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1.
MMWR Recomm Rep ; 69(1): 1-11, 2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-32053584

RESUMO

Comprehensive guidelines for treatment of latent tuberculosis infection (LTBI) among persons living in the United States were last published in 2000 (American Thoracic Society. CDC targeted tuberculin testing and treatment of latent tuberculosis infection. Am J Respir Crit Care Med 2000;161:S221-47). Since then, several new regimens have been evaluated in clinical trials. To update previous guidelines, the National Tuberculosis Controllers Association (NTCA) and CDC convened a committee to conduct a systematic literature review and make new recommendations for the most effective and least toxic regimens for treatment of LTBI among persons who live in the United States.The systematic literature review included clinical trials of regimens to treat LTBI. Quality of evidence (high, moderate, low, or very low) from clinical trial comparisons was appraised using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria. In addition, a network meta-analysis evaluated regimens that had not been compared directly in clinical trials. The effectiveness outcome was tuberculosis disease; the toxicity outcome was hepatotoxicity. Strong GRADE recommendations required at least moderate evidence of effectiveness and that the desirable consequences outweighed the undesirable consequences in the majority of patients. Conditional GRADE recommendations were made when determination of whether desirable consequences outweighed undesirable consequences was uncertain (e.g., with low-quality evidence).These updated 2020 LTBI treatment guidelines include the NTCA- and CDC-recommended treatment regimens that comprise three preferred rifamycin-based regimens and two alternative monotherapy regimens with daily isoniazid. All recommended treatment regimens are intended for persons infected with Mycobacterium tuberculosis that is presumed to be susceptible to isoniazid or rifampin. These updated guidelines do not apply when evidence is available that the infecting M. tuberculosis strain is resistant to both isoniazid and rifampin; recommendations for treating contacts exposed to multidrug-resistant tuberculosis were published in 2019 (Nahid P, Mase SR Migliori GB, et al. Treatment of drug-resistant tuberculosis. An official ATS/CDC/ERS/IDSA clinical practice guideline. Am J Respir Crit Care Med 2019;200:e93-e142). The three rifamycin-based preferred regimens are 3 months of once-weekly isoniazid plus rifapentine, 4 months of daily rifampin, or 3 months of daily isoniazid plus rifampin. Prescribing providers or pharmacists who are unfamiliar with rifampin and rifapentine might confuse the two drugs. They are not interchangeable, and caution should be taken to ensure that patients receive the correct medication for the intended regimen. Preference for these rifamycin-based regimens was made on the basis of effectiveness, safety, and high treatment completion rates. The two alternative treatment regimens are daily isoniazid for 6 or 9 months; isoniazid monotherapy is efficacious but has higher toxicity risk and lower treatment completion rates than shorter rifamycin-based regimens.In summary, short-course (3- to 4-month) rifamycin-based treatment regimens are preferred over longer-course (6-9 month) isoniazid monotherapy for treatment of LTBI. These updated guidelines can be used by clinicians, public health officials, policymakers, health care organizations, and other state and local stakeholders who might need to adapt them to fit individual clinical circumstances.

2.
Clin Infect Dis ; 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32044987

RESUMO

BACKGROUND: Predictors of latent tuberculosis infection (LTBI) among close contacts of persons with infectious tuberculosis (TB) are incompletely understood, particularly the number of exposure hours. METHODS: We prospectively enrolled adult patients with culture-confirmed pulmonary TB and their close contacts at 9 health departments in the United States and Canada. Patients with TB were interviewed and close contacts were interviewed and screened for TB and LTBI during contact investigations. RESULTS: LTBI was diagnosed in 1390 (46%) of 3040 contacts, including 624 (31%) of 2027 US/Canadian-born and 766 (76%) of 1013 non-US/Canadian-born contacts. In multivariable analysis, age ≥5 years, male sex, non-US/Canadian birth, smear-positive index patient, and shared bedroom with an index patient (P < .001 for each), as well as exposure to >1 index patient (P < .05), were associated with LTBI diagnosis. LTBI prevalence increased with increasing exposure duration, with an incremental prevalence increase of 8.2% per 250 exposure hours (P < .0001). For contacts with <250 exposure hours, no difference in prevalence was observed per 50 exposure hours (P = .63). CONCLUSIONS: Hours of exposure to a patient with infectious TB is an important LTBI predictor, with a possible risk threshold of 250 hours. More exposures, closer exposure proximity, and more extensive index patient disease were additional LTBI predictors.

