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.

Prognostic value of indeterminate IFN-γ release assay results in HIV-1 infection.

In this prospective, longitudinal study on 948 HIV-1-infected patients, subjects with an indeterminate IFN-γ (gamma interferon) release assay (IGRA) result at baseline were at significantly higher risk of developing AIDS-defining manifestations other than tuberculosis (TB) irrespective of CD4(+) T cell count. Thus, in HIV-1-infected patients with advanced quantitative CD4(+) T cell depletion, an indeterminate IGRA might indicate an additional loss of global T cell function, warranting detailed clinical evaluation and careful follow-up.

Does HIV infection affect growth and puberty of Cameroonian children?

OBJECTIVES: This study aimed to describe growth and pubertal development of adolescents with HIV infection under highly active antiretroviral therapy (HAART) in Cameroon. DESIGN: Through an observational study, we included 74 adolescents aged 9-17 years who were taking HAART and had attended two care units in Cameroon for at least 6 months. Weight and height were measured and transferred to 2007 WHO curves for 5- to 19-year-olds. Stunting was defined by a height for age z-score less than -2 standard deviations. Wasting was defined by a BMI z-score for age less than -2 standard deviations. Pubertal development was assessed using Tanner stages. We looked into the association between HIV infection characteristics, HAART regimen, and growth/puberty abnormalities with multivariate analysis. The Mann-Whitney U-test was used to compare median values with a p-value ≤0.05. RESULTS: The median age was 13 (11.2-14.7) years. Stunting affected 44% of the children. Wasting affected 9.7% of the adolescents. The age at onset of puberty was in the normal range in both boys and girls. Adolescents aged 12-14 years (OR 3.4 [95% CI, 1.3-8.8], p=0.012) with a past history of opportunistic infection and taking HAART with protease inhibitors were more likely to have stunting. CONCLUSION: In the Cameroonian setting, growth was mainly affected by stunting, but pubertal development was normal in all patients. This may reflect the benefits of HAART in children with HIV infection.

A locally produced nutritional supplement in community-based HIV and AIDS patients.

This study examined the potential effect of a nutritional supplement on the anthropometric profiles (body measurements such as body mass index [BMI], fat percentage and waist-hip ratio) of HIV-positive/AIDS patients and the correlation between anthropometric profile, CD4+T cell count and viral load. At baseline, of the 35 patients recruited into the study, 32 (94.1%) showed a fat percentage below normal range. Twenty-four of the patients (68.6%) had a BMI within normal range, while a greater percentage of the patients had a normal waist-hip ratio. Of the 28 patients that completed the study, 26 (96.3%) reported a fat percentage of below 18.5%. The results showed that 19 (67.9%) of the 28 patients had a BMI within the normal range after nutrient intervention. There was a significant positive correlation between the BMI and fat percentage. At the end of the study the CD4+T cell count showed no correlation with any of the anthropometric indices while the viral load showed a significant negative correlation with the lean body mass and BMI. The short duration of the study probably limited the positive trend of the supplement.

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.

Use of bioelectrical impedance analysis to determine body composition changes in HIV-associated wasting.

AIDS wasting syndrome results in loss of lean body mass and body cell mass. This 12-week, open-label study used bioelectrical impedance analysis to measure body composition changes in 24 patients with AIDS wasting syndrome receiving recombinant human growth hormone (r-hGH). The primary endpoint was percentage monthly change in body weight before/after r-hGH. Secondary endpoints included change from baseline in body composition (bioelectrical impedance analysis), isometric strength and CD4+ count. Twenty patients completed the study: r-hGH resulted in mean weight gains (+2.7%, P = 0.146), and significant increases in mean body cell mass (+8.0%, P = 0.0211), lean body mass (+4.8%, P = 0.0373) and water (+5.5%, P < 0.023). Body fat decreased throughout, but not significantly. r-hGH was generally well tolerated; the most frequent adverse events were fever (7.3%) and diarrhoea (6.3%). Thus, bioelectrical impedance analysis can detect improved body cell mass independent of changes in body weight resulting from r-hGH treatment in patients with AIDS wasting syndrome.

Increase in body cell mass and decrease in wasting are associated with increasing potency of antiretroviral therapy for HIV infection.

