Switch to raltegravir decreases soluble CD14 in virologically suppressed overweight women: the Women, Integrase and Fat Accumulation Trial.

OBJECTIVES: Soluble CD14 (sCD14) is a monocyte activation marker associated with increased mortality in HIV infection. We assessed 48-week changes in sCD14 and other inflammatory biomarkers in virologically suppressed, HIV-infected women switching to raltegravir (RAL) from a protease inhibitor (PI) or nonnucleoside reverse transcriptase inhibitor (NNRTI). METHODS: HIV-infected women with central adiposity and HIV-1 RNA < 50 HIV-1 RNA copies/mL continued their thymidine-sparing nucleoside reverse transcriptase inhibitor (NRTI) backbone and were randomized to switch to open-label RAL at week 0 (immediate) or 24 (delayed). In an exploratory analysis, inflammatory biomarkers were measured on stored fasting plasma. RESULTS: Of the 37 evaluable subjects, 78% were non-White; the median age was 43 years, the median body mass index (BMI) was 32 kg/m(2) and the median CD4 count was 558 cells/µL. At baseline, biomarker values were similar between groups. After 24 weeks, median sCD14 significantly declined in subjects switching to RAL [-21% (P < 0.001) vs. PI/NNRTI -5% (P = 0.49); between-group P < 0.01]. After 48 weeks, immediate-switch subjects maintained this decline and delayed-switch subjects experienced a similar decline following the switch to RAL (-10%; within-group P < 0.01). Immediate-switch subjects also experienced an initial increase in tumour necrosis factor (TNF)-α that was neither maintained after 48 weeks nor seen in delayed-switch subjects. After adjustment for multiple testing, only declines in sCD14 remained significant. CONCLUSIONS: In this randomized trial of women with central adiposity, a switch to RAL from a PI or NNRTI was associated with a statistically significant decline in sCD14. Further studies are needed to determine whether integrase inhibitors have improved monocyte activation profiles compared with PIs and/or NNRTIs, and whether measured differences between antiretroviral agents translate to demonstrable clinical benefit.

Pilot randomized trial of nutritional supplementation in patients with tuberculosis and HIV-tuberculosis coinfection receiving directly observed short-course chemotherapy for tuberculosis.

OBJECTIVE: To investigate the effects of nutritional supplementation on the outcome and nutritional status of south Indian patients with tuberculosis (TB) with and without human immunodeficiency virus (HIV) coinfection on anti-tuberculous therapy. METHOD: Randomized controlled trial on the effect of a locally prepared cereal-lentil mixture providing 930 kcal and a multivitamin micronutrient supplement during anti-tuberculous therapy in 81 newly diagnosed TB alone and 22 TB-HIV-coinfected patients, among whom 51 received and 52 did not receive the supplement. The primary outcome evaluated at completion of TB therapy was outcome of TB treatment, as classified by the national programme. Secondary outcomes were body composition, compliance and condition on follow-up 1 year after cessation of TB therapy and supplementation. RESULTS: There was no significant difference in TB outcomes at the end of treatment, but HIV-TB coinfected individuals had four times greater odds of poor outcome than those with TB alone. Among patients with TB, 1/35 (2.9%) supplemented and 5/42(12%) of those not supplemented had poor outcomes, while among TB-HIV-coinfected individuals, 4/13 (31%) supplemented and 3/7 (42.8%) non-supplemented patients had poor outcomes at the end of treatment, and the differences were more marked after 1 year of follow-up. Although there was some trend of benefit for both TB alone and TB-HIV coinfection, the results were not statistically significant at the end of TB treatment, possibly because of limited sample size. CONCLUSION: Nutritional supplements in patients are a potentially feasible, low-cost intervention, which could impact patients with TB and TB-HIV. The public health importance of these diseases in resource-limited settings suggests the need for large, multi-centre randomized control trials on nutritional supplementation.

Nutritional supplementation in HIV-infected individuals in South India: a prospective interventional study.

BACKGROUND: Malnutrition in human immunodeficiency virus (HIV)-infected individuals is associated with faster disease progression, higher mortality rates, and suboptimal response to antiretroviral therapy (ART). METHODS: We conducted a prospective interventional study to evaluate the effects of an oral macronutrient supplement among HIV-infected adults in South India. Patients attending Tuberculosis Research Centre clinics from June 2005 through December 2007 had baseline nutritional assessment and laboratory investigations performed. Patients at 1 center received nutritional counseling and standard care, whereas patients at 2 centers additionally received a macronutrient providing 400 cal and 15 g of protein daily. Study outcomes were changes in anthropometry, body composition, blood chemistry, and immune status at 6 months. RESULTS: In total, 636 ART-naive patients were enrolled in the study; 361 completed 6 months of follow-up (282 received supplements and 79 received standard care). Mean age +/- standard deviation (SD) was 31 +/- 7 years, mean weight +/- SD was 50 +/- 10 kg, and 42% were male. Significant increases in body weight, body mass index, midarm circumference, fat-free mass, and body cell mass were observed in the supplement group but not in the control group at 6 months; gains were greater in patients with CD4 cell counts <200 cells/microL. No changes were observed in lipid levels, whereas the CD4 cell count decreased in the control group. However, after adjusting for baseline differences, these changes were not statistically significantly different between the groups. CONCLUSIONS: Macronutrient supplementation did not result in significantly increased weight gain compared with standard care (including nutritional counseling) among patients with moderately advanced HIV disease. The effect of supplementation on specific subsets of patients and on preserving immune function needs further research.