3.
Artigo em Inglês | MEDLINE | ID: mdl-31904701

RESUMO

BACKGROUND: People living with HIV (PLWH) experience high rates of mood disorders (major depression and bipolar affective disorder) which in the general population have been associated with non-communicable disease (NCD) risk. We examined whether prevalent mood disorders are associated with incident NCDs and multimorbidity (accumulation of ≥2 NCDs) in PLWH. SETTING: Adult HIV clinic cohort in Nashville, Tennessee, between 1998-2015. METHODS: PLWH with ≥1 year of follow-up in the clinic were assessed for cardiovascular disease, metabolic syndrome (any three of hypertension, hyperlipidemia, diabetes, or obesity), chronic kidney and liver disease, non-AIDS-defining cancers, and dementia. Only mood disorders documented during the first year of care were included. Cumulative incidence and adjusted subhazard ratios were calculated for risk of NCDs and multimorbidity with death as a competing risk. Multivariable Cox models estimated mortality risk following multimorbidity. RESULTS: Of 4,140 adults, 24% had a mood disorder diagnosed in the first year of care, 51% had ≥1 NCD at baseline, and there were 2588 incident NCDs during the study period. Mood disorders were associated with increased risk of first NCD (adjusted subhazard ratio [aSHR] = 1.29, 95% confidence interval [CI] 1.06-1.57), incident multimorbidity (aSHR ranging from 1.04 to 1.42) and metabolic syndrome (aSHR = 1.29, 95%CI 1.02-1.64). Mood disorders were not conclusively associated with mortality risk following multimorbidity. CONCLUSIONS: PLWH with mood disorders were at increased risk of incident NCDs and multimorbidity, particularly metabolic syndrome. Focused prevention and treatment of NCDs may reduce the burden of multimorbidity in this high-risk group.

4.
Artigo em Inglês | MEDLINE | ID: mdl-31789047

RESUMO

HIV and Hepatitis C virus (HCV) co-infection is associated with poor health outcomes. This study was designed to assess risk factors for and mortality with co-infection prior to direct-acting antiviral treatment availability in a state with an evolving opioid epidemic. HCV infection was determined from review of the medical record at two clinics serving the majority of people living with HIV (PLWH) in care in Middle Tennessee from 2004 to 2013. Association of potential risk factors with HCV-positivity was assessed using logistic regression. Association of HCV-positivity with mortality was assessed with a Cox proportional hazards model, adjusting for selected covariates. A total of 3501 patients were included: 24% female; 51% men who have sex with men; 47% white; 44% African-American/black; median age of 38 at their first visit; median most recent CD4 count 502 cells/µL (301, 716) and HIV viral load 47 copies/mL (39, 605), followed for a median of 3.0 (1, 5) years. Prevalence of HCV was 13%. Those with a history of injection drug use (IDU) demonstrated the highest odds of HCV-positivity (OR 12.94; 95% CI 9.39-17.83). There were 305 deaths; median age at death was 47 years (40, 53). HCV co-infection was associated with greater mortality (HR 1.61; 95% CI 1.20-2.17; p<0.001). Among PLWH, HCV co-infection was associated with IDU and an independent predictor of mortality. These results affirm the importance of HCV co-infection and inform interventions targeting the continuum of HCV care, uptake of HCV treatment, and the impact of drug use in this population.

