Relationship of Diet to Gut Microbiota and Inflammatory Biomarkers in People with HIV

While changes in microbiome composition have been associated with HIV, the effect of diet and its potential impact on inflammation remains unclear. Methods: Twenty-seven people living with HIV (PWH) on antiretroviral therapy (ART) were studied. A comprehensive dietary analysis was performed and two types of dietary patterns were determined. We explored the associations of each dietary pattern with gut microbiota and plasma inflammatory biomarkers. Results: We appreciated two dietary patterns, Mediterranean-like (MEL) and one Western-like (WEL). Compared to participants with the WEL pattern, participants with MEL pattern showed higher abundance of Lachnospira (p-value = 0.02) and lower levels of the inflammatory biomarkers D-dimer (p-value = 0.050) and soluble TNF-alpha receptor 2 (sTNFR2) (p-value = 0.049). Men who have sex with men (MSM) with MEL pattern had lower abundance of Erysipelotrichaceae (p-value < 0.001) and lower levels of D-dimer (p-value = 0.026) than MSM with WEL pattern. Conclusion: MEL pattern favours Lachnospira abundance, and protects against Erysipelotrichaceae abundance and higher levels of the inflammatory biomarkers D-dimer and sTNFR2, precursors of inflammatory processes in HIV-infected patients. Our study contributes to understanding the determinants of a healthier diet and its connections with gut microbiota and inflammation.     

The inflammatory status of old age can be nurtured from the intestinal environment

PURPOSE OF REVIEW: Recent studies suggest an association between inflammation status and the presence of chronic disease in the elderly. The review examines publications that address the low level of chronic inflammation and emphasizes how an altered host-microbiota interaction at the gut level could contribute to maintaining a low systemic inflammatory status in the elderly. RECENT FINDINGS: The first population cross-sectional studies with relevant numbers of healthy elderlies show age-related global changes in gut microbiota with a consistent increase in nonpathogenic Gram-negative mainly Enterobacteria and country-specific changes in bifidobacteria. Noninvasive methods have permitted us to detect subclinical intestinal inflammation in the elderly population. Furthermore, few studies report on immune and/or inflammatory response; however, prebiotics, probiotics or synbiotics might improve the inflammatory condition of the elderly. SUMMARY: A better understanding of the mechanisms of host-gut microbiota cross-talk would significantly help in the design of novel nutritional strategies targeting immune reactivity at the mucosal level.     

Effect of probiotic bacteria on microbial host defense, growth, and immune function in human immunodeficiency virus type-1 infection

The hypothesis that probiotic administration protects the gut surface and could delay progression of Human Immunodeficiency Virus type1 (HIV-1) infection to the Acquired Immunodeficiency Syndrome (AIDS) was proposed in 1995. Over the last five years, new studies have clarified the significance of HIV-1 infection of the gut associated lymphoid tissue (GALT) for subsequent alterations in the microflora and breakdown of the gut mucosal barrier leading to pathogenesis and development of AIDS. Current studies show that loss of gut CD4+ Th17 cells, which differentiate in response to normal microflora, occurs early in HIV-1 disease. Microbial translocation and suppression of the T regulatory (Treg) cell response is associated with chronic immune activation and inflammation. Combinations of probiotic bacteria which upregulate Treg activation have shown promise in suppressing pro inflammatory immune response in models of autoimmunity including inflammatory bowel disease and provide a rationale for use of probiotics in HIV-1/AIDS. Disturbance of the microbiota early in HIV-1 infection leads to greater dominance of potential pathogens, reducing levels of bifidobacteria and lactobacillus species and increasing mucosal inflammation. The interaction of chronic or recurrent infections, and immune activation contributes to nutritional deficiencies that have lasting consequences especially in the HIV-1 infected child. While effective anti-retroviral therapy (ART) has enhanced survival, wasting is still an independent predictor of survival and a major presenting symptom. Congenital exposure to HIV-1 is a risk factor for growth delay in both infected and non-infected infants. Nutritional intervention after 6 months of age appears to be largely ineffective. A meta analysis of randomized, controlled clinical trials of infant formulae supplemented with Bifidobacterium lactis showed that weight gain was significantly greater in infants who received B. lactis compared to formula alone. Pilot studies have shown that probiotic bacteria given as a supplement have improved growth and protected against loss of CD4+ T cells. The recognition that normal bacterial flora prime neonatal immune response and that abnormal flora have a profound impact on metabolism has generated insight into potential mechanisms of gut dysfunction in many settings including HIV-1 infection. As discussed here, current and emerging studies support the concept that probiotic bacteria can provide specific benefit in HIV-1 infection. Probiotic bacteria have proven active against bacterial vaginosis in HIV-1 positive women and have enhanced growth in infants with congenital HIV-1 infection. Probiotic bacteria may stabilize CD4+ T cell numbers in HIV-1 infected children and are likely to have protective effects against inflammation and chronic immune activation of the gastrointestinal immune system.     

Effect of zinc and vitamin A supplementation on antibody responses to a pneumococcal conjugate vaccine in HIV-positive injection drug users: a randomized trial

HIV-infected individuals have impaired immune responses to vaccines and high rates of pneumococcal disease. The effect of vitamin A and zinc supplementation on the immunogenicity of a 7-valent pneumococcal CRM-197 conjugate vaccine (PC-7) was evaluated in 118 HIV+ injection drug users. Subjects were randomized to oral 400,000 IU vitamin A, 300 mg zinc, vitamin A + zinc, or placebo, then immunized. Geometric mean titer increased 1.3-3.3-fold for all pneumococcal serotypes. PC-7 elicited an immune response in HIV-infected adults but neither vitamin A nor zinc altered the immunogenicity of the evaluated vaccines.     

Impact of Maternal Nutritional Supplementation during Pregnancy and Lactation on the Infant Gut or Breastmilk Microbiota: A Systematic Review

Recent evidence indicates that maternal dietary intake, including dietary supplements, during pregnancy and lactation may alter the infant gut or breastmilk microbiota, with implications for health outcomes in both the mother and infant. To review the effects of maternal nutritional supplementation during pregnancy and lactation on the infant gut or breastmilk microbiota a systematic literature search was conducted. A total of 967 studies published until February 2020 were found, 31 were eligible and 29 randomized control trials were included in the qualitative synthesis. There were 23 studies that investigated the effects of probiotic supplementation, with the remaining studies investigating vitamin D, prebiotics or lipid-based nutrient supplements (LNS). The effects of maternal nutritional supplementation on the infant gut microbiota or breastmilk microbiota were examined in 21 and 12 studies, respectively. Maternal probiotic supplementation during pregnancy and lactation generally resulted in the probiotic colonization of the infant gut microbiota, and although most studies also reported alterations in the infant gut bacterial loads, there was limited evidence of effects on bacterial diversity. The data available show that maternal probiotic supplementation during pregnancy or lactation results in probiotic colonization of the breastmilk microbiota. There were no observed effects between probiotic supplementation and breastmilk bacterial counts of healthy women, however, administration of Lactobacillus probiotic to nursing women affected by mastitis was associated with significant reductions in breastmilk Staphylococcal loads. Maternal LNS supplementation during pregnancy and lactation increased bacterial diversity in the infant gut, whilst vitamin D and prebiotic supplementation did not alter either infant gut bacterial diversity or counts. Heterogeneity in study design precludes any firm conclusions on the effects of maternal nutritional supplementation during pregnancy and lactation on the infant gut or breastmilk microbiota, warranting further research.     

Effects of galactooligosaccharide and long-chain fructooligosaccharide supplementation during pregnancy on maternal and neonatal microbiota and immunity--a randomized, double-blind, placebo-controlled study

BACKGROUND: Galactooligosaccharides (GOS) and long-chain fructooligosaccharides (lcFOS) proliferate bifidobacteria in infant gut microbiota. However, it is not known how GOS and FOS influence the microbiota of pregnant women and whether a potential prebiotic effect is transferred to the offspring. OBJECTIVES: We aimed to test how supplementation with GOS and lcFOS (GOS/lcFOS) in the last trimester of pregnancy affects maternal and neonatal gut microbiota. Variables of fetal immunity were assessed as a secondary outcome. DESIGN: In a randomized, double-blind, placebo-controlled pilot study, 48 pregnant women were supplemented 3 times/d with 3 g GOS/lcFOS (at a ratio of 9:1) or maltodextrin (placebo) from week 25 of gestation until delivery. Percentages of bifidobacteria and lactobacilli within total bacterial counts were detected by fluorescent in situ hybridization and quantitative polymerase chain reaction in maternal and neonatal (days 5, 20, and approximately 182) stool samples. Variables of fetal immunity were assessed in cord blood by using flow cytometry and cytokine multiplex-array analysis. RESULTS: The proportions of bifidobacteria in the maternal gut were significantly higher in the supplemented group than in the placebo group (21.0% and 12.4%, respectively; P = 0.026); the proportion of lactobacilli did not differ between the groups. In neonates, bifidobacteria and lactobacilli percentages, diversity and similarity indexes, and fetal immune parameters did not differ significantly between the 2 groups. Mother-neonate similarity indexes of bifidobacteria decreased over time. CONCLUSIONS: GOS/lcFOS supplementation has a bifidogenic effect on maternal gut microbiota that is not transferred to neonates. The increased maternal bifidobacteria did not affect fetal immunity as measured by a comprehensive examination of cord blood immunity variables.     

Potential Role of Probiotics for Inflammaging: A Narrative Review

Background and aims: Inflammaging, a chronic, low-grade inflammation (LGI), is one of the mechanisms of adaptation of an organism to aging. Alterations in the composition of gut microbiota and gut permeability are among the main sources of LGI. They may be modulated by supplementation with live microorganisms, i.e. probiotics. This narrative review was performed with the aim to critically examine the current evidence from randomized clinical trials (RCTs) on the effects of probiotics on pro-inflammatory and anti-inflammatory cytokines and C-reactive protein (CRP) in healthy older subjects. Methodology: RCTs on the effects of probiotics on inflammatory parameters in subjects older than 65 years published in English and Italian from 1990 to October 2020 were searched in PubMed. Studies that were not RCTs, those using probiotics together with prebiotics (synbiotics), and studies performed in subjects with acute or chronic diseases were excluded. The findings of RCTs were reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Results: A total of nine RCTs met the eligibility criteria and were included in this narrative review. Four articles reported that probiotic supplementation significantly affected inflammatory parameters, respectively, by reducing TGF-β1 concentrations, IL-8, increasing IL-5 and Il-10, and IFN-γ and IL-12. Conclusions: Based on this narrative review, probiotic supplementation showed a limited effect on inflammatory markers in healthy individuals older than 65 years. Besides being few, the studies analyzed have methodological limitations, are heterogeneous, and provide results which are incomparable.     

Effects of Probiotic Mixture Supplementation on the Immune Response to the 13-Valent Pneumococcal Conjugate Vaccine in People Living with HIV

Background: In people living with HIV, combination antiretroviral therapy (cART) reduces the risk of death, but the persistent immune-deficient state predisposes them to pneumococcal infections. Current guidelines encourage administering pneumococcal vaccine Prevenar 13 to patients living with HIV. Since probiotic supplementation could act as adjuvants and improve vaccine immunogenicity by modulating gut microbiota, the present study aimed to assess whether the effect of a formulation containing a combination of specific probiotics (Vivomixx^®) could improve the immune response to 13-valent pneumococcal conjugate vaccine (PCV13) in adult people living with HIV. Methods: Thirty patients who were clinically stable and virologically suppressed, without opportunistic infections during this time and no ART changes in the 12 months before the study started were enrolled. Patients were divided into two groups: (1) received a placebo dose and (2) received Vivomixx^® (1800 billion CFU) for four weeks before and after the vaccination with a single dose of PCV13. Results: Vivomixx^® supplementation induced a better response to PCV13 immunization, as shown by greater change in anti-Pn CPS13 IgG and increase in salivary IgA, IL-10 and IL-8. Conclusions: Additional investigations will help to clearly and fully elucidate the optimal strains, doses, and timing of administration of probiotics to improve protection upon vaccination in immunocompromised individuals and the elderly.     

Comprehensive Safety Monitoring of 12‐Month Daily 7000‐IU Vitamin D3 Supplementation in Human Immunodeficiency Virus–Infected Children and Young Adults

Background: There is uncertainty whether long‐term daily dosing with vitamin D₃ (cholecalciferol) supplementation (vitD₃) above the 4000‐IU/d dietary reference intake upper tolerable limit in children and adults is safe. As part of a randomized placebo‐controlled trial, we determined if supplementation with 7000‐IU/d vitD₃ for 12 months in human immunodeficiency virus (HIV)–Infected subjects was safe and/or associated with metabolic outcomes. Material and Methods: A total of 58 HIV‐infected subjects—aged 9–24.9 years and stratified by mode of HIV acquisition (perinatal or behavioral)—were recruited, randomized to 7000‐IU/d vitD₃ or placebo, and followed at 3, 6, and 12 months with physical examinations, blood and urine sampling for measures of 25(OH)D (serum 25‐hydroxyvitamin D), metabolic status, safety measures, and HIV immune status. Safety was defined by a low incidence (<5%) of the study‐defined serious adverse events—that is, elevated serum calcium plus 25(OH)D >160 ng/mL—and no changes in hematologic, liver, renal, metabolic, lipid, or inflammatory status. Results: Randomization groups did not differ in demographic characteristics, vitamin D status, or HIV disease status at baseline. Over the 12 months, serum 25(OH)D increased with supplementation. No subject experienced a serious adverse safety event; none had 25(OH)D >80 ng/mL at any time. There were no clinically significant changes in hematologic, liver, renal, metabolic, lipid, or inflammatory status. Conclusions: Safety of daily 7000‐IU vitD₃ supplementation in children and young adults with HIV was comprehensively monitored over 12 months. High‐dose daily vitD₃ supplementation was efficacious in improving vitamin D status, and there were no safety events.     

Study Protocol for a Randomised Controlled Trial Investigating the Effects of Maternal Prebiotic Fibre Dietary Supplementation from Mid-Pregnancy to Six Months’ Post-Partum on Child Allergic Disease Outcomes

Infant allergy is the most common early manifestation of an increasing propensity for inflammation and immune dysregulation in modern environments. Refined low-fibre diets are a major risk for inflammatory diseases through adverse effects on the composition and function of gut microbiota. This has focused attention on the potential of prebiotic dietary fibres to favourably change gut microbiota, for local and systemic anti-inflammatory effects. In pregnancy, the immunomodulatory effects of prebiotics may also have benefits for the developing fetal immune system, and provide a potential dietary strategy to reduce the risk of allergic disease. Here, we present the study protocol for a double-blinded, randomised controlled trial investigating the effects of maternal prebiotics supplementation on child allergic disease outcomes. Eligible pregnant women have infants with a first-degree relative with a history of medically diagnosed allergic disease. Consented women are randomised to consume either prebiotics (galacto-oligosaccharides and fructo-oligosaccharides) or placebo (maltodextrin) powder daily from 18–20 weeks’ gestation to six months’ post-partum. The target sample size is 652 women. The primary outcome is infant medically diagnosed eczema; secondary outcomes include allergen sensitisation, food allergies and recurrent wheeze. Breast milk, stool and blood samples are collected at multiple timepoints for further analysis.     

Effects of a Low Dose of Fish Oil on Inflammatory Markers of Brazilian HIV-Infected Adults on Antiretroviral Therapy: A Randomized,Parallel, Placebo-Controlled Trial

