Nutritional status is the major factor affecting grip strength of African HIV patients before and during antiretroviral treatment.

OBJECTIVES: Low grip strength is a marker of frailty and a risk factor for mortality among HIV patients and other populations. We investigated factors associated with grip strength in malnourished HIV patients at referral to ART, and at 12 weeks and 2-3 years after starting ART. METHODS: The study involved HIV-infected Zambian and Tanzanian participants recruited to the NUSTART trial when malnourished (body mass index <18.5 kg/m2 ) and requiring ART. The relationship of grip strength to nutritional, infectious and demographic factors was assessed by multivariable linear regression at referral for ART (n = 1742) and after 12 weeks (n = 778) and 2-3 years of ART (n = 273). RESULTS: In analyses controlled only for sex, age and height, most nutrition and infection-related variables were associated with grip strength. However, in multivariable analyses, consistent associations were seen for fat-free mass index, mid-upper arm circumference, haemoglobin and systolic blood pressure, and a variable association with fat mass index in men. C-reactive protein and CD4 count had limited independent effects on grip strength, while receiving tuberculosis treatment was associated with weaker grip strength. CONCLUSIONS: In this population of originally malnourished HIV patients, poor grip strength was more strongly and independently associated with nutritional than with infection and inflammation variables. Programmes to improve health and survival of HIV patients should incorporate nutritional assessment and management and could use grip strength as a functional indicator of improving nutrition.

[Wasting syndrome in HIV-infected patients].

The review of literature analyzes scientific data on wasting syndrome in HIV-infected patients. It considers its etiology, diagnosis,and therapeutic approaches.

Human Immunodeficiency Virus Infection and Male Hypogonadism: A Review.

Hypogonadism is a common complication among HIV infected patients. The prevalence of hypogonadism is 30 to 50% in HIV infected men with wasting syndrome and 20 to 25% in those without wasting syndrome. HIV infection affects the entire hypothalamus-pituitary-gonadal axis via both direct and indirect effects, which are defined in four categories, 1) direct effect of HIV particles, 2) opportunistic infections, 3) HIV-related malignancy and its treatment, and 4) medications that are used for HIV infection or its opportunistic infection. The association between HIV infection, hypogonadism, and cardiovascular diseases has yet to be determined; however, there are data that HIV infection and its treatment, particularly protease inhibitors, worsened the metabolic profiles, which were surrogate markers of cardiovascular diseases. Considerably more attention should be paid to the diagnosis of hypogonadism in this group particularly because HIV infection increases both sex hormone-binding globulin and total testosterone level. Testosterone replacement shows benefits on mood, body composition, and seems to benefit the metabolic profile in HIV infected men with low body mass index.

High Viremia and Wasting Before Antiretroviral Therapy Are Associated With Pneumonia in Early-Treated HIV-Infected Kenyan Infants.

BACKGROUND: Human immunodeficiency virus (HIV)-infected children are particularly susceptible to acute respiratory infections (ARIs). We determined incidence and cofactors for ARIs in HIV-infected infants receiving antiretroviral therapy (ART). METHODS: Human immunodeficiency virus-infected infants initiated ART at ≤12 months of age and were observed monthly for 2 years in Nairobi. Acute respiratory infection rates and cofactors were determined using Andersen-Gill models, allowing for multiple events per infant. RESULTS: Among 111 HIV-infected infants, median age at ART initiation was 4.5 months. Pre-ART median CD4% was 19%, and 29% had wasting. During 24-months follow-up while on ART, upper respiratory infection (URI) and pneumonia rates were 122.6 and 34.7 per 100 person-years (py), respectively. Infants with higher pre-ART viral load (VL) (plasma HIV ribonucleic acid [RNA] ≥7 log10 copies/mL) had 4.12-fold increased risk of pneumonia (95% confidence interval [CI], 2.17-7.80), and infants with wasting (weight-for-height z-score < -2) had 2.87-fold increased risk (95% CI, 1.56-5.28). Infants with both high pre-ART VL and wasting had a higher pneumonia rate (166.8 per 100 py) than those with only 1 of these risk factors (44.4 per 100 py) or neither (17.0 per 100 py). Infants with exposure to wood fuel had significantly higher risk of URI (hazard ratio [HR] = 1.82; 95% CI, 1.44-2.28) and pneumonia (HR = 3.31; 95% CI, 1.76-6.21). CONCLUSIONS: In early ART-treated HIV-infected infants, higher HIV RNA and wasting before ART were independent risk factors for pneumonia. Wood fuel use was associated with URI and pneumonia. Additional data on air pollution and respiratory outcomes in HIV-infected children may help optimize interventions to improve their lung health.

