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.

Prevalence and cost of HIV-associated weight loss in a managed care population.

OBJECTIVE: To estimate the prevalence of HIV-associated weight loss among HIV patients in a US managed care population, and compare demographic and clinical characteristics of HIV patients with and without evidence of HIV-associated weight loss. RESEARCH DESIGN AND METHODS: A retrospective observational study was conducted using a large, geographically diverse US managed care population to identify commercial enrollees with HIV/AIDS from 1/1/2005-7/31/2007, based on a combination of HIV/AIDS diagnosis codes or antiretroviral treatment. HIV-associated weight loss status was defined according to an algorithm combining evidence for weight loss-associated conditions, anorexia symptoms, and various treatments for weight loss or wasting. Among HIV patients continuously enrolled in the health plan for one year, patient demographics, treatments, and comorbidities were compared between patients with and without evidence for weight loss. RESULTS: A total of 22,535 patients with HIV/AIDS were identified, including 2098 who met the criteria for weight loss (estimated prevalence 9.3%; 95% CI: 8.9% - 9.7%). Among 12,187 continuously enrolled patients with HIV, 1006 (8.3%) had evidence of HIV-associated weight loss. Patients with HIV-associated weight loss were older (44.1 vs. 42.6 years), and more men had HIV-associated weight loss than women (8.8% vs. 5.3%). A number of comorbidities were more common among patients with HIV-associated weight loss. On average, these patients also had more ambulatory (24.0 vs. 13.4), ER (1.4 vs. 0.8), and inpatient visits (0.5 vs. 0.1). Total annual health care costs for patients with HIV-associated weight loss were more than double (mean $45,686 vs. $19,960) the costs for HIV patients without weight loss. CONCLUSIONS: Despite the availability of effective antiretroviral therapy, weight loss remains a problem among patients with HIV. Based on this analysis, almost 1 in 10 managed care patients with HIV have evidence of HIV-associated weight loss. These patients tend to have more comorbidities, use more health care resources, and incur greater costs compared to patients without HIV-associated weight loss. Patients with HIV-associated weight loss were generally sicker than the non-weight loss cohort; thus, the increased costs observed in this population may not be directly or wholly attributable to HIV-associated weight loss. In addition, limitations common to analyses of administrative claims data should be considered when interpreting these results.

Cost-effectiveness of clinical interventions for AIDS wasting.

Economic studies of HIV/AIDS interventions are important for providing cost-effective care. This paper presents a costeffectiveness study of a three-arm clinical trial conducted at Tufts University School of Medicine/New England Medical Center in Boston, Massachusetts that treated 50 patients with AIDS wasting from March 1998 through January 2001. This study compared the costs and impacts of a nutritional counseling intervention alone (NC arm), the nutrition intervention with oxandrolone (OX arm), and the nutrition intervention with progressive resistance training (PRTarm) for the treatment of AIDS wasting. The cost of each intervention was derived for both the three-month clinical trial and a six-month estimated community model (ECM), its projected adaptation to community-based medical care. The cost determination involved obtaining and multiplying unit economic costs and quantities expended of each resource within each study arm. The ECM average cost per client in the cost-effectiveness analysis incorporated both institutional and societal perspectives. The costeffectiveness analysis compared the cost of each intervention to its quality-adjusted life-year (QALY) gain (Zeckhauser and Shepard, 1976). From a societal perspective, for the NC arm, the cost per client totaled US dollars 983 for the actual and US dollars 596 under the ECM. For the OX arm, the cost per client totaled US dollars 3,772 for the actual study and US dollars 3,385 under the ECM. For the PRT arm, the cost per client totaled US dollars 3,189 for the actual study and US dollars 2,987 under the ECM. Under the societal perspective the cost per QALY was US dollars 55,000 (range: US dollars 51,000 to US dollars 83,000) for the NC arm, US dollars 151,000 (range: US dollars 149,000 to US dollars 171,000) for the OX arm, and US dollars 65,000 (range: US dollars 44,000 to US dollars 104,000) for the PRTarm. When using only an institutional perspective, the cost per QALY was US dollars 45,000 (range: US dollars 42,000-US dollars 64,000) for the NC arm, US dollars 147,000 (range: US dollars 147,000 to US dollars 163,000) for the OX arm, and US dollars 31,000 (US dollars 21,000 to US dollars 44,000) for the PRTarm. This paper shows that cost and cost-effectiveness analyses can be adapted to a community setting by combining information from community practice and costs with data from a randomized trial. Compared to other AIDS treatments, such as highly active antiretroviral therapies, all three interventions were affordable, but their cost-effectiveness was intermediate. Oxandrolone was the least cost effective of the interventions, even compared to nutrition alone, as it included similar or somewhat greater costs for less of an increase in quality of life. PRT was the most cost-effective treatment for AIDS wasting, particularly from an institutional perspective. Third party payers should consider coverage of PRT.

Counteracting muscle wasting in HIV-infected individuals.

HIV-infected persons often experience a loss of lean tissue mass, which includes decreases in skeletal muscle mass. This HIV-associated wasting is significant because it has been associated with accelerated disease progression and increased morbidity. Signalling related to several circulating molecules, including tumour necrosis factor (TNF)-alpha, growth hormone, insulin-like growth factor (IGF)-1 and testosterone, has been associated with the aetiology of muscle wasting. Additionally, nutritional status related to malnutrition and specific dietary deficiencies may be involved. In an attempt to counter muscle wasting in HIV-infected persons, treatments have been suggested that target these mechanisms. Nutritional supplementation, cytokine reduction, hormone therapy and resistance exercise training are potential treatments for this condition. Resistance exercise training, which is more easily accessible to this population than other treatments, holds promise in counteracting the process of HIV wasting, as it has been successfully used to increase lean tissue mass in healthy and clinical populations. This review will explore the HIV/AIDS muscle-wasting syndrome, its aetiology, and the treatments used to counteract wasting.

ESPEN Guidelines on Enteral Nutrition: Wasting in HIV and other chronic infectious diseases.

Undernutrition (wasting) is still frequent in patients infected with the human immunodeficiency virus (HIV), despite recent decreases in the prevalence of undernutrition in western countries (as opposed to developing countries) due to the use of highly active antiretroviral treatment. Undernutrition has been shown to have a negative prognostic effect independently of immunodeficiency and viral load. These guidelines are intended to give evidence-based recommendations for the use of enteral nutrition (EN) by means of oral nutritional supplements (ONS) and tube feeding (TF) in HIV-infected patients. They were developed by an interdisciplinary expert group in accordance with officially accepted standards and is based on all relevant publications since 1985. Nutritional therapy is indicated when significant weight loss (>5% in 3 months) or a significant loss of body cell mass (>5% in 3 months) has occurred, and should be considered when the body mass index (BMI) is <18.5 kg/m(2). If normal food intake including nutritional counselling and optimal use of ONS cannot achieve an adequate nutrient intake, TF with standard formulae is indicated. Due to conflicting results from studies investigating the impact of immune-modulating formulae, these are not generally recommended. The results obtained in HIV patients may be extrapolated to other chronic infectious diseases, in the absence of available data.

Nutrition and HIV infection: review of weight loss and wasting in the era of highly active antiretroviral therapy from the nutrition for healthy living cohort.

Despite major advances in the treatment and survival of patients infected with human immunodeficiency virus (HIV), weight loss and wasting remain common problems. In the HIV-infected population, weight loss is associated with lower CD4+ cell counts and is an independent predictor of mortality. The etiology of weight loss and wasting is complex and multifactorial. We discuss, on the basis of a large longitudinal cohort that examined nutritional status in HIV infection, data on weight loss and wasting from the present clinical era. The definition, prevalence, and significance of HIV-associated weight loss and wasting are summarized. The etiology of weight loss is discussed for 2 main categories: inadequate nutrient intake and altered metabolism. Finally, studies of interventions to treat HIV-associated weight loss and wasting are discussed. This information is intended to raise awareness among health care providers of HIV-infected patients that weight loss and wasting remain important acquired immunodeficiency syndrome-defining conditions, despite the advent of HAART.

A comparison of the clinical and cost-effectiveness of 3 intervention strategies for AIDS wasting.

OBJECTIVE: To compare oxandrolone (OX) or strength training with nutrition alone (NA) for AIDS wasting. SUBJECTS: Fifty patients with AIDS; 47 completing the study. INTERVENTIONS: Randomization to (1) NA with placebo pills, (2) nutrition with 10 mg of OX administered orally twice a day, or (3) nutrition with progressive resistance training (PRT) for 12 weeks. MAIN OUTCOME MEASURES: Midthigh cross-sectional muscle area (CSMA), physical functioning (PF), costs, and cost-effectiveness in dollars/quality-adjusted life-years (dollars/QALYs). RESULTS: The OX and PRT subjects had increases in CSMA (7.0% +/- 2.5%, P = 0.01; 5.0% +/- 2.0%, P = 0.04, respectively), although these increases did not differ significantly from the NA arm (NA: 1.0% +/- 1.0%; OX vs. NA: P = 0.09; PRT vs. NA: P = 0.26). Only PRT caused significant improvements in PF (mean +/- SE: 10.4 +/- 3.8 points on a 100-point scale) and 7 measures of strength (P values: 0.04 to <0.001). There were no overall differences between groups in PF change. Among patients with impaired baseline PF, however, OX was significantly less effective than NA and PRT was significantly better than NA. All treatments led to increases in protein intake and performance; NA and PRT also increased caloric intake. The institutional costs per subject in this trial were 983 dollars for NA, 3772 dollars for OX, and 3189 dollars for PRT. At a community-based level of intensity, the institutional costs per QALY were 45,000 dollars (range: 42,000 dollars-64,000 dollars) for NA, 147,000 dollars (range: 147,000 dollars-163,000 dollars) for OX, and 31,000 dollars (range: 21,000 dollars-44,000 dollars) for PRT. CONCLUSIONS: OX and PRT induce similar improvements in body composition, but PRT improves quality of life more than nutrition or OX, particularly among patients with impaired PF. PRT was the most cost-effective intervention, and OX was the least cost-effective intervention.

HIV/AIDS wasting syndrome in Manipur - a case report.

A-30-years old married man with HIV/AIDS wasting syndrome is being reported. The patient had history of injecting heroin with rampant sharing with his drug partners, weight loss, night sweats, productive cough, severe muscle wasting, chronic diarrhoea >30 days and fever > 30 days. This syndrome indicates the long-standing complication of HIV infection. Blood, sputum, CSF, faeces and urine routine and culture examination findings to rule out opportunistic infections were repeatedly negative. No malignant cells were found. HIV testing was positive. The CD 4 positive T-lymphocyte count was measured before and after six months of treatment. In the present case report, evaluation of the symptoms yielded no specific pathogen and had no evidence of opportunistic infections. He is being placed under observation with highly active antiretroviral therapy (HAART) along with nutritional support. He is improving clinically and immunologically by raising in the patient's CD4 count. Early antiretroviral therapy along with meticulous nutritional support is ideal to improve the quality of life of AIDS patients.

Diagnosis and management of body morphology changes and lipid abnormalities associated with HIV Infection and its therapies.