5.
J Int AIDS Soc ; 22(12): e25423, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31814312

RESUMO

INTRODUCTION: Identification of persons living with human immunodeficiency virus (HIV)-associated tuberculosis (TB) at increased risk for unfavourable TB outcomes would inform efforts to improve such outcomes. We sought to identify factors associated with a decreased risk of unfavourable TB treatment outcomes among people living with HIV-infection (PLHIV) in low- and middle-income countries (LMIC), with a specific focus on directly observed therapy (DOT) compared with self-administered therapy (SAT) during the continuation phase of anti-TB therapy. METHODS: We conducted a retrospective cohort study among adults diagnosed with HIV-associated TB in Africa, Asia and the Americas from 2012 to 2013; data were collected from 2012 to 2016. Unfavourable TB treatment outcomes (death during TB treatment, and TB treatment failure or recurrence) were defined according to World Health Organization criteria. Receipt of DOT was obtained at the site level and defined as ≥5 days of DOT per week. The person administering DOT and treatment location varied by site. Lack of receipt of DOT was defined as SAT. Multivariable logistic regression estimated the adjusted odds of unfavourable TB treatment outcomes. RESULTS: Among 1862 adults with HIV-associated TB included, 252 (13.5%) had unfavourable TB outcomes (226 deaths, 26 recurrences/failures). Overall, 1825 (98%) received DOT in the intensive phase and 1617 (87%) received DOT in the continuation phase. DOT in the continuation phase was not significantly associated with unfavourable TB outcomes (aOR 1.43, 95% CI 0.86 to 2.38) compared to SAT. Body mass index (BMI) change during anti-TB treatment (per 2 units increase, aOR 0.74, 95% CI 0.68 to 0.82) and CD4+ count at TB diagnosis (200 vs. 50  cells/µL, aOR 0.54, 95% CI 0.39 to 0.73) were both independently associated with decreased odds of unfavourable TB treatment outcomes. CONCLUSIONS: In this large, international cohort of people living with HIV-associated TB in LMIC who received intensive phase DOT, DOT during the continuation phase of anti-TB therapy was not associated with a decreased odds of unfavourable TB treatment outcomes compared to SAT. Randomized trials evaluating the effect of continuation-phase DOT on TB outcomes among PLHIV are needed.

6.
Int J Infect Dis ; 92: 21-28, 2019 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-31843671

RESUMO

BACKGROUND: Host genetic polymorphisms may be important in determining susceptibility to Mycobacterium tuberculosis (Mtb) infection, but their role is not fully understood. Detection of microbial DNA and activation of type I interferon (IFN) pathways regulate macrophage responses to Mtb infection. METHODS: We examined whether seven candidate gene SNPs were associated with tuberculin skin test (TST) positivity in close contacts of microbiologically confirmed pulmonary TB patients in Brazil. Independent associations with TST positivity were tested using multivariable logistic regression (using genotypes and clinical variables) and genetic models. RESULTS: Among 482 contacts of 145 TB index cases, 296 contacts were TST positive. Multivariable regression analysis adjusted for population admixture, age, family relatedness, sex and clinical variables related to increased TB risk demonstrated that SNPs in PYHIN1-IFI16-AIM2 rs1101998 (adjusted OR [aOR]: 3.72; 95%CI=1.15-12.0; p=0.028) and in PYHIN1-IFI16-AIM2 rs1633256 (aOR=24.84; 95%CI=2.26-272.95; p=0.009) were associated with TST positivity in a recessive model. Furthermore, an IRF7 polymorphism (rs11246213) was associated with reduced odds of TST positivity in a dominant model (aOR: 0.50, 95%CI: 0.26-0.93; p=0.029). CONCLUSIONS: Polymorphisms in PYHIN1-IFI16-AIM2 rs1633256, rs1101998 and in IRF7 rs11246213 were associated with altered susceptibility to Mtb infection in this Brazilian cohort.

7.
Artigo em Inglês | MEDLINE | ID: mdl-31711306

RESUMO

RATIONALE: Noninferiority trials of latent tuberculosis (LTBI) treatment are challenging because of imperfect LTBI diagnostic tests. OBJECTIVES: To assess the effect on study outcomes of different enrollment strategies for a noninferiority trial of LTBI treatment. METHODS: We mathematically simulated a two-arm, randomized, controlled trial of LTBI in which the experimental therapy was 50% efficacious and the control was 80% efficacious, with an absolute 0.75% noninferiority margin. Five enrollment strategies were assessed: 1) Enroll based on no LTBI diagnostic test, 2) Enroll based on a positive tuberculin skin test (TST), 3) Enroll based on a positive interferon gamma release assay (IGRA), 4) Enroll based on either a positive TST or IGRA, 5) Enroll regardless of test result, assuming 70% had negative TSTs, 20% positive TSTs, and 10% unknown results. MEASUREMENTS AND MAIN RESULTS: Under most LTBI prevalence assumptions, enrolling based on a positive IGRA was least likely to result in falsely declaring noninferiority of the experimental regimen. Enrolling based on no test or regardless of test result resulted in falsely declaring noninferiority unless underlying population LTBI prevalence was over 45%. Enrolling based on a mix of TST and IGRA substantially reduced the likelihood of falsely declaring noninferiority over enrolling based on TST alone, even if as many as 70% of participants were enrolled based on positive TST. CONCLUSIONS: Noninferiority trials of LTBI should enroll based on the most specific diagnostic tests available (IGRAs) to avoid misclassifying inferior treatment regimens as noninferior.

