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1.  Association of Pre-Treatment Nutritional Status with Change in CD4 Count after Antiretroviral Therapy at 6, 12, and 24 Months in Rwandan Women 
PLoS ONE  2011;6(12):e29625.
Body mass index (BMI) independently predicts mortality in studies of HIV infected patients initiating antiretroviral therapy (ART). We hypothesized that poorer nutritional status would be associated with smaller gains in CD4 count in Rwandan women initiating ART.
Methods and Findings
The Rwandan Women's Interassociation Study and Assessment, enrolled 710 ART-naïve HIV-positive and 226 HIV-negative women in 2005 with follow-up every 6 months. The outcome assessed in this study was change in CD4 count at 6, 12, and 24 months after ART initiation. Nutritional status measures taken prior to ART initiation were BMI; height adjusted fat free mass (FFMI); height adjusted fat mass (FMI), and sum of skinfold measurements. 475 women initiated ART. Mean (within 6 months) pre-ART CD4 count was 216 cells/µL. Prior to ART initiation, the mean (±SD) BMI was 21.6 (±3.78) kg/m2 (18.3% malnourished with BMI<18.5); and among women for whom the following were measured, mean FFMI was 17.10 (±1.76) kg/m2; FMI 4.7 (±3.5) kg/m2 and sum of skinfold measurements 4.9 (±2.7) cm. FFMI was significantly associated with a smaller change in CD4 count at 6 months in univariate analysis (−6.7 cells/uL per kg/m2, p  = 0.03) only. In multivariate analysis after adjustment for covariates, no nutritional variable was associated with change in CD4 count at any follow up visit.
In this cohort of African women initiating ART, no measure of malnutrition prior to ART was consistently associated with change in CD4 count at 6, 12, and 24 months of follow up, suggesting that poorer pre-treatment nutritional status does not prevent an excellent response to ART.
PMCID: PMC3247268  PMID: 22216334
2.  Insulin Resistance Change and Antiretroviral Therapy Exposure in HIV-Infected and Uninfected Rwandan Women: A Longitudinal Analysis 
PLoS ONE  2015;10(4):e0123936.
We longitudinally assessed predictors of insulin resistance (IR) change among HIV-uninfected and HIV-infected (ART-initiators and ART-non-initiators) Rwandan women.
HIV-infected (HIV+) and uninfected (HIV-) women provided demographic and clinical measures: age, body mass index (BMI) in Kg/(height in meters)2, Fat-Mass (FMI) and Fat-Free-Mass (FFMI) index, fasting serum glucose and insulin. Homeostasis Model Assessment (HOMA) was calculated to estimate IR change over time in log10 transformed HOMA measured at study enrollment or prior to ART initiation in 3 groups: HIV- (n = 194), HIV+ ART-non-initiators (n=95) and HIV+ ART-initiators (n=371). ANCOVA linear regression models of change in log10-HOMA were fit with all models included the first log10 HOMA as a predictor.
Mean±SD log10-HOMA was -0.18±0.39 at the 1st and -0.21±0.41 at the 2nd measure, with mean change of 0.03±0.44. In the final model (all women) BMI at 1st HOMA measure (0.014; 95% CI=0.006-0.021 per kg/m2; p<0.001) and change in BMI from 1st to 2nd measure (0.024; 95% CI=0.013-0.035 per kg/m2; p<0.001) predicted HOMA change. When restricted to subjects with FMI measures, FMI at 1st HOMA measure (0.020; 95% CI=0.010-0.030 per kg/m2; p<0.001) and change in FMI from 1st to 2nd measure (0.032; 95% CI=0.020-0.043 per kg/m2; p<0.0001) predicted change in HOMA. While ART use did not predict change in log10-HOMA, untreated HIV+ women had a significant decline in IR over time. Use or duration of AZT, d4T and EFV was not associated with HOMA change in HIV+ women.
Baseline BMI and change in BMI, and in particular fat mass and change in fat mass predicted insulin resistance change over ~3 years in HIV-infected and uninfected Rwandan women. Exposure to specific ART (d4T, AZT, EFV) did not predict insulin resistance change in ART-treated HIV-infected Rwandan women.
PMCID: PMC4400132  PMID: 25880634
3.  Associations of HIV infection with insulin and glucose levels in antiretroviral-naïve Rwandan women: a cross-sectional analysis 
BMJ Open  2013;3(12):e003879.
The purpose of these analyses was to determine the associations of HIV infection and related immune dysfunction with a glucose homeostasis in the population of antiretroviral-naïve HIV-infected and uninfected Rwandan women. We hypothesise that insulin resistance and its consequences in the developing countries may be further elevated with HIV infection itself regardless of antiretroviral therapy.
Study design
Cross-sectional analysis of a longitudinal cohort.
Community-based women's associations.
In 2005, 710 HIV-infected (HIV positive) antiretroviral naïve and 226 HIV-uninfected (HIV negative) women were enrolled in the Rwanda Women's Interassociation Study and Assessment (RWISA). Clinical and demographic parameters, CD4 count, fasting insulin and glucose levels, anthropometric measurements and Bioelectrical Impedance Analysis (BIA) were obtained. Linear models were fit to log-transformed Homeostasis Model Assessment (HOMA) with results exponentiated back to a multiplicative effect on the original scale.
Primary outcome measures
The outcome, insulin resistance, was measured by the HOMA, calculated as fasting insulin (μU/mL)×fasting glucose (mmol/L)⁄22.5.
In adjusted models, HIV-positive women were less insulin resistant than HIV-negative; an HIV-positive woman tended to have 0.728 times as much (95% CI 0.681 to 0.861) HOMA than a comparable HIV-negative woman. Among the HIV-positive women, those with CD4 <200 cells/µL tended to have 0.741 times as much HOMA (95% CI 0.601 to 0.912) as did comparable women with CD4 >350 cells/µL. The older age was independently associated with a lower HOMA insulin resistance. After adjusting for body mass index, fat and fat-free mass were not independently associated with HOMA.
This study found that HIV infection and more advanced HIV infection (CD4 counts <200 cells/µL) were associated with greater insulin sensitivity in antiretroviral naïve African women. These findings provide baseline information for the interpretation of future studies on the effect of antiretroviral therapy on metabolic insulin sensitivity derangements in African population.
PMCID: PMC3855496  PMID: 24319275
Diabetes & Endocrinology; Epidemiology
4.  Association of Abnormal Liver Function Parameters with HIV Serostatus and CD4 Count in Antiretroviral-Naive Rwandan Women 
We determined the associations of HIV infection/CD4 count with markers of hepatocellular damage [elevated aspartate aminotransferase (AST) and alanine aminotransferase (ALT)] and liver synthetic function (decreased albumin) in HIV-infected (HIV+) antiretroviral therapy (ART)-naive and uninfected (HIV−) Rwandan women. In 2005, 710 HIV+ ART-naive and 226 HIV− women enrolled in the Rwanda Women's Interassociation Study and Assessment. Liver enzymes were measured with abnormality defined as either AST or ALT ≥1.25 times the upper limit of normal. Low serum albumin level was defined as <3.5 g/dl. Multivariable logistic regression analysis identified independent predictors of elevated AST/ALT and low serum albumin. HIV− women had the lowest prevalence (6.6%) of abnormal AST/ALT, with the highest prevalence (16.4%) in HIV+ women with CD4 <200 cells/μl (p=0.01). The odds of having serum albumin <3.5 g/dl was 5.7-fold higher in HIV+ than HIV− women (OR=5.68, 95% CI: 3.32–9.71). The risk of low albumin decreased from low to high CD4 count, with OR=2.62, 95% CI: 1.66, 4.14 and OR=1.57, 95% CI: 1.01, 2.43 in HIV+ women with a CD4 count <200 and 200–350 cells/μl, respectively vs. HIV+ with CD4 >350 (p<0.001 and p<0.05 for all comparisons). Our findings suggest that HIV-associated liver damage may occur in ART-naive patients. Although liver abnormality prevalences in this cohort of HIV-infected Rwandan women are less than reported in developed countries, caution is needed for risk assessment measures to monitor and screen HIV-infected patients pre- and post-ART initiation in African clinical settings to curtail potential risks associated with HIV infection.
PMCID: PMC4505765  PMID: 25924728
5.  Effect of HIV Infection on Body Composition and Fat Distribution in Rwandan Women 
To assess the association of HIV infection with body weight and composition in Rwandan women.
Body weight and composition, the latter determined by bioelectrical impedance analysis (BIA) and by anthropometry, were compared in 620 HIV-positive and 211 HIV-negative participants. Associations of HIV with body composition were assessed, and t tests compared the groups.