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.

Cachexia: pathophysiology and clinical relevance.

Cachexia causes weight loss and increased mortality. It affects more than 5 million persons in the United States. Other causes of weight loss include anorexia, sarcopenia, and dehydration. The pathophysiology of cachexia is reviewed in this article. The major cause appears to be cytokine excess. Other potential mediators include testosterone and insulin-like growth factor I deficiency, excess myostatin, and excess glucocorticoids. Numerous diseases can result in cachexia, each by a slightly different mechanism. Both nutritional support and orexigenic agents play a role in the management of cachexia.

Nutritional and metabolic abnormalities in pre-AIDS HIV infection.

Since the earliest reports of human immunodeficiency virus (HIV) disease, undernutrition has been associated with HIV infection, typically with the late stages of the disease (namely acquired immunodeficiency syndrome), and may advance to severe wasting and cachexia. Specific micronutrient deficiencies are also recognized to occur with HIV infection, but their actual effect on the clinical course of the disease is hard to assess. The studies reviewed provide more insight into the complex interface between undernutrition and, in some cases, obesity and HIV/acquired immunodeficiency syndrome and highlight the possibility of alleviating or curing undernutrition by means of simple and comparatively inexpensive dietary adjustments.

[Muscular complications of human immunodeficiency virus (HIV) infection in the era of effective anti-retroviral therapy]. / Complications musculaires de l'infection par le virus de l'immunodéficience humaine (VIH) à l'ère des trithérapies.

Introduction of highly active antiretroviral therapy (HAART) has dramatically modified the natural history of HIV disease, but lengthening the survival of HIV-infected individuals has been associated with an increasing prevalence of iatrogenic conditions. Muscular complications of HIV infection are classified as follows: (1) HIV-associated myopathies and related conditions including polymyositis, inclusion-body myositis, nemaline myopathy, diffuse infiltrative lymphocytosis syndrome (DILS), HIV-wasting syndrome, vasculitis, myasthenic syndromes, and chronic fatigue; (2) iatrogenic conditions including mitochondrial myopathies, HIV-associated lipodystrophy syndrome, and immune restoration syndrome; (3) opportunistic infections and tumor infiltrations of skeletal muscle; and (4) rhabdomyolysis. These features are described in the present review.

Metabolic and morphologic complications of HIV infection.

In the era of highly active antiretroviral therapy, long-term complications of HIV infection and antiretroviral therapy deserve heightened attention. Morphologic and metabolic complications seen during the course of HIV infection encompass a variety of entities that may share a common pathophysiologic pathway. This review article will discuss clinical syndromes such as wasting, lipoatrophy/lipohypertrophy, polymetabolic syndrome as well as hyperlipidemia, cardiovascular disease, lactic acidosis, and metabolic bone disease in HIV-infected patients.

HIV-associated wasting in the era of highly active antiretroviral therapy: a syndrome of residual HIV infection in monocytes and macrophages?

Human immunodeficiency virus (HIV) infection in peripheral blood mononuclear cells (PBMCs) might be influencing the development of wasting in the era of potent antiretroviral therapy. In a retrospective study of 57 subjects, HIV proviral DNA levels in PBMCs were higher in subjects whose body weight decreased by >5% one year after initiation of highly active antiretroviral therapy, compared with subjects whose body weight was stable or increased (median HIV proviral DNA load, 8.9 vs. 0.9 copies/10(6) PBMCs; P = .006).

HIV-related wasting in HIV-infected drug users in the era of highly active antiretroviral therapy.