8.
J Infect Dis ; 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31724035

RESUMO

BACKGROUND: Weight change may inform tuberculosis (TB) treatment response, but its predictive power may be confounded by HIV. METHODS: We prospectively followed adults with culture-confirmed, drug-susceptible, pulmonary TB receiving standard 4-drug therapy (isoniazid, rifampin, pyrazinamide, ethambutol) in Brazil and examined median weight change two months after treatment initiation by HIV status using quantile regression, and unsuccessful TB treatment outcome (treatment failure, TB recurrence, or death) by HIV and weight change status using Cox regression. RESULTS: Among 547 participants, 102 (19%) were HIV-positive, and 35 (6%) had an unsuccessful outcome. After adjusting for confounders, persons living with HIV (PLWH) gained a median 1.3 kg (95% confidence interval (CI): -2.8, 0.1) less than HIV-negative individuals during the first two months of TB treatment. PLWH were at increased risk of an unsuccessful outcome (adjusted HR=4.8, 95% CI: 2.1, 10.9). Weight change was independently associated with outcome, with risk of unsuccessful outcome decreasing 12% (95% CI: 0.81, 0.95) per 1 kg increase. CONCLUSIONS: PLWH gained less weight during the first two months of TB treatment, and lack of weight gain and HIV independently predicted unsuccessful TB treatment outcomes. Weight, an easily-collected biomarker, may identify patients who would benefit from alternative treatment strategies.

9.
Clin Chest Med ; 40(4): 839-848, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31731988

RESUMO

Treatment of latent tuberculosis infection (LTBI) is an important component of TB control and elimination. LTBI treatment regimens include once-weekly isoniazid plus rifapentine for 3 months, daily rifampin for 4 months, daily isoniazid plus rifampin for 3-4 months, and daily isoniazid for 6-9 months. Isoniazid monotherapy is efficacious in preventing TB disease, but the rifampin- and rifapentine-containing regimens are shorter and have similar efficacy, adequate safety, and higher treatment completion rates. Novel vaccine strategies, host immunity-directed therapies and ultrashort antimicrobial regimens for TB prevention, such as daily isoniazid plus rifapentine for 1 month, are under evaluation.

10.
Clin Infect Dis ; 2019 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-31629369

RESUMO

We assessed association between cured tuberculosis and mortality among persons with HIV in Latin America. We compared survival among persons with and without tuberculosis at enrollment in HIV care, starting 9 months after clinic enrollment. In multivariable analysis, tuberculosis was associated with higher long-term mortality (hazard ratio=1.57; 95% confidence interval=1.25-1.99).

11.
Clin Infect Dis ; 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31665254

RESUMO

BACKGROUND: Diagnosis of active tuberculosis (ATB) currently relies on detection of M. tuberculosis (Mtb). Identifying patients with extrapulmonary TB (EPTB) remains challenging because microbiological confirmation is often not possible. Highly accurate blood-based tests could improve diagnosis of both EPTB and pulmonary TB (PTB), and timely initiation of anti-TB therapy. METHODS: A case-control study was performed using discriminant analyses to validate an approach using Mtb-specific CD4+T-cell activation markers in blood to discriminate PTB and EPTB from latent TB infection (LTBI) as well as EPTB from PTB in 270 Brazilian individuals. We further tested the effect of HIV co-infection on diagnostic performance. Frequencies of IFNγ+CD4+T-cells expressing CD38, HLADR, and/or Ki67 were assessed by flow cytometry. RESULTS: EPTB and PTB were associated with higher frequencies of CD4+T-cells expressing CD38, HLADR or Ki67 compared to LTBI (all p-values < .001). Moreover, frequencies of HLADR+ (p= .03) or Ki67+ (p< .001) cells accurately distinguished EPTB from PTB. HIV infection did not affect the capacity of these markers to distinguish ATB from LTBI or EPTB from PTB. CONCLUSION: Cell activation markers in Mtb-specific CD4+T-cells distinguished ATB from LTBI, and EPTB from PTB, regardless of HIV infection status. These parameters provide an attractive approach for developing blood-based diagnostic tests for both active and latent TB.

