HIV enteropathy: HAART reduces HIV-induced stem cell hyperproliferation and crypt hypertrophy to normal in jejunal mucosa.

OBJECTIVE: To analyse the structural and kinetic response of small intestinal crypt epithelial cells including stem cells to highly active antiretroviral therapy (HAART). DESIGN: Crypt size and proliferative activity of transit and stem cells in jejunal mucosa were quantified using morphometric techniques. METHODS: Crypt length was measured by counting the number of enterocytes along one side of a number of crypts in each biopsy specimen and the mean crypt length was calculated. Proliferating crypt cells were identified with MIB-1 monoclonal antibody, and the percentage of crypt cells in proliferation was calculated at each cell position along the length of the crypt (proliferation index). Data were obtained from 9 HIV-positive test patients co-infected with microsporidia, 34 HIV-positive patients receiving HAART and 13 control cases. RESULTS: Crypt length was significantly greater in test patients than in controls, but crypt length in patients receiving HAART was normal. The proliferation index was greater in test subjects than in controls in stem and transit cell compartments, and was decreased in patients treated with HAART only in the stem cell region of the crypt. CONCLUSIONS: Villous atrophy in HIV enteropathy is attributed to crypt hypertrophy and encroachment of crypt cells onto villi. HAART restores normal crypt structure by inhibition of HIV-driven stem cell hyperproliferation at the crypt bases.

Altered host-microbe interaction in HIV: a target for intervention with pro- and prebiotics.

The intestinal immune system is severely affected by HIV and circulating microbial products from the intestinal tract that provide an ongoing source of systemic inflammation and concomitant viral replication. In addition, HIV-infected individuals can have a deregulated immune response that may hamper the anti-viral capacity of the host. Various probiotic organisms and prebiotic agents have been shown to enhance intestinal epithelial barrier functions, reduce inflammation, and support effective Th-1 responses. As these characteristics may benefit HIV patients, this review aims to provide a theoretical framework for the development of probiotic and prebiotic interventions specifically for this population.

Gastric and intestinal barrier impairment in tropical enteropathy and HIV: limited impact of micronutrient supplementation during a randomised controlled trial.

BACKGROUND: Although micronutrient supplementation can reduce morbidity and mortality due to diarrhoea, nutritional influences on intestinal host defence are poorly understood. We tested the hypothesis that micronutrient supplementation can enhance barrier function of the gut. METHODS: We carried out two sub-studies nested within a randomised, double-blind placebo-controlled trial of daily micronutrient supplementation in an urban community in Lusaka, Zambia. In the first sub-study, gastric pH was measured in 203 participants. In the second sub-study, mucosal permeability, lipopolysaccharide (LPS) and anti-LPS antibodies, and serum soluble tumour necrosis factor receptor p55 (sTNFR55) concentrations were measured in 87 participants. Up to three stool samples were also analysed microbiologically for detection of asymptomatic intestinal infection. Gastric histology was subsequently analysed in a third subset (n = 37) to assist in interpretation of the pH data. Informed consent was obtained from all participants after a three-stage information and consent process. RESULTS: Hypochlorhydria (fasting gastric pH > 4.0) was present in 75 (37%) of participants. In multivariate analysis, HIV infection (OR 4.1; 95%CI 2.2-7.8; P < 0.001) was associated with hypochlorhydria, but taking anti-retroviral treatment (OR 0.16; 0.04-0.67; P = 0.01) and allocation to micronutrient supplementation (OR 0.53; 0.28-0.99; P < 0.05) were protective. Hypochlorhydria was associated with increased risk of salmonellosis. Mild (grade 1) gastric atrophy was found in 5 participants, irrespective of Helicobacter pylori or HIV status. Intestinal permeability, LPS concentrations in serum, anti-LPS IgG, and sTNFR55 concentrations did not differ significantly between micronutrient and placebo groups. Anti-LPS IgM was reduced in the micronutrient recipients (P <0.05). CONCLUSIONS: We found evidence of a specific effect of HIV on gastric pH which was readily reversed by anti-retroviral therapy and not mediated by gastric atrophy. Micronutrients had a modest impact on gastric pH and one marker of bacterial translocation. TRIAL REGISTRATION: Current Controlled Trials ISRCTN31173864.

Idiopathic AIDS enteropathy and treatment of gastrointestinal opportunistic pathogens.

Diarrhea in patients with acquired immune deficiency syndrome (AIDS) has proven to be both a diagnostic and treatment challenge since the discovery of the human immunodeficiency virus (HIV) virus more than 30 years ago. Among the main etiologies of diarrhea in this group of patients are infectious agents that span the array of viruses, bacteria, protozoa, parasites, and fungal organisms. In many instances, highly active antiretroviral therapy remains the cornerstone of therapy for both AIDS and AIDS-related diarrhea, but other targeted therapies have been developed as new pathogens are identified; however, some infections remain treatment challenges. Once identifiable infections as well as other causes of diarrhea are investigated and excluded, a unique entity known as AIDS enteropathy can be diagnosed. Known as an idiopathic, pathogen-negative diarrhea, this disease has been investigated extensively. Atypical viral pathogens, including HIV itself, as well as inflammatory and immunologic responses are potential leading causes of it. Although AIDS enteropathy can pose a diagnostic challenge so too does the treatment of it. Highly active antiretroviral therapy, nutritional supplementation, electrolyte replacements, targeted therapy for infection if indicated, and medications for symptom control all are key elements in the treatment regimen. Importantly, a multidisciplinary approach among the gastroenterologist, infectious disease physician, HIV specialists, oncology, and surgery is necessary for many patients.

[Gastrointestinal manifestations of HIV infection]. / Gastrointestinale Manifestationen der HIV-Infektion.

BACKGROUND: HIV-related immunodeficiency particularly affects the mucosal immune system. Therefore, the gastrointestinal tract is target to numerous HIV-associated diseases. Since the introduction of highly active antiretroviral therapy (HAART) the prevalence of HIV-related secondary diseases has significantly declined. Their clinical appearance, however, remained unchanged. RESULTS: This review summarizes the most important gastrointestinal complications of HIV disease and their treatment focusing on key symptoms and signs. In addition, appropriate diagnostic strategies are proposed. CONCLUSIONS: Given the high number of secondary gastrointestinal diseases and their potential impact on prognosis and quality of life of HIV-infected patients, it is important to employ an effective diagnostic and therapeutic approach to these patients. Control of HIV replication and immune deficiency by HAART offers new therapeutic options in cryptosporidiosis and microsporidiosis and is crucial for the long-term prevention of opportunistic enteric infections or HIV-related malignancies.

Palliative care and AIDS: 2--Gastrointestinal symptoms.

With the use of more intensive antiretroviral therapies (highly-active antiretroviral therapy, HAART) particularly in first world countries, reductions in the mortality and morbidity of HIV infection are being seen. However, though the prevalence of symptoms may change, symptom control does continue to be a problem for many people with HIV, particularly as their disease progresses. This is the second of 2 CME articles about palliative care and HIV infection. The first gave a background to palliative care, and covered symptom control of pain. This article gives suggestions for the treatment of common gastrointestinal symptoms in HIV infection; nausea and vomiting, cachexia and anorexia and chronic diarrhoea.

Managing and treating. AIDS-related diarrhea.

Diarrhea is a significant problem for most people with AIDS. Its causes are multifactorial, ranging from infectious organisms to malignancies and functional problems. A thorough evaluation will usually determine the etiology and guide treatment. With HAART, dramatic improvements in immune status have caused a decline in opportunistic infections, including those that cause diarrhea. It is a sign of hope for all patients with HIV.

Diagnosis and management of AIDS-related diarrhea.

The spectrum of illness associated with the acquired immunodeficiency syndrome (AIDS) has been increasing since the initial description in 1981. While virtually all organ systems may be affected, the gastrointestinal tract appears to be a major target. Diarrhea is the most common symptom, affecting up to half of all AIDS patients during the course of their disease. Although diarrhea occurs frequently, its optimal management remains controversial. An extensive evaluation including stool studies and endoscopic biopsies of both the colon and small intestine has been widely recommended to identify all potential pathogenic organisms. An alternative approach is a more limited evaluation consisting of stool and blood cultures followed by symptomatic treatment with antidiarrheal agents if no specific organisms are identified. The clinical presentation of the most common opportunistic pathogens are reviewed, including several recently discovered organisms. Recommendations for treatment are followed by a brief discussion of management strategies used to care for patients with AIDS-related diarrhea.