National Institutes of Health Funding for Tuberculosis Comorbidities Is Disproportionate to Their Epidemiologic Impact.

Tuberculosis (TB) is a leading infectious killer worldwide. We systematically searched the National Institutes of Health Research, Portfolio Online Reporting Tools Expenditures and Results (RePORTER) website to compare research funding for key TB comorbidities-undernutrition, alcohol use, human immunodeficiency virus, tobacco use, and diabetes-and found a large mismatch between the population attributable fraction of these risk factors and the funding allocated to them.

High levels of HIV drug resistance among adults failing second-line antiretroviral therapy in Namibia.

To support optimal third-line antiretroviral therapy (ART) selection in Namibia, we investigated the prevalence of HIV drug resistance (HIVDR) at time of failure of second-line ART. A cross-sectional study was conducted between August 2016 and February 2017. HIV-infected people ≥15 years of age with confirmed virological failure while receiving ritonavir-boosted protease inhibitor (PI/r)-based second-line ART were identified at 15 high-volume ART clinics representing over >70% of the total population receiving second-line ART. HIVDR genotyping of dried blood spots obtained from these individuals was performed using standard population sequencing methods. The Stanford HIVDR algorithm was used to identify sequences with predicted resistance; genotypic susceptibility scores for potential third-line regimens were calculated. Two hundred thirty-eight individuals were enrolled; 57.6% were female. The median age and duration on PI/r-based ART at time of enrolment were 37 years and 3.46 years, respectively. 97.5% received lopinavir/ritonavir-based regimens. The prevalence of nucleoside reverse transcriptase inhibitor (NRTI), non-nucleoside reverse transcriptase inhibitor (NNRTI), and PI/r resistance was 50.6%, 63.1%, and 13.1%, respectively. No significant association was observed between HIVDR prevalence and age or sex. This study demonstrates high levels of NRTI and NNRTI resistance and moderate levels of PI resistance in people receiving PI/r-based second-line ART in Namibia. Findings underscore the need for objective and inexpensive measures of adherence to identify those in need of intensive adherence counselling, routine viral load monitoring to promptly detect virological failure, and HIVDR genotyping to optimize selection of third-line drugs in Namibia.

Enteric parasitic infections in children and dogs in resource-poor communities in northeastern Brazil: Identifying priority prevention and control areas.

The aim of this study was to determine the prevalence and risk factors of the main enteric parasitic infections that affect children and dogs in the municipality of Ilhéus, Bahia, Brazil; and to identify the geopolitical areas that should receive priority interventions to combat them. Between March and November 2016, fecal samples of 143 dogs and 193 children aged 1 month to 5 years were collected in 40 rural and semirural communities using a systematic sampling approach, stratified by district. Samples were collected by legal guardians of the children and / or dog owners. Eggs, larvae, cysts and oocysts of parasites were concentrated by centrifugal-flotation and centrifugal-sedimentation, and acid-resistant staining was used to visualize parasites. One hundred and thirty-two children (68.4%), 111 dogs (77.6%) and 199 (73.7%) dog fecal samples collected from streets were parasitized. Giardiasis, cryptosporidiosis, amoeba infections and hookworm were the most frequent infections in all studied populations, in addition to trichuriasis in dogs and ascaridiasis in children. A predominance of Giardia and hookworms was observed in children and dogs, respectively. The coastal districts of Aritaguá, Olivença and the main district had a higher parasitic diversity and overlapping of important potential zoonotic infections. Age over one year (p<0.001), adjusted OR = 3.65; 95% CI = 1.86-7.16) and income below the minimum monthly salary (p = 0.02, adjusted OR = 2.78, 95% CI = 1.17-6.59) were the main factors associated with intestinal parasitic infections in children and dogs, respectively. The coastal districts of Aritaguá and Olivença and the main district should be prioritized through enteric disease control programs, and the factors associated with infections must be considered in the design of health interventions in these districts. The integration between affirmative income actions and investments to improve the health infrastructure of these communities may work more effectively than current preventive measures to combat enteric parasites.