12.
Am J Epidemiol ; 2019 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-31602475

RESUMO

Improvements in life expectancy among people with HIV (PWH) receiving antiretroviral treatment in the United States and Canada may differ among key populations. Given the difference in substance use among key populations and the current opioid epidemic, drug- and alcohol-related deaths maybe contributing to the disparities in life expectancy. We sought to estimate in life expectancy at age 20 in key populations (and their comparison groups) in three time periods (2004-7, 2008-11, 2012-15), and the potential increase in expected life expectancy with a simulated 20% reduction in drug- and alcoholrelated deaths using the novel Lives Saved Simulation model. Among 92,289 PWH, life expectancy increased in all key populations and comparison groups from 2004-7 to 2012-15. Disparities in survival of approximately a decade persisted among Black vs. White men who have sex with men and people with (vs. without) a history of injection drug use. A 20% reduction in drug- and alcohol-related mortality would have the greatest life expectancy benefit for Black men who have sex with men, White women, and people with a history of injection drug use. Our findings suggest that preventing drug- and alcoholrelated deaths among PWH could narrow disparities in life expectancy among some key populations, but other causes of death must be addressed to further narrow the disparities.

13.
N Engl J Med ; 381(14): 1333-1346, 2019 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-31577875

RESUMO

BACKGROUND: The safety, efficacy, and appropriate timing of isoniazid therapy to prevent tuberculosis in pregnant women with human immunodeficiency virus (HIV) infection who are receiving antiretroviral therapy are unknown. METHODS: In this multicenter, double-blind, placebo-controlled, noninferiority trial, we randomly assigned pregnant women with HIV infection to receive isoniazid preventive therapy for 28 weeks, initiated either during pregnancy (immediate group) or at week 12 after delivery (deferred group). Mothers and infants were followed through week 48 after delivery. The primary outcome was a composite of treatment-related maternal adverse events of grade 3 or higher or permanent discontinuation of the trial regimen because of toxic effects. The noninferiority margin was an upper boundary of the 95% confidence interval for the between-group difference in the rate of the primary outcome of less than 5 events per 100 person-years. RESULTS: A total of 956 women were enrolled. A primary outcome event occurred in 72 of 477 women (15.1%) in the immediate group and in 73 of 479 (15.2%) in the deferred group (incidence rate, 15.03 and 14.93 events per 100 person-years, respectively; rate difference, 0.10; 95% confidence interval [CI], -4.77 to 4.98, which met the criterion for noninferiority). Two women in the immediate group and 4 women in the deferred group died (incidence rate, 0.40 and 0.78 per 100 person-years, respectively; rate difference, -0.39; 95% CI, -1.33 to 0.56); all deaths occurred during the postpartum period, and 4 were from liver failure (2 of the women who died from liver failure had received isoniazid [1 in each group]). Tuberculosis developed in 6 women (3 in each group); the incidence rate was 0.60 per 100 person-years in the immediate group and 0.59 per 100 person-years in the deferred group (rate difference, 0.01; 95% CI, -0.94 to 0.96). There was a higher incidence in the immediate group than in the deferred group of an event included in the composite adverse pregnancy outcome (stillbirth or spontaneous abortion, low birth weight in an infant, preterm delivery, or congenital anomalies in an infant) (23.6% vs. 17.0%; difference, 6.7 percentage points; 95% CI, 0.8 to 11.9). CONCLUSIONS: The risks associated with initiation of isoniazid preventive therapy during pregnancy appeared to be greater than those associated with initiation of therapy during the postpartum period. (Funded by the National Institutes of Health; IMPAACT P1078 TB APPRISE ClinicalTrials.gov number, NCT01494038.).


