Intestinal microbiota, microbial translocation, and systemic inflammation in chronic HIV infection.

BACKGROUND: Despite effective antiretroviral therapy (ART), patients with chronic human immunodeficiency virus (HIV) infection have increased microbial translocation and systemic inflammation. Alterations in the intestinal microbiota may play a role in microbial translocation and inflammation. METHODS: We profiled the fecal microbiota by pyrosequencing the gene encoding 16S ribosomal RNA (rRNA) and measured markers of microbial translocation and systemic inflammation in 21 patients who had chronic HIV infection and were receiving suppressive ART (cases) and 16 HIV-uninfected controls. RESULTS: The fecal microbial community composition was significantly different between cases and controls. The relative abundance of Proteobacteria, Gammaproteobacteria, Enterobacteriales, Enterobacteriaceae, Erysipelotrichi, Erysipelotrichales, Erysipelotrichaceae, and Barnesiella was significantly enriched in cases, whereas that of Rikenellaceae and Alistipes was depleted. The plasma soluble CD14 level (sCD14) was significantly higher and the endotoxin core immunoglobulin M (IgM) level lower in cases, compared with controls. There were significant positive correlations between the relative abundances of Enterobacteriales and Enterobacteriaceae and the sCD14 level; the relative abundances of Gammaproteobacteria, Enterobacteriales, and Enterobacteriaceae and the interleukin 1ß (IL-1ß) level; the relative abundances of Enterobacteriales and Enterobacteriaceae and the interferon γ level; and the relative abundances of Erysipelotrichi and Barnesiella and the TNF-α level. There were negative correlations between endotoxin core IgM and IL-1ß levels. CONCLUSIONS: Patients who have chronic HIV infection and are receiving suppressive ART display intestinal dysbiosis associated with increased microbial translocation and significant associations between specific taxa and markers of microbial translocation and systemic inflammation. This was an exploratory study, the findings of which need to be confirmed.

Lipoprotein-associated phospholipase A2, a novel cardiovascular inflammatory marker, in HIV-infected patients.

BACKGROUND: Lipoprotein-associated phospholipase A2 (Lp-PLA2) is an emerging biomarker of cardiovascular disease. This study was conducted to describe the distribution of Lp-PLA2 in a cohort of human immunodeficiency virus (HIV)-infected adults and to determine associations between Lp-PLA2, cardiometabolic risk factors, and subclinical atherosclerosis in this population. METHODS: Lp-PLA2 was assessed in 341 (25% women, 52% white, 74% on highly active antiretroviral therapy [HAART]) participants of a cohort with detailed characterization of atherogenic risk factors, including surrogate markers of carotid and coronary atherosclerosis. RESULTS: Mean Lp-PLA2 mass was 313 ± 105 ng/mL and activity 173 ± 49 nmol/minute/mL. Seventy-five percent of participants had abnormal Lp-PLA2. Those in the highest Framingham Risk Score tertile had significantly higher Lp-PLA2 activity. Participants with abnormal carotid intima-media thickness (cIMT) had higher Lp-PLA2 mass and activity. Those with coronary artery calcium (CAC) scores >100 had significantly higher Lp-PLA2 mass than those with lower or nondetectable calcium. Those on HAART and protease inhibitor (PI)-based treatment had significantly higher Lp-PLA2 mass and activity than those who were treatment-naive or not on PIs. In multivariate regression, HAART and PI use were positively associated with Lp-PLA2 activity and mass after adjusting for age, race, sex, low-density and high-density lipoprotein cholesterol levels, triglyceride level, and smoking. Adding Lp-PLA2 activity tertiles to the model improved the predictive value for abnormal common cIMT, but not internal cIMT or CAC score. CONCLUSIONS: Lp-PLA2 is highly abnormal in HIV-infected patients and is associated with several cardiovascular and HIV treatment-specific risk factors. Lp-PLA2 may be used as an additional and more vascular specific biomarker for cardiovascular risk stratification in HIV-positive patients.

Immune response and intestinal permeability in children with acute gastroenteritis treated with Lactobacillus rhamnosus GG: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Probiotics have a possible role in the treatment of pediatric acute gastroenteritis. We report the effect of the probiotic Lactobacillus rhamnosus GG (LGG) on intestinal function, immune response, and clinical outcomes in Indian children with cryptosporidial or rotavirus diarrhea. METHODS: Children with gastroenteritis aged 6 months to 5 years, testing positive for either rotavirus or Cryptosporidium species in stool (coinfections were excluded), were randomized to LGG (ATCC 53103) or placebo, once daily for 4 weeks. Baseline demographic and clinical details were obtained. Sera were tested for immunoglobulin G (IgG) and immunoglobulin A (IgA) antibodies to Cryptosporidium and rotavirus, and the lactulose to mannitol ratio for intestinal permeability was determined at baseline and at the end of follow-up. RESULTS: Of the 124 children enrolled, 82 and 42 had rotavirus and cryptosporidial diarrhea, respectively. Median diarrheal duration was 4 days; one-third of the children had severe diarrhea. Baseline and clinical parameters were comparable between children receiving LGG and placebo. At the end of follow-up, fewer children with rotavirus diarrhea on LGG had repeated diarrheal episodes (25% vs 46%; P = .048) and impaired intestinal function (48% vs 72%; P = .027). Significant increase in IgG levels postintervention (456 vs 2215 EU; P = .003) was observed in children with rotavirus diarrhea receiving LGG. Among children with cryptosporidial diarrhea, those receiving LGG showed significant improvement in intestinal permeability. CONCLUSIONS: LGG has a positive immunomodulatory effect and may be useful in decreasing repeated episodes of rotavirus diarrhea. Improvement in intestinal function in children with rotavirus and cryptosporidial gastroenteritis emphasizes the role of probiotics in treating intestinal impairment after infection. CLINICAL TRIALS REGISTRATION: CTRI/2010/091/000339.

Urinary eicosanoid metabolites in HIV-infected women with central obesity switching to raltegravir: an analysis from the women, integrase, and fat accumulation trial.

Chronic inflammation is a hallmark of HIV infection. Eicosanoids reflect inflammation, oxidant stress, and vascular health and vary by sex and metabolic parameters. Raltegravir (RAL) is an HIV-1 integrase inhibitor that may have limited metabolic effects. We assessed urinary F2-isoprostanes (F2-IsoPs), prostaglandin E2 (PGE-M), prostacyclin (PGI-M), and thromboxane B2 (TxB2) in HIV-infected women switching to RAL-containing antiretroviral therapy (ART). Thirty-seven women (RAL = 17; PI/NNRTI = 20) with a median age of 43 years and BMI 32 kg/m(2) completed week 24. TxB2 increased in the RAL versus PI/NNRTI arm (+0.09 versus -0.02; P = 0.06). Baseline PGI-M was lower in the RAL arm (P = 0.005); no other between-arm cross-sectional differences were observed. In the PI/NNRTI arm, 24-week visceral adipose tissue change correlated with PGI-M (rho = 0.45; P = 0.04) and TxB2 (rho = 0.44; P = 0.005) changes, with a trend seen for PGE-M (rho = 0.41; P = 0.07). In an adjusted model, age ≥ 50 years (N = 8) was associated with increased PGE-M (P = 0.04). In this randomized trial, a switch to RAL did not significantly affect urinary eicosanoids over 24 weeks. In women continuing PI/NNRTI, increased visceral adipose tissue correlated with increased PGI-M and PGE-M. Older age (≥ 50) was associated with increased PGE-M. Relationships between aging, adiposity, ART, and eicosanoids during HIV-infection require further study.

Pharmacy and self-report adherence measures to predict virological outcomes for patients on free antiretroviral therapy in Tamil Nadu, India.

Over 480,000 individuals receive free antiretroviral therapy (ART) in India yet data associating ART adherence with HIV viral load for populations exclusively receiving free ART are not available. Additionally estimates of adherence using pharmacy data on ART pick-up are not available for any population in India. After 12-months ART we found self-reported estimates of adherence were not associated with HIV viral load. Individuals with <100% adherence using pharmacy data predicted HIV viral load, and estimates combining pharmacy data and self-report were also predictive. Pharmacy adherence measures proved a feasible method to estimate adherence in India and appear more predictive of virological outcomes than self-report. Predictive adherence measures identified in this study warrant further investigation in populations receiving free ART in India to allow for identification of individuals at risk of virological failure and in need of adherence support.

Racial differences in central hemodynamic burden in men with HIV: preliminary findings.

OBJECTIVES: African Americans infected with HIV are almost 3 times more likely to die from cardiovascular disease (CVD) than their White HIV-infected counterparts. The purpose of this study was to examine racial differences in novel measures of vascular function and CVD risk in African American and White men infected with HIV. DESIGN: Our study uses a cross-sectional approach. SETTING: Participants were recruited from the nutrition/infectious disease clinic at a large metropolitan hospital. PARTICIPANTS: African American men (n=21) and White men (n=21) with HIV on stable anti-retroviral therapy were included in this study. MAIN OUTCOME MEASURES: High resolution ultrasound was used to assess brachial artery flow mediated dilation (FMD). Applanation tonometry was used to measure carotid-femoral and carotid-radial pulse wave velocity (PWV), carotid augmentation index (Alx) and carotid-brachial pulse pressure (PP) amplification. Left ventricular (LV) pressure effort was derived from the contour of the central BP waveform. RESULTS: There were no racial differences in brachial FMD (African American: 4.9 +/- 1.1 vs White: 5.4 +/- 1.0%; P>.05) or carotid-femoral PWV (African American: 8.9 +/- .6 vs White: 8.7 +/- .4 m/s; P>.05). African American men with HIV had significantly higher carotid-radial PWV (11.3 +/- .4 vs 9.8 +/- .3 m/s; P<.05), higher carotid Alx (6 +/- 3 vs -1 +/- 2%; P<.05), higher LV pressure effort (2262 +/- 369 vs 1030 +/- 140 dyne sec/cm2; P<.05) and lower PP amplification (1.10 +/- .03 vs 1.24 +/- .03; P<.05) compared to White men with HIV. CONCLUSION: Elevated CVD risk in African American men with HIV may be partially mediated by increased central hemodynamic burden and not endothelial dysfunction or increased aortic stiffness.

Longitudinal Analysis of the Intestinal Microbiota among a Cohort of Children in Rural and Urban Areas of Pakistan.

The profile of the intestinal microbiota is known to be altered in malnourished young children in low- and middle-income countries. However, there are limited studies longitudinally evaluating the intestinal microbiota in malnourished young children in resource-limited settings over the first two years of life. In this longitudinal pilot study, we determined the effect of age, residential location, and intervention on the composition, relative abundance, and diversity of the intestinal microbiota in a representative sample of children under 24 months of age with no diarrhea in the preceding 72 h in the urban and rural areas of Sindh, Pakistan nested within a cluster-randomized trial evaluating the effect of zinc and micronutrients on growth and morbidity (ClinicalTrials.gov Identifier: NCT00705445). The major findings were age-related with significant changes in alpha and beta diversity with increasing age. There was a significant increase in the relative abundance of the Firmicutes and Bacteroidetes phyla and a significant decrease in that of the Actinobacteria and Proteobacteria phyla (p < 0.0001). There were significant increases in the relative abundances of the major genera Bifidobacterium, Escherichia/Shigella and Streptococcus (p < 0.0001), and no significant change in the relative abundance of Lactobacillus. Using the LEfSE algorithm, differentially abundant taxa were identified between children in the first and second years of age, between those residing in rural and urban areas, and those who received different interventions at different ages from 3 to 24 months. The numbers of malnourished (underweight, wasted, stunted) or well-nourished children at each age, in each intervention arm, and at urban or rural sites were too small to determine if there were significant differences in alpha or beta diversity or differentially abundant taxa among them. Further longitudinal studies with larger numbers of well-nourished and malnourished children are required to fully characterize the intestinal microbiota of children in this region.