Background: The benefits of antiretroviral therapy for HIV-infected subjects have been limited by an increased risk of metabolic and cardiovascular diseases. The objective of this study was to assess the effects of a low dose of marine omega-3 fatty acids on inflammatory marker concentrations in HIV-infected subjects under antiretroviral therapy (ART). Methods: This was a randomized, parallel, placebo-controlled trial that investigated the effects of 3 g fish oil/day (540 mg of eicosapentaenoic acid—EPA plus 360 mg of docosahexaenoic acid—DHA) or 3 g soy oil/day (placebo) for 24 weeks in 83 male and non-pregnant female HIV-infected adults on ART. Results: There were no differences between groups for the measures at baseline. Multilevel analyses revealed no statistically significant relationship between the longitudinal changes in high sensitivity-C reactive protein (hs-CRP) (Wald Chi2 = 0.17, p = 0.918), fibrinogen (Wald Chi2 = 3.82, p = 0.148), and factor VIII (Wald Chi2 = 5.25, p = 0.073) with fish oil. No significant changes in interleukin-6 (IL6), interleukin-1 beta (IL1-beta) and tumor necrosis factor-alpha (TNF-alpha) serum concentrations were observed with fish oil supplements for 12 weeks. Conclusions: Compared to placebo, a low dose of 900 mg omega-3 fatty acids (EPA plus DHA) in fish oil capsules did not change hs-CRP, fibrinogen, factor VIII, IL6, IL1-beta and TNF-alpha serum concentrations in HIV-infected subjects on ART. Further investigations should consider the assessment of more sensitive inflammatory markers or higher doses to evaluate the effects of marine omega-3 fatty acids in this population. Registered at the Nederlands Trial Register, Identifier no. NTR1798.     

Micronutrients and vertical transmission of HIV-1

ABSTRACT Vertical transmission of HIV from mother to infant can occur during pregnancy, at the time of delivery, or post-natally through breast-feeding and is a major factor in the continuing spread of HIV infection. Inadequate nutritional status may increase the risk of vertical HIV transmission by influencing mater-nal and child factors for transmission. The potential effects on these factors include impaired systemic immune function in pregnant women, fetuses, and children; an increased rate of clinical, immunologic, and virologic disease progression; impaired epithelial integrity of the placenta and genital tract; increased viral shedding in breast milk from inflammation of breast tissue; increased risk of low birth weight and preterm birth; and impaired gastrointestinal immune function and integrity in fetuses and children. Micronutrient deficiencies are prevalent in many HIV-infected populations, and numerous studies have reported that these deficiencies impair immune responses, weaken epithelial integrity, and are associated with accelerated HIV disease progression. Although low serum vitamin A concentrations were shown to be associated with an increased risk of vertical HIV transmission in prospective cohort studies, randomized, placebo-controlled trials have reported that vitamin A and other vitamin supplements do not appear to have an effect on HIV transmission during pregnancy or the intrapartum period. However, the ability of prenatal and postpartum micronutrient supplements to reduce transmission during the breast-feeding period is still unknown.     

A pilot study of the safety and efficacy of supplemental arginine to enhance immune function in persons with HIV/AIDS

OBJECTIVE: We collected preliminary data on the safety and efficacy of supplemental arginine to improve natural killer cell cytotoxicity in a sample of persons with human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS). METHODS: In a randomized, double-blind, placebo-controlled pilot study in an academic medical center-based infectious disease clinic, 11 clinically stable, HIV-infected adults had been treated with highly active, antiretroviral therapy and had HIV plasma RNA levels of less than 10 000 copies/mL. Participants were randomly assigned to receive 19.6 g of arginine/d (n = 6) or placebo (n = 5) for 14 d. Plasma HIV RNA levels, neuropsychologic functioning, and self-reported adverse events were analyzed for safety of treatment. Efficacy was measured by natural killer cell cytotoxicity. RESULTS: None of the participants experienced any adverse clinical, virologic, or neuropsychologic events that necessitated withdrawal from the study. The arginine-supplemented group showed a mean natural killer cell cytotoxicity increase of 18.9 lytic units, whereas the placebo group showed an increase of 0.3 lytic units. This difference was not statistically significant (P = 0.79). CONCLUSIONS: Short-term arginine supplementation is safe for persons with HIV/AIDS. Additional studies with larger samples and longer periods are warranted to determine the effects of arginine supplementation on other indices of immune function and on clinical outcomes such as intercurrent illnesses.     

Optimizing paediatric HIV care in Kenya: challenges in early infant diagnosis

PROBLEM: In 2003, the goal of the Kenyan Ministry of Health was to avail antiretroviral treatment (ART) to 50% of the estimated 250 000 eligible individuals by the end of 2005. By July 2005, 45 000 adults and more than 2000 children were on treatment. A study was conducted to determine the barriers to identification of HIV-infected children. APPROACH: Existing government policies were reviewed and the ART register of the Kenya National AIDS Control Programme was used to identify facilities providing ART. This paper reports the findings around diagnosis and staging of HIV infection in children. LOCAL SETTING: At the time of the study, 58 health facilities were providing ART to children. Only one institution had achieved universal HIV testing in the antenatal clinics. Six facilities systematically followed up HIV-exposed children. HIV antibody testing was not readily available to the children. Although four research centres were capable of carrying out diagnostic HIV polymerase chain reaction (PCR), the services were restricted to research purposes. Other constraints were inadequate physical infrastructure, inadequate systems for quality control in the laboratories and shortage of staff. LESSONS LEARNT: The policy framework to support identification of HIV-infected children had been established, albeit with narrow focus on sick children. The assessment identified the weaknesses in the structures for systematic diagnosis of HIV through laboratory or clinical-based algorithms. The researchers concluded that health staff training and implementation of a systematic standard approach to identification of HIV-infected children is urgently required.     

Impairment of nutritional,educational status and quality of life among children infected with and belonging to families affected by human immunodeficiency virus/acquired immune deficiency syndrome

The human immunodeficiency virus (HIV) epidemic has ramified impact on family members of people living with the disease, especially in vulnerable groups such as children, which has been neglected while addressing the overt burden in infected individuals. The objectives of this study were to evaluate the impact of HIV on the nutritional and educational status in HIV-infected and -affected children and to compare quality of life (QoL) in these children with controls. A cross-sectional controlled study was conducted among children aged 5–11 years. HIV-infected children and children accompanying parents seeking treatment in an antiretroviral treatment (ART) centre were sampled. Controls were obtained from the field practice area of a teaching hospital. A semi-structured questionnaire and anthropometric measures were used to evaluate the impact on the nutritional and educational status. The General Health Assessment for Children (GHAC) instrument was used to measure QoL. Thirty-eight infected children, 149 children living with family members infected with HIV and 200 controls were sampled. The mean age was 8.55 ± 1.78, with 203 male children and 184 female children. The mean nutritional Z-scores were impacted in the affected and infected groups and significant differences were obtained on the domains of educational status on a proportions test. Most QoL domains were affected and the significance was retained in multivariate regression analysis after controlling for sociodemographic factors. HIV-infected and -affected children have poorer outcome on nutritional and educational indicators with impaired QoL. Identifying and defining vulnerability in these children can help mitigate the wider impact of HIV.     

Effects of Synbiotic Supplementation on Chronic Inflammation and the Gut Microbiota in Obese Patients with Type 2 Diabetes Mellitus: A Randomized Controlled Study

The aim of this study was to investigate the effects of 24-week synbiotic supplementation on chronic inflammation and the gut microbiota in obese patients with type 2 diabetes. We randomized 88 obese patients with type 2 diabetes to one of two groups for 24 weeks: control or synbiotic (Lacticaseibacillus paracasei strain Shirota (previously Lactobacillus casei strain Shirota) and Bifidobacterium breve strain Yakult, and galactooligosaccharides). The primary endpoint was the change in interleukin-6 from baseline to 24 weeks. Secondary endpoints were evaluation of the gut microbiota in feces and blood, fecal organic acids, high-sensitivity C-reactive protein, lipopolysaccharide-binding protein, and glycemic control. Synbiotic administration for 24 weeks did not significantly affect changes in interleukin-6 from baseline to 24 weeks (0.35 ± 1.99 vs. −0.24 ± 1.75 pg/mL, respectively). Relative to baseline, however, at 24 weeks after synbiotic administration there were positive changes in the counts of Bifidobacterium and total lactobacilli, the relative abundances of Bifidobacterium species such as Bifidobacterium adolescentis and Bifidobacterium pseudocatenulatum, and the concentrations of acetic and butyric acids in feces. No significant changes in inflammatory markers were found in the synbiotic group compared to the control group. However, synbiotic administration at least partially improved the gut environment in obese patients with type 2 diabetes.     