With the advent of potent combination antiretroviral therapy (ART), there has been a reduction in the incidence of wasting. However, few studies have investigated specific body composition changes associated with these treatments. This study aimed to investigate longitudinally the association of increasingly potent ART with changes in body cell mass and wasting utilizing bioelectric impedance analysis (BIA). In this longitudinal cohort study, 159 HIV-positive men were assessed semiannually from 1995 to 1997 for body composition utilizing BIA, CD4 lymphocyte count, HIV viral load, medical and depressive symptoms. Wasting was defined as body cell mass/height below the 90th percentile based on HIV positive norms. ART potency at each visit was scored utilizing published clinical guidelines, ranging from 1 (0-1 antiretrovirals) to 5 (3 or more antiretrovirals including a potent protease inhibitor). Viral resistance testing was not used. The mixed-effects model and the generalized estimating equations approaches were used to determine longitudinal correlates of body cell mass and of wasting, respectively. Over the 2 years of follow-up, potent combination ART use increased from 6% to 79%. Concurrently, a significant increase in mean body cell mass and a reduction in prevalence of wasting were seen, while total body weight, fat mass, and total body water did not change. Increasingly potent ART was associated with significant increases in body cell mass and reduction in wasting. Other significant correlates of increased body cell mass included higher CD4 count and decreased severity of HIV-related symptoms, fatigue and depression. The current study found that higher potency ART taken for relatively short term (2 years) was associated with an increase in body cell mass and a reduction in wasting and that these changes were associated with both medical (CD4, HIV symptoms) and behavioral (fatigue, depression) improvements. One caveat is this study did not distinguish among types of potent ART regimens. Given only some antiretrovirals appear linked to many body composition changes, regardless of their effect on viral load, it may be the type of regimen used that accounted for the relationship seen between viral load and body composition changes.

Tumor necrosis factor-alpha levels in patients with HIV with wasting in South Asia.

Tumor necrosis factor (TNF)-alpha is thought to play an important role in wasting; but TNF-alpha levels have not been consistently found to be high in AIDS wasting. We conducted this study to determine any correlation between TNF-alpha levels and wasting in HIV-positive patients in a developing country. TNF-alpha levels were measured in four groups of patients: Group 1, HIV/AIDS with wasting (n = 25); group 2, HIV/AIDS without wasting (n = 47); group 3, HIV-negative patients with tuberculosis with wasting (n = 25); and group 4, healthy controls (n = 25). Wasting was defined as a body bass index (BMI)

Effect of recombinant human growth hormone on exercise capacity in patients with HIV-associated wasting on HAART.

Over 700 patients with HIV-associated wasting while receiving HAART were randomly assigned to double-blind treatment for 12 weeks with recombinant human growth hormone (rhGH) daily or on alternate days, or to placebo. Maximum exercise intensity increased by a median of 2.35kJ in the alternate-days group and 2.60 kJ in the daily group but decreased by 0.25kJ in the placebo group. The median difference between the daily and placebo groups was 2.85 kJ (P < .0001). These improvements suggest that rhGH treatment may enable patients with wasting to perform activities of daily living that would be exhausting without rhGH treatment.

Profound immunosuppression across the spectrum of opportunistic disease among hospitalized HIV-infected adults in Abidjan, Côte d'Ivoire.

OBJECTIVES: To describe the spectrum of opportunistic disease in HIV-infected patients admitted to hospital in Abidjan, Côte d'Ivoire, and to describe the level of immunosuppression at which these diseases occur. DESIGN: Cross-sectional study. SETTING: In-patient wards of the University Hospital Infectious Diseases Unit. PATIENTS: A total of 250 adult patients recruited by systematic sampling at the point of hospital admission. MAIN MEASURES: HIV status; CD4 count; diagnoses, confirmed by microbiological/radiological investigations whenever possible; and outcome of hospitalization (death or discharge). RESULTS: Overall, 79% patients were HIV-positive. The most frequent diagnoses in HIV-positive patients were septicaemia (20%, with non-typhoid salmonellae, Escherichia coli and Streptococcus pneumoniae the most common organisms), HIV wasting (16%), meningitis (14%), tuberculosis (TB; 13%), isosporiasis (10%), cerebral toxoplasmosis (7%) and bacterial enteritis (7%). Most HIV-positive patients had evidence of severe immunosuppression: 39% had CD4 counts < 50 x 10(6)/l, 17% had 50-99 x 10(6)/l, and 20% had 100-199 x 10(6)/l. In-hospital mortality among HIV-positive patients was 38% compared with 27% among HIV-negative patients [age-adjusted odds ratio (OR), 1.5; 95% confidence interval (CI), 0.7-2.9]. Among HIV-positive patients, the highest case-fatality rates were among patients with meningitis, toxoplasmosis and TB: in a multivariate analysis the strongest independent risk factors for death were an abnormal level of consciousness (OR, 9.3; 95% CI, 3.5-24.6), a haemoglobin concentration below 8 g/dl (OR, 4.2; 95% CI, 1.4-12.8) and age > 40 years (OR, 3.9; 95% CI, 1.5-10.2). CONCLUSIONS: Our data show that, as in industrialized countries, most HIV-infected individuals admitted to and dying in hospital in Abidjan are profoundly immunosuppressed. Potentially preventable infections are the main causes of in-hospital morbidity and mortality among HIV-infected persons in Abidjan, and the evaluation of appropriate primary prophylactic regimes is a priority.

