Suchergebnisse

Only Vanderbilt University affiliated authors are listed on VUIR. For a full list of authors, access the version of record at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7036649/ ; Improvements in life expectancy among people living with human immunodeficiency virus (PLWH) receiving antiretroviral treatment in the United States and Canada might differ among key populations. Given the difference in substance use among key populations and the current opioid epidemic, drug- and alcohol-related deaths might be contributing to the disparities in life expectancy. We sought to estimate life expectancy at age 20 years in key populations (and their comparison groups) in 3 time periods (2004-2007, 2008-2011, and 2012-2015) and the potential increase in expected life expectancy with a simulated 20% reduction in drug- and alcohol-related deaths using the novel Lives Saved Simulation model. Among 92,289 PLWH, life expectancy increased in all key populations and comparison groups from 2004-2007 to 2012-2015. Disparities in survival of approximately a decade persisted among black versus 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 alcohol-related deaths among PLWH could narrow disparities in life expectancy among some key populations, but other causes of death must be addressed to further narrow the disparities. ; This work was supported by the National Institutes of Health (grants U01AI069918, F31AI124794, F31DA037788, G12MD007583, K01AI093197, K01AI131895, K23EY013707, K24AI065298, K24AI118591, K24DA000432, KL2TR000421, M01RR000052, N01CP01004, N02CP055504, N02CP91027, P30AI027757, P30AI027763, P30AI027767, P30AI036219, P30AI050410, P30AI094189, P30AI110527, P30MH62246, R01AA016893, R01CA165937, R01DA011602, R01DA012568, R01AG053100, R24AI067039, U01AA013566, U01AA020790, U01AI031834, U01AI034989, U01AI034993, U01AI034994, U01AI035004, U01AI035039, U01AI035040, U01AI035041, U01AI035042, U01AI037613, U01AI037984, U01AI038855, U01AI038858, U01AI042590, U01AI068634, U01AI068636, U01AI069432, U01AI069434, U01AI103390, U01AI103397, U01AI103401, U01AI103408, U01DA03629, U01DA036935, U01HD032632, U10EY008057, U10EY008052, U10EY008067, U24AA020794,U54MD007587, UL1RR024131, UL1TR000004, UL1TR000083, UL1TR000454, UM1AI035043, Z01CP010214, and Z01CP010176), the Centers for Disease Control and Prevention (contracts CDC-200-2006-18797 and CDC-200-2015-63931), the Agency for Healthcare Research and Quality (contract 90047713), the Health Resources and Services Administration (contract 90051652), the Canadian Institutes of Health Research (grants CBR-86906, CBR-94036, HCP-97105, and TGF-96118), the Ontario Ministry of Health and Long Term Care, and the Government of Alberta (Canada). Additional support was provided by the National Cancer Institute, National Institute of Mental Health, and National Institute on Drug Abuse, as well as the Johns Hopkins Center for AIDS Research (grant P30AI094189).

AbstractIntroductionExtrapulmonary 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).MethodsWe 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 DiscussionWe 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.ConclusionsDiagnosis 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.

AbstractIntroductionIdentification 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.MethodsWe 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.ResultsAmong 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.ConclusionsIn 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.

Background. CD4 count at start of combination antiretroviral therapy (ART) is strongly associated with short-term survival, but its association with longer-term survival is less well characterized. Methods. We estimated mortality rates (MRs) by time since start of ART (<0.5, 0.5-0.9, 1-2.9, 3-4.9, 5-9.9, and ≥10 years) among patients from 18 European and North American cohorts who started ART during 1996-2001. Piecewise exponential models stratified by cohort were used to estimate crude and adjusted (for sex, age, transmission risk, period of starting ART [1996-1997, 1998-1999, 2000-2001], and AIDS and human immunodeficiency virus type 1 RNA at baseline) mortality rate ratios (MRRs) by CD4 count at start of ART (0-49, 50-99, 100-199, 200-349, 350-499, ≥500 cells/µL) overall and separately according to time since start of ART. Results. A total of 6344 of 37 496 patients died during 359 219 years of follow-up. The MR per 1000 person-years was 32.8 (95% confidence interval [CI], 30.2-35.5) during the first 6 months, declining to 16.0 (95% CI, 15.4-16.8) during 5-9.9 years and 14.2 (95% CI, 13.3-15.1) after 10 years' duration of ART. During the first year of ART, there was a strong inverse association of CD4 count at start of ART with mortality. This diminished over the next 4 years. The adjusted MRR per CD4 group was 0.97 (95% CI, .94-1.00; P = .054) and 1.02 (95% CI, .98-1.07; P = .32) among patients followed for 5-9.9 and ≥10 years, respectively. Conclusions. After surviving 5 years of ART, the mortality of patients who started ART with low baseline CD4 count converged with mortality of patients with intermediate and high baseline CD4 counts. ; This work is jointly funded by the UK Medical Research Council (MRC) (grant number MR/J002380/1) and the UK Department for International Development (DFID) under the MRC/DFID Concordat agreement and is also part of the EDCTP2 program supported by the European Union. J. A. C. S. is funded by a National Institute for Health Research Senior Investigator award ...