BACKGROUND: A decrease in the rate of human immunodeficiency virus (HIV) infection-related wasting has been reported in the era of highly active antiretroviral therapy (HAART). We investigated this concern in a hard-to-reach population of HIV-infected drug users in Miami, Florida. METHODS: After informed consent was obtained, 119 HIV-infected drug users were administered questionnaires involving demographic, medical history, and food-security information. Blood samples were drawn for immunological and viral studies. HIV-related wasting over a period of > or =6 months was defined as a body mass index of <18.5 kg/m2, unintentional weight loss of > or =10% over 6 months, or a weight of <90% of the ideal body weight. RESULTS: The prevalence of HIV-related wasting was 17.6%. A significantly higher proportion of those who experienced wasting (81%) reported that there were periods during the previous month when they went for > or =1 day without eating (i.e., food insecurity), compared with those who did not experience wasting (57%). Although a greater percentage of patients who experienced wasting were receiving HAART, their HIV RNA levels were more than twice as high (mean+/-standard deviation [SD], 166,689+/-238,002 copies/mL; median log HIV RNA level +/- SD, 10.2+/-2.7 log10 copies/mL) as those for the group that did not experience wasting (mean+/-SD, 72,156 +/- 149,080; median log HIV RNA level+/-SD, 9.2+/-2.3 log10 copies/mL). Participants who experienced wasting were more likely to be heavy alcohol drinkers and users of cocaine. In multivariate analysis that included age, sex, food security, alcohol use, cocaine use, viral load, and receipt of antiretroviral therapy, the only significant predictors of wasting were > or =1 day without eating during the previous month (odds ratio [OR], 1.96; 95% confidence interval [CI], 1.18-3.26; P=.01) and viral load (OR, 1.64; 95% CI, 1.00-2.69; P=.05). CONCLUSIONS: HIV-related wasting continues to be common among HIV-infected drug users, even among HAART recipients. Food insecurity and viral load were the only independent predictors of wasting. The social and economic conditions affecting the lifestyle of HIV-infected drug users constitute a challenge for prevention and treatment of wasting.

Nutritional aspects of HIV-infected children receiving highly active antiretroviral therapy.

The presentation of the nutritional problems of HIV-infected children is changing over time with improved antiretroviral regimens. Early reports of HIV infection in the 1980s, included such problems as malnutrition and wasting. However, as treatment and prophylactic regimens improve, the current nutritional problems of HIV-infected children in developed countries include truncal obesity and insulin resistance in addition to malnutrition. Background data on the wasting syndrome, etiology of malnutrition, nutritional effects of highly active antiretroviral therapies, and nutritional intervention strategies for HIV-infected children will be presented.

Altered concentrations of appetite regulators may contribute to the development and maintenance of HIV-associated wasting.

OBJECTIVE: To examine the relation of circulating appetite neuropeptides, CCK-8 sulphate (CCK-8s) and beta-endorphin, and the tumour necrosis factor-alpha (TNF-alpha) and soluble TNF receptors (sTNFR) to the anorexia and wasting associated with HIV-infection. DESIGN: Cross-sectional analysis. SETTING: A university-based HIV/AIDS ambulatory clinic in Madrid, Spain. PARTICIPANTS: Thirty-six randomly selected AIDS patients without concomitant diseases or secondary infections were classified into two groups: 19 patients with wasting and 17 with normal body weight, and 18 healthy controls. MEASUREMENTS: Nutritional status was evaluated by anthropometry, laboratory parameters and self-report of appetite. Plasma levels of TNF-alpha and sTNFR proteins p55 (sTNFR-p55) and p75 (sTNFR-p75) were determined by enzyme immunoassay, whereas CCK-8s and beta-endorphin levels were measured by radioimmunoassay. RESULTS: AIDS patients with wasting had significantly higher plasma concentrations of CCK-8s, but lower levels of beta-endorphin when compared to well-nourished AIDS patients (P < 0.01) or controls (P < 0.001). Mean levels of TNF-alpha, and sTNFR-p55 and sTNFR-p75 were greater in AIDS patients with wasting than in asymptomatic AIDS patients or in controls. No significant association was observed between any of these circulating peptides and the parameters of malnutrition. CONCLUSIONS: An activation of the TNF system, together with reciprocal changes in plasma concentrations of two neuropeptides with opposing appetite regulation, that is increased concentrations of CCK-8s but lower levels of beta-endorphin, are associated with the presence of HIV wasting. We hypothesize that these changes may contribute to the development of HIV wasting by producing a pathological inhibition of appetite.

Malabsorption and wasting in AIDS patients with microsporidia and pathogen-negative diarrhea.