Pharmacy adherence measures to assess adherence to antiretroviral therapy: review of the literature and implications for treatment monitoring.

Prescription or pill-based methods for estimating adherence to antiretroviral therapy (ART), pharmacy adherence measures (PAMs), are objective estimates calculated from routinely collected pharmacy data. We conducted a literature review to evaluate PAMs, including their association with virological and other clinical outcomes, their efficacy compared with other adherence measures, and factors to consider when selecting a PAM to monitor adherence. PAMs were classified into 3 categories: medication possession ratio (MPR), pill count (PC), and pill pick-up (PPU). Data exist to recommend PAMs over self-reported adherence. PAMs consistently predicted patient outcomes, but additional studies are needed to determine the most predictive PAM parameters. Current evidence suggests that shorter duration of adherence assessment (≤ 6 months) and use of PAMs to predict future outcomes may be less accurate. PAMs which incorporate the number of days for which ART was prescribed without the counting of remnant pills, are reasonable minimum-resource methods to assess adherence to ART.

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.

Metabolic syndrome and subclinical atherosclerosis in patients infected with HIV.

BACKGROUND: The present study examines the association between carotid and coronary atherosclerosis and metabolic syndrome in human immunodeficiency virus (HIV)-infected adults. METHODS: We measured the common and internal carotid intima-media thickness (c-IMT) using B-mode ultrasonography, and we measured coronary artery calcium (CAC) using high-resolution, electrocardiographic, synchronized, computed tomography, for 314 HIV-infected men and women. Metabolic syndrome was defined by National Cholesterol Education Program/Adult Treatment Panel III criteria. We compared the c-IMT measurements and CAC scores of patients with metabolic syndrome with the scores of those without metabolic syndrome using a Wilcoxon test for continuous variables and a chi2 test for categorical variables. To examine the association between surrogate markers and metabolic syndrome, we used logistic regression analysis. RESULTS: Participants with metabolic syndrome were more likely to have a common c-IMT measurement >0.8 mm than were those without metabolic syndrome (17% vs.7%; P=.009), but both groups were equally likely to have an internal c-IMT measurement >1.0 mm (20% vs. 13%; P=.15). Any positive CAC score was more likely to occur for participants with metabolic syndrome (80.3% vs. 46.7%; P<.0001). In a multivariate model adjusted for sex, age, ethnicity, and smoking status, participants with metabolic syndrome were more likely than those without metabolic syndrome to have an abnormal common c-IMT measurement (odds ratio [OR], 2.9; P=.020) and detectable CAC scores (OR, 4.9; P<.0001) but not a higher internal c-IMT measurement (OR, 1.6; P=.255). CONCLUSION: Our study demonstrates that HIV-infected individuals with metabolic syndrome may be at increased risk for subclinical atherosclerosis and supports screening for metabolic syndrome among HIV-infected patients at risk for cardiovascular disease.

Dietary supplement use and nutrient intake in HIV-infected persons.

Dietary supplement use was assessed in 368 HIV-infected patients enrolled in the Nutrition for Healthy Living cohort. The objective was to describe the dietary, demographic, and health characteristics of the HIV-infected persons who use different types of dietary supplements. Each patient was categorized in 1 of 4 dietary supplement groups. Extremes in intake of micronutrients were common. Men and women who consumed no supplements reported inadequate intakes of a number of micronutrients. Men using nonvitamin/nonmineral (NVNM) supplements had diets higher in fiber, protein, and 13 of 14 vitamins and minerals. Almost 90% of male NVNM supplement users ingested 1 or more vitamins or minerals in amounts above the tolerable upper limit. Male NVNM supplement users were more likely to be white, well educated, and receiving highly active antiretroviral therapy and more likely to have higher annual incomes, higher CD4 counts, and lower HIV RNA levels. HIV-infected women who were using NVNM supplements exhibited similar trends. Micronutrient inadequacy and excess are relatively common in persons living with HIV infection. Practitioners need to judiciously address optimal nutrient intake from both diet and dietary supplements in this population.

