Human immunodeficiency virus (HIV) modifies CD4-positive cells, resulting in immunodeficiency and a wide range of gastrointestinal (GI) manifestations. The burden of HIV-related GI illnesses has significantly evolved with the widespread use of antiretroviral therapy (ART). While ART has effectively reduced the occurrence of opportunistic infections, it has led to an increase in therapy-related GI illnesses. Common esophageal conditions in HIV patients include gastroesophageal reflux disease, idiopathic esophageal ulcers, herpes simplex virus, cytomegalovirus (CMV), and candidal esophagitis. Kaposi's sarcoma, a hallmark of acquired immunodeficiency syndrome, may affect the entire GI system. Gastritis and peptic ulcer disease are also frequently seen in patients with HIV. Diarrhea, often linked to both opportunistic infections and ART, requires careful evaluation. Bloody diarrhea, often a sign of colitis caused by bacterial infections such as Shigella or Clostridium difficile, is prevalent. Small bowel lymphoma, although rare, is increasing in prevalence. Anorectal disorders, including proctitis, fissures, and anal squamous cell carcinoma, are particularly relevant in homosexual men, underlining the importance of timely diagnosis. This review comprehensively explores the epidemiology, pathogenesis, and treatment considerations for the various GI disorders associated with HIV, highlighting the importance of accurate diagnosis and effective treatment to improve outcomes for HIV-infected patients.

Microsporidiosis is an opportunistic infection that produces chronic diarrhoea and cholangiopathy in patients with AIDS, mainly caused by two species of microsporidia, Enterocytozoon bieneusi and Encephalitozon intestinalis. The aim of this work was to develop an integral system for the diagnosis of microsporidiosis of the intestine and biliary tract in HIV-infected patients, comprising microscopic and molecular techniques.

The study population comprised 143 adult patients of both sexes with diagnosis of HIV infection, with chronic diarrhoea, and with or without HIV-associated cholangiopathy. Stool studies for microsporidia identification of spores were performed on each patient. A video esofagogastroduodenoscopy with biopsy collection was also carried out for routine histology and semi-thin sections stained with Azure II. Species identification was carried out by transmission electron microscopy and/or polymerase chain reaction for the species E. bieneusi and E. intestinalis.

Out of the 143 patients a total of 12.6% (n = 18) were infected with microsporidia. Microsporidia species identified in most cases was E. bieneusi (16/18 cases), followed by E. intestinalis (4/18), all of these last ones in coinfection with E. bieneusi.

Clinical, imaging, microscopic and molecular analyses, when applied in a systematic and integrated approach, allow diagnosis and identification of microsporidia at species level in AIDS patients with chronic diarrhoea, and with or without HIV-associated cholangiopathy.

The primary aim of this prospective study was to determine the prevalence of exocrine pancreatic insufficiency (EPI) in people living with HIV (PLHIV) on suppressive antiretroviral therapy (ART).

PLHIV ≥18 years of age and on ART for >6 months and with HIV RNA <50 copies/mL plasma were included. Faecal elastase-1 measurement was performed on a single stool sample, serum markers of malnutrition were collected, and participants answered a short questionnaire about gastrointestinal symptoms. Participants with EPI and symptoms were offered pancreatic enzyme replacement therapy (PERT), and the result of this therapy was also evaluated.

Of 100 participants, 32% had EPI (faecal elastase-1 < 200 μg/g) and 20% severe EPI (faecal elastase-1 < 100 μg/g). We did not find any correlation between self-reported symptoms and degree of EPI. Twelve out of the 32 participants with EPI accepted to start PERT. Nine out of 12 (75%) reported improvement or became asymptomatic within 14 days.

EPI is common in PLHIV on effective ART. We could, however, not find a correlation between gastrointestinal symptoms and the presence of EPI. Assessment of pancreatic exocrine function could be considered in PLHIV particularly in those with gastrointestinal discomfort, since there is a possible gain in treating them with relief of symptoms and improved quality of life. The effects of PERT in PLHIV on effective ART need further study.

Intestinal infections are a significant cause of morbidity and mortality in people living with HIV/AIDS (PLWHA) especially in developing countries. The present study was conducted to assess the clinical and microbiological spectrum in HIV/AIDS cases with diