (difference -5.6%, 95% confidence interval -23.7 to 12.6; P = .52). Based on the district's historic average of 0.7 child contacts per index case, 14% and 15% of child contacts completed 6 months of TPT in the symptom and TST arms, respectively (P = .89). CONCLUSIONS: Symptom-based screening did not improve the proportion of identified child contacts evaluated or initiated on TPT, compared to TST-based screening. Further research is needed to identify bottlenecks and evaluate interventions to ensure all child contacts receive TPT. CLINICAL TRIALS REGISTRATION: NCT03074799.
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Teste Tuberculínico , Tuberculose , Criança , Pré-Escolar , Busca de Comunicante , Características da Família , Humanos , África do Sul , Tuberculose/diagnóstico , Tuberculose/epidemiologia , Tuberculose/prevenção & controleRESUMO
BACKGROUND: Tuberculosis (TB) remains the leading cause of death among human immunodeficiency virus (HIV)-infected individuals globally. Screening for TB at the point of HIV diagnosis with a high-sensitivity assay presents an opportunity to reduce mortality. METHODS: We performed a cluster randomized trial of TB screening among adults newly diagnosed with HIV in 12 primary health clinics in rural Thyolo, Malawi. Clinics were allocated in a 1:1 ratio to perform either point-of-care Xpert MTB/RIF assay (Xpert) or point-of-care light-emitting diode fluorescence microscopy (LED-FM) for individuals screening positive for TB symptoms. Asymptomatic participants were offered isoniazid preventive therapy in both arms. Investigators, but not clinic staff or participants, were masked to allocation. Our primary outcome was the incidence rate ratio (RR) of all-cause mortality within 12 months of HIV diagnosis. RESULTS: Prevalent TB was diagnosed in 24 of 1001 (2.4%) individuals enrolled in clinics randomized to Xpert, compared with 10 of 841 (1.2%) in clinics randomized to LED-FM. All-cause mortality was 22% lower in the Xpert arm than in the LED-FM arm (6.7 vs 8.6 per 100 person-years; RR, 0.78 [95% confidence interval {CI}, .58-1.06]). A planned subgroup analysis suggested that participants with more advanced HIV (World Health Organization clinical stage 3 or 4) disease had lower mortality in clinics randomized to Xpert than to LED-FM (RR, 0.43 [95% CI, .22-.87]). CONCLUSIONS: In rural Malawi, using point-of-care Xpert MTB/RIF to test symptomatic patients for TB at the time of HIV diagnosis reduced all-cause 12-month mortality among individuals with advanced HIV. CLINICAL TRIALS REGISTRATION: NCT01450085.
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Infecções por HIV/complicações , Programas de Rastreamento/métodos , Microscopia de Fluorescência/métodos , Técnicas de Diagnóstico Molecular/métodos , Tuberculose/diagnóstico , Tuberculose/mortalidade , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Incidência , Malaui , Masculino , Pessoa de Meia-Idade , População Rural , Sensibilidade e Especificidade , Análise de Sobrevida , Adulto JovemRESUMO
Background: Before the wide availability of antiretroviral therapy (ART), tuberculosis and human immunodeficiency virus (HIV) disease among pregnant women resulted in poor maternal and neonatal outcomes, including high rates of mother-to-child transmission of both HIV and tuberculosis. We aimed to describe the impact of tuberculosis among HIV-infected mothers on obstetric and infant outcomes in a population with access to ART. Methods: In this prospective cohort study, we followed up HIV-infected pregnant women with or without tuberculosis disease from January 2011 through January 2014 in Soweto, South Africa. Two controls were enrolled for each case patient, matched by enrollment time, maternal age, gestational age, and planned delivery clinic and followed up for 12 months after delivery. Results: We recruited 80 case patients and 155 controls, resulting in 224 live-born infants. Infants of mothers with HIV infection and tuberculosis disease had a higher risk of low birth weight (20.8% vs 10.7%; P = .04), prolonged hospitalization at birth (51% vs 16%; P < .001), infant death (68 vs 7 deaths per 1000 births; P < .001), and tuberculosis disease (12% vs 0%; P < .001) despite appropriate maternal therapy and infant tuberculosis preventive therapy. HIV transmission was higher among these infants (4.1% vs 1.3%; P = .20), though this difference was not statistically significant. Obstetric outcomes in coinfected women were also poorer with higher risks of maternal hospitalization (25% vs 11%; P = .005) and preeclampsia (5.5% vs 0.7%; P = .03). Conclusions: Tuberculosis in HIV coinfected pregnant women remains a significant threat to the health of both mothers and infants. Improving tuberculosis prevention and early diagnosis among pregnant women is critical.
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Infecções por HIV/complicações , Mortalidade Infantil , Transmissão Vertical de Doenças Infecciosas/estatística & dados numéricos , Tuberculose/complicações , Adolescente , Adulto , Fármacos Anti-HIV/uso terapêutico , Antituberculosos/uso terapêutico , Feminino , Idade Gestacional , Infecções por HIV/tratamento farmacológico , HIV-1 , Hospitalização/estatística & dados numéricos , Humanos , Lactente , Recém-Nascido de Baixo Peso , Recém-Nascido , Mães , Pré-Eclâmpsia , Gravidez , Complicações Infecciosas na Gravidez/microbiologia , Complicações Infecciosas na Gravidez/virologia , Estudos Prospectivos , África do Sul/epidemiologia , Tuberculose/tratamento farmacológico , Adulto Jovem , Zidovudina/uso terapêuticoRESUMO
Background: Among adults with signs and symptoms of pulmonary tuberculosis (TB), recognition of transmissible TB has implications for airborne infection isolation and public health activities. Sputum smear-negative TB patients account for around one-fifth of tuberculosis transmission. The tuberculosis transmission risk of TB patients with negative results on nucleic acid amplification test (NAAT) of respiratory specimens has not been established. We sought to estimate the tuberculosis transmission risk of NAAT-negative TB patients. Methods: We retrospectively reviewed Maryland TB program data collected from 2004 to 2009, during which time NAAT using the Mycobacterium Tuberculosis Direct Test (MTD) was performed routinely. Patients with sputum Mycobacterium tuberculosis (M.tb) isolates having matching genotypes were assigned to clusters. Transmission sequence was approximated by collection order of individuals' first culture-positive specimens. Minimum transmission risks of NAAT (MTD)-negative TB patients and of smear-negative TB patients were estimated based on individuals' positions within clusters. Results: Among 809 patients with culture-confirmed TB, M.tb genotypes were available for 782 (96.7%). For NAA-negative TB patients, the minimum transmission risk estimate was 5.1% (95% CI 0-11.4). For smear-negative TB patients, the minimum transmission risk estimate was 11.2% (95% CI 7.2-15.3). Conclusions: Minimum transmission risk of NAAT-negative TB patients was lower than that of smear-negative TB patients. However, transmission risk of NAA-negative TB patients appears to not be negligible.
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Mycobacterium tuberculosis/isolamento & purificação , Escarro/microbiologia , Tuberculose Pulmonar/transmissão , Adulto , Análise por Conglomerados , Feminino , Genótipo , Humanos , Masculino , Maryland , Prontuários Médicos , Pessoa de Meia-Idade , Mycobacterium tuberculosis/genética , Técnicas de Amplificação de Ácido Nucleico , Estudos Retrospectivos , Células-Tronco , Tuberculose Pulmonar/diagnóstico , Adulto JovemRESUMO
Background: Newborns of HIV-infected mothers are given daily doses of nevirapine to prevent HIV-1 acquisition. Infants born to mothers with TB should also receive TB preventive therapy. TB preventive regimens include isoniazid for 6 months or rifampicin plus isoniazid for 3 months (RH preventive therapy). The effect of concomitant RH preventive therapy on nevirapine concentrations in infants is unknown. Patients and methods: Tshepiso was a prospective case-control cohort study of pregnant HIV-infected women with and without TB whose newborn infants received standard doses of nevirapine for HIV prophylaxis. Infants born to mothers with TB also received RH preventive therapy. Infant plasma nevirapine concentrations were measured at 1 and 6 weeks. The effects of RH preventive therapy on nevirapine disposition were investigated in a population pharmacokinetic model. Results: Of 164 infants undergoing pharmacokinetic sampling, 46 received RH preventive therapy. After adjusting for weight using allometric scaling, the model estimated a 33% reduction in nevirapine trough concentrations with RH preventive therapy compared with TB-unexposed infants not receiving concomitant rifampicin and a 30% decline in trough concentrations in a typical infant between day 7 and 35 post-partum. Conclusions: Rifampicin-based TB preventative treatment reduces nevirapine concentrations significantly in HIV-exposed infants. Although the nevirapine exposures required to prevent HIV acquisition in breastfeeding infants are undefined, given the potential risks associated with underdosing nevirapine in this setting, it is prudent to avoid rifampicin-based preventive therapy in HIV-exposed children receiving prophylactic nevirapine.