Neurodevelopment: The Impact of Nutrition and Inflammation During Preconception and Pregnancy in Low-Resource Settings.

The rapid pace of fetal development by far exceeds any other stage of the life span, and thus, environmental influences can profoundly alter the developmental course. Stress during the prenatal period, including malnutrition and inflammation, impact maternal and fetal neurodevelopment with long-term consequences for physical and mental health of both the mother and her child. One primary consequence of maternal malnutrition, inflammation, and other sources of prenatal stress is a poor birth outcome, such as prematurity or growth restriction. These phenotypes are often used as indications of prenatal adversity. In fact, the original evidence supporting the fetal programming hypothesis came from studies documenting an association between birth phenotype and the development of subsequent physical and mental health problems. Fetal growth restriction in both term and preterm infants is associated with neonatal morbidities and a wide variety of behavioral and psychological diagnoses in childhood and adolescence, including attention-deficit/hyperactivity disorder, anxiety, depression, internalizing and thought problems, poor social skills, and autism spectrum disorder. Improving maternal-child health requires interventions that begin before pregnancy and continue throughout gestation and into the postpartum period. Such interventions might include supporting pregnancy intention, maternal nutrition, health/medical care, mental health, and providing social support. This article discusses the impact of maternal nutrition and inflammation during preconception and pregnancy among women living in low-resource settings, with an emphasis on key knowledge gaps that need to be addressed to guide program and policy decisions at local, regional and global levels.

Risk of cardiovascular disease in a cohort of HIV-infected adults: a study using carotid intima-media thickness and coronary artery calcium score.

BACKGROUND: There is concern that human immunodeficiency virus (HIV) infection and the use of highly active antiretroviral therapy lead to accelerated atherosclerosis and increased risk of cardiovascular disease. We measured 2 surrogate markers of subclinical atherosclerosis, carotid intima-media thickness (c-IMT) and coronary artery calcium (CAC) scores, in HIV-infected adults. METHODS: A cross-sectional analysis of 242 men and 85 women with HIV infection was used. Carotid ultrasonography and coronary computed tomography were performed, and their associations with cardiovascular risk factors were examined. RESULTS: Among men, the mean (+/- standard deviation [SD]) common c-IMT was 0.62+/-0.2 mm, the mean (+/-SD) internal c-IMT was 0.76+/-0.5 mm, and 136 patients (56.1%) had detectable CAC. Among women, the mean (+/-SD) common c-IMT was 0.59+/-0.2 mm, the mean (+/-SD) internal c-IMT was 0.66+/-0.4 mm, and 40 patients (47.1%) had detectable CAC. Neither the c-IMT nor the CAC score differed by antiretroviral therapy class or individual medications for either sex. For men, age and waist circumference independently predicted common c-IMT; age, systolic blood pressure, and high-sensitivity C-reactive protein level independently predicted internal c-IMT; and age, apolipoprotein B level, and high-sensitivity C-reactive protein level independently predicted CAC score. For women, age and body mass index independently predicted common c-IMT; age independently predicted internal c-IMT; and age and glucose level independently predicted CAC score. CONCLUSIONS: Our participants had more abnormal surrogate markers than expected at a relatively young age, but those were not associated with use of highly active antiretroviral therapy or protease inhibitors. At present, the positive associations were primarily with traditional and novel cardiovascular risk factors. Some HIV-specific (not treatment-specific) factors were observed; they may become more evident with prolonged HIV infection and treatment.

Dietary glycemic index of human immunodeficiency virus-positive men with and without fat deposition.