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/prevenção & controle , Antituberculosos/uso terapêutico , Infecções por HIV/tratamento farmacológico , Isoniazida/uso terapêutico , Complicações Infecciosas na Gravidez/tratamento farmacológico , Resultado da Gravidez , Tuberculose/prevenção & controle , Adolescente , Adulto , Antituberculosos/efeitos adversos , Método Duplo-Cego , Feminino , Humanos , Lactente , Mortalidade Infantil , Recém-Nascido , Recém-Nascido de muito Baixo Peso , Isoniazida/efeitos adversos , Testes de Função Hepática , Período Pós-Parto , Gravidez , Nascimento Prematuro/epidemiologia , Estudos Prospectivos , Adulto Jovem
14.
J Int AIDS Soc ; 22(9): e25392, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31507083

RESUMO

INTRODUCTION: Extrapulmonary tuberculosis (EPTB) is difficult to confirm bacteriologically and requires specific diagnostic capacities. Diagnosis can be especially challenging in under-resourced settings. We studied diagnostic modalities and clinical outcomes of EPTB compared to pulmonary tuberculosis (PTB) among HIV-positive adults in antiretroviral therapy (ART) programmes in low- and middle-income countries (LMIC). METHODS: We collected data from HIV-positive TB patients (≥16 years) in 22 ART programmes participating in the International Epidemiology Databases to Evaluate AIDS (IeDEA) consortium in sub-Saharan Africa, Asia-Pacific, and Caribbean, Central and South America regions between 2012 and 2014. We categorized TB as PTB or EPTB (EPTB included mixed PTB/EPTB). We used multivariable logistic regression to assess associations with clinical outcomes. RESULTS AND DISCUSSION: We analysed 2695 HIV-positive TB patients. Median age was 36 years (interquartile range (IQR) 30 to 43), 1102 were female (41%), and the median CD4 count at TB treatment start was 114 cells/µL (IQR 40 to 248). Overall, 1930 had PTB (72%), and 765 EPTB (28%). Among EPTB patients, the most frequently involved sites were the lymph nodes (24%), pleura (15%), abdomen (11%) and meninges (6%). The majority of PTB (1123 of 1930, 58%) and EPTB (582 of 765, 76%) patients were diagnosed based on clinical criteria. Bacteriological confirmation (using positive smear microscopy, culture, Xpert MTB/RIF, or other nucleic acid amplification tests result) was obtained in 897 of 1557 PTB (52%) and 183 of 438 EPTB (42%) patients. EPTB was not associated with higher mortality compared to PTB (adjusted odd ratio (aOR) 1.0, 95% CI 0.8 to 1.3), but TB meningitis was (aOR 1.9, 95% CI 1.0 to 3.1). Bacteriological confirmation was associated with reduced mortality among PTB patients (aOR 0.7, 95% CI 0.6 to 0.8) and EPTB patients (aOR 0.3 95% CI 0.1 to 0.8) compared to TB patients with a negative test result. CONCLUSIONS: Diagnosis of EPTB and PTB at ART programmes in LMIC was mainly based on clinical criteria. Greater availability and usage of TB diagnostic tests would improve the diagnosis and clinical outcomes of both EPTB and PTB.

16.
AIDS Res Hum Retroviruses ; 35(10): 960-967, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31407605

RESUMO

Incidence of noncommunicable diseases (NCDs), including cardiovascular disease (CVD), cirrhosis, and non-AIDS-defining cancers (NADCs), have been associated with HIV viremia, CD4 cell counts, and CD4/CD8 ratio in persons living with HIV (PLWH). This study examined the importance of these markers to mortality risk following NCD diagnosis. We examined factors associated with mortality following incident CVD, cirrhosis, or NADCs in a clinical cohort of PLWH between 1998 and 2015. We calculated Kaplan-Meier estimates and used multivariable Cox proportional hazard models. We included 341 patients with NCDs (CVD = 169, cancer = 103, and cirrhosis = 67), of whom 129 died. Median age at NCD diagnosis was 49 years and median proportion of time before NCD with virologic suppression was 64%. Median survival after CVD was longer than for cancer or cirrhosis (11.6 years vs. 4.8 and 3.4 years, respectively; log rank test p < .001). In multivariable Cox proportional hazard models, higher CD4/CD8 ratio preceding NCD (adjusted hazard ratio [aHR] per 0.1 increase = 0.92 [95% confidence interval 0.85-0.99]) and higher CD4 nadir (aHR per 100 cells/µL = 0.84 [0.72-0.97]) were associated with decreased mortality risk. Neither CD4 cell count before NCD nor HIV viremia was statistically associated with mortality in adjusted models. When restricted to 116 patients with virologic suppression for ≥80% of time before NCD, only CD4 nadir was associated with mortality risk. Low CD4/CD8 ratio and CD4 nadir were associated with increased mortality risk after NCD, suggesting that prior immunosuppression or ongoing immune imbalance remain important for outcomes following serious NCDs.