Diet–Microbiota Interactions in Inflammatory Bowel Disease

Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gastrointestinal tract. Although the precise etiology of IBD is largely unknown, it is widely thought that diet contributes to the development of IBD. Diet shapes the composition of the gut microbiota, which plays critical roles in intestinal homeostasis. In contrast, intestinal inflammation induces gut dysbiosis and may affect the use of dietary nutrients by host cells and the gut microbiota. The interaction of diet and the gut microbiota is perturbed in patients with IBD. Herein, we review the current knowledge of diet and gut microbiota interaction in intestinal homeostasis. We also discuss alterations of diet and gut microbiota interaction that influence the outcome and the nutritional treatment of IBD. Understanding the complex relationships between diet and the gut microbiota provides crucial insight into the pathogenesis of IBD and advances the development of new therapeutic approaches.     

Development of an instrument to assess nutritional risk factors for children infected with human immunodeficiency virus

OBJECTIVE: To produce a simple and effective instrument to evaluate and monitor the nutritional risk of children infected with the human immunodeficiency virus (HIV). DESIGN: The test instrument was developed in consultation with 5 physicians, 5 nutritionists, and 5 social workers with expertise in caring for HIV-infected children. Patient information was collected through medical record review for 19 sociodemographic, 10 anthropometric, 4 biochemical, 6 dietary intake, and 19 medical factors. As a part of routine nutrition care, anthropometric data were obtained and the caregiver was asked to complete a 3-day diet record. Also recorded were the most recent CD4+ T-cell numbers and serum HIV p24 antigen and plasma HIV RNA levels. SUBJECTS/SETTING: Thirty-nine HIV-infected children were selected using quota sampling; that is, subjects were stratified by clinical class as defined by the Centers for Disease Control and Prevention. STATISTICAL ANALYSIS: The severity or degree of potential nutritional risk in each section (anthropometric, biochemical, dietary intake, and medical data) was graded (0 to 4, 0 = low risk) and summed. Reliability of internal consistency was determined through covariance matrixes. Validity was determined through Pearson product moment correlation coefficients to measure convergent and divergent validity; predictive validity was determined using analysis of variance. Correlation for validity was compared to 6 selected dependent variables: weight for height, weight growth velocity, lean body mass, serum albumin level, CD4+ T-cell numbers, and quantitative plasma HIV RNA levels. RESULTS: Of the 38 factors that were analyzed for reliability, 11 fell in the strongly reliable range: height for age, weight for age, clinical class, somatic protein stores, mid-arm circumference, weight for height, serum albumin, immunologic status, body mass index, energy intake, and opportunistic infection. CONCLUSIONS: Anthropometric, dietary intake, and medical data were reliable indicators of nutritional risk. The entire instrument was reliable after 8 of the weakest items were removed. The instrument was found to be valid and a good predictor of nutritional risk in HIV-infected children.     

Tuberculosis among Children and Adolescents at HIV Treatment Centers in Sub-Saharan Africa

HIV-infected children and adolescents are at increased risk for tuberculosis (TB). Antiretroviral therapy (ART) reduces TB risk in HIV-infected adults, but its effectiveness in HIV-infected children and adolescents is unknown. We analyzed data from 7 integrated pediatric HIV/TB centers in 6 countries in sub-Saharan Africa. We used a Bayesian mixed-effect model to assess association between ART and TB prevalence and used adaptive lasso regression to analyze risk factors for adverse TB outcomes. The study period encompassed 57,525 patient-years and 1,160 TB cases (2,017 cases/100,000 patient-years). Every 10% increase in ART uptake resulted in a 2.33% reduction in TB prevalence. Favorable TB outcomes were associated with increased time in care and early ART initiation, whereas severe immunosuppression was associated with death. These findings support integrated HIV/TB services for HIV-infected children and adults and demonstrate the association of ART uptake with decreased TB incidence in high HIV/TB settings.