This study focused on dietary glycemic index because insulin resistance can be important in the pathogenesis of fat deposition in human immunodeficiency virus (HIV). We evaluated differences in past dietary glycemic intake between men with HIV who developed fat deposition and those who did not. This was a nested case-control study consisting of 37 cases and 37 controls from the Nutrition for Healthy Living cohort. Food records from 6 to 24 months prior to development of fat deposition in cases were analyzed and compared with controls. Cases were defined as men with a waist-to-hip ratio >0.95 and body mass index (calculated as kg/m(2)) between 23 and 26. Controls were matched by age, race, body mass index, highly active antiretroviral therapy use, and CD4 count. Food records were analyzed using t tests for normally distributed nutrients and Wilcoxon rank-sum tests for nutrients with skewed distributions. Glycemic index was calculated for each meal and day. There was no significant difference in glycemic index for meals and day between participants with or without fat deposition. Both groups had a moderate dietary glycemic index intake. This study showed no association between dietary glycemic index and development of fat deposition in HIV. Instead, results of this study depict the potential benefits associated with eating high-quality diets, primarily adequate fiber and protein intake. Diet can be important in preventing development of fat deposition in patients with HIV.

Longitudinal Analysis of the Intestinal Microbiota in Persistently Stunted Young Children in South India.

Stunting or reduced linear growth is very prevalent in low-income countries. Recent studies have demonstrated a causal relationship between alterations in the gut microbiome and moderate or severe acute malnutrition in children in these countries. However, there have been no primary longitudinal studies comparing the intestinal microbiota of persistently stunted children to that of non-stunted children in the same community. In this pilot study, we characterized gut microbial community composition and diversity of the fecal microbiota of 10 children with low birth weight and persistent stunting (cases) and 10 children with normal birth weight and no stunting (controls) from a birth cohort every 3 months up to 2 years of age in a slum community in south India. There was an increase in diversity indices (P <0.0001) with increasing age in all children. However, there were no differences in diversity indices or in the rates of their increase with increasing age between cases and controls. The percent relative abundance of the Bacteroidetes phylum was higher in stunted compared to control children at 12 months of age (P = 0.043). There was an increase in the relative abundance of this phylum with increasing age in all children (P = 0.0380) with no difference in the rate of increase between cases and controls. There was a decrease in the relative abundance of Proteobacteria (P = 0.0004) and Actinobacteria (P = 0.0489) with increasing age in cases. The microbiota of control children was enriched in probiotic species Bifidobacterium longum and Lactobacillus mucosae, whereas that of stunted children was enriched in inflammogenic taxa including those in the Desulfovibrio genus and Campylobacterales order. Larger, longitudinal studies on the compositional and functional maturation of the microbiome in children are needed.

Understanding the role of HIV load in determining weight change in the era of highly active antiretroviral therapy.

BACKGROUND: In this prospective cohort study, we determined the relationship between human immunodeficiency virus (HIV) RNA load and body weight in patients with HIV infection. METHODS: Repeated-measures analysis was restricted to patients with >or=2 study visits, 4-9-month intervals between study visits, and complete data on virus load, resting energy expenditure (REE), and highly active antiretroviral therapy (HAART). The outcome was change in body weight across study intervals. The main predictor was virus load. Separate analyses were performed for weight change in patients receiving and patients not receiving HAART. RESULTS: The eligible sample consisted of 318 participants associated with 1886 study intervals. Sixty-one patients (19%) were women, and 173 (54%) were undergoing HAART at the time of enrollment. There was a significant interaction (P=.01) between virus load and HAART use. In the absence of HAART, each log(10) increase in virus load was associated with a 0.92-kg decrease in body weight (P=.003), but during HAART, virus load was not significantly associated with weight change. During HAART, a CD4(+) cell count decrease of 100 cells/mm(3), rather than a change in the virus load, was associated with a 0.35-kg decrease in body weight (P<.001). REE was independently associated with weight change in both models (P<.001). CONCLUSIONS: Patients with HIV infection who are losing weight and are not taking HAART should be considered for HAART. Patients who are already receiving HAART and have unsuppressed virus loads may benefit virologically from an intensified regimen, because such a regimen may lead to complete suppression if there is an accompanying increase in CD4(+) cell counts. Further research is needed to understand the strong independent effect of changes in REE among patients receiving and patients not receiving HAART.