OBJECTIVE: To define the clinical syndrome, nutritional status and malabsorptive status in patients with HIV and chronic diarrhea and either microsporidia or no identified pathogen. PATIENTS: HIV-positive patients from an urban, hospital-based infectious disease clinic with chronic diarrhea who had undergone exhaustive gastrointestinal and stool studies for enteric pathogens and were found to have either microsporidia or no pathogen. METHODS: Patients were evaluated for clinical history, physical, body composition, nutritional and malabsorptive studies including D-xylose, Schilling test, determinations of 24 h stool fat, weight and nitrogen, and 24 h urea nitrogen. RESULTS: Ten patients with microsporidia were studied, four of whom were infected with Septata intestinalis, six with Enterocytozoon bieneusi; nine patients had no identified pathogen. Patients in both groups were comparable in stage of HIV disease, and demonstrated abnormal nutritional status and malabsorptive parameters. Patients with no pathogen had significantly longer duration of symptoms prior to presentation; however, patients with microsporidia had significantly greater malabsorption of fat, D-xylose, vitamin B12, and significantly lower serum levels of zinc. Nutritional status and malabsorption were similarly depressed in patients infected with either species of microsporidia. CONCLUSION: HIV-infected patients with chronic diarrhea associated with either microsporidial infection or with no identified pathogen had abnormal parameters of absorption and malnutrition, and those infected with microsporidia demonstrated more severe malabsorption.

Contribution of nucleoside analogue reverse transcriptase inhibitors to subcutaneous fat wasting in patients with HIV infection.

BACKGROUND: Progressive subcutaneous fat wasting, fat accumulation, dyslipidaemia and insulin resistance in HIV-infected patients on antiretroviral therapy has been attributed to the long-term toxicity of HIV protease inhibitors (PI). More recently, fat wasting has been observed in patients who have never taken a PI, implicating an independent effect of nucleoside analogue reverse transcriptase inhibitor (NRTI) therapy. OBJECTIVES: To determine the relative contribution of NRTI and PI, as well as any other factors, to fat wasting in HIV-infected patients. DESIGN: Longitudinal cohort study involving 277 participants of the Western Australian HIV Cohort Study. METHODS: The time to onset of clinically apparent fat wasting in patients receiving different antiretroviral regimens was compared using standardized clinical criteria. Regional fat measured by dual energy X-ray absorptiometry (DEXA) in 161 patients was also compared. The average rate of percentage fat reduction was estimated in 70 patients who had consecutive DEXA scans at approximately 6-monthly intervals. Multiple confounding factors were considered in the analyses. RESULTS: Progressive subcutaneous fat wasting, indistinguishable from that described in PI-treated patients, does occur in PI-naive, NRTI-treated patients. In patients taking triple combination antiretroviral therapy, age (relative risk = 1.052 per year; P < 0.0001), white race (relative risk = 3.9; P = 0.023), longer duration of dual NRTI therapy prior to addition of PI (relative risk = 1.021 per month; P = 0.0046) and increased cumulative time on stavudine-containing regimens compared with time on zidovudine-containing regimens (relative risk = 1.085 per month; P < 0.0001) are associated with increased risk of fat wasting. Stavudine increases the risk of fat wasting by 265% per year compared with zidovudine. However PI therapy is associated with faster progression to clinically apparent wasting compared with dual NRTI therapy without PI. The results of DEXA scanning supports these clinical data and suggest a non-linear decline in fat over time. CONCLUSIONS: NRTIs do have an independent contribution to fat wasting, but PI are the predominant influence and may act synergistically with NRTIs. NRTIs appear to predispose individuals to slowly progressive fat loss, which is markedly accelerated when a PI and NRTIs are combined. Of the NRTIs, stavudine leads to an earlier onset of clinically apparent fat wasting compared with zidovudine. Fat wasting associated with NRTI use may be a manifestation of mitochondrial toxicity, which may be exacerbated by PI use.

Role of acquired immune deficiency syndrome-defining conditions in human immunodeficiency virus-associated wasting.

To evaluate the contribution of acquired immune deficiency syndrome-defining conditions (ADCs) in human immunodeficiency virus (HIV)-associated wasting, we analyzed longitudinal data from 671 participants in a nutrition and HIV cohort study. Data on ADCs, height, and weight were collected at baseline and during 6 monthly study visits. The frequency of ADCs decreased over time, but the relative risk (RR) of wasting (decrease in body mass index [BMI] to <20 kg/m(2)) increased with a history of >1 ADC; the RR of wasting increased 1.3-fold with each additional historical ADC. Any ADC during the 6 months prior to a study visit was associated with a decrease in BMI to <20 kg/m(2). The risk of wasting increased 2.7-fold with each additional recent ADC. These risks were not altered when adjusted for socioeconomic status, CD4 cell count, energy intake, or baseline BMI. Although ADCs contribute to the development of wasting, their contribution is relatively small.

Serum hormones in men with human immunodeficiency virus-associated wasting.