HIV-positive women were younger (−7.0 years, P < .001) and shorter (− 2.1 cm, P < .001). Mean body weight, body mass index (BMI), total body fat, and waist-to-hip ratio (WHR) were similar. Mean fat-free mass was 2.5% greater in HIV-negative participants, and 19% of HIV-positive group had BMI <18.5 kg/m2 versus 26% of the HIV-negative group (P < .05). CD4 counts and body composition were not associated.
Malnutrition was common in this cohort of Rwandan women. However, HIV infection was not associated with nutritional status. Factors other than malnutrition may influence quality-of-life outcomes in HIV-infected Rwandan women. Initiatives to improve nutritional status should be population-wide and not restricted to the HIV-infected population.
PMCID: PMC4460979  PMID: 20530472
HIV; malnutrition; body composition; Rwanda; women; fat distribution
6.  Assessment of haematological parameters in HIV-infected and uninfected Rwandan women: a cross-sectional study 
BMJ Open  2012;2(6):e001600.
Although haematological abnormalities are common manifestations of HIV infection, few studies on haematological parameters in HIV-infected persons have been undertaken in sub-Saharan Africa. The authors assessed factors associated with haematological parameters in HIV-infected antiretroviral-naïve and HIV-uninfected Rwandan women.
Study design
Cross-sectional analysis of a longitudinal cohort.
Community-based women's associations.
710 HIV-infected (HIV+) antiretroviral-naïve and 226 HIV-uninfected (HIV−) women from the Rwanda Women's Interassociation Study Assessment. Haematological parameters categorised as (abnormal vs normal) were compared by HIV status and among HIV+ women by CD4 count category using proportions. Multivariate logistic regression models using forward selection were fit.
Prevalence of anaemia (haemoglobin (Hb) <12.0 g/dl) was higher in the HIV+ group (20.5% vs 6.3%; p<0.001), and increased with lower CD4 counts: ≥350 (7.6%), 200–349 (16%) and <200 cells/mm3 (32.2%). Marked anaemia (Hb <10.0 g/dl) was found in 4.2% of HIV+ and none of the HIV− women (p<0.001), and was highest in HIV+ women with CD4 <200 cells/mm3 (8.4%). The HIV+ were more likely than HIV− women (4.2 vs 0.5%, respectively, p=0.002) to have moderate neutropenia with white blood cells <2.0×103 cells/mm3 and 8.4% of HIV+ women with CD4 <200 cells/mm3 had moderate neutropenia. In multivariate logistic regression analysis, BMI (OR 0.87/kg/m2, 95% CI 0.82 to 0.93; p<0.001), CD4 200–350 vs HIV− (OR 3.59, 95% CI 1.89 to 6.83; p<0.001) and CD4 <200 cells/mm3 vs HIV− (OR 8.09, 95% CI 4.37 to 14.97; <0.001) had large independent associations with anaemia. There were large independent associations of CD4 <200 cells/mm3 vs HIV− (OR 7.18, 95% CI 0.78 to 65.82; p=0.081) and co-trimoxazole and/or dapsone use (OR 5.69, 95% CI 0.63 to 51.45; p=0.122) with moderate neutropenia.
Anaemia was more common than neutropenia or thrombocytopenia in the HIV-infected Rwandan women. Future comparisons of haematological parameters in HIV-infected patients before and after antiretroviral therapy initiation are warranted.
PMCID: PMC3533001  PMID: 23169875
7.  Body Composition in Patients with Chronic Obstructive Pulmonary Disease 
Mædica  2014;9(1):25-32.
Body composition assessment in chronic obstructive pulmonary disease (COPD) is important, as weight loss and muscular wasting are responsible for low exercise capacity in these patients, and low body mass index (BMI) and fat free mass index (FFMI) are important prognostic factors. Our study aims were: (a) to describe body composition in COPD patients referred to a pulmonary rehabilitation center in Bucharest; (b) to examine the relationships between body composition and disease severity (bronchial obstruction, exercise capacity, quality of life); (c) to test if segmental wasting of lower limbs muscle mass (measured by segmental body composition analysis) correlates with decreased exercise capacity.
Material and methods:
We studied 36 consecutive COPD patients referred to our clinic for pulmonary rehabilitation. Patients performed pulmonary function tests, six minutes walking test (6MWT), and health status was evaluated with COPD Assessment Test (CAT). Body composition measurements were performed by direct segmental multi-frequency bioelectrical impedance analysis (BIA).
This study offers the first data on body composition of Romanian COPD patients
The prevalence of nutritional depletion (defined by low BMI and/or low FFMI) among our COPD patients was 22.2%. Mean FFMI was significantly lower in normal or underweight patients versus overweight or obese patients. Patients with low FFMI had lower exercise capacity at the 6MWT and higher CAT scores than patients with normal FFMI.
Depending on the BMI and FFMI values the patients were divided in four categories: normal, semistarvation, sarcopenia and cachexia. The group of patients with sarcopenia (low FFMI and normal BMI) had the lowest mean MIP (Maximal Inspiratory Pressure), the lowest mean 6MWD (six minutes walking distance) and the higher CAT mean scores among all groups. Exercise capacity was significantly lower in muscular depleted patients (with low skeletal muscle mass index - SSMI). MIP correlated significantly with FFMI and SMMI. No correlations were found between parameters of body composition and FEV1 or CAT. Segmental body composition assessment revealed that unbalanced upper/lower skeletal muscle mass is associated with a lower exercise capacity as measured by 6WMT.
This study offers the first data on body composition of Romanian COPD patients. The prevalence of nutritional depletion is similar to that found in other European studies. No significant correlations were found between FFMI and severity of the disease (bronchial obstruction, distance walked, CAT score). FFMI and SSMI correlated significantly with MIP. Sarcopenic patients had the lowest mean 6MWD, the lowest mean MIP and the highest CAT mean scores. SMMI significantly correlated with 6MWD. Segmental body composition assessment of revealed that "unbalanced" patients had lower results at 6MWT. These results show that body composition evaluation is useful for the assessment of COPD patients referred to pulmonary rehabilitation and should be routinely performed
PMCID: PMC4268286  PMID: 25553122
body composition; chronic obstructive pulmonary disease; pulmonary rehabilitation
8.  Structural determinants of food insufficiency, low dietary diversity and BMI: a cross-sectional study of HIV-infected and HIV-negative Rwandan women 
BMJ Open  2012;2(2):e000714.
In Sub-Saharan Africa, the overlapping epidemics of undernutrition and HIV infection affect over 200 and 23 million people, respectively, and little is known about the combined prevalence and nutritional effects. The authors sought to determine which structural factors are associated with food insufficiency, low dietary diversity and low body mass index (BMI) in HIV-negative and HIV-infected Sub-Saharan women.
Study design
Cross-sectional analysis of a longitudinal cohort.
Community-based women's organisations.
161 HIV-negative and 514 HIV-infected Rwandan women.
Primary and secondary outcome measures
Primary outcomes included food insufficiency (reporting ‘usually not’ or ‘never’ to ‘Do you have enough food?’), low household dietary diversity (Household Dietary Diversity Score ≤3) and BMI <18.5 (kg/m2). The authors also measured structural and behavioural factors including: income, household size, literacy and alcohol use.
Food insufficiency was prevalent (46%) as was low dietary diversity (43%) and low BMI (15%). Food insufficiency and dietary diversity were associated with low income (adjusted odds ratio (aOR)=2.14 (95% CI 1.30 to 3.52) p<0.01), (aOR=6.51 (95% CI 3.66 to 11.57) p<0.001), respectfully and illiteracy (aOR=2.00 (95% CI 1.31 to 3.04) p<0.01), (aOR=2.10 (95% CI 1.37 to 3.23) p<0.001), respectfully and were not associated with HIV infection. Alcohol use was strongly associated with food insufficiency (aOR=3.23 (95% CI 1.99 to 5.24) p<0.001). Low BMI was inversely associated with HIV infection (aOR≈0.5) and was not correlated with food insufficiency or dietary diversity.
Rwandan women experienced high rates of food insufficiency and low dietary diversity. Extreme poverty, illiteracy and alcohol use, not HIV infection alone, may contribute to food insufficiency in Rwandan women. Food insufficiency, dietary diversity and low BMI do not correlate with one another; therefore, low BMI may not be an adequate screening tool for food insufficiency. Further studies are needed to understand the health effects of not having enough food, low food diversity and low weight in both HIV-negative and HIV-infected women.
Article summary
Article focus
What structural determinants are associated with food insufficiency, low dietary diversity and low BMI in HIV-negative and HIV-infected women in Rwanda?
What is the prevalence of food insufficiency, low dietary diversity and low BMI in HIV-negative and HIV-infected women in Rwanda and are these outcomes correlated with each other?
1: Poverty, low literacy status and alcohol use are associated with food insufficiency, low dietary diversity and low BMI.