Impact of Substance Use Disorder on Midterm Mortality After Valve Surgery for Endocarditis.

BACKGROUND: Fueled by the burgeoning opioid epidemic, valve surgeries for substance use disorder-related infective endocarditis (SUD-IE) are increasing. The impact of substance use disorder on postvalve replacement morbidity needs further investigation. METHODS: We queried The Society of Thoracic Surgeons Adult Cardiac Surgery Database for all valve surgeries for infective endocarditis at Tufts Medical Center (2002-2016) and collected demographic and disease-related data, including timing of mortality subclassified as short-term (<6 months including operative), midterm (6 months to 5 years), and extended-term (>5 years). Patients with documentation of illicit drug use before the operation were considered to have SUD-IE. Deaths were confirmed through review of medical record and matching with the Massachusetts Vital Statistics Database. We performed univariate and multivariate proportional hazard regressions examining the impact of substance use disorder mortality in people who received a valve replacement. RESULTS: In the cohort of 228 patients, 80 (35%) had SUD-IE. Eight-six people (38%) died, and overall mortality was higher in people with SUD-IE compared with non-SUD-IE (48% vs 32%, P = .025). SUD-IE was associated with a higher risk of overall mortality (adjusted hazard ratio, 2.41; 95% confidence interval, 1.38-4.20; P = .002). Although the difference between short-term or extended-term mortality was not significant, SUD-IE was associated with increased frequency of midterm mortality (53% vs 31%, P = .003). CONCLUSIONS: Our data reflect high rates of postvalve surgery morbidity and mortality in people with SUD-IE at a tertiary care center. The midterm postoperative period is a vulnerable period for people with SUD-IE worthy of further investigation.

Population-based surveillance of HIV drug resistance emerging on treatment and associated factors at sentinel antiretroviral therapy sites in Namibia.

OBJECTIVE: The World Health Organization (WHO) prospective surveys of acquired HIV drug resistance (HIVDR) evaluate HIVDR emerging after the first year of antiretroviral therapy (ART) and associated factors. METHODS: Consecutive ART starters in 2009 were enrolled at 3 sentinel sites in Namibia. Genotyping was performed at start and after 12 months in patients with HIV viral load (VL) >1000 copies per mL. HIVDR outcomes were: HIVDR prevention (VL ≤1000 copies/mL), possible HIVDR (VL >1000 copies/mL without detectable HIVDR or loss to follow-up or ART stop), and HIVDR (VL >1000 copies/mL with detectable HIVDR). Adherence was assessed using medication possession ratio (MPR). RESULTS: Of 394 starters, at 12 months, 80% were on first-line ART, 1% died, 4% transferred out, 1% stopped ART, <1% switched to second-line, and 15% were lost to follow-up. Among patients on first-line, 77% had VL testing, and 94% achieved VL ≤1000 copies per mL. At baseline, 7% had HIVDR. After 12 months, among patients with VL testing, 5% had HIVDR. A majority of patients failing therapy had high-level resistance to nonnucleoside reverse transcriptase inhibitors but none to protease inhibitors. All sites achieved the WHO target of ≥70% HIVDR prevention. Factors associated with not achieving HIVDR prevention were: baseline resistance to nonnucleoside reverse transcriptase inhibitors [odds ratio (OR) 3.0, P = 0.023], WHO stage 3 or 4 at baseline (OR 2.0, P = 0.012), and MPR <75% (OR 4.9, P = 0.021). CONCLUSIONS: Earlier ART initiation and removal of barriers to on-time drug pickups may help to prevent HIVDR. These data inform decisions at national and global levels on the effectiveness of first- and second-line regimens.

Food insecurity, depression, and social support in HIV-infected Hispanic individuals.

Previous research has identified an association between food insecurity and depression in a variety of world regions in both healthy and HIV-infected individuals. We examined this association in 183 HIV-infected Hispanic adults from the greater Boston area. We measured depression with the Burnam depression screen and food insecurity with the Radimer/Cornell Questionnaire. Dietary intake was assessed with an adapted version of the Block Food Frequency Questionnaire. Logistic regression models were created with depression as the outcome variable and food insecurity as the main predictor. In bivariate analyses, food insecurity was significantly associated with depression [odds ratio (OR) 2.5; 95% confidence interval (CI) 1.1, 5.5; p = 0.03]. When we accounted for social support, food insecurity was no longer significant. We found no differences in the quality or quantity of dietary intake between the food insecure and food secure groups. Our findings highlight the importance of social support in the association between food insecurity and depression. Food insecurity may reflect social support more than actual dietary intake in this population.

Progression of carotid intima-media thickness and coronary artery calcium over 6 years in an HIV-infected cohort.

OBJECTIVE: To evaluate changes in cardiovascular disease risk surrogate markers in a longitudinal cohort of HIV-infected adults over 6 years. DESIGN: Internal carotid artery (ICA) and common carotid artery (CCA) intima-media thickness (IMT), coronary artery calcium (CAC), vascular, and HIV risk factors were prospectively examined over 6 years in HIV-infected adults from 2002 to 2010. SETTING: Longitudinal cohort study with participants from urban center and surrounding communities. SUBJECTS/PARTICIPANTS: Three hundred forty-five HIV-infected participants were recruited from a longitudinal cohort study. Two hundred eleven participants completed the study and were included in this analysis. MAIN OUTCOME MEASURES: Total and yearly ICA and CCA IMT change; CAC score progression. RESULTS: Participants were 27% female and 49% nonwhite; mean age at start was 45 ± 7 years. The median change in ICA and CCA over 6 years was 0.15 mm (0.08, 0.28) and 0.12 mm (0.09, 0.15), respectively. Age, baseline triglycerides ≥150 mg/dL, and pack-years smoking were associated with ICA IMT change; age, cholesterol, nadir CD4 count, and protease inhibitor use were associated with CCA IMT change. Diabetes, HIV viral load, and highly active antiretroviral therapy duration were associated with CAC progression. CONCLUSIONS: Carotid IMT and CAC progressed in this HIV-infected cohort. Some HIV-specific characteristics were associated with surrogate marker changes, but the majority of risk factors continue to be traditional. Aggressive identification and management of modifiable risk factors may reduce progression of cardiovascular disease risk in this population.

Lower nutritional status and higher food insufficiency in frail older US adults.

Frailty is a state of decreased physical functioning and a significant complication of ageing. We examined frailty, energy and macronutrient intake, biomarkers of nutritional status and food insufficiency in US older adult (age ≥ 60 years) participants of the Third National Health and Nutrition Examination Survey (n 4731). Frailty was defined as meeting ≥ 2 and pre-frailty as meeting one of the following four-item criteria: (1) slow walking; (2) muscular weakness; (3) exhaustion and (4) low physical activity. Intake was assessed by 24 h dietary recall. Food insufficiency was self-reported as 'sometimes' or 'often' not having enough food to eat. Analyses were adjusted for sex, race, age, smoking, education, income, BMI, other co-morbid conditions and complex survey design. Prevalence of frailty was highest among people who were obese (20·8 %), followed by overweight (18·4 %), normal weight (16·1 %) and lowest among people who were underweight (13·8 %). Independent of BMI, daily energy intake was lowest in people who were frail, followed by pre-frail and highest in people who were not frail (6648 (se 130), 6966 (se 79) and 7280 (se 84) kJ, respectively, P< 0·01). Energy-adjusted macronutrient intakes were similar in people with and without frailty. Frail (adjusted OR (AOR) 4·7; 95 % CI 1·7, 12·7) and pre-frail (AOR 2·1; 95 % CI 0·8, 5·8) people were more likely to report being food insufficient than not frail people. Serum albumin, carotenoids and Se levels were lower in frail adults than not frail adults. Research is needed on targeted interventions to improve nutritional status and food insufficiency among frail older adults, while not necessarily increasing BMI.