AbstractIntroductionWeight gain following antiretroviral therapy (ART) initiation is common, potentially predisposing some persons with HIV (PWH) to cardio‐metabolic disease. We assessed relationships between ART drug class and weight change among treatment‐naïve PWH initiating ART in the North American AIDS Cohort Collaboration on Research and Design (NA‐ACCORD).MethodsAdult, treatment‐naïve PWH in NA‐ACCORD initiating integrase strand transfer inhibitor (INSTI), protease inhibitor (PI) or non‐nucleoside reverse‐transcriptase inhibitor (NNRTI)‐based ART on/after 1 January 2007 were followed through 31 December 2016. Multivariate linear mixed effects models estimated weight up to five years after ART initiation, adjusting for age, sex, race, cohort site, HIV acquisition mode, treatment year, and baseline weight, plasma HIV‐1 RNA level and CD4+ cell count. Due to shorter follow‐up for PWH receiving newer INSTI drugs, weights for specific INSTIs were estimated at two years. Secondary analyses using logistic regression and all covariates from primary analyses assessed factors associated with >10% weight gain at two and five years.ResultsAmong 22,972 participants, 87% were male, and 41% were white. 49% started NNRTI‐, 31% started PI‐ and 20% started INSTI‐based regimens (1624 raltegravir (RAL), 2085 elvitegravir (EVG) and 929 dolutegravir (DTG)). PWH starting INSTI‐based regimens had mean estimated five‐year weight change of +5.9kg, compared to +3.7kg for NNRTI and +5.5kg for PI. Among PWH starting INSTI drugs, mean estimated two‐year weight change was +7.2kg for DTG, +5.8kg for RAL and +4.1kg for EVG. Women, persons with lower baseline CD4+ cell counts, and those initiating INSTI‐based regimens had higher odds of >10% body weight increase at two years (adjusted odds ratio = 1.37, 95% confidence interval: 1.20 to 1.56 vs. NNRTI).ConclusionsPWH initiating INSTI‐based regimens gained, on average, more weight compared to NNRTI‐based regimens. This phenomenon may reflect heterogeneous effects of ART agents on body weight regulation that require further exploration.

IntroductionLatinos living with HIV in the Americas share a common ethnic and cultural heritage. In North America, Latinos have a relatively high rate of new HIV infections but lower rates of engagement at all stages of the care continuum, whereas in Latin America antiretroviral therapy (ART) services continue to expand to meet treatment needs. In this analysis, we compare HIV treatment outcomes between Latinos receiving ART in North America versus Latin America.MethodsHIV‐positive adults initiating ART at Caribbean, Central and South America Network for HIV (CCASAnet) sites were compared to Latino patients (based on country of origin or ethnic identity) starting treatment at North American AIDS Cohort Collaboration on Research and Design (NA‐ACCORD) sites in the United States and Canada between 2000 and 2011. Cox proportional hazards models compared mortality, treatment interruption, antiretroviral regimen change, virologic failure and loss to follow‐up between cohorts.ResultsThe study included 8400 CCASAnet and 2786 NA‐ACCORD patients initiating ART. CCASAnet patients were younger (median 35 vs. 37 years), more likely to be female (27% vs. 20%) and had lower nadir CD4 count (median 148 vs. 195 cells/µL, p<0.001 for all). In multivariable analyses, CCASAnet patients had a higher risk of mortality after ART initiation (adjusted hazard ratio (AHR) 1.61; 95% confidence interval (CI): 1.32 to 1.96), particularly during the first year, but a lower hazard of treatment interruption (AHR: 0.46; 95% CI: 0.42 to 0.50), change to second‐line ART (AHR: 0.56; 95% CI: 0.51 to 0.62) and virologic failure (AHR: 0.52; 95% CI: 0.48 to 0.57).ConclusionsHIV‐positive Latinos initiating ART in Latin America have greater continuity of treatment but are at higher risk of death than Latinos in North America. Factors underlying these differences, such as HIV testing, linkage and access to care, warrant further investigation.