2: Food insufficiency, low dietary diversity and low BMI are highly prevalent and are correlated with one another.
Key messages
Food insufficiency and low dietary diversity are highly prevalent (46% and 43%, respectively) and are associated with low income and illiteracy and strongly associated with alcohol use.
BMI (kg/m2) is not correlated with food insufficiency or dietary diversity.
Significance: food insufficiency and low dietary diversity, known contributors to poor health, are highly prevalent in HIV-negative and HIV-infected women in Rwanda. Low BMI may not be an adequate screening tool for food insufficiency. Extreme poverty, low literacy and alcohol use may contribute to food insufficiency and low dietary diversity. These structural factors may be useful targets to prevent the adverse health effects of food insufficiency and low dietary diversity.
Strengths and limitations of this study
Large cohort of HIV-negative and HIV-infected women, very detailed tools used for food insufficiency and dietary diversity
Cross-sectional design, our measurement of food insufficiency is solely by self-report.
PMCID: PMC3329607  PMID: 22505309
9.  Antiretroviral Therapy for Prevention of Tuberculosis in Adults with HIV: A Systematic Review and Meta-Analysis 
PLoS Medicine  2012;9(7):e1001270.
In a systematic review and meta-analysis, Amitabh Suthar and colleagues investigate the association between antiretroviral therapy and the reduction in the incidence of tuberculosis in adults with HIV infection.
Human immunodeficiency virus (HIV) infection is the strongest risk factor for developing tuberculosis and has fuelled its resurgence, especially in sub-Saharan Africa. In 2010, there were an estimated 1.1 million incident cases of tuberculosis among the 34 million people living with HIV worldwide. Antiretroviral therapy has substantial potential to prevent HIV-associated tuberculosis. We conducted a systematic review of studies that analysed the impact of antiretroviral therapy on the incidence of tuberculosis in adults with HIV infection.
Methods and Findings
PubMed, Embase, African Index Medicus, LILACS, and clinical trial registries were systematically searched. Randomised controlled trials, prospective cohort studies, and retrospective cohort studies were included if they compared tuberculosis incidence by antiretroviral therapy status in HIV-infected adults for a median of over 6 mo in developing countries. For the meta-analyses there were four categories based on CD4 counts at antiretroviral therapy initiation: (1) less than 200 cells/µl, (2) 200 to 350 cells/µl, (3) greater than 350 cells/µl, and (4) any CD4 count.
Eleven studies met the inclusion criteria. Antiretroviral therapy is strongly associated with a reduction in the incidence of tuberculosis in all baseline CD4 count categories: (1) less than 200 cells/µl (hazard ratio [HR] 0.16, 95% confidence interval [CI] 0.07 to 0.36), (2) 200 to 350 cells/µl (HR 0.34, 95% CI 0.19 to 0.60), (3) greater than 350 cells/µl (HR 0.43, 95% CI 0.30 to 0.63), and (4) any CD4 count (HR 0.35, 95% CI 0.28 to 0.44). There was no evidence of hazard ratio modification with respect to baseline CD4 count category (p = 0.20).
Antiretroviral therapy is strongly associated with a reduction in the incidence of tuberculosis across all CD4 count strata. Earlier initiation of antiretroviral therapy may be a key component of global and national strategies to control the HIV-associated tuberculosis syndemic.
Review Registration
International Prospective Register of Systematic Reviews CRD42011001209
Please see later in the article for the Editors' Summary.
Editors' Summary
Tuberculosis—a contagious bacterial infection— is a global public-health problem. In 2010, 8.8 million people developed active tuberculosis and 1.4 million people died from the disease. Tuberculosis can be cured by taking powerful antibiotics regularly for several months, and between 1995 and 2010, 46 million people with tuberculosis were successfully treated using DOTS—a directly observed antibiotic regimen designed by the World Health Organization (WHO). Now, though, the HIV epidemic is compromising global tuberculosis control efforts. HIV-positive people are very susceptible to tuberculosis because HIV, the virus that causes AIDS, destroys the immune system cells (including CD4 lymphocytes) that normally combat tuberculosis. In 2010, 1.1 million of the new (incident) cases of tuberculosis were among the 34 million people living with HIV, and 350,000 people died of HIV-associated tuberculosis, making tuberculosis the leading cause of death among HIV-positive people. To tackle HIV-associated tuberculosis, which occurs mainly in developing countries, WHO now recommends that HIV and tuberculosis programs use collaborative approaches such as the Three I's for HIV/TB strategy—intensified tuberculosis case-finding among HIV-positive people, isoniazid preventative therapy for HIV-positive people without active tuberculosis, and (tuberculosis) infection control in healthcare facilities, social settings, and households.
Why Was This Study Done?
Despite progress in scaling up the Three I's for HIV/TB strategy, complementary interventions are still needed to prevent tuberculosis in HIV-positive people. Antiretroviral therapy (ART) lowers the viral load of people infected with HIV and restores their immune system function and could, therefore, prevent HIVassociated tuberculosis, in addition to treating HIV infection. WHO recommends ART for all HIV-positive adults with a CD4 count of less than 350 cells/μl of blood and for all HIVpositive, tuberculosis-positive individuals irrespective of their CD4 count. However, the evidence for ART's preventative impact on tuberculosis has not been systematically examined. Here, the researchers undertake a systematic review (a search that uses predefined criteria to identify all the research on a given topic) and a meta-analysis (a statistical method for combining the results of studies) to investigate the impact of ART initiated at various CD4 counts on the development of tuberculosis in HIV-positive adults in developing countries.
What Did the Researchers Do and Find?
The researchers found 11 studies that compared tuberculosis incidence by ART status in HIV-infected adults over periods longer than six months on average in developing countries and undertook meta-analyses of these studies based on four categories of CD4 count at ART initiation (less than 200 cells/μl, 200–350 cells/μl, greater than 350 cells/μl, and any CD4 count). For all these categories, ART was strongly associated with a reduction in the incidence of tuberculosis. For example, the meta-analysis of the two studies that reported on participants in whom ART was initiated at a CD4 count less than 200 cells/μl yielded a hazard ratio (HR) of 0.16. That is, study participants starting ART when their CD4 count was below 200 cells/μl were about one-sixth as likely to develop tuberculosis as participants not receiving ART. In the metaanalysis of all 11 studies, study participants receiving ART were about one-third as likely to develop tuberculosis as study participants receiving no ART, irrespective of their CD4 count (HR 0.35). Importantly, the CD4 count at which ART was initiated did not significantly alter the magnitude of ART's preventive effect on tuberculosis development.
What Do These Findings Mean?
These findings suggest that ART is strongly associated with a reduction in the incidence of tuberculosis in HIV-positive adults in developing countries, whatever the CD4 count at ART initiation. Because most of the studies in this meta-analysis were observational, these results do not show that ART causes a reduction in tuberculosis incidence—other unknown factors shared by the study participants who received ART may be responsible for their lower tuberculosis incidence. Moreover, factors such as variations in diagnostic methods among the studies included in this meta-analysis may have affected the accuracy of these findings. Nevertheless, the key finding that ART is associated with a significant reduction in tuberculosis cases among adults with CD4 counts greater than 350 cells//μl should be considered by healthcare providers, policymakers, and people living with HIV when weighing the benefits and risks of early ART initiation. It also suggests that early ART initiation (in combination with expanded HIV testing) could be a key component of future global and national strategies to control HIV-associated tuberculosis.
Additional Information
Please access these websites via the online version of this summary at
WHO provides information on all aspects of tuberculosis, including information on tuberculosis and HIV, on the Three I's for HIV/TB, and on ART for tuberculosis prevention (some information is in several languages)
The TB/HIV Working Group is part of the Stop TB Partnership, which is working toward tuberculosis elimination; patient stories about tuberculosis/HIV co-infection are also available on their site
The US Centers for Disease Control and Prevention has information about tuberculosis and about tuberculosis and HIV co-infection
The US National Institute of Allergy and Infectious Diseases also has detailed information on all aspects of tuberculosis including HIV-associated tuberculosis
Information is available from Avert, an international AIDS charity, on HIV-related tuberculosis (in English and Spanish), and from Aidsmap, a non-governmental organization, on HIV-associated tuberculosis
PMCID: PMC3404110  PMID: 22911011
10.  Reference Values and Age Differences in Body Composition of Community-Dwelling Older Japanese Men and Women: A Pooled Analysis of Four Cohort Studies 
PLoS ONE  2015;10(7):e0131975.
To determine age- and sex-specific body composition reference values and investigate age differences in these parameters for community-dwelling older Japanese men and women, using direct segmental multi-frequency bioelectrical impedance analysis.
We conducted a pooled analysis of data collected in four cohort studies between 2008 and 2012: Kusatsu Longitudinal Study, Hatoyama Cohort Study, Itabashi Cohort Study, and Kashiwa Cohort Study. The pooled analysis included cross-sectional data from 4478 nondisabled, community-dwelling adults aged 65-94 years (2145 men, 2333 women; mean age: 72.9 years in men and 72.6 years in women). Body weight, fat mass (FM), percentage FM, fat-free mass (FFM), and appendicular lean soft tissue mass were measured using the InBody 720 and 430 (Biospace Co. Ltd, Seoul, Korea). The values were then normalized by height in meters squared to determine body mass index (BMI), FM index (FMI), FFM index (FFMI), and skeletal muscle mass index (SMI).
Simple means (standard deviation) of BMI, percentage FM, FMI, FFMI, and SMI were 23.4 (2.9) kg/m2, 24.9 (6.3)%, 5.96 (2.09) kg/m2, 17.4 (1.5) kg/m2, and 7.29 (0.76) kg/m2, respectively, in men and 22.7 (3.3) kg/m2, 31.7 (7.1)%, 7.40 (2.61) kg/m2, 15.3 (1.2) kg/m2, and 5.86 (0.67) kg/m2, respectively, in women. We then calculated quartiles and quintiles for these indices after stratifying for sex and 5-year age group. FFMI and SMI decreased significantly with age in both sexes (P < 0.001 for trends), but FFMI remained constant among the women with only a 1% decrease up to age 84 years. Percentage FM increased significantly, with age (P < 0.001 in men and P = 0.045 in women for trends), but FMI was unchanged in both sexes (P = 0.147 in men and P = 0.176 in women for trends).
The present data should be useful in the clinical evaluation of body composition of older Japanese and for international comparisons. The small age-related decrease in FFMI may be a noteworthy characteristic of body composition change in older Japanese women.
PMCID: PMC4492501  PMID: 26147341
11.  Predicting fat-free mass index and sarcopenia: A pilot study in community-dwelling older adults 
Age  2013;35(6):2423-2434.
Age-related muscle loss, termed sarcopenia, has been linked to an increased risk of falls, disability, and mortality. The purpose of this study was to develop a predictive measurement tool to estimate normalized fat-free mass index (FFMI), a means of identifying sarcopenia, in community-dwelling older adults. Functionally relevant measurements including mobility tests, food records, circumference measures, balance, and gait variables were included to ensure this model was comprehensive and accessible to clinicians. Eighty-five community-dwelling older adults (42 male) aged 75.2 ± 5.7 years participated. Each completed two questionnaires regarding general health and physical activity levels. Anthropometric, strength, balance, gait, nutrition, and body composition tests were then conducted. A fat-free mass value, determined by bioelectrical impedance analysis, was normalized by height (FFMI). FFMI along with grip strength and gait speed was used to classify sarcopenia. FFMI was significantly correlated with all circumference measures (waist, arm, calf, and thigh) and body mass index (BMI), but no nutritional parameters. In males, maximum grip strength and a novel quiet balance measure, time outside of a 95 % confidence ellipse (TOE), were both positively correlated to FFMI. In females, age and double-support time correlated to FFMI. The prediction equation that accounted for the most variability of FFMI included the independent variables: sex, step time, BMI, and TOE (adjusted R2 = 0.9272). The proposed linear regression model can successfully predict FFMI values to a high level of accuracy in men and women. With this information, sarcopenia can be predicted by clinicians, and early interventions can be planned and implemented.
PMCID: PMC3824997  PMID: 23322451
Sarcopenia; Community-dwelling older adults; Gait; Balance; Fat-free mass index (FFMI); Bioelectrical impedance analysis (BIA)
12.  Nutrition and inflammation serum biomarkers are associated with 12-week mortality among malnourished adults initiating antiretroviral therapy in Zambia 
A low body mass index (BMI) at antiretroviral therapy (ART) initiation is a strong predictor of mortality among HIV-infected adults in resource-constrained settings. The relationship between nutrition and inflammation-related serum biomarkers and early treatment outcomes (e.g., less than 90 days) in this population is not well described.
An observational cohort of 142 HIV-infected adults in Lusaka, Zambia, with BMI under 16 kg/m2 or CD4+ lymphocyte counts of less than 50 cells/mm3, or both, was followed prospectively during the first 12 weeks of ART. Baseline and serial post-treatment phosphate, albumin, ferritin and highly sensitive C-reactive protein (hsCRP) serum levels were measured. The primary outcome was mortality.
Lower baseline phosphate and albumin serum levels, and higher ferritin and hsCRP, were significantly associated with mortality prior to 12 weeks (p < 0.05 for all comparisons), independent of known risk factors for early ART-associated mortality in sub-Saharan Africa. The time-dependent interval change in albumin was associated with mortality after adjusting for the baseline value (AHR 0.62 [0.43, 0.89] per 5 g/L increase), but changes in the other biomarkers were not.
The predictive value of serum biomarkers for early mortality in a cohort of adults with malnutrition and advanced HIV in a resource-constrained setting was primarily driven by pre-treatment values, rather than post-ART changes. Interventions to promote earlier HIV diagnosis and treatment, address nutritional deficiencies, and identify the etiologies of increased systemic inflammation may improve ART outcomes in this vulnerable population.
PMCID: PMC3094357  PMID: 21477359
13.  Dieting status influences associations between dietary patterns and body composition in adolescents: a cross-sectional study 
Nutrition Journal  2013;12:51.
Associations between food choice and body composition in previous studies of adolescents have been inconsistent. This may be due to the body composition measures used, or these associations may be affected by the dieting status of adolescents. The objective of this study was to investigate the association between dietary patterns and body composition in adolescents, and determine if these associations are moderated by dieting status.
Information on food consumption and current dieting status was collected, using a web-based survey, in 681 adolescents (mean age 15.8 (SD 0.9) years) from schools in Otago, New Zealand. Non-dieters were defined as those reporting not being on a diet as they were “happy with their weight”. Principal components analysis (PCA) was used to determine dietary patterns. Body mass index (BMI), waist circumference (WC), waist-to-height ratio (WHtR), fat mass index (FMI), and fat-free mass index (FFMI) were examined as outcomes. Generalized estimating equations were used to examine associations between dietary patterns and body composition.
PCA produced three dietary patterns: ‘Treat Foods’, ‘Fruits and Vegetables’, and ‘Basic Foods’. A standard deviation increase in ‘Basic Foods’ was associated with a 3.58% decrease in FMI (95%CI −6.14, -0.94) in the total sample. When separate sex analysis was undertaken significant negative associations were found in boys only, between the ‘Basic Food’ score and WC, WHtR, FMI, and FFMI, while the ‘Fruits and Vegetables’ pattern was negatively associated with FMI. Associations between ‘Treat Foods’ and BMI, WC, and WHtR in non-dieters were positive, while these associations were negative for all other participants.
Significant associations were found between dietary patterns and indices of both central and total adiposity, but not BMI. Therefore using only BMI measures may not be useful in this age group. Since our results were significant for boys and not girls, nutrition messages designed to prevent obesity may be particularly important for adolescent boys. As an interaction between dieting status and ‘Treat Foods’ existed, future studies should also explore the role of dieting when investigating food choice and body composition.
PMCID: PMC3646700  PMID: 23617772
Dietary patterns; Body composition; Dieting status; Adolescents; New Zealand
14.  Fat-free mass index: changes and race/ethnic differences in adulthood 
Nutritional status is assessed by measuring BMI or percent body fat (%fat). BMI can misclassify persons who carry more weight as fat-free mass and %fat can be misleading in cases of malnutrition or in disease states characterized by wasting of lean tissue. The fat-free mass index (FFMI) is proposed to assess body composition in individuals who have a similar body composition but differ in height allowing identification of those suffering from malnutrition, wasting or those that possess a relatively high muscle mass. The purpose was to determine whether the FFMI differs in a group of racially/ethnically diverse adults.
Subjects were a multi-ethnic sample (Caucasian, CA; African American, AA; Hispanic, HIS and Asian, AS) of 1339 healthy males (n = 480) and females (n = 859) ranging in age from 18–110 years. Total body fat, total fat-free mass and bone mineral density were estimated using dual energy X-ray absorptiometry.
FFMI differed among the four ethnic groups (P ≤ 0.05) for both genders. A curvilinear relationship was found between age and FFMI for both genders although the coefficients in the quadratic model differed between genders (P ≤ 0.001) indicating the rate of change in FFMI differed between genders. The estimated turning point where FFMI started to decline was in the mid 20s for male and mid 40s for female participants. An age × gender interaction was found such that the rate of decline was greater in male than female participants (P ≤ 0.001). For both genders, FFMI was greatest in AA and the least in AS (P ≤ 0.001). There was no significant interaction between race and age or age2 (P = 0.06). However, male participants consistently had a greater FFMI than female participants (P ≤ 0.001).
These findings have clinical implications for identifying individuals who may not be recognized as being malnourished based on their BMI or %fat but whose fat-free mass corrected for height is relatively low.
PMCID: PMC3306818  PMID: 20531353
fat-free mass index; fat-free mass; body mass index (BMI); percent body fat; nutritional assessment
15.  Body composition in adolescent idiopathic scoliosis 
European Spine Journal  2012;22(2):324-329.
Study design
A controlled prospective cross-sectional case study.
To investigate body mass index (BMI) and corporal composition in girls with adolescent idiopathic scoliosis (AIS) and compare them with a normal population matched by sex and age.
Summary and background data
There is controversy as to whether there are real anthropometric alterations in patients with AIS. Relative to the weight or the BMI, some studies find differences and other studies do not detect them. AIS and anorexia nervosa (AN) make their debut during adolescence and both may be associated with an alteration of their subjective physical perception. Some authors propose a link between AIS and AN supported both by an alteration of physical perception and lower BMI. No studies on body composition in AIS have been published.
Adolescent idiopathic scoliosis patient surgery candidates during 2008 were studied. Body composition was evaluated using the bioelectrical impedance analysis (Bodystat, Isle of Man, UK). A study population of more than 5,000 patients that was published by Kyle et al. (Nutrition 17:534–541, 2001) was chosen as a control (group 1). Another control group (group 2) of healthy volunteers matched by sex and age was selected among a school age and university population in Barcelona, Spain. A variance analysis was used to analyze differences between the mean values of the control group 1, the European control group, and the AIS patient surgery candidates (Epiinfo 6.2001). Comparisons between the AIS patients and control group 2 were performed with the T Student test of unpaired samples using the SPSS 15.0 (Statistical Package Social Science) software.
Twenty-seven women with a mean age of 17.4 years. BMI was 18.9 kg/m2 (SD 1.7; 95 % CI 18.31–19.73). In the variance analysis, a significant difference between AIS and group 1 in BMI was observed (21.0 vs. 18.9, p = 0.000004); fat-free mass (FFM = 42.6 vs. 38.9, p = 0.0000009) and fat mass (FM = 15.6 vs. 13.7, p = 0.03). Significant differences in BMI (22.13 vs. 18.9, p = 0.001; 95 % CI difference 1.85–4.60), fat mass index (FMi = 7.17 vs. 4.97, p = 0.000; 95 % CI difference 1.36–3.05) and fat-free mass index (FFMi = 14.95 vs. 13.09, p = 0.001; 95 % CI difference 0.26–1.86) between AIS and group 2 were also seen.
The conclusion is that there is a real alteration of body composition in AIS. The BMI, FFMi and FMi are lower than in the general population in the series under study.
PMCID: PMC3555626  PMID: 22886589
Adolescent idiopathic scoliosis; Body mass index; Body composition
16.  Potential of Spirulina Platensis as a Nutritional Supplement in Malnourished HIV-Infected Adults in Sub-Saharan Africa: A Randomised, Single-Blind Study 
Malnutrition is a major global public health issue and its impact on communities and individuals is more dramatic in Sub-Saharan Africa, where it is compounded by widespread poverty and generalized high prevalence of human immunodeficiency virus (HIV). Therefore, malnutrition should be addressed through a multisectorial approach, and malnourished individuals should have access to nutritional rehabilitation molecules that are affordable, accessible, rich in nutrient and efficient. We thus assessed the efficacy of two affordable and accessible nutritional supplements, spirulina platensis versus soya beans among malnourished HIV-infected adults.
Undernourished patients, naïve of, but eligible to antiretroviral treatment (ART), aged 18 to 35 years were enrolled and randomly assigned to two groups. The first group received spirulina (Group A) as food supplement and the second received soya beans (Group B). Patients were initiated ART simultaneously with supplements. Food supplements were auto-administered daily, the quantity being calculated according to weight to provide 1.5 g/kg body weight of proteins with 25% from supplements (spirulina and soya beans). Patients were monitored at baseline and followed-up during twelve weeks for anthropometric parameters, body composition, haemoglobin and serum albumin, CD4 count and viral load.
Fifty-two patients were enrolled (Group A: 26 and Group B: 26). The mean age was 26.4 ± 4.9 years (Group A) and 28.7 ± 4.8 (Group B) with no significant difference between groups (P = 0.10). After 12 weeks, weight and BMI significantly improved in both groups (P < 0.001 within each group). The mean gain in weight and BMI in Group A and B were 4.8 vs. 6.5 kg, (P = 0.68) and 1.3 vs. 1.90 Kg/m2, (P = 0.82) respectively. In terms of body composition, fat free mass (FFM) did not significantly increase within each group (40.5 vs. 42.2 Kg, P = 0.56 for Group A; 39.2 vs. 39.0 Kg, P = 0.22 for Group B). But when compared between the two groups at the end of the trial, FFM was significantly higher in the spirulina group (42.2 vs. 39.0 Kg, P = 0.01). The haemoglobin level rose significantly within groups (P < 0.001 for each group) with no difference between groups (P = 0.77). Serum albumin level did not increase significantly within groups (P < 0.90 vs. P < 0.82) with no difference between groups (P = 0.39). The increase in CD4 cell count within groups was significant (P < 0.01 in both groups), with a significantly higher CD4 count in the spirulina group compared to subjects on soya beans at the end of the study (P = 0.02). Within each group, HIV viral load significantly reduced at the end of the study (P < 0.001 and P = 0.04 for spirulina and soya beans groups respectively). Between the groups, the viral load was similar at baseline but significantly reduced in the spirulina group at the end of the study (P = 0.02).
We therefore conclude in this preliminary study, firstly, that both spirulina and soja improve on nutritional status of malnourished HIV-infected patients but in terms of quality of nutritional improvement, subjects on spirulina were better off than subjects on soya beans. Secondly, nutritional rehabilitation improves on immune status with a consequent drop in viral load but further investigations on the antiviral effects of this alga and its clinical implications are strongly needed.
PMCID: PMC3738485  PMID: 23946659
malnutrition; spirulina; nutritional rehabilitation; HIV infected persons; anthropometric measurements; body composition; CD4 cells count; viral load
17.  TNF-α is associated with loss of lean body mass only in already cachectic COPD patients 
Respiratory Research  2012;13(1):48.
Systemic inflammation may contribute to cachexia in patients with chronic obstructive pulmonary disease (COPD). In this longitudinal study we assessed the association between circulating C-reactive protein (CRP), tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and IL-6 levels and subsequent loss of fat free mass and fat mass in more than 400 COPD patients over three years.
The patients, aged 40–76, GOLD stage II-IV, were enrolled in 2006/07, and followed annually. Fat free mass and fat mass indexes (FFMI & FMI) were calculated using bioelectrical impedance, and CRP, TNF-α, IL-1ß, and IL-6 were measured using enzyme immunoassays. Associations with mean change in FFMI and FMI of the four inflammatory plasma markers, sex, age, smoking, FEV1, inhaled steroids, arterial hypoxemia, and Charlson comorbidity score were analyzed with linear mixed models.
At baseline, only CRP was significantly (but weakly) associated with FFMI (r = 0.18, p < 0.01) and FMI (r = 0.27, p < 0.01). Univariately, higher age, lower FEV1, and use of beta2-agonists were the only significant predictors of decline in FFMI, whereas smoking, hypoxemia, Charlson score, and use of inhaled steroids predicted increased loss in FMI. Multivariately, high levels of TNF-α (but not CRP, IL-1ß or IL-6) significantly predicted loss of FFMI, however only in patients with established cachexia at entry.
This study does not support the hypothesis that systemic inflammation is the cause of accelerated loss of fat free mass in COPD patients, but suggests a role for TNF-α in already cachectic COPD patients.
PMCID: PMC3487870  PMID: 22708547
Inflammation; TNF-α; COPD; Cachexia
18.  The Role of HIV-Related Stigma in Utilization of Skilled Childbirth Services in Rural Kenya: A Prospective Mixed-Methods Study 
PLoS Medicine  2012;9(8):e1001295.
Janet Turan and colleagues examined the role of the perception of women in rural Kenya of HIV-related stigma during pregnancy on their subsequent utilization of maternity services.
Childbirth with a skilled attendant is crucial for preventing maternal mortality and is an important opportunity for prevention of mother-to-child transmission of HIV. The Maternity in Migori and AIDS Stigma Study (MAMAS Study) is a prospective mixed-methods investigation conducted in a high HIV prevalence area in rural Kenya, in which we examined the role of women's perceptions of HIV-related stigma during pregnancy in their subsequent utilization of maternity services.