Weight loss is commonly associated with increased morbidity and mortality in individuals with human immunodeficiency virus (HIV) infection. We performed a nested case-control study of 26 HIV-infected subjects recruited from a cohort of gay men enrolled in the Multicenter Acquired Immunodeficiency Syndrome Cohort Study. To test the hypothesis that hormonal changes precede and may induce the wasting syndrome, we performed a nested case-control study and analyzed serum gonadal steroids and GH in samples of HIV-infected men with or without weight loss, uncomplicated by diarrhea or ever having an opportunistic infection. We studied 13 cases (mean age +/- SD, 45 +/- 7.2 yr) with a mean weight loss of 13 +/- 3.6%, considered to have the wasting syndrome by Centers for Disease Control criteria (weight loss of > 10%) and 13 controls matched for age and duration of follow-up. Serum bioavailable testosterone (T) levels decreased in the case group (P < 0.05) before the definition of wasting was attained, although weight loss had already begun. More impressive declines occurred in serum T (P = 0.012), free T (P = 0.0025), and bioavailable T (P < 0.0001) during the 6 months immediately before documentation of wasting. These changes were concurrent with an increase in serum FSH (P = 0.0135) without a change in serum LH. We conclude that a decline in bioavailable T occurs early in the course of events leading to wasting, suggesting that changes in gonadal hormones may contribute to the multifactorial etiology of the wasting syndrome.

Circadian growth hormone secretion in asymptomatic human immune deficiency virus infection and acquired immunodeficiency syndrome.

Although anabolic effects of GH supplementation have been reported in acquired immune deficiency syndrome (AIDS) patients, the effects of human immunodeficiency virus (HIV) infection per se on GH secretion are unknown. Therefore, we evaluated the characteristics of GH secretion in eight asymptomatic HIV-infected men, eight clinically stable male AIDS patients, and eight healthy controls. Wasting AIDS patients were not included to circumvent the confounding effects of opportunistic disease on GH secretion. Samples for GH analysis were taken at 10-min intervals over 24 h. GH was measured by immunoradiometric assay (detection limit, 0.08 mU/L). Insulin-like growth factor I (IGF-I) and IGF-binding protein-3 were measured every 6 h. The pulsatile secretion of GH was evaluated by Cluster and DESADE analyses. No differences in number of peaks, peak amplitude, peak length, peak interval, or GH secretion per 24 h were found among the studied groups. IGF-I and IGF-binding protein-3 concentrations were not different among groups. Circadian GH secretion in asymptomatic HIV infection and AIDS without wasting is not different from that in healthy subjects. Therefore, anabolic effects documented in clinical trials with recombinant human GH in AIDS patients are not merely explained by alterations in the GH/IGF-I axis induced by HIV infection per se.

Human immunodeficiency virus-associated wasting and mechanisms of cachexia associated with inflammation.

Profound weight loss and progressive depletion of muscle mass is a common sequela of chronic diseases such as cancer, tuberculosis, and human immunodeficiency virus (HIV) infection. Studies of HIV-associated wasting have revealed several possible mechanisms. Alterations in anabolic hormones, energy intake, energy expenditure, and production of proinflammatory cytokines, which cause cachexia, may contribute to wasting in HIV-infected patients. These studies have revealed the complexity of the interactions between cytokines and the hormones that typically regulate catabolic-anabolic homeostasis. Despite this complexity, HIV-associated wasting should be manageable. Several strategies are currently under investigation, including anabolic steroid and human growth hormone therapy, appetite stimulants, nutritional supplementation, and cytokine antagonists. Some of these approaches have shown early promise. Further research in these areas should facilitate development of effective intervention strategies and lead to improvements in quality of life for patients suffering from wasting syndromes.

The etiology of wasting in the human immunodeficiency virus and acquired immunodeficiency syndrome.

Wasting is a debilitating complication of the human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) and is a major cause of morbidity and mortality. The etiology of wasting in HIV/AIDS is complex and its origins are multifactorial. Both patterns of simple starvation and the more complex metabolic and endocrine alterations associated with stress and trauma have been described in patients with the AIDS wasting syndrome. Observations suggest that the pathophysiology of the wasting in individual patients with HIV/AIDS may vary according to the primary cause of wasting and underlying disease activity. Optimal treatment of the AIDS wasting syndrome will depend on a thorough evaluation of all possible contributing factors. This review addresses the pathophysiologic basis of weight loss in HIV/AIDS, based on the current literature.