17.
Am J Public Health ; 109(9): 1266-1272, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31318589

RESUMO

Objectives. To use statewide surveillance data to examine trends and disparities in mortality and progression from HIV to AIDS comprehensively in Tennessee over the past 20 years.Methods. Individuals diagnosed with HIV in Tennessee from 1996 to 2016 were identified through the Tennessee Department of Health Enhanced HIV/AIDS Reporting System. Clinical AIDS and all-cause mortality were the outcomes. Cox regression yielded adjusted hazard ratios (AHRs) for death and competing risk regression yielded adjusted subhazard ratios (SHRs) for AIDS, with death as the competing event.Results. Individuals with a history of heterosexual contact (AHR = 1.20; 95% confidence interval [CI] = 1.12, 1.29) and injection drug use (AHR = 1.27; 95% CI = 1.18, 1.38) had increased hazards of death relative to those with a history of male-to-male sexual contact. Hazards of death were lower among White (AHR = 0.79; 95% CI = 0.73, 0.85) and Hispanic (AHR = 0.50; 95% CI = 0.40, 0.63) individuals than among Black individuals. Those with heterosexual contact (SHR = 1.20; 95% CI = 1.12, 1.29) and injection drug use (SHR = 1.27; 95% CI = 1.18, 1.38) had a greater risk of AIDS than those with male-to-male sexual contact. White individuals (SHR = 0.85; 95% CI = 0.81, 0.90) had a lower risk of AIDS than Black individuals, and female individuals (SHR = 0.84; 95% CI = 0.79, 0.90) had a lower risk than male individuals.Conclusions. The trends, disparities, and outcomes assessed in our study will inform HIV testing and care linkage program design and implementation in Tennessee.


Assuntos
Síndrome de Imunodeficiência Adquirida , Terapia Antirretroviral de Alta Atividade , Síndrome de Imunodeficiência Adquirida/epidemiologia , Síndrome de Imunodeficiência Adquirida/mortalidade , Adulto , Progressão da Doença , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Tennessee/epidemiologia , Adulto Jovem
18.
BMC Infect Dis ; 19(1): 366, 2019 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-31039752

RESUMO

BACKGROUND: Independent of HIV infection, extrapulmonary TB (EPTB) risk is increased in women, persons of black race or foreign birth, and by genetic variants in vitamin D receptor (VDR), interleukin-1 beta (IL-1ß), and toll-like receptor (TLR)-2; functional correlates are unclear. We evaluated macrophage expression of VDR, TLR2, cathelicidin, and TNF-α, and production of IL-1ß in HIV-seronegative persons with previous EPTB, previous pulmonary TB, latent M. tuberculosis infection, and uninfected TB contacts. Persons with previous pleural TB were excluded due to enhanced immune responses at the site of disease. METHODS: Macrophages were stimulated with TLR-2 agonist M. tuberculosis lipoprotein (LpqH), live and gamma-irradiated M. tuberculosis. RESULTS: M. tuberculosis - infected macrophages from persons with previous EPTB had increased VDR expression (29.17 relative value unit increase in median expression vs. uninfected contacts, after adjusting for foreign-born status; P = 0.02). Macrophages from persons with previous EPTB had a 38.88 µg/mL increase in median IL-1ß production after stimulation with LpqH compared to uninfected contacts (P = 0.01); the effect was similar (44.99 µg/mL) but not statistically significant after controlling for foreign-born status. Median 25-hydroxyvitamin D levels were low but not significantly different between groups. CONCLUSIONS: There was increased macrophage expression of VDR after stimulation with live M. tuberculosis in persons with previous extrapulmonary TB. If post-treatment VDR expression reflects expression prior to disease, it may identify persons at risk for extrapulmonary TB.