Predicting CD4 count using total lymphocyte count: a sustainable tool for clinical decisions during HAART use.

Understanding the total lymphocyte count (TLC)-CD4 count relationship could aide design predictive instruments for making clinical decisions during antiretroviral therapy, especially in underserved resource-poor settings. We performed multiple regression analyses to assess the prediction of CD4 count using TLC on 771 participants with 4,836 visits. In linear and logistic regression TLC, hemoglobin, gender, history of AIDS, and weight predicted CD4 count and CD4 < 200, respectively, before and after highly active antiretroviral therapy (HAART) use. On HAART, the adjusted odds ratios (OR) for TLC < 1500 (optimal TLC cutoff) were 5.1 (95%CI 4.0, 6.5; P < 0.001), and off HAART, 4.6 (95%CI 3.4, 6.2: P < 0.001) with high predictive power. TLC predicts CD4 count and CD4 < 200 cells/microL well during HAART. Including the additional factors improves performance. TLC is simple and inexpensive and can be used in many ways to develop clinical decision-making tools in underserved resource-poor settings during HAART therapy.

Body composition in adults infected with human immunodeficiency virus in Khon Kaen, Thailand.

A cross-sectional study of 77 patients infected with human immunodeficiency virus (HIV) in Khon Kaen, Thailand examined association of nutritional status with active opportunistic infections (AOIs)/HIV status and assessed degree of correlation between bioelectrical impedance analysis (BIA) and anthropometry. Many patients (41.3%) were malnourished using World Health Organization criteria for underweight, and malnutrition was associated with AOI status. Unconditional odds ratios (P < 0.05) for AOI as opposed to no AOI were 4.57 for underweight, 9.87 for severe underweight, 2.55 for triceps < 10th percentile, and 5.22 for mid-arm circumference < 10th percentile. Body fat composition from BIA, anthropometry, and body mass index were moderate to highly correlated (P < 0.001), with the highest correlation between BIA and subscapular skinfold (r = 0.86) and the lowest between BIA and triceps skinfold (r = 0.54). Insights were gained about relative value of using various measurements to assess nutritional status of HIV-infected populations.

Nutrition assessment, counseling, and support interventions to improve health-related outcomes in people living with HIV/AIDS: a systematic review of the literature.

BACKGROUND: Although numerous studies have shown that severe to moderate wasting at the time of antiretroviral therapy initiation is strongly predictive of mortality, it remains unclear whether nutritional interventions at or before antiretroviral therapy initiation will improve outcomes. This review examines data on nutrition assessment, counseling, and support interventions in resource-limited settings. METHODS: We identified articles published between 2005 and 2014 on the effectiveness of nutrition assessment, counseling, and support interventions, particularly its impact on 5 outcomes: mortality, morbidity, retention in care, quality of life, and/or prevention of ongoing HIV transmission. We rated the overall quality of individual articles and summarized the body of evidence and expected impact for each outcome. RESULTS: Twenty-one articles met all inclusion criteria. The overall quality of evidence was weak, predominantly because of few studies being designed to directly address the question of interest. Only 2 studies were randomized trials with no food support control groups. The remainder were randomized studies of one type of food support versus another, cohort (nonrandomized) studies, or single-arm studies. Ratings of individual study quality ranged from "medium" to "weak," and the quality of the overall body of evidence ranged from "fair" to "poor." We rated the expected impact on all outcomes as "uncertain." CONCLUSIONS: Rigorous better designed studies in resource-limited settings are urgently needed to understand the effectiveness of nutrition assessment and counseling alone, as well as studies to understand better modalities of food support (targeting, timing, composition, form, and duration) to improve both short- and long-term patient retention in care and treatment, and clinical outcomes.