High rates of serum selenium deficiency among HIV- and HCV-infected and uninfected drug users in Buenos Aires, Argentina.

OBJECTIVE: To describe the prevalence of low serum Se and determine whether HIV, hepatitis C virus (HCV) and/or the types of drugs used are associated with serum Se in a cohort of infected and uninfected drug users. DESIGN: Independent correlates of low serum Se levels based on data collected from food recalls, physical examinations and clinical questionnaires were identified using multivariate regression analysis. SETTING: Buenos Aires, Argentina SUBJECTS: A total of 205 (twenty-five female and 180 male) former and current drug users. RESULTS: Drug users had an average serum Se level of 69·8 (sd 32·8) µg/d, [corrected] and 82 % were considered deficient (<85 µg/l). [corrected] Multivariate analyses found that HIV- and/or HCV-infected individuals had lower mean Se compared with healthy, uninfected drug users (HIV/HCV co-infection: -25·3 µg/l (se 7·6), P = 0·001; HIV alone: -28·9 µg/l (se 6·9), P < 0·001; HCV alone: -19·4 µg/l (se 7·1), P = 0·006). Current and previous drug use was associated with higher serum Se. Cigarette smoking and heavy alcohol consumption were not found to be associated with Se status. CONCLUSIONS: Low serum Se levels are highly prevalent among drug users in Buenos Aires, Argentina. Se supplementation and/or dietary interventions may be warranted in drug users who are at high risk for HIV and/or HCV infection.

Predictors of Weight Change in Male HIV-Positive Injection Drug Users Initiating Antiretroviral Therapy in Hanoi, Vietnam.

We examined clinical and nutritional predictors of weight change over two consecutive 6-month intervals among 99 HIV-positive male injection drug users initiating antiretroviral therapy (ART) in Hanoi, Vietnam. The average weight gain was 3.1 ± 4.8 kg in the first six months after ART and 0.8 ± 3.0 kg in the following six months. Predictors of weight change differed by interval. In the first interval, CD4 < 200 cells/µL, excellent/very good adherence to ART, bothersome nausea, and liquid supplement use were all associated with positive weight changes. Moderate to heavy alcohol use and tobacco smoking were associated with negative weight changes. In the second interval, having a CD4 count <200 cells/µL at the beginning of the interval and tobacco smoking were the only significant predictors and both were associated with negative weight changes. We identified several potential areas for interventions to promote weight gain immediately after starting ART in this population. Studies are needed to determine whether improving weight prior to, or at, ART initiation will result in improved outcomes on ART.

Malnutrition in a population of HIV-positive and HIV-negative drug users living in Chennai, South India.

BACKGROUND: Malnutrition is a strong predictor of poor outcomes in people living with HIV (PLHIV). Drug users are at increased risk of malnutrition regardless of whether or not they are infected with HIV. Little data exists on the nutritional status of drug users (with or without HIV infection) in India. METHODS: We describe and compare the nutrition and metabolic status of 107 HIV-positive and 193 HIV-negative male clients of a community-based drop-in center for injection drug users in Chennai, India. Measures of nutrition and metabolic status include body composition, dietary intake, food insecurity, and serum lipid levels. RESULTS: We found poor overall nutritional status in both the HIV-positive and HIV-negative clients, with HIV-positive men faring worse on some parameters. Both groups had extremely low percent body fat, but levels in HIV-positive participants were significantly lower (6.5% versus 7.9%, p=.01). HIV-positive men also had significantly lower total caloric and fat intakes compared to HIV-negative men. A considerable proportion (70%) of both HIV-positive and HIV-negative drug users were food insecure. HDL cholesterol levels were significantly lower and below normal range in the HIV-positive compared to HIV-negative men. CONCLUSIONS: The high levels of food insecurity and poor nutritional status in this population, regardless of HIV status, indicates critical need for intervention. Improving nutritional status in those who are infected with HIV prior to initiation of antiretroviral treatment may help patients to reap the full benefits of therapy.

Nutrition issues in the HIV-infected injection drug user: findings from the nutrition for healthy living cohort.