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Fármacos Anti-HIV/sangue , Antituberculosos/uso terapêutico , Infecções por HIV/prevenção & controle , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Isoniazida/uso terapêutico , Nevirapina/sangue , Rifampina/uso terapêutico , Tuberculose/prevenção & controle , Adulto , Fármacos Anti-HIV/administração & dosagem , Antituberculosos/sangue , Antituberculosos/farmacocinética , Aleitamento Materno , Estudos de Casos e Controles , Quimioterapia Combinada , Feminino , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , HIV-1/isolamento & purificação , Humanos , Lactente , Recém-Nascido , Masculino , Mães , Nevirapina/administração & dosagem , Profilaxia Pós-Exposição , Gravidez , Complicações Infecciosas na Gravidez/tratamento farmacológico , Estudos Prospectivos , Tuberculose/complicaçõesRESUMO
BACKGROUND: Pregnancy and tuberculosis treatment or prophylaxis can affect efavirenz pharmacokinetics, maternal human immunodeficiency virus type 1 (HIV-1) treatment outcomes, and mother-to-child transmission (MTCT) risk. METHODS: We evaluated a prospective cohort of pregnant, HIV-infected women with and without tuberculosis in Soweto, South Africa. Pharmacokinetic sampling was performed at gestation week 37 and during the postpartum period. Efavirenz trough concentrations (Cmin) were predicted using population pharmacokinetic models. HIV-viral load was measured at delivery for mothers and at 6 weeks of age for infants. RESULTS: Ninety-seven women participated; 44 had tuberculosis. Median efavirenz Cmin during pregnancy was 1.35 µg/mL (interquartile range [IQR], 0.90-2.07 µg/mL; 27% had an efavirenz Cmin of < 1 µg/mL), compared with a median postpartum value of 2.00 µg/mL (IQR, 1.40-3.59 µg/mL; 13% had an efavirenz Cmin of < 1 µg/mL). A total of 72% of pregnant women with extensive CYP2B6 genotypes had an efavirenz Cmin of <1 µg/mL. Rifampin did not reduce the efavirenz Cmin. Isoniazid (for prophylaxis or treatment), though, reduced the rate of efavirenz clearance. At delivery, median durations of ART were 13 weeks (IQR, 9-18 weeks) and 21 weeks (IQR, 13-64 weeks) for women with and those without tuberculosis, respectively; 55% and 83%, respectively, had a viral load of <20 copies/mL (P = .021). There was 1 case of MTCT. CONCLUSIONS: Pregnancy increased the risk of low efavirenz concentrations, but MTCT was rare. A detectable HIV-viral load at delivery was more common among pregnant women with tuberculosis, in whom ART was generally initiated later.
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Fármacos Anti-HIV/farmacocinética , Benzoxazinas/farmacocinética , Infecções por HIV/tratamento farmacológico , Complicações Infecciosas na Gravidez/tratamento farmacológico , Adolescente , Adulto , Alcinos , Fármacos Anti-HIV/administração & dosagem , Benzoxazinas/administração & dosagem , Estudos de Coortes , Coinfecção/tratamento farmacológico , Coinfecção/virologia , Ciclopropanos , Feminino , Infecções por HIV/complicações , Infecções por HIV/virologia , HIV-1/isolamento & purificação , Humanos , Plasma/química , Plasma/virologia , Gravidez , Complicações Infecciosas na Gravidez/virologia , Estudos Prospectivos , África do Sul , Tuberculose/complicações , Carga Viral , Adulto JovemRESUMO
BACKGROUND: The duration of protection against tuberculosis provided by isoniazid preventive therapy is not known for human immunodeficiency virus (HIV)-infected individuals living in settings of medium tuberculosis incidence. METHODS: We conducted an individual-level analysis of participants in a cluster-randomized, phased-implementation trial of isoniazid preventive therapy. HIV-infected patients who had positive tuberculin skin tests (TSTs) were followed until tuberculosis diagnosis, death, or administrative censoring. Nelson-Aalen cumulative hazard plots were generated and hazards were compared using the log-rank test. Cox proportional hazards models were fitted to investigate factors associated with tuberculosis diagnosis. RESULTS: Between 2003 and 2009, 1954 patients with a positive TST were studied. Among these, 1601 (82%) initiated isoniazid. Overall tuberculosis incidence was 1.39 per 100 person-years (PY); 0.53 per 100 PY in those who initiated isoniazid and 6.52 per 100 PY for those who did not (adjusted hazard ratio [aHR], 0.17; 95% confidence interval [CI], .11-.25). Receiving antiretroviral therapy at time of a positive TST was associated with a reduced risk of tuberculosis (aHR, 0.69; 95% CI, .48-1.00). Nelson-Aalen plots of tuberculosis incidence showed a constant risk, with no acceleration in 7 years of follow-up for those initiating isoniazid preventive therapy. CONCLUSIONS: Isoniazid preventive therapy significantly reduced tuberculosis risk among HIV-infected patients with a positive TST. In a medium-prevalence setting, 6 months of isoniazid in HIV-infected patients with positive TST reduces tuberculosis risk over 7 years of follow-up, in contrast to results of studies in higher-burden settings in Africa.
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Antituberculosos/uso terapêutico , Infecções por HIV/tratamento farmacológico , Isoniazida/uso terapêutico , Tuberculose/epidemiologia , Tuberculose/prevenção & controle , Adulto , Brasil/epidemiologia , Feminino , Seguimentos , Infecções por HIV/complicações , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prevalência , Modelos de Riscos Proporcionais , Teste Tuberculínico , Tuberculose/diagnóstico , Adulto JovemRESUMO
Effective treatment of tuberculosis during pregnancy is essential for preventing maternal and fetal mortality, but little is known about the effects of pregnancy on the disposition of antituberculosis drugs. We explored the effects of pregnancy on the pharmacokinetics of rifampin, the key sterilizing drug in tuberculosis treatment, in Tshepiso, a prospective cohort study involving pregnant HIV-infected women with or without tuberculosis in Soweto, South Africa. Participants receiving standard first-line tuberculosis treatment underwent sparse sampling for rifampin at 37 weeks' gestation or delivery and then postpartum. Cord blood was collected when possible. A population pharmacokinetic model was developed to investigate the effects of pregnancy on rifampin pharmacokinetics. Among the 48 participants, median age and weight were 28 years and 67 kg, respectively. A one-compartment model with first-order elimination, transit compartment absorption, and allometric scaling described the data well. Pregnancy reduced rifampin clearance by 14%. The median (interquartile range) model-estimated rifampin area under the concentration-time curve over 24 h (AUC0-24) during pregnancy or intrapartum was 40.8 h · mg/liter (27.1 to 54.2 h · mg/liter) compared to 37.4 h · mg/liter (26.8 to 50.3 h · mg/liter) postpartum. The maximum concentrations were similar during pregnancy and postpartum. Rifampin was detectable in 36% (8/22) of cord blood samples, and 88% (42/48) of the women had successful treatment outcomes. There was one case of perinatal tuberculosis. In conclusion, rifampin clearance is modestly reduced during the last trimester of pregnancy. Exposures are only slightly increased, so dose adjustment during pregnancy is not needed. Rifampin was detected in cord blood samples when delivery occurred soon after dosing. The consequences of exposure to this potent inducer of metabolizing enzymes among HIV-exposed infants are unclear.
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Antibióticos Antituberculose/farmacocinética , Infecções por HIV/tratamento farmacológico , Complicações Infecciosas na Gravidez/tratamento farmacológico , Rifampina/farmacocinética , Tuberculose/tratamento farmacológico , Adulto , Antibióticos Antituberculose/uso terapêutico , Área Sob a Curva , Estudos de Coortes , Coinfecção/tratamento farmacológico , Feminino , Sangue Fetal/efeitos dos fármacos , Humanos , Recém-Nascido , Período Pós-Parto , Gravidez , Estudos Prospectivos , Rifampina/uso terapêutico , África do Sul , Resultado do TratamentoRESUMO
BACKGROUND: Each year, 1 million children develop TB resulting in over 200,000 child deaths. TB preventive treatment (TPT) is highly effective in preventing TB but remains poorly implemented for household child contacts. Home-based child contact management and TPT services may improve access to care. In this study, we aim to evaluate the effectiveness and cost-effectiveness of home-based contact management with TPT initiation in two TB high-burden African countries, Ethiopia and South Africa. METHODS: This pragmatic cluster randomized trial compares home-based versus facility-based care delivery models for contact management. Thirty-six clinics with decentralized TB services (18 in Ethiopia and 18 in South Africa) were randomized in a 1:1 ratio to conduct either home-based or facility-based contact management. The study will attempt to enroll all eligible close child contacts of infectious drug-sensitive TB index patients diagnosed and treated for TB by one of the study clinics. Child TB contact management, including contact tracing, child evaluation, and TPT initiation and follow-up, will take place in the child's home for the intervention arm and at the clinic for the control arm. The primary outcome is the cluster-level ratio of the number of household child contacts less than 15 years of age in Ethiopia and less than 5 years of age in South Africa initiated on TPT per index patient, comparing the intervention to the control arm. Secondary outcomes include child contact identification and the TB prevention continuum of care. Other implementation outcomes include acceptability, feasibility, fidelity, cost, and cost-effectiveness of the intervention. DISCUSSION: This implementation research trial will determine whether home-based contact management identifies and initiates more household child contacts on TPT than facility-based contact management. TRIAL REGISTRATION: NCT04369326 . Registered on April 30, 2020.