AbstractIntroductionHIV‐1 infection leads to chronic inflammation and to an increased risk of non‐AIDS mortality. Our objective was to determine whether AIDS‐defining events (ADEs) were associated with increased overall and cause‐specific non‐AIDS related mortality after antiretroviral therapy (ART) initiation.MethodsWe included HIV treatment‐naïve adults from the Antiretroviral Therapy Cohort Collaboration (ART‐CC) who initiated ART from 1996 to 2014. Causes of death were assigned using the Coding Causes of Death in HIV (CoDe) protocol. The adjusted hazard ratio (aHR) for overall and cause‐specific non‐AIDS mortality among those with an ADE (all ADEs, tuberculosis (TB), Pneumocystis jiroveci pneumonia (PJP), and non‐Hodgkin's lymphoma (NHL)) compared to those without an ADE was estimated using a marginal structural model.ResultsThe adjusted hazard of overall non‐AIDS mortality was higher among those with any ADE compared to those without any ADE (aHR 2.21, 95% confidence interval (CI) 2.00 to 2.43). The adjusted hazard of each of the cause‐specific non‐AIDS related deaths were higher among those with any ADE compared to those without, except metabolic deaths (malignancy aHR 2.59 (95% CI 2.13 to 3.14), accident/suicide/overdose aHR 1.37 (95% CI 1.05 to 1.79), cardiovascular aHR 1.95 (95% CI 1.54 to 2.48), infection aHR (95% CI 1.68 to 2.81), hepatic aHR 2.09 (95% CI 1.61 to 2.72), respiratory aHR 4.28 (95% CI 2.67 to 6.88), renal aHR 5.81 (95% CI 2.69 to 12.56) and central nervous aHR 1.53 (95% CI 1.18 to 5.44)). The risk of overall and cause‐specific non‐AIDS mortality differed depending on the specific ADE of interest (TB, PJP, NHL).ConclusionsIn this large multi‐centre cohort collaboration with standardized assignment of causes of death, non‐AIDS mortality was twice as high among patients with an ADE compared to without an ADE. However, non‐AIDS related mortality after an ADE depended on the ADE of interest. Although there may be unmeasured confounders, these findings suggest that a common pathway may be independently driving both ADEs and NADE mortality. While prevention of ADEs may reduce subsequent death due to NADEs following ART initiation, modification of risk factors for NADE mortality remains important after ADE survival.

IntroductionMaps are powerful tools for visualization of differences in health indicators by geographical region, but multi‐country maps of HIV indicators do not exist, perhaps due to lack of consistent data across countries. Our objective was to create maps of four HIV indicators in North, Central, and South American countries.MethodsUsing data from the North American AIDS Cohort Collaboration on Research and Design (NA‐ACCORD) and the Caribbean, Central, and South America network for HIV epidemiology (CCASAnet), we mapped median CD4 at presentation for HIV clinical care, proportion retained in HIV primary care, proportion prescribed antiretroviral therapy (ART), and the proportion with suppressed plasma HIV viral load (VL) from 2010 to 2012 for North, Central, and South America. The 15 Canadian and US clinical cohorts and 7 clinical cohorts in Argentina, Brazil, Chile, Haiti, Honduras, Mexico, and Peru represented approximately 2–7% of persons known to be living with HIV in these countries.ResultsStudy populations were selected for each indicator: median CD4 at presentation for care was estimated among 14,811 adults; retention was estimated among 87,979 adults; ART use was estimated among 84,757 adults; and suppressed VL was estimated among 51,118 adults. Only three US states and the District of Columbia had a median CD4 at presentation >350 cells/mm3. Haiti, Mexico, and several states had >85% retention in care; lower (50–74%) retention in care was observed in the US West, South, and Mid‐Atlantic, and in Argentina, Brazil, and Peru. ART use was highest (90%) in Mexico. The percentages of patients with suppressed VL in the US South and Northeast were lower than in most of Central and South America.ConclusionsThese maps provide visualization of gaps in the quality of HIV care and allow for comparison between and within countries as well as monitoring policy and programme goals within geographical boundaries.