Methods and Findings
From 2007–2009, 1,777 pregnant women with unknown HIV status completed an interviewer-administered questionnaire assessing their perceptions of HIV-related stigma before being offered HIV testing during their first antenatal care visit. After the visit, a sub-sample of women was selected for follow-up (all women who tested HIV-positive or were not tested for HIV, and a random sample of HIV-negative women, n = 598); 411 (69%) were located and completed another questionnaire postpartum. Additional qualitative in-depth interviews with community health workers, childbearing women, and family members (n = 48) aided our interpretation of the quantitative findings and highlighted ways in which HIV-related stigma may influence birth decisions. Qualitative data revealed that health facility birth is commonly viewed as most appropriate for women with pregnancy complications, such as HIV. Thus, women delivering at health facilities face the risk of being labeled as HIV-positive in the community. Our quantitative data revealed that women with higher perceptions of HIV-related stigma (specifically those who held negative attitudes about persons living with HIV) at baseline were subsequently less likely to deliver in a health facility with a skilled attendant, even after adjusting for other known predictors of health facility delivery (adjusted odds ratio = 0.44, 95% CI 0.22–0.88).
Our findings point to the urgent need for interventions to reduce HIV-related stigma, not only for improving quality of life among persons living with HIV, but also for better health outcomes among all childbearing women and their families.
Please see later in the article for the Editors' Summary.
Editors' Summary
Every year, nearly 350,000 women die from pregnancy- or childbirth-related complications. Almost all these “maternal” deaths occur in developing countries. In sub-Saharan Africa, for example, the maternal mortality ratio (the number of maternal deaths per 100,000 live births) is 500 whereas in industrialized countries it is only 12. Most maternal deaths are caused by hemorrhage (severe bleeding after childbirth), post-delivery infections, obstructed (difficult) labor, and blood pressure disorders during pregnancy. All these conditions can be prevented if women have access to adequate reproductive health services and if trained health care workers are present during delivery. Notably, in sub-Saharan Africa, infection with HIV (the virus that causes AIDS) is an increasingly important contributor to maternal mortality. HIV infection causes maternal mortality directly by increasing the occurrence of pregnancy complications and indirectly by increasing the susceptibility of pregnant women to malaria, tuberculosis, and other “opportunistic” infections—HIV-positive individuals are highly susceptible to other infections because HIV destroys the immune system.
Why Was This Study Done?
Although skilled delivery attendants reduce maternal mortality, there are many barriers to their use in developing countries including cost and the need to travel long distances to health facilities. Fears and experiences of HIV-related stigma and discrimination (prejudice, negative attitudes, abuse, and maltreatment directed at people living with HIV) may also be a barrier to the use of skilled childbirth service. Maternity services are prime locations for HIV testing and for the provision of interventions for the prevention of mother-to-child transmission (PMTCT) of HIV, so pregnant women know that they will have to “deal with” the issue of HIV when visiting these services. In this prospective mixed-methods study, the researchers examine the role of pregnant women's perceptions of HIV-related stigma in their subsequent use of maternity services in Nyanza Province, Kenya, a region where 16% women aged 15–49 are HIV-positive and where only 44.2% of mothers give birth in a health facility. A mixed-methods study combines qualitative data—how people feel about an issue—with quantitative data—numerical data about outcomes.
What Did the Researchers Do and Find?
In the Maternity in Migori and AIDS Stigma (MAMAS) study, pregnant women with unknown HIV status living in rural regions of Nyanza Province answered questions about their perceptions of HIV-related stigma before being offered HIV testing during their first antenatal clinic visit. After delivery, the researchers asked the women who tested HIV positive or were not tested for HIV and a sample of HIV-negative women where they had delivered their baby. They also gathered qualitative information about barriers to maternity and HIV service use by interviewing childbearing women, family members, and community health workers. The qualitative data indicate that labor in a health facility is commonly viewed as being most appropriate for women with pregnancy complications such as HIV infection. Thus, women delivering at health facilities risk being labeled as HIV positive, a label that the community associates with promiscuity. The quantitative data indicate that women with more negative attitudes about HIV-positive people (higher perceptions of HIV-related stigma) at baseline were about half as likely to deliver in a health facility with a skilled attendant as women with more positive attitudes about people living with HIV.
What Do These Findings Mean?
These findings suggest that HIV-related stigma is associated with the low rate of delivery by skilled attendants in rural areas of Nyanza Province and possibly in other rural regions of sub-Saharan Africa. Community mobilization efforts aimed at increasing the use of PMTCT services may be partly responsible for the strong perception that delivery in a health facility is most appropriate for women with HIV and other pregnancy complications and may have inadvertently strengthened the perception that women who give birth in such facilities are likely to be HIV positive. The researchers suggest, therefore, that health messages should stress that delivery in a health facility is recommended for all women, not just HIV-positive women or those with pregnancy complications, and that interventions should be introduced to reduce HIV-related stigma. This combined strategy has the potential to increase the use of maternity services by all women and the use of HIV and PMTCT services, thereby reducing some of the most pressing health problems facing women and their children in sub-Saharan Africa.
Additional Information
Please access these Web sites via the online version of this summary at
The United Nations Children's Fund (UNICEF) provides information on maternal mortality, including the WHO/UNICEF/UNFPA/World Bank 2008 country estimates of maternal mortality; a UNICEF special report tells the stories of seven mothers living with HIV in Lesotho
The World Health Organization provides information on maternal health, including information about Millennium Development Goal 5, which aims to reduce maternal mortality (in several languages); the Millennium Development Goals, which were agreed by world leaders in 2000, are designed to eradicate extreme poverty worldwide by 2015
Immpact is a global research initiative for the evaluation of safe motherhood intervention strategies
Maternal Death: The Avoidable Crisis is a briefing paper published by the independent humanitarian medical aid organization Médecins Sans Frontières (MSF) in March 2012
Information is available from Avert, an international AIDS charity on all aspects of HIV/AIDS, including information on women, HIV and AIDS, on HIV and pregnancy, on HIV and AIDS stigma and discrimination, and on HIV in Kenya (in English and Spanish); Avert also has personal stories from women living with HIV
The Stigma Action Network (SAN) is a collaborative endeavor that aims to comprehensively coordinate efforts to develop and expand program, research, and advocacy strategies for reducing HIV stigma worldwide, including mobilizing stakeholders, delivering program and policy solutions, and maximizing investments in HIV programs and services globally
The People Living with Stigma Index aims to address stigma relating to HIV and advocate on key barriers and issues perpetuating stigma; it has recently published Piecing it together for women and girls, the gender dimensions of HIV-related stigma
The Health Policy Project has prepared a review of the academic and programmatic literature on stigma and discrimination as barriers to achievement of global goals for maternal health and the elimination of new child HIV infections (see under Resources)
More information on the MAMAS study is available from the UCSF Center for AIDS Prevention Studies
PMCID: PMC3424253  PMID: 22927800
19.  Bacterial Vaginosis Associated with Increased Risk of Female-to-Male HIV-1 Transmission: A Prospective Cohort Analysis among African Couples 
PLoS Medicine  2012;9(6):e1001251.
In a prospective study, Craig Cohen and colleagues investigate the association between bacterial vaginosis and the risk of female-to-male HIV-1 transmission.
Bacterial vaginosis (BV), a disruption of the normal vaginal flora, has been associated with a 60% increased risk of HIV-1 acquisition in women and higher concentration of HIV-1 RNA in the genital tract of HIV-1–infected women. However, whether BV, which is present in up to half of African HIV-1–infected women, is associated with an increase in HIV-1 transmission to male partners has not been assessed in previous studies.
Methods and Findings
We assessed the association between BV on female-to-male HIV-1 transmission risk in a prospective study of 2,236 HIV-1–seropositive women and their HIV-1 uninfected male partners from seven African countries from a randomized placebo-controlled trial that enrolled heterosexual African adults who were seropositive for both HIV-1 and herpes simplex virus (HSV)-2, and their HIV-1–seronegative partners. Participants were followed for up to 24 months; every three months, vaginal swabs were obtained from female partners for Gram stain and male partners were tested for HIV-1. BV and normal vaginal flora were defined as a Nugent score of 7–10 and 0–3, respectively. To reduce misclassification, HIV-1 sequence analysis of viruses from seroconverters and their partners was performed to determine linkage of HIV-1 transmissions. Overall, 50 incident HIV-1 infections occurred in men in which the HIV-1–infected female partner had an evaluable vaginal Gram stain. HIV-1 incidence in men whose HIV-1–infected female partners had BV was 2.91 versus 0.76 per 100 person-years in men whose female partners had normal vaginal flora (hazard ratio 3.62, 95% CI 1.74–7.52). After controlling for sociodemographic factors, sexual behavior, male circumcision, sexually transmitted infections, pregnancy, and plasma HIV-1 RNA levels in female partners, BV was associated with a greater than 3-fold increased risk of female-to-male HIV-1 transmission (adjusted hazard ratio 3.17, 95% CI 1.37–7.33).