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Tuberculose , Criança , Humanos , Pré-Escolar , Tuberculose/diagnóstico , Tuberculose/prevenção & controle , África do Sul/epidemiologia , Etiópia/epidemiologia , Instituições de Assistência Ambulatorial , Protocolos Clínicos , Busca de Comunicante/métodosRESUMO
Tuberculosis (TB) causes 1 in 3 deaths among people living with HIV (PLHIV). Diagnosing and treating latent tuberculosis infection (LTBI) is critical to reducing TB incidence and mortality. Blood-based screening tests (e.g., QuantiFERON-TB Gold Plus (QFT+)) and shorter-course TB preventive therapy (TPT) regimens such as 3HP (3 months weekly isoniazid-rifapentine) hold significant promise to improve TB outcomes. We qualitatively explored barriers and solutions to optimizing QFT+ and 3HP among PLHIV in three cities in Brazil. We conducted 110 in-depth interviews with PLHIV, health care providers (HCP) and key informants (KI). Content analysis was conducted including the use of case summaries and comparison of themes across populations and contexts. LTBI screening and treatment practices were dependent on HCP's perceptions of whether they were critical to improving TB outcomes. Many HCP lacked a strong understanding of LTBI and perceived the current TPT regimen as complicated. HCP reported that LTBI screening and treatment were constrained by clinic staffing challenges. While PLHIV generally expressed willingness to consider any test or treatment that doctors recommended, they indicated HCP rarely discussed LTBI and TPT. TB testing and treatment requests were constrained by structural factors including financial and food insecurity, difficulties leaving work for appointments, stigma and family responsibilities. QFT+ and 3HP were viewed by all participants as tools that could significantly improve the LTBI cascade by avoiding complexities of TB skin tests and longer LTBI treatment courses. QFT+ and 3HP were perceived to have challenges, including the potential to increase workload on over-burdened health systems if not implemented alongside improved supply chains, staffing, and training, and follow-up initiatives. Multi-level interventions that increase understanding of the importance of LTBI and TPT among HCP, improve patient-provider communication, and streamline clinic-level operations related to QFT+ and 3HP are needed to optimize their impact among PLHIV and reduce TB mortality.
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Left ventricular hypertrophy (LVH) associates with increased risk for cardiovascular disease. Hypertension leads to LVH in adults, but its role in the pathogenesis of LVH in children is not as well established. To examine left ventricular mass and evaluate factors associated with LVH in children with stages 2 through 4 chronic kidney disease (CKD), we analyzed cross-sectional data from children who had baseline echocardiography (n = 366) and underwent ambulatory BP monitoring (n = 226) as a part of the observational Chronic Kidney Disease in Children (CKiD) cohort study. At baseline, 17% of children had LVH (11% eccentric and 6% concentric) and 9% had concentric remodeling of the left ventricle. On the basis of a combination of ambulatory and casual BP assessment (n = 198), 38% of children had masked hypertension (normal casual but elevated ambulatory BP) and 18% had confirmed hypertension (both elevated casual and ambulatory BP). There was no significant association between LVH and kidney function. LVH was more common in children with either confirmed (34%) or masked (20%) hypertension compared with children with normal casual and ambulatory BP (8%). In multivariable analysis, masked (odds ratio 4.1) and confirmed (odds ratio 4.3) hypertension were the strongest independent predictors of LVH. In conclusion, casual BP measurements alone are insufficient to predict the presence of LVH in children with CKD. The high prevalence of masked hypertension and its association with LVH supports early echocardiography and ambulatory BP monitoring to evaluate cardiovascular risk in children with CKD.
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Hipertensão/epidemiologia , Hipertrofia Ventricular Esquerda/epidemiologia , Nefropatias/complicações , Adolescente , Pressão Sanguínea/fisiologia , Criança , Doença Crônica , Estudos de Coortes , Estudos Transversais , Ecocardiografia , Feminino , Humanos , Hipertensão/fisiopatologia , Hipertrofia Ventricular Esquerda/diagnóstico por imagem , Hipertrofia Ventricular Esquerda/fisiopatologia , Nefropatias/fisiopatologia , Masculino , Análise Multivariada , National Institutes of Health (U.S.) , Prevalência , Fatores de Risco , Índice de Gravidade de Doença , Estados UnidosRESUMO
OBJECTIVES: In Brazil, annual tuberculin skin tests (TSTs) are recommended for people living with HIV (PLWH) with CD4 >350, with tuberculosis preventive therapy provided on test conversion. We aimed to determine the yield of repeat TSTs for PLWH. DESIGN: Secondary analysis of the stepped-wedge, cluster-randomized THRio trial for isoniazid preventive therapy (IPT) to prevent tuberculosis (TB). METHODS: We analyzed data from newly registered PLWH with negative baseline TST results. We calculated the number of TST conversions after 1 and/or 2 years among patients eligible for follow-up TSTs, the proportion of converters initiating IPT, and incidence of TB/death. RESULTS: Among 1770 PLWH with a negative baseline TST, 679 (38%) were female and median age was 36 years (IQR 29-43). Eighty-six (5%) developed TB or died within 1 year. Among 1684 eligible for a follow-up 1-year TST, 582 (35%) were tested and 53 (9%) were positive. Forty-nine converters (92%) started IPT. Of 529 patients with a negative 1-year TST, 7 (1%) developed TB or died over the following year. Of 522 patients eligible for a 2-year TST, 158 (30%) were tested and 13 (8%) were positive. Ten converters (77%) started IPT. Of 1102 patients who did not receive a 1-year TST, 33 (3%) developed TB or died. Of the 1069 patients eligible for a 2-year TST, 259 (24%) were tested and 34 (13%) were positive. Thirty converters (88%) started IPT. CONCLUSIONS: In this cohort of PLWH in Brazil, TST conversion was high among those retested, but only 48% received a follow-up TST within 2 years.
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Antituberculosos/administração & dosagem , Infecções por HIV/complicações , Isoniazida/administração & dosagem , Teste Tuberculínico/estatística & dados numéricos , Tuberculose/diagnóstico , Tuberculose/prevenção & controle , Adulto , Terapia Antirretroviral de Alta Atividade , Antituberculosos/uso terapêutico , Brasil/epidemiologia , Contagem de Linfócito CD4 , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Humanos , Isoniazida/uso terapêutico , Masculino , Tuberculina , Teste Tuberculínico/métodos , Tuberculose/epidemiologiaRESUMO
OBJECTIVES: In 2018, Brazilian guidelines changed to recommend tuberculosis (TB) preventive therapy for all people with HIV and a CD4 cell count 350 cells/µl or less, but only for those with a positive tuberculin skin test (TST) if CD4 cell count is than 350 cells/µl. We determined the potential effectiveness of CD4-based guidelines for TB testing and preventive therapy. DESIGN: Secondary analysis of the stepped-wedge, cluster-randomized THRio trial for isoniazid preventive therapy (IPT). METHODS: We analyzed data from 4114 newly registered patients with HIV in 29 clinics followed until TB diagnosis, death, or administrative censoring. We compared incidence rates of TB and TB/death between CD4, TST, IPT, and antiretroviral therapy categories. RESULTS: Initial CD4 cell count was 350 cells/µl or less in 2138 (52%) and more than 350 cells/µl in 1976 (48%) patients. TST was performed for 2922 (71%), of whom 657 (16%) were TST-positive [278 (13%) CD4â≤â350 vs. 379 (19%) CD4â>â350]. A total of 619 (15%) received IPT and 2806 (68%) received antiretroviral therapy. For patients with CD4 cell count 350 cells/µl or less who did not receive IPT, the incidence rate of TB was 1.79/100 person-years (pys) and TB/death was 3.89/100âpys. For patients with CD4 cell count more than 350 who did not receive IPT, the incidence rates of TB and TB/death were 0.57/100 and 1.49/100âpys for TST-negatives, and 1.05/100 and 1.64/100âpys for TST-unknowns. CONCLUSION: TB incidence was high among all patients who did not receive IPT, including those with CD4 cell count more than 350 cells/µl and negative or unknown TST results. TB preventive therapy should be provided to all people living with HIV in medium burden settings, regardless of CD4 cell count and TST status.
Assuntos
Antituberculosos/uso terapêutico , Contagem de Linfócito CD4 , Infecções por HIV/complicações , Isoniazida/uso terapêutico , Tuberculose/prevenção & controle , Adulto , Fármacos Anti-HIV/uso terapêutico , Brasil/epidemiologia , Feminino , Infecções por HIV/tratamento farmacológico , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Tuberculose/epidemiologiaRESUMO
OBJECTIVES: Tuberculosis preventive therapy for people living with HIV is effective, widely recommended, and increasingly prescribed, but completion rates are less than ideal, and adherence is not typically monitored. We sought to quantify adherence to isoniazid preventive therapy using a urine metabolite assay. DESIGN: Two cross-sectional surveys. SETTING: Rio de Janeiro, Brazil, 2008-2009; and Northwest Province, South Africa, 2018-2019. PARTICIPANTS: Two hundred and three Brazilian and 93 South African patients attending HIV clinics with active prescriptions for isoniazid preventive therapy MAIN OUTCOME MEASURES:: Self-reported isoniazid adherence, paired with semiquantitative measurement of urine isoniazid metabolites. RESULTS: By self-report, 90% of patients [95% confidence interval (CI) 86-93%] reported having taken a dose of isoniazid on the day of enrollment or the preceding day, and 91% (95% CI 87-94%) reported missing an average of one dose or fewer per week. By urine testing, only 65% (95% CI 59-70%) of all patients, and 69% (95% CI 63-74%) of those who reported having taken isoniazid on the current or preceding day, had detectable urine metabolites (expected in 95% of patients at 24âh). Longer time since starting preventive therapy was independently associated with a negative urine test for isoniazid metabolites (adjusted prevalence ratio 1.11 per month of isoniazid, 95% CI 1.05-1.18). CONCLUSION: Adherence to isoniazid preventive therapy among patients with HIV in Brazil and South Africa is inadequate, is overestimated by self-report, and declines with time on treatment. Shorter regimens for TB preventive therapy may improve adherence and completion, but adherence support for all patients may be necessary.
Assuntos
Antituberculosos/uso terapêutico , Infecções por HIV/complicações , Isoniazida/uso terapêutico , Adesão à Medicação/estatística & dados numéricos , Tuberculose/prevenção & controle , Adulto , Fármacos Anti-HIV/uso terapêutico , Brasil/epidemiologia , Estudos Transversais , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Humanos , Isoniazida/urina , Masculino , Pessoa de Meia-Idade , Prevalência , África do Sul/epidemiologia , Tuberculose/epidemiologia , Tuberculose/urinaRESUMO
PURPOSE: Many children with chronic kidney disease have urinary incontinence due to urological disorders and/or a urine concentrating defect. We determined the prevalence and impact of incontinence on health related quality of life in children with chronic kidney disease. MATERIALS AND METHODS: The Chronic Kidney Disease in Children study is a prospective, observational cohort of children recruited from 47 sites in the United States and Canada. Eligibility requirements are age 1 to 16 years and an estimated glomerular filtration rate of 30 to 90 ml per minute per 1.73 m(2). Demographics, continence status, glomerular filtration rate and physical examination were assessed at study entry. Health related quality of life was measured using the parent and child versions of PedsQL. PedsQL scores in participants 5 years old or older were compared among children who were toilet trained and not bed-wetting, bed-wetting or not toilet trained using multivariate linear regression. RESULTS: Overall median age of the 329 participants was 12.5 years, 61.4% were male, 70% were white and 55.5% had a urological disorder. Of participants 71.4% were toilet trained at study enrollment, 23.1% had bed-wetting and 5.5% were not toilet trained. Children who were not yet toilet trained had an average total score that was 13.5 points lower (95% CI -25.2, -1.8) on the PedsQL child report than in those who were toilet trained (p = 0.02). Physical functioning (-15.0, 95% CI -28.2, -1.9) and school functioning (-15.3, 95% CI -29.8, -0.8) were also lower in this group (p = 0.03 and 0.04, respectively). On the PedsQL parent proxy report physical functioning (-14.2, 95% CI -26.7, -1.6) was similarly affected by child incontinence (p = 0.03). CONCLUSIONS: Urinary incontinence is common in pediatric patients with chronic kidney disease and associated with lower health related quality of life on the PedsQL child and parent proxy reports. Early recognition of and treatment for urinary incontinence may improve health related quality of life in this population.
Assuntos
Nefropatias/complicações , Qualidade de Vida , Incontinência Urinária/complicações , Criança , Doença Crônica , Feminino , Humanos , Masculino , Estudos ProspectivosRESUMO
BACKGROUND: We assessed HIV RNA suppression, resistance, and CD4 T-cell count 12 months postpartum among pregnant women retained in care in an observational cohort study. METHODS: We prospectively followed two groups of HIV-infected pregnant women--with or without tuberculosis--recruited from prenatal clinics in South Africa. Women who received antiretroviral therapy during pregnancy and reported being on therapy 12 months postpartum were included. Serum samples from women with HIV viremia 12 months postpartum were tested for drug resistance. RESULTS: Of 103 women in the study, median age and CD4 T-cell count at enrollment were 29 years [interquartile range (IQR): 26-32] and 317 cells per cubic millimeter (IQR: 218-385), respectively; 43 (42%) had tuberculosis at baseline. During pregnancy, 87% of the women achieved an HIV RNA <400 copies per milliliter compared with 71% at 12 months postpartum (P < 0.001). Factors independently associated with an HIV RNA <400 copies per milliliter at 12 months were age ≥ 30 years, detectable plasma efavirenz concentration, and HIV RNA <400 copies per milliliter while pregnant; there was a trend toward both a detectable viral load and peripartum depression. HIV drug resistance results were available from 25 women, and 12 (48%) had major drug resistance mutations. CD4 T-cell count declined a median of 13 cells per cubic millimeter (IQR: -66 to 140) from delivery to 12 months in women with viremia at 12 months. CONCLUSIONS: Success with maintaining virologic control declined postpartum among HIV-infected women who remained in care and on antiretroviral therapy, and CD4 T-cell count decline and drug resistance were common.
Assuntos
Fármacos Anti-HIV/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Linfócitos T CD4-Positivos/citologia , Farmacorresistência Viral/imunologia , Infecções por HIV , Adulto , Contagem de Linfócito CD4 , Estudos de Coortes , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , HIV-1 , Humanos , Período Pós-Parto , Gravidez , Estudos Prospectivos , RNA Viral/análise , África do Sul , Falha de Tratamento , Carga Viral , Adulto JovemRESUMO
BACKGROUND: The combination of rifapentine and moxifloxacin administered daily with other anti-tuberculosis drugs is highly active in mouse models of tuberculosis chemotherapy. The objective of this phase 2 clinical trial was to determine the bactericidal activity, safety, and tolerability of a regimen comprised of rifapentine, moxifloxacin, isoniazid, and pyrazinamide administered daily during the first 8 weeks of pulmonary tuberculosis treatment. METHODS: Adults with sputum smear-positive pulmonary tuberculosis were randomized to receive either rifapentine (approximately 7.5 mg/kg) plus moxifloxacin (investigational arm), or rifampin (approximately 10 mg/kg) plus ethambutol (control) daily for 8 weeks, along with isoniazid and pyrazinamide. The primary endpoint was sputum culture status at completion of 8 weeks of treatment. RESULTS: 121 participants (56% of accrual target) were enrolled. At completion of 8 weeks of treatment, negative cultures using Löwenstein-Jensen (LJ) medium occurred in 47/60 (78%) participants in the investigational arm vs. 43/51 (84%, p = 0.47) in the control arm; negative cultures using liquid medium occurred in 37/47 (79%) in the investigational arm vs. 27/41 (66%, p = 0.23) in the control arm. Time to stable culture conversion was shorter for the investigational arm vs. the control arm using liquid culture medium (p = 0.03), but there was no difference using LJ medium. Median rifapentine area under the concentration-time curve (AUC0-24) was 313 mcg*h/mL, similar to recent studies of rifapentine dosed at 450-600 mg daily. Median moxifloxacin AUC0-24 was 28.0 mcg*h/mL, much lower than in trials where rifapentine was given only intermittently with moxifloxacin. The proportion of participants discontinuing assigned treatment for reasons other than microbiological ineligibility was higher in the investigational arm vs. the control arm (11/62 [18%] vs. 3/59 [5%], p = 0.04) although the proportions of grade 3 or higher adverse events were similar (5/62 [8%] in the investigational arm vs. 6/59 [10%, p = 0.76] in the control arm). CONCLUSION: For intensive phase daily tuberculosis treatment in combination with isoniazid and pyrazinamide, a regimen containing moxifloxacin plus low dose rifapentine was at least as bactericidal as the control regimen containing ethambutol plus standard dose rifampin. TRIAL REGISTRATION: www.ClinicalTrials.gov NCT00728507.
Assuntos
Antituberculosos/uso terapêutico , Fluoroquinolonas/uso terapêutico , Rifampina/análogos & derivados , Tuberculose Pulmonar/tratamento farmacológico , Adulto , Antituberculosos/administração & dosagem , Antituberculosos/efeitos adversos , Antituberculosos/farmacocinética , Estudos de Casos e Controles , Quimioterapia Combinada , Feminino , Fluoroquinolonas/administração & dosagem , Humanos , Isoniazida/administração & dosagem , Isoniazida/uso terapêutico , Masculino , Pessoa de Meia-Idade , Moxifloxacina , Pirazinamida/administração & dosagem , Pirazinamida/uso terapêutico , Rifampina/administração & dosagem , Rifampina/uso terapêuticoRESUMO
BACKGROUND: The timing of highly active antiretroviral therapy (HAART) after a tuberculosis diagnosis in HIV-infected patients can affect clinical outcomes and survival. We compared survival after tuberculosis diagnosis in HIV-infected adults who initiated HAART and tuberculosis therapy simultaneously to those who delayed the start of HAART for at least two months. METHODS: The THRio cohort includes 17,983 patients receiving HIV care in 29 public clinics in Rio de Janeiro, Brazil. HAART-naïve patients at the time of a new TB diagnosis between September 2003 and June 2008 were included. Survival was measured in days from diagnosis of TB. We compared survival among patients who initiated HAART within 60 days of TB treatment (simultaneous - ST) to those who started HAART >60 days of TB treatment or never started (deferred - DT). Kaplan-Meier plots and Cox proportional hazards regression analyses were conducted. RESULTS: Of 947 patients diagnosed with TB, 572 (60%) were HAART naïve at the time of TB diagnosis; 135 were excluded because of missing CD4 count results. Among the remaining 437 TB patients, 56 (13%) died during follow-up: 25 (10%) among ST patients and 31 (16%) in DT group (p=0.08). ST patients had lower median CD4 counts at TB diagnosis than DT patients (106 vs. 278, p<0.001). Cox proportional hazards utilizing propensity score analysis showed that DT patients were more likely to die (adjusted HR=1.89; 95% CI: 1.05-3.40; p=0.03). CONCLUSION: HAART administered simultaneously with TB therapy was associated with improved survival after TB diagnosis. HAART should be given to patients with HIV-related TB as soon as clinically feasible.