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.

Comparison of total body potassium with other techniques for measuring lean body mass in men and women with AIDS wasting.

BACKGROUND: Lean body mass is an important predictor of survival and functional status in patients with AIDS wasting. The bias between different techniques for assessing body composition in AIDS wasting is not known. DESIGN: We compared total body potassium (TBK) with fat-free mass (FFM) determined by dual-energy X-ray absorptiometry (DXA), bioelectrical impedance analysis (BIA), and skinfold-thickness measurement (SKF) in 132 patients (63 men, 69 women) with AIDS wasting (weight < 90% of ideal body weight, or weight loss > 10% of original, or both). None of the subjects exhibited clinical lipodystrophy. Comparisons were made by using different BIA equations. RESULTS: Lean body mass determined by DXA was highly correlated with TBK in men (r = 0.79, P: < 0.0001) and women (r = 0.84, P: < 0.0001). FFM(BIA) and FFM(DXA) were significantly different (P: < 0.01 in men and P: < 0.0001 in women). The difference between FFM(DXA) and FFM(BIA) was significantly greater with greater weight and body fat, particularly in HIV-infected women (r = -0.39, P: = 0.001 for weight; r = -0.60, P: < 0.0001 for fat). The comparability of FFM and fat mass determined by DXA and BIA was dependent on the specific BIA equation used. Among men, no single BIA equation was more highly predictive of fat mass and FFM in comparison with DXA. CONCLUSIONS: The differences between DXA, BIA, and SKF in the determination of fat mass and FFM are significant in patients with AIDS wasting. BIA overestimates FFM compared with DXA in those with greater body fat. Standard BIA equations may not accurately estimate FFM and fat mass in men and women with AIDS wasting.

Treatment guidelines for HIV-associated wasting.

Patients with acquired immunodeficiency syndrome (AIDS) often suffer from weight loss manifested by a loss of body cell mass (BCM). The causes of human immunodeficiency virus (HIV)-associated wasting may include anorexia, malabsorption, and a variety of altered metabolic states. Malabsorption and diarrhea may result from gastrointestinal tract opportunistic infections or from direct effects of HIV on the gastrointestinal tract. Infection with HIV may produce metabolic derangements that alter nutrient utilization, resulting in loss of BCM. Nutritional assessment of the patient with AIDS should include an evaluation of BCM and physical and psychosocial functioning. Antiretroviral therapy and eradication of opportunistic infections do not always reverse wasting. Treatment should include nutritional counseling. Total parenteral nutrition is sometimes of benefit, particularly in patients with damaged gastrointestinal tracts. Dronabinol and megestrol acetate may promote weight gain; however, dronabinol may have adverse effects, and most of the gain with megestrol acetate is in fat rather than BCM. If gonadal dysfunction is present, testosterone replacement therapy should be included in the treatment plan. Some studies suggest that oral anabolic steroids may improve muscle strength and body composition. In randomized, placebo-controlled trials, mammalian-derived human growth hormone (rhGH[m]) has produced sustained weight and BCM gains in AIDS patients. If a patient continues to lose BCM after the above factors have been addressed and corrected, a 12-week course of rhGH[m] is indicated. Halting the progression of HIV-associated wasting may improve survival, enhance physical and social functioning, and enrich quality of life.

Disease progression in HIV-infected patients treated with stavudine vs. zidovudine.

BACKGROUND AND OBJECTIVES: This prospective, observational study compared disease progression and death in HIV-1 patients treated with stavudine vs. zidovudine in the Collaborations in HIV Outcomes Research/U.S. (CHORUS) cohort. METHODS: Patients with a first occurrence of CD4 count <500 cells/microL (n=3301) were grouped as: no nucleoside reverse transcriptase inhibitor (NRTI) use; other NRTI without stavudine or zidovudine; stavudine with no zidovudine, with or without other NRTIs; and zidovudine with no stavudine, with or without other NRTIs. The risk for death or disease progression was evaluated in unadjusted analyses and using a Cox proportional hazards model, adjusting for: study site, age, gender, race, route of HIV infection, previous AIDS-defining conditions, number of previous antiretroviral regiments, CD4 count, HIV-1 RNA, and treatment variables. Sensitivity analyses were conducted to determine the sensitivity of the results to major modeling assumptions. A landmark analysis was conducted to determine the absolute difference in time to event. RESULTS: During a median follow-up of 2.4 years, there were 57 deaths and 348 AIDS-defining conditions in 405 patients. Stavudine treatment compared with zidovudine resulted in a greater percentage of patients with AIDS-defining events (14.5 vs. 10.9%; P=.013), and an increased risk of disease progression (HR=1.30; 95% CI: 1.01,1.7; P=.04). This result was not sensitive to modeling assumptions. Landmark analysis demonstrated an absolute difference in time to 95% event-free survival of 2.7 months for those with a CD4< or =200 cells/microL and 11 months for those 6 months after model entry. CONCLUSIONS: In unadjusted and adjusted analyses of 3301 HIV-1 infected patients, stavudine containing combination therapy was associated with an increased risk of disease progression or death compared to therapy containing zidovudine. Most of the difference was attributable to new cases of wasting.

Clinical complications of HIV infection.

HIV infection results in a profound weakening of the immune system that leaves the patient vulnerable to a bewildering array of clinical complications. Understanding of the pathogenesis of these clinical complications, knowledge of the current stage and treatment of HIV infection, and recognition of certain clinical syndromes can help the clinician sort through these potential complications, prioritize them, and formulate a plan for diagnosis and treatment. This article provides a summary of the clinical presentation, diagnosis, treatment, and prevention of the most common complications of HIV infection.

Tissue wasting in patients with chronic obstructive pulmonary disease.

Malnutrition is common among individuals suffering from hypoxemic chronic obstructive pulmonary disease (COPD), advanced HIV disease, and in patients with chronic, severe congestive heart failure. Although increased morbidity and mortality has been associated with weight loss in these conditions, the pathophysiology of malnutrition remains somewhat unclear for each. In COPD, the primary postulated mechanism is hypermetabolism resulting in elevated total caloric expenditure arising from increased airway resistance, increased O2 cost of ventilation, increased dietary induced thermogenesis, inefficient substrate use and perhaps, increased levels of proinflammatory cytokines. In AIDS, postulated mechanisms include hypermetabolism arising from increased activation of proinflammatory cytokines, along with futile cycling of fatty acids and de novo lipogenesis early in the course of HIV infection; intestinal malabsorption and anorexia also play a role in many inflicted individuals. In cardiac cachexia, dietary and metabolic factors, and levels and activity of cytokines, thyroid hormone, catecholamines and cortisol have been suggested as being responsible for causing weight loss in a most cases.

Growth failure as the first expression of malnutrition in children with human immunodeficiency virus infection.

BACKGROUND: To define the onset, pattern, and earliest manifestations of malnutrition related to HIV infection. METHODS: A retrospective cross-sectional analysis of changes in weight and growth in a group of 54 children with perinatally acquired HIV infection was conducted. Eight children had asymptomatic HIV infection, 26 had symptomatic infection, and 20 had symptomatic infection and were referred for nutritional support. RESULTS: We found an early decline in the rate of linear growth with a relative preservation of the weight-for-age. Weight-for-height measurements were preserved until there was advanced HIV-related disease. CONCLUSIONS: This pattern can result in a false impression of adequate nutrition and emphasizes the importance of longitudinal growth data of the child with HIV infection. Evidence of linear growth failure before clinical wasting is apparent is an absolute indication for aggressive nutritional support.

AIDS defining diseases in the UK: the impact of PCP prophylaxis and twelve years of change.

We examined all reports of adult AIDS cases made to the 2 national surveillance centres in the UK for changes in AIDS defining conditions between January 1982 and September 1994. Differences and changes among persons diagnosed since January 1988 who had and had not been aware of their HIV infection prior to their AIDS diagnosis were of particular interest. Pneumocystis carinii pneumonia (PCP) is the AIDS defining disease most often reported at the initial AIDS diagnosis. Its proportion of all AIDS cases has increased significantly between January 1982 and December 1987 and decreased markedly thereafter. Since January 1988 a significant decrease in the proportion of cases diagnosed with cryptosporidial infection was also observed while increases were observed in the proportion of cases diagnosed with: HIV wasting (chi(1)(2) = 5.56) PML (chi(1)(2) = 19.47), mycobacterium avium complex (chi(1)(2) = 35.76) and pulmonary tuberculosis (chi(1)(2) = 144.0). For cases diagnosed between January 1988 and September 1994, PCP was more likely to be diagnosed in patients previously unaware of their HIV infection (P < 0.01) as was extrapulmonary TB (P < 0.01). In contrast, the following diseases were more likely to be diagnosed in patients already aware of their HIV infection prior to the diagnosis of AIDS: oesophageal candidiasis (P < 0.001), HIV wasting (P = 0.07), mycobacterium avium complex (P = 0.0001), cytomegalovirus disease (P < 0.001), HIV encephalopathy (P = 0.0009) and cryptosporidial infection (P = 0.02). Prophylaxis and anti-retroviral therapy appear to have had a significant impact on the temporal changes of the most frequently diagnosed AIDS diseases. While PCP prophylaxis has substantially reduced the likelihood of a PCP diagnosis at AIDS, the corresponding increase in other opportunistic infections suggests that there may be a need for improved prophylaxis for these conditions.