Body-shape changes and lipid abnormalities are common metabolic disorders in HIV-infected persons. It is likely that numerous factors contribute to body-morphology changes, including antiretroviral therapy, HIV infection itself, and immune reconstitution under antiretroviral therapy. A recent large cross-sectional investigation, the Fat Redistribution and Metabolism (FRAM) study, suggests that lipoatrophy is the most common feature of body-shape changes. Recent findings suggest modest benefit in reversing fat wasting by switching to abacavir from stavudine or zidovudine but no benefit from rosiglitazone treatment or switching from protease inhibitor to nonnucleoside reverse transcriptase inhibitor therapy. Human growth hormone treatment reduces fat accumulation, but treatment is expensive and gains in this regard are lost when treatment is stopped. Guidelines for treating lipid abnormalities in the non-HIV-infected population generally apply to HIV-infected persons; however, drug-drug interactions and overlapping toxicities between HIV and lipid therapies must be recognized. Although antiretroviral agents can raise lipid levels, there are data to suggest that in the case of cholesterol, HIV therapy reverses HIV infection-induced reductions of all cholesterol subsets. There are conflicting data regarding whether there is increased cardiovascular morbidity and mortality in the HIV-infected population. On balance, it appears that cardiovascular disease due to HIV-associated lipid disorders currently is a relatively infrequent problem, but once that is increasing in magnitude. This article summarizes a presentation by David A. Wohl, MD, at the February 2004 International AIDS Society-USA course in Atlanta.

Collaborative recommendations: the approach to diagnosis and treatment of HIV wasting.

Loss of lean body mass in patients with HIV, commonly referred to as wasting, remains a significant threat to outcome in the era of highly active antiretroviral therapy. It does not require advanced immune deficiency to progress. It is appropriate to reevaluate guidelines for diagnosis and treatment of wasting in the context of the increasing detail with which the risks and causes of HIV wasting are being understood. A wide range of therapies can be effective in preventing weight loss, but the pharmacologic options for restoring body cell mass, a key measure of HIV wasting, are far more limited. A collaborative meeting of clinicians and researchers with an interest in HIV wasting was held to evaluate published guidelines in the context of current clinical data.

Testosterone replacement for hypogonadism: clinical findings and best practices.

Hypogonadism is highly prevalent in HIV-infected patients and has been associated with the late stages of AIDS and AIDS wasting. There are a number of studies exploring treatment options. Testosterone replacement, with the exception of the transscrotal delivery patch, has been observed to have a beneficial effect on lean body mass and body weight in hypogonadal and eugonadal men with the AIDS wasting syndrome. Resistance exercise training also has had favorable effects on body weight and muscle cell mass. In hypogonadal men with AIDS treated with testosterone replacement therapy, researchers noted a positive effect on depression scores.

Weight loss, wasting, and survival in HIV-positive patients: current strategies.

Wasting syndrome has been a common HIV-related condition reported in the United States. Three analyses from the Tufts Nutrition for Healthy Living study shed new light on the syndrome. Analysis of Cox proportional hazards models showed that losses in weight, fat-free mass, body cell mass, and fat mass, both from baseline weight and from weight at previous follow-up, were all significant indicators of mortality in patients with the HIV wasting syndrome. In the second analysis, the prevalence of 5% weight loss from the previous visit was shown to be 35% greater in the late HAART era, from 1998 to 2003, than in the early HAART era of 1995 to 1997 (P < .02). This corresponds with earlier observations that the diagnosis of HIV wasting had been increasing during the decade of the 1990s. In the third analysis, the researchers found that body weight, fat-free mass, and body mass index improved in patients receiving nutritional intervention compared with patients receiving placebo.

Arginine: Clinical potential of a semi-essential amino acid..

Arginine, a semi-essential amino acid, is involved in numerous areas of human biochemistry, including ammonia detoxification, hormone secretion, and immune modulation. Arginine is also well known as a precursor to nitric oxide (NO), a key component of endothelial-derived relaxing factor, an endogenous messenger molecule involved in a variety of endothelium-dependent physiological effects in the cardiovascular system. Because of arginine's NO-stimulating effects, it can be utilized in therapeutic regimens for angina pectoris, congestive heart failure, hypertension, coronary heart disease, preeclampsia, intermittent claudication, and erectile dysfunction. In addition, arginine has been studied in the treatment of HIV/AIDS, athletic performance, burns and trauma, cancer, diabetes and syndrome X, gastrointestinal diseases, male and female infertility, interstitial cystitis, immunomodulation, and senile dementia. Toxicity, dosage considerations, and contraindications are also reviewed.