OBJECTIVE: The purpose of this paper is to highlight disparities between injection drug users (IDUs) and those who had never been IDUs from the Nutrition for Healthy Living (NFHL) cohort. Although IDUs were enrolled in the cohort throughout its duration, few analyses have sought to highlight findings specific to them. METHODS: NFHL, a prospective, longitudinal cohort conducted from 1995-2005, included 881 human immunodeficiency virus (HIV) -infected men and women over the age of 18. Subjects were seen every 6 months; body composition and dietary and laboratory data were collected. Individuals were classified as current IDUs, past IDUs, and never-IDUs. The classification of ever-IDU combined current and past users. RESULTS: In NFHL, a higher proportion of ever-IDUs were women, African American, had a high school education or less, smoked, and were housing insecure and food insecure compared to never-IDUs. Ever-IDUs had lower total, soluble, and insoluble fiber and individual micronutrient intakes. A higher proportion of ever-IDUs had hepatitis C and HIV-related symptoms, used highly active antiretroviral therapy (HAART) less, and had a CD4 count <500 cells/mm3, than never-IDUs, at the study endpoint. CONCLUSIONS: The course of HIV infection in past and current IDUs appears to be unique and requires more investigation. Physiologic and sociodemographic characteristics of IDUs contribute to poor disease management and nutritional status. Classic manifestations of HIV persist in IDUs in the HAART era.

Drug use and other risk factors related to lower body mass index among HIV-infected individuals.

Malnutrition is associated with morbidity and mortality in HIV-infected individuals. Little research has been conducted to identify the roles that clinical, illicit drug use and socioeconomic characteristics play in the nutritional status of HIV-infected patients. This cross-sectional analysis included 562 HIV-infected participants enrolled in the Nutrition for Healthy Living study conducted in Boston, MA and Providence, RI. The relationship between body mass index (BMI) and several covariates (type of drug use, demographic, and clinical characteristics) were examined using linear regression. Overall, drug users had a lower BMI than non-drug users. The BMI of cocaine users was 1.4 kg/m(2) less than that of patients who did not use any drugs, after adjusting for other covariates (p=0.02). The BMI of participants who were over the age of 55 years was 2.0 kg/m(2) less than that of patients under the age of 35, and BMI increased by 0.3 kg/m(2) with each 100 cells/mm(3) increase in CD4 count. HAART use, adherence to HAART, energy intake, AIDS status, hepatitis B and hepatitis C co-infections, cigarette smoking and depression were not associated with BMI in the final model. In conclusion, BMI was lower in drug users than non-drug users, and was lowest in cocaine users. BMI was also directly associated with CD4 count and inversely related to age more than 55 years old. HIV-infected cocaine users may be at higher risk of developing malnutrition, suggesting the need for anticipatory nutritional support.

Injection drug use is an independent risk factor for iron deficiency and iron deficiency anemia among HIV-seropositive and HIV-seronegative women.

The risk factors for iron deficiency and iron deficiency anemia among female injection drug users are not well characterized. We measured hemoglobin and plasma ferritin and obtained demographic information and injection drug use history in the last 6 months in a cross-sectional study of 200 female injection drug users (134 HIV-positive and 66 HIV-negative). The women were participants in a natural history study, the AIDS Linked to Intravenous Experiences study in Baltimore, Maryland. In multivariate analyses adjusting for age, hepatitis C virus status, and HIV status, injection drug use within the last 6 months was associated with iron deficiency (odds ratio [OR] = 2.61, 95% confidence interval [CI]: 1.33 to 5.09) and iron deficiency anemia (OR = 6.65, 95% CI: 2.33 to 18.9). Among 134 HIV-positive women, injection drug use in the last 6 months was associated with iron deficiency (OR = 2.43, 95% CI: 1.08 to 5.48) and iron deficiency anemia (OR = 6.05, 95% CI: 1.82 to 20.1) in multivariate analyses adjusting for hepatitis C virus status and CD4 lymphocyte count. Injection drug use seems to be associated with iron deficiency and iron deficiency anemia. Further longitudinal studies are needed to gain insight into the nature of this association.