Assuntos
Macrófagos/metabolismo , Mycobacterium tuberculosis/fisiologia , Receptores de Calcitriol/metabolismo , Tuberculose/patologia , Adulto , Idoso , Proteínas de Bactérias/imunologia , Estudos de Casos e Controles , DNA Bacteriano/genética , DNA Bacteriano/metabolismo , Feminino , Raios gama , Expressão Gênica , Humanos , Interleucina-1beta/análise , Macrófagos/citologia , Macrófagos/microbiologia , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/efeitos da radiação , Receptores de Calcitriol/genética , Receptor 2 Toll-Like/agonistas , Tuberculose/imunologia , Vitamina D/análogos & derivados , Vitamina D/sangue
19.
Clin Infect Dis ; 2019 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-31127813

RESUMO

BACKGROUND: Close contacts of persons with pulmonary tuberculosis (TB) have high rates of TB disease. METHODS: We prospectively enrolled adult TB patients and their close contacts at nine United States and Canadian sites. TB patients and contacts were interviewed to identify potential index patient, contact, and exposure risk factors for TB. Contacts were evaluated for latent TB infection (LTBI) and TB, and the effectiveness of LTBI treatment for preventing contact TB was examined. RESULTS: Among 4490 close contacts, multivariable risk factors for TB were age < 5 years, US/Canadian birth, human immunodeficiency virus infection, skin test induration > 10 mm, shared bedroom with an index patient, exposure to more than one index patient, and index patient weight loss (P<.05 for each). Of 1406 skin test-positive contacts, TB developed in 49 (9.8%) of 446 who did not initiate treatment, 8 (1.8%) of 443 who received partial treatment, and 1 (0.2%) of 517 who completed treatment (1951, 290, and 31 cases/100,000 person years, respectively; P<.001). TB was diagnosed in 4.2% of US/Canadian-born compared with 2.3% of foreign-born contacts (P=.002), and rates of TB for US/Canadian-born and foreign-born contacts who did not initiate treatment were 3592 and 811 per 100,000 person years, respectively (P<.001). CONCLUSIONS: Treatment for LTBI was highly effective in preventing TB among close contacts of infectious TB patients. A number of index patient, contact, and exposure characteristics associated with increased risk of contact TB were identified. These findings help inform contact investigation, LTBI treatment, and other public health prevention efforts.

20.
J Acquir Immune Defic Syndr ; 82(1): 71-80, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31107304

RESUMO

BACKGROUND: Hepatitis B virus (HBV) infection is a leading cause of end-stage liver disease (ESLD) and hepatocellular carcinoma (HCC) in HIV. Factors contributing to the high rates of liver complications among HIV/HBV-coinfected individuals remain unknown. SETTING: North American AIDS Cohort Collaboration on Research and Design. METHODS: We performed a retrospective cohort study among HIV/HBV-coinfected patients in 10 US and Canadian cohorts of the North American AIDS Cohort Collaboration on Research and Design that validated ESLD (ascites, spontaneous bacterial peritonitis, variceal hemorrhage, and/or hepatic encephalopathy) and HCC diagnoses from 1996 to 2010. Multivariable Cox regression was used to examine adjusted hazard ratios [aHRs with 95% confidence interval (CIs)] of liver complications (first occurrence of ESLD or HCC) associated with hypothesized determinants and with increasing durations of HIV suppression (≤500 copies/mL). RESULTS: Among 3573 HIV/HBV patients with 13,790 person-years of follow-up, 111 liver complications occurred (incidence rate = 8.0 [95% CI: 6.6 to 9.7] events/1000 person-years). Rates of liver complication were increased with non-black/non-Hispanic race [aHR = 1.76 (1.13-2.74)], diabetes mellitus [aHR = 2.07 (1.20-3.57)], lower time-updated CD4 cell count [<200 cells/mm: aHR = 2.59 (1.36-4.91); 201-499 cells/mm: aHR = 1.75 (1.01-3.06) versus ≥500 cells/mm], heavy alcohol use [aHR = 1.58 (1.04-2.39)], and higher FIB-4 at start of follow-up [>3.25: aHR = 9.79 (5.73-16.74); 1.45-3.25: aHR = 3.20 (1.87-5.47) versus FIB-4 <1.45]. HIV suppression for ≥6 months was associated with lower liver complication rates compared with those with unsuppressed HIV [aHR = 0.56 (0.35-0.91)]. CONCLUSIONS: Non-black/non-Hispanic race, diabetes, lower CD4 cell count, heavy alcohol use, and advanced liver fibrosis were determinants of liver complications among HIV/HBV patients. Sustained HIV suppression should be a focus for HIV/HBV-coinfected patients to reduce the risks of ESLD/HCC.

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