Role of nutrition in the management of HIV infection/AIDS.

In patients with HIV infection/AIDS, in addition to the antiretrovival therapy nutritional support is needed to maintain optimum nutrition during the symptomatic period, to prevent further deterioration of nutritional status during acute episodes of infections and to improve nutritional status during the stable symptom free period. This can be achieved by (a) nutritional assessment, (b) nutritional screening, (c) nutritional intervention and by providing (d) psychosocial support for nutrition.

New-Fill to treat facial wasting.

Looking in the mirror can be a humbling experience. For HIV positive people with facial wasting, or lipoatropy, the experience can be traumatic. Facial lipoatropy refers to subcutaneous fat loss in the cheeks and temples resulting in a bony, emaciated appearance. The condition may mild to severe. As with other symptoms of lipodystrophy, or body fat abnormality syndrome (such as fat loss in the limbs and buttocks, and fat accumulation in the abdomen), the only thing known for certain about facial wasting is that it exists; precise causes have not been identified and successful strategies to prevent the condition remain elusive. A recently developed cosmetic treatment for facial wasting, polylactic acid (PLA) or New-Fill, appears to be well tolerated in European clinical trials and anecdotal reports. Although the treatment has been approved in Europe and Mexico, the future of PLA access in the U.S. remains uncertain.

Effects of nutritional rehabilitation on intestinal function and on CD4 cell number in children with HIV.

BACKGROUND: A complex interplay of malnutrition, intestinal dysfunction, and immune impairment increases the progression of human immunodeficiency virus (HIV) disease in children. The authors tested the hypothesis that nutritional support improves intestinal and immune functions in children infected with human immunodeficiency virus (HIV). METHODS: A questionnaire was circulated through reference centers for pediatric HIV infection to evaluate the effects of nutritional rehabilitation, total parenteral nutrition (TPN) and enteral nutrition (EN), in children. Information included changes in body weight, CD4 cell numbers, and intestinal absorption-as judged by the xylose load-before and after clinical nutritional support and the outcome of children. RESULTS: Sixty-two children underwent nutritional support: 46 received TPN and 16 received EN. All but three had full-blown acquired immunodeficiency syndrome, and all were severely malnourished. Baseline clinical conditions were worse in children receiving TPN than in those receiving EN. Intestinal dysfunction was detected in all children who received xylose oral load. A significant increase in CD4 cell count, xylose levels, and body weight followed EN. A similar pattern was observed after TPN, but none of the parameters significantly changed. Twenty-seven children who received TPN and three who received EN eventually died. Fourteen who received TPN and eight who received EN were shifted to oral feeding, and five who received TPN and five who received EN continued with clinical nutritional support at the end of the observation period. CONCLUSIONS: Nutritional intervention may restore intestinal absorption and increase CD4 cell numbers. The efficacy of nutritional intervention is enhanced if provided before a terminal stage of HIV infection. These data provide evidence of a close association among nutritional condition, intestinal absorption, and immune impairment.

Nutrition and HIV infection.

Infection by the human immunodeficiency virus (HIV) is characterized by progressive destruction of the immune system, which leads to recurrent opportunistic infections and malignancies, progressive debilitation and death. Malnutrition is one major complication of HIV infection and is recognized as a significant prognostic factor in advanced disease. Malnutrition is multifactorial and poorly treated during the course of HIV. Even if a standardized approach to the management of active weight loss has not been well established, early nutritional intervention is important in HIV infected patients to maximize gain of lean body mass. From early in the era of highly active antiretroviral therapy (HAART), an initial decreased incidence of malnutrition was noted only in western countries while a variety of changes in the distribution of body fat and associated metabolic abnormalities have been recognized under the banner of lipodystrophy.