High-fiber diet in HIV-positive men is associated with lower risk of developing fat deposition.

BACKGROUND: Lipodystrophy has been described with increasing frequency in patients infected with HIV. This study focused on the identification of dietary components that may predispose HIV-positive patients to the development of fat deposition. OBJECTIVE: We evaluated differences in past dietary intake between men with HIV who developed fat deposition and those who did not. DESIGN: This nested case-control study consisted of 47 cases and 47 controls from the Nutrition for Healthy Living cohort. Food records from 6 to 24 mo before development of fat deposition in cases were analyzed and compared with food records from controls by using t tests for normally distributed nutrients and Wilcoxon rank-sum tests for nutrients with skewed distributions. RESULTS: HIV-positive patients without fat deposition had greater overall energy intakes (kcal/kg; P = 0.03) and greater intakes of total protein (P = 0.01), total dietary fiber (P = 0.01), soluble dietary fiber (P = 0.01), insoluble dietary fiber (P = 0.03), and pectin (P = 0.02) than did HIV-positive patients with fat deposition. Those without fat deposition also tended to currently perform more resistance training (P = 0.05) and to not be current smokers (P = 0.05). CONCLUSION: Our results indicate that an overall high-quality diet, rich in fiber and adequate in energy and protein, may be beneficial in preventing the development of fat deposition in persons infected with HIV. The results of this study further emphasize that a healthy lifestyle, including exercise and avoidance of unhealthy behaviors such as smoking, may also be similarly beneficial.

Long-term effects of androgen deprivation therapy in prostate cancer patients.

BACKGROUND: Prostate cancer (PCa) is one of the most common cancers in men and has an increasing incidence. In 1999, 37 000 men died from PCa in the USA. Androgen deprivation therapy (ADT) with GnRH agonists is frequently employed in the treatment of recurrent and metastatic PCa by inducing medical castration, rendering these men hypogonadal. Because hypogonadism in men is associated with a wide range of complications, we attempted to determine the effects of long-term ADT in men with PCa. METHODS: We conducted a cross-sectional study at a tertiary care centre to determine the effect of ADT on lean body mass (LBM), muscle strength, bone mineral density (BMD), sexual function, and quality of life (QOL) in men with PCa. Three groups of men were enrolled: (1) 20 men with PCa who were undergoing medical castration with GnRH agonists for at least 12 months prior to the onset of the study (ADT group); (2) 18 age-matched men with nonmetastatic PCa who were post prostatectomy and/or radiotherapy but had not yet undergone ADT (non-ADT group); and (3) 20 age-matched normal men who were healthy and ambulatory (control group). RESULTS: Men on ADT had castrate levels of serum total testosterone (P < 0.0001), free testosterone (P < 0.0001) and oestradiol (P < 0.0001), which were significantly lower than in the other groups. Total body (P = 0.03) and lumbar spine (P < 0.0001) BMD was significantly lower in patients on ADT compared to other groups and was associated with higher levels of urinary N-telopeptide (P = 0.02). The ADT group had higher fat mass compared to the other groups (P = 0.0001) and significantly reduced upper body strength (P = 0.001) when compared to non-ADT patients. The ADT group had lower overall scores on Watt's Sexual Function Questionnaire compared to other groups (P = 0.0001), in particular a decrease in desire, arousal and frequency of spontaneous early morning erections. The ADT group also had lower overall QOL scores, resulting in significant limitation of physical function (P = 0.001), role limitation (P = 0.02) and perception of physical health (P = 0.004). CONCLUSIONS: This study suggests that osteoporosis, unfavourable body composition, sexual dysfunction and reduced quality of life are seen in patients receiving androgen deprivation therapy for at least 12 months. Longitudinal studies in this patient population will shed further light on the timing of the development and the extent of these complications. Meanwhile, this information will assist both physicians and patients with prostate cancer to make informed decisions regarding androgen deprivation therapy.