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.

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.

Weight loss and wasting remain common complications in individuals infected with human immunodeficiency virus in the era of highly active antiretroviral therapy.

It has been postulated that the use of highly active antiretroviral therapy (HAART) would reduce the occurrence of human immunodeficiency virus (HIV)-associated weight loss and wasting. To test this assumption, we evaluated, by means of longitudinal analysis, a prospective cohort of 469 HIV-infected individuals enrolled in a study of the impact of HIV on nutrition. Overall, 156 individuals in the cohort (33.5%) met at least 1 of these definitions of wasting. Furthermore, 58% of the cohort (289 patients) lost >1.5 kg of weight in a 6-month period between any 2 study visits. More than 50% of the cohort was receiving HAART at the time that they met 1 of the definitions of wasting; with regard to the occurrence of wasting; no differences were related to therapy.

A comparison of two dosing regimens of zidovudine in Thai adults with early symptomatic HIV infection. Conducting clinical HIV trials in South-East Asia.

AIM: To compare the clinical and immunological efficacy, and tolerance of two dosage regimens of zidovudine (ZDV) in an adult Thai population with early symptomatic human immunodeficiency virus (HIV) disease and to identify important clinical issues associated with conducting HIV trials in South-East Asia. METHODS: HIV-infected Thai adults, with early symptomatic HIV disease and CD4 lymphocyte counts less than 400/mm3, who were managed in the infectious diseases clinics at two university teaching hospitals in Bangkok, Thailand, were enrolled in a randomised, open-label, dose-regimen comparison trial of ZDV. Two oral ZDV dosing regimens: regimen A, 100 mg tid+200 mg nocte (ZDV-A) vs regimen B, 250 mg bid (ZDV-B) were compared. The main outcome measures were: 1. Clinical efficacy: rate of progression to acquired immunodeficiency syndrome (AIDS) or death. 2. Immunologic efficacy: changes in CD4 lymphocyte numbers compared to baseline; rate of decline of CD4 lymphocyte numbers to less than 100/mm3. 3. Toxicity, as defined by clinical symptomatology and laboratory parameters. RESULTS: Two hundred and four patients were enrolled (103 ZDV-A; 101 ZDV-B) of whom 195 were followed beyond baseline. Patients were typical of those encountered with HIV in Thailand: mean age 33 years; 89% male; 88% heterosexual HIV acquisition; mean baseline CD4 lymphocyte count 241/mm3. Follow-up while on therapy was comparable for the two groups (mean+/-SD): 533+/-236 days (ZDV-A) vs 592+/-210 days (ZDV-B). One hundred and eleven patients (57%; 51 ZDV-A; 60 ZDV-B) were treated for at least 22 months (669+/-30 days). Clinical and immunological outcomes for ZDV-A and ZDV-B, including rate of progression to AIDS or death, development of non-AIDS-defining opportunistic infections, mean changes in CD4 lymphocyte numbers/mm3, difference in area under the CD4:time distribution curve and difference in the rate of decline of CD4 lymphocyte numbers to less than 100/mm3, were not significantly different. The presence of oral hairy leukoplakia or unintentional weight loss of 10-20% at enrollment were significantly associated with the later development of AIDS (p=0.03 and 0.04, respectively). ZDV-associated toxicity was similar for both regimens. Maintaining protocol adherence and appropriate clinical follow-up emerged as important practical issues. CONCLUSION: In Thai adults, ZDV 100 mg tid+200 mg nocte and ZDV 250 mg bid have similar clinical and immunological efficacy. Rates of ZDV toxicity are comparable to those reported in non-Asian populations. Despite limitations in medical care access and maintaining long-term follow-up, successful trials of antiretroviral agents are feasible in South-East Asia and multi-drug treatment trials should be pursued in appropriate institutions.

Diarrheal disease in patients infected with human immunodeficiency virus in Bangkok, Thailand.

Diarrheal disease and its associated morbidities occur frequently in patients infected with human immunodeficiency virus (HIV) and may be associated with a decreased quality of life. We studied the spectrum of symptoms, measures of nutritional status, and the enteric pathogens associated with diarrheal disease in a group of 24 patients infected with HIV in Bangkok, Thailand compared with a group of 19 patients infected with HIV without diarrhea cared for at the same clinic. Patients with diarrhea appeared to have more advanced disease by CD4 cell counts and complained more frequently of symptoms such as anorexia, gas, and bloating than patients without diarrhea. Patients with diarrhea had a tendency toward a lower nutritional status, as measured by body mass index and mid arm circumference. Stool culture and examination revealed that enteric pathogens including Salmonella species and Cryptosporidium parvum sporidia were recovered at equal frequencies in patients with and without diarrhea (27% of the patients with diarrhea and 25% of the patients without diarrhea). Microsporidia was identified in one patient with diarrhea. It was not possible to identify a pathogen in 73% of the patients with diarrhea and 75% of the patients without diarrhea, suggesting that additional agents or factors may be responsible for the diarrheal symptoms in the patients with diarrhea. More extensive studies to identify potentially treatable pathogens in HIV-infected patients with diarrhea in Thailand are warranted and further attempts to better define the syndrome of pathogen-negative diarrheal disease in patients infected with HIV might result in the development of more targeted interventions in these patients.

Successful treatment of diarrheal disease associated with enteroaggregative Escherichia coli in adults infected with human immunodeficiency virus.

The presence of enteroaggregative Escherichia coli (EAggEC) in stool has been strongly associated with persistent diarrhea. No treatment trials have been done to demonstrate that clearance of EAggEc results in an improvement of diarrheal symptoms. Twenty-four adults infected with the human immunodeficiency virus (HIV) with diarrhea and EAggEC were randomized to a double-blind placebo-control cross-over treatment trial (ciprofloxacin 500 mg orally twice daily for 7 days vs. placebo). After treatment with ciprofloxacin, the subjects had significantly fewer (50%) stools per day (from 5.0+/-2. 9 to 2.4+/-1.9). Intestinal symptoms decreased by 42% after active treatment. EAggEc were eradicated from stool of all participants after active treatment. These data strengthen the link between the presence of the EAggEc in stool and their role in the pathogenesis of diarrheal disease. It is likely that EAggEc are a treatable cause of diarrheal disease in some persons with HIV and no other apparent enteric pathogen.

Enteroaggregative Escherichia coli as a potential cause of diarrheal disease in adults infected with human immunodeficiency virus.

Stools of 68 human immunodeficiency virus (HIV)-infected adults with diarrhea and 60 without diarrhea were examined for enteroaggregative Escherichia coli (EAggEc) by HeLa cell adherence assay. EAggEc were present in stools of 30 patients with and 18 without diarrhea (P = .05). CD4 cell counts of patients with EAggEc and diarrhea were significantly lower than those of patients with EAggEc without diarrhea (P = .02). There was no difference in the mean duration of diarrheal symptoms or in the number of stools per day between patients with EAggEc and those without. None of the EAggEc strains were positive by polymerase chain reaction for adherence fimbria, but 11 strains were positive for EAggEc heat-stable toxin EAST/1. Of the EAggEc strains, 51% were resistant to trimethoprim-sulfamethoxazole and 65% were resistant to ampicillin. EAggEc may be a pathogen in HIV-infected patients with diarrhea; HIV-infected patients with EAggEc appear to be more symptomatic when HIV disease is more advanced.

Parasitic sinusitis and otitis in patients infected with human immunodeficiency virus: report of five cases and review.

We describe five cases of parasitic sinusitis and otitis in patients infected with human immunodeficiency virus (HIV) and review 14 reported cases. The pathogens identified in our group of patients included agents such as Microsporidium, Cryptosporidium, and Acanthamoeba species. The clinical features common to these patients included a long history of HIV seropositivity associated with advanced immunosuppression and multiple opportunistic infections as well as long-standing local symptoms refractory to multiple courses of antibacterial agents. Symptoms often included fever and chills in addition to local tenderness and discharge. Invasive diagnostic procedures were necessary to obtain the final diagnosis and to initiate appropriate therapy. Although most patients responded at least partially to specific therapy, relapses and recurrences were frequent in patients who did not receive long-term suppressive therapy. The general outcome for HIV-infected patients with parasitic sinusitis and otitis was poor; however, deaths were generally associated with other complications of the underlying HIV infection.

Recombinant human tumor necrosis factor and recombinant murine interleukin-1 alter the binding of Escherichia coli to intestine, mucin glycoprotein, and the HT29-C1 intestinal cell line.