This study identified an association between BV and increased risk of HIV-1 transmission to male partners. Several limitations may affect the generalizability of our results including: all participants underwent couples HIV counseling and testing and enrolled in an HIV-1 prevention trial, and index participants had a baseline CD4 count ≥250 cells/mm3 and were HSV-2 seropositive. Given the high prevalence of BV and the association of BV with increased risk of both female HIV-1 acquisition and transmission found in our study, if this association proves to be causal, BV could be responsible for a substantial proportion of new HIV-1 infections in Africa. Normalization of vaginal flora in HIV-1–infected women could mitigate female-to-male HIV-1 transmission.
Trial Registration: NCT00194519
Please see later in the article for the Editors' Summary
Editors' Summary
Since the first reported case of AIDS in 1981, the number of people infected with HIV, the virus that causes AIDS, has risen steadily. By the end of 2010, 34 million people were living with HIV/AIDS. At the beginning of the epidemic more men than women were infected with HIV. Now, however, 50% of all adults infected with HIV are women and in sub-Saharan Africa, where two-thirds of HIV-positive people live, women account for 59% of people living with HIV. Moreover, among 15–24 year-olds, women are eight times more likely than men to be HIV-positive. This pattern of infection has developed because most people in sub-Saharan Africa contract HIV through unprotected heterosexual sex. The risk of HIV transmission for both men and women in Africa and elsewhere can be reduced by abstaining from sex, by only having one or a few partners, by always using condoms, and by male circumcision. In addition, several studies suggest that antiretroviral therapy (ART) greatly reduces HIV transmission.
Why Was This Study Done?
Unfortunately, in sub-Saharan Africa, only about a fifth of HIV-positive people are currently receiving ART, which means that there is an urgent need to find other effective ways to reduce HIV transmission in this region. In this prospective cohort study (a type of study that follows a group of people for some time to see which personal characteristics are associated with disease development), the researchers investigate whether bacterial vaginosis—a condition in which harmful bacteria disrupt the normal vaginal flora—increases the risk of female-to-male HIV transmission among African couples. Bacterial vaginosis, which is extremely common in sub-Saharan Africa, has been associated with an increased risk of HIV acquisition in women and induces viral replication and shedding in the vagina in HIV-positive women, which may mean that HIV-positive women with bacterial vaginosis are more likely to transmit HIV to their male partners than women without this condition. If this is the case, then interventions that reduce the incidence of bacterial vaginosis might be valuable HIV prevention strategies.
What Did the Researchers Do and Find?
The researchers analyzed data collected from 2,236 heterosexual African couples enrolled in a clinical trial (the Partners in Prevention HSV/HIV Transmission Study) whose primary aim was to investigate whether suppression of herpes simplex virus infection could prevent HIV transmission. In all the couples, the woman was HIV-positive and the man was initially HIV-negative. The female partners were examined every three months for the presence of bacterial vaginosis and the male partners were tested regularly for HIV infection. The researchers also determined whether the men who became HIV-positive were infected with the same HIV strain as their partner to check that their infection had been acquired from this partner. The HIV incidence in men whose partners had bacterial vaginosis was 2.9 per 100 person-years (that is, 2.9 out of every 100 men became HIV-positive per year) whereas the HIV incidence in men whose partners had a normal vaginal flora was 0.76 per 100 person-years. After controlling for factors that might affect the risk of HIV transmission such as male circumcision and viral levels in female partner's blood, the researchers estimated that bacterial vaginosis was associated with a 3.17-fold increased risk of female-to-male HIV transmission in their study population.
What Do These Findings Mean?
These findings suggest that HIV-positive African women with bacterial vaginosis are more than three times as likely to transmit HIV to their male partners as those with a normal vaginal flora. It is possible that some unknown characteristic of the men in this study might have increased both their own risk of HIV infection and their partner's risk of bacterial vaginosis. Nevertheless, because bacterial vaginosis is so common in Africa (half of the women in this study had bacterial vaginosis at least once during follow-up) and because this condition is associated with both female HIV acquisition and transmission, these findings suggest that bacterial vaginosis could be responsible for a substantial proportion of new HIV infections in Africa. Normalization of vaginal flora in HIV-infected women by frequent presumptive treatment with antimicrobials (treatment with a curative dose of antibiotics without testing for bacterial vaginosis) or possibly by treatment with probiotics (live “good” bacteria) might, therefore, reduce female-to-male HIV transmission in sub-Saharan Africa.
Additional Information
Please access these Web sites via the online version of this summary at
Information is available from the US National Institute of Allergy and infectious diseases on all aspects of HIV infection and AIDS and on bacterial vaginosis
The US Centers for Disease Control and Prevention has information on all aspects of HIV/AIDS, including specific information about HIV/AIDS and women; it also has information on bacterial vaginosis (in English and Spanish)
NAM/aidsmap provides basic information about HIV/AIDS, and summaries of recent research findings on HIV care and treatment, and information on bacterial vaginosis and HIV transmission (in several languages)
Information is available from Avert, an international AIDS nonprofit group on many aspects of HIV/AIDS, including detailed information on HIV and AIDS prevention, on women, HIV and AIDS and on HIV/AIDS in Africa (in English and Spanish); personal stories of women living with HIV are available; the website Healthtalkonline also provides personal stories about living with HIV
More information about the Partners in Prevention HSV/HIV Transmission Study is available
PMCID: PMC3383741  PMID: 22745608
20.  Preoperative Nutritional Status of the Surgical Patients in Jeju 
Clinics in Orthopedic Surgery  2014;6(3):350-357.
To assess the preoperative nutritional status of patients with various disorders and to provide data for pre- and postoperative patient management plans, particularly in the elderly. There is no published information on age-matched and disease-matched preoperative nutritional/immunologic status for orthopedic patients, especially in the elderly, in Jeju.
In total, 331 patients with four categories of orthopedic conditions were assessed: 92 elective surgery patients, 59 arthroplasty patients, 145 patients with fractures, and 35 infection patients. Malnutrition was defined as body mass index (BMI) below 18 kg/m2 of expected body weight (below 20% of normal), serum albumin/globulin ratio below 1.5 (normal range, 1.5 to 2.3), albumin level below 3.5 g/dL, total lymphocyte count below 1,500 cells/mm3, and lymphocyte/monocyte ratio below 5 versus 1.
In 92 elective surgery patients, the average BMI was 23 kg/m2, hemoglobin was 15 g/dL, lymphocytes (2,486 cells)/monocytes (465 cells) ratio was 6.1, and the albumin (4.4 g/dL)/globulin (2.5 g/dL) ratio as a protein quotient was 1.7. Among the 59 hip and knee arthroplasty patients, the average BMI was 25 kg/m2, hemoglobin was 12 g/dL, lymphocytes (2,038 cells)/monocytes (391 cells) ratio was 6.6, and albumin (4.1 g/dL)/globulin (2.4 g/dL) ratio was 1.6. No subject showed malnutrition. Among the 145 fracture patients, the average BMI was 23 kg/m2. The hemoglobin level was 13 g/dL, monocytes (495 cells)/lymphocytes (1,905 cells) ratio was 1 versus 4.6, and albumin (4.1 d/gL)/globulin (2.5 d/gL) ratio was 1.6. However, both ratios decreased after 70 years of age. Among the 17 of 35 infection patients, albumin levels were below 3.5 g/dL, the average BMI was 22 kg/m2, lymphocytes (1,532 cells)/monocytes (545 cells) ratio was 2.4 versus 1, and albumin (3.0 g/dL)/globulin (3.3 g/dL) ratio was 0.9, while in 18 patients albumin levels were over 3.5 g/dL, the average BMI was 22 kg/m2, hemoglobin was 12 g/dL, lymphocytes (1,998 cells)/monocytes (583 cells) ratio was 3 versus 1, and albumin/globulin ratio was 1.4. Thus, in the infection group, approximately 50% of the patients showed poor nutrition and immunosuppression.
It was found that nutritional and immune condition deteriorated gradually to some degree in elderly patients over 60 years of age.
PMCID: PMC4143525  PMID: 25177463
Nutrition; Preoperative; Surgical conditions; Age
21.  Comparison of Nutritional Parameters among Adult and Elderly Hemodialysis Patients 
Aim: The aim of this study was to compare the nutritional biochemical parameters, prealbumin levels, and bioimpedance analysis parameters of adult and elderly hemodialysis (HD) patients.
Methods: This prospective cross-sectional study included 50 adult HD patients (42.0 % female). Nutritional status was assessed by post-dialysis multifrequency bioimpedance analysis (BIA), serum prealbumin and other nutritional biochemical parameters.
Results: Mean age of patients was 57.4±15.1 years (range: 30-83 years) and mean dialysis duration was 68.3 ± 54.5 months (range: 3-240 months). When the patients were divided into two groups according to age of patients (<65 and ≥65), prealbumin (p=0.003), blood urea nitrogen (BUN) (p=0.000), serum creatinine (p=0.013), albumin (p=0.016), protein catabolic rate per normalized body weight (nPCR) (p=0.001), intracellular water (ICW)/total body weight (0.003) , body fat mass (p00.000), lean body mass (p=0.031), lean dry mass (p=0.001), illness marker (p=0.005), basal metabolism (p=0.007), body mass index (BMI) (p=0.028), body fat mass index (BFMI) (p=0.000), fat free mass index (FFMI) (p=0.040) values were significantly different between the groups. In the elderly patients (age ≥65), body fat mass, illness marker, BMI, BFMI were higher compared to adult patients (age <65). Additionally, in the elderly patients, prealbumin, BUN, creatinine, albumin, nPCR, ICW/ total body weight, lean body weight, lean dry weight, basal metabolism and FFMI were lower than adult patients.
Conclusions: Our results indicate that BFMI were higher, albumin, prealbumin, nPCR and lean body mass and FFMI were lower in elderly patients compared to adults. These results imply that elderly HD patients may be prone sarcopenic obesity and may require special nutritional support.
PMCID: PMC3198259  PMID: 22022216
Body composition analysis; bioelectric impedance; lean body mass; intracellular fluid; elderly hemodialysis patients; protein energy malnutrition.
22.  Health Related Quality of Life in HIV-infected and at-risk Women: The Impact of Illicit Drug Use and Hepatitis C on a Community Preference Weighted Measure* 
To assess the impact of illicit drug use and chronic hepatitis C virus (HCV) on health related quality of life (HRQoL) in women with HIV or at-risk for HIV infection.
Cross-sectional analysis of data from the Women's Interagency Health Study (WIHS) of women with HIV (n=2508) and at high risk of HIV infection (n=889) in the US. A Short-Form-6D (SF-6D) HRQoL measure derived from the Medical Outcomes Study–HIV (MOS-HIV) questionnaire, HIV infection status, CD4 cell count (a measure of immune status), antiretroviral treatment, current illicit drug use (heroin and/or cocaine), and HCV status were assessed at a recent study visit. We developed multivariate linear regression models adjusting for age, race/ethnicity, education, and testing for interactions.
HIV-infected women with ≤200 CD4 cells/uL had lower mean HRQoL scores (0.69) than either HIV-infected women with >200 CD4 cells/uL (0.78) or HIV-uninfected women (0.80) (p<0.01). In multivariate analysis, illicit drug use, chronic HCV, and low CD4 count were independently associated with lower HRQoL. There was a differential effect of HCV and illicit drug use for HIV-infected women depending on CD4 cell count: HIV-infected women with >200 CD4 cells/uL had a significantly greater reduction in HRQoL associated with illicit drug use (−0.063) and chronic HCV (−0.036) than women with ≤200 CD4 cells/uL (−0.017, −0.005 respectively).
Poorly-controlled HIV, illicit drug use, and chronic HCV are associated with lower HRQoL. Illicit drug use and chronic HCV have greater HRQoL impacts for HIV-infected women with well-controlled HIV versus those with poorly-controlled HIV, which may affect clinical and policy priorities.
PMCID: PMC3980200  PMID: 24106234
HIV; HRQoL; Opiate Dependence; Health Utility; Illicit Drug use; HCV
23.  Birth Weight and Risk of Adiposity among Adult Inuit in Greenland 
PLoS ONE  2014;9(12):e115976.
The Inuit population in Greenland has undergone rapid socioeconomic and nutritional changes simultaneously with an increasing prevalence of obesity. Therefore, the objective was to examine fetal programming as part of the aetiology of obesity among Inuit in Greenland by investigating the association between birth weight and measures of body composition and fat distribution in adulthood.
The study was based on cross-sectional data from a total of 1,473 adults aged 18–61 years in two population-based surveys conducted in Greenland between 1999–2001 and 2005–2010. Information on birth weight was collected from birth records. Adiposity was assessed by anthropometry, fat mass index (FMI), fat-free mass index (FFMI), and visceral (VAT) and subcutaneous adipose tissue (SAT) estimated by ultrasound. The associations to birth weight were analyzed using linear regression models and quadratic splines. Analyses were stratified by sex, and adjusted for age, birthplace, ancestry and family history of obesity.
Spline analyses showed linear relations between birth weight and adult adiposity. In multiple regression analyses, birth weight was positively associated with BMI, waist circumference, FMI, FFMI and SAT with generally weaker associations among women compared to men. Birth weight was only associated with VAT after additional adjustment for waist circumference and appeared to be specific and inverse for men only.
Higher birth weight among Inuit was associated with adiposity in adulthood. More studies are needed to explore a potential inverse association between birth size and VAT.
PMCID: PMC4281098  PMID: 25551382
24.  Body Composition and Energy Expenditure Predict Ad-Libitum Food and Macronutrient Intake in Humans 
Obesity is the result of chronic positive energy balance. The mechanisms underlying the regulation of energy homeostasis and food intake are not understood. Despite large increases in fat mass (FM), recent evidence indicates that fat-free mass (FFM) rather than FM is positively associated with intake in humans.
In 184 humans (73F/111M; age 34.5±8.8y; % body fat [PFAT] 31.6±8.1%) we investigated the relationship of FFM index (FFMI kg*m2), FM index (FMI kg*m2;), and 24-hour energy expenditure (EE, n=127) with ad-libitum food intake using a 3d vending machine paradigm. Mean daily calories (CAL), and macronutrient intake (PRO, CHO, FAT) were determined and used to calculate the relative caloric contribution of each (%PRO, %CHO, %FAT) and percent of caloric intake over weight maintaining energy needs (%WMEN).
FFMI was positively associated with CAL (p<0.0001), PRO (p=0.0001), CHO (p=0.0075), and FAT (p<0.0001). This remained significant after adjusting for FMI. Total EE predicted CAL and macronutrient intake (all p<0.0001). FMI was positively associated with CAL (p=0.019), PRO (p=0.025) and FAT (p=0.0008). In models with both FFMI and FMI, FMI was negatively associated with CAL (p=0.019) and PRO (p=0.033). Both FFMI and FMI were negatively associated with %CHO and positively associated with %FAT (all p<0.001). EE and FFMI (adjusted for FMI) were positively (EE p=0.0085; FFMI p=0.0018) and FMI negatively (p=0.0018; adjusted for FFMI) associated with %WMEN.
Food and macronutrient intake is predicted by FFMI and to a lesser degree by FMI. FFM and FM may have opposing effects on energy homeostasis.
PMCID: PMC3909024  PMID: 23736368
Body composition; fat-free mass; fat mass; food intake; macronutrient intake
25.  Use of Bioelectrical Impedance Analysis for the Assessment of Nutritional Status in Critically Ill Patients 
Clinical Nutrition Research  2015;4(1):32-40.
Malnutrition is common in the critically ill patients and known to cause a variety of negative clinical outcomes. However, various conventional methods for nutrition assessment have several limitations. We hypothesized that body composition data, as measured using bioelectrical impedance analysis (BIA), may have a significant role in evaluating nutritional status and predicting clinical outcomes in critically ill patients. We gathered clinical, biochemical, and BIA data from 66 critically ill patients admitted to an intensive care unit. Patients were divided into three nutritional status groups according to their serum albumin level and total lymphocyte counts. The BIA results, conventional indicators of nutrition status, and clinical outcomes were compared and analyzed retrospectively. Results showed that the BIA indices including phase angle (PhA), extracellular water (ECW), and ECW/total body water (TBW) were significantly associated with the severity of nutritional status. Particularly, PhA, an indicator of the health of the cell membrane, was higher in the well-nourished patient group, whereas the edema index (ECW/TBW) was higher in the severely malnourished patient group. PhA was positively associated with albumin and ECW/TBW was negatively associated with serum albumin, hemoglobin, and duration of mechanical ventilation. In non-survivors, PhA was significantly lower and both ECW/TBW and %TBW/fat free mass were higher than in survivors. In conclusion, several BIA indexes including PhA and ECW/TBW may be useful for nutritional assessment and represent significant prognostic factors in the care of critically ill patients.
PMCID: PMC4337921  PMID: 25713790
Electric impedance; Critical illness; Intensive care units; Nutrition assessment

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