Little is known about the effects of cytokines at the intestinal mucosal surface on the adherence of bacteria. We examined the effects of recombinant tumor necrosis factor (TNF) and interleukin-1 (IL-1) on the adherence of various strains of Escherichia coli to intestinal mucosa in vivo and in in vitro models. We studied the effects of TNF or IL-1 injected intraperitoneally on the ability of a rabbit enteric pathogen (RDEC-1) and a nonpathogenic E. coli (1392-) to colonize rabbit small bowel and found that there was a trend toward increased colonization by the RDEC-1 organisms in the TNF-treated rabbits, and a significant increase in colonization by the RDEC-1 organisms in the IL-1-treated animals (P < 0.01). Both TNF and IL-1 altered the density and the level of glycosylation of the small bowel mucus glcoprotein purified from the treated and untreated rabbits, and TNF treatment significantly increased the number of bacteria bound by this purified mucin (P < 0.01 for all strains). HT29-C1 intestinal cells in tissue culture were also grown in media with TNF or IL-1 and used in bacterial binding assays. The cells provided with media with 50 pg/mL of either cytokine bound significantly more of the three bacterial strains than cells in untreated media (P < 0.01 for all strains). The cytokines TNF and IL-1 have the potential to alter bacterial adherence to intestinal mucosa in vivo and in vitro; additional studies to clarify the role that these alterations in adherence may play in the clinical syndromes characterized by increased levels of intestinal cytokines are warranted.

Oral nutrition for the patient with HIV infection.

In the era of highly active antiretroviral therapy, it is unclear what percentage of patients with HIV infection will develop nutritional issues, including weight loss, diarrheal illness and anorexia. The purpose of this article is to discuss nutritional concerns that can occur with HIV infection and potential treatment strategies. We have included 3 case studies identifying these issues and a nutritional assessment guideline. Nutrition interventions, exercise recommendations, and other alternative strategies to combat HIV associated weight loss is discussed.

A medium chain triglyceride-based diet in patients with HIV and chronic diarrhea reduces diarrhea and malabsorption: a prospective, controlled trial.

Our objective was to determine whether a medium-chained triglyceride (MCT)-based diet, compared to a long-chain triglyceride (LCT)-based diet, conveys a beneficial effect on diarrhea and fat malabsorption in human immunodeficiency virus (HIV)-infected individuals with chronic diarrhea and weight loss. A secondary objective was to evaluate the pathogens associated with the diarrhea and to evaluate whether the etiologic agent was a determinant of response to the nutritional intervention. Prospective, randomized double-blind comparative trial was conducted in 24 adult patients with HIV, diarrhea of greater than 4-wk duration, fat malabsorption, and loss of 10-20% of ideal body weight, these patients were recruited from our outpatient infectious disease clinic. Evaluations of diarrheal pathogens were made by complete stool examination, upper and lower endoscopy with quantitative culture, and biopsy. Body composition determinations, and measurements of fat, carbohydrate, and vitamin absorption pre- and postintervention. Patients were randomly assigned to one of two complete nutritional products with either medium- or long-chain triglyceride fat exclusively for 12 d followed by treatment of infectious pathogens. Ten patients were found to have Microsporidium and 9 patients had no identifiable pathogen. All patients responded to intervention with both nutritional products overall with 45% fewer stools, decreased stool fat and weight, and a significant increase in urine nitrogen. The group that received the MCT product demonstrated significantly decreased stool number (mean 4 to 2.5), stool fat (mean 14 to 5.4 g), and stool weight (mean 428 to 262 g) compared with baseline (P < 0.01 for all). Patients with both species of microsporidia and with pathogen negative diarrhea had good response. We found that HIV patients with diarrhea, regardless of etiology, and documented fat malabsorption may benefit symptomatically from a diet composed of an MCT-based liquid supplement.

Enterocytozoon bieneusi infection and diarrheal disease in patients who were not infected with human immunodeficiency virus: case report and review.

We describe the identification of the protozoan parasite Enterocytozoon bieneusi in the stool of a patient who was not infected with HIV but who presented with persistent diarrheal disease and severe abdominal complaints. The patient was not infected with HIV but had been noted to have a decreased CD4 cell count since at least 1992 and had had a prior episode of cryptococcal meningitis. The organisms were detected in stool smears with a modified trichrome stain and were identified to the species level by transmission electron microscopy of the stool. The patient responded readily and dramatically to treatment with albendazole, with resolution of symptoms and clearance of the organisms from the stool. Eight or possibly nine other cases of E. bieneusi infection associated with diarrheal disease in individuals who were not infected with HIV were identified in the English-language literature. In two individuals with intact immune function, symptoms were self-limited and diarrheal disease resolved within 2 weeks. The cases summarized herein suggest that E. bieneusi may be more commonly associated with sporadic diarrheal disease than was previously suspected and that the immune system may play a role in the control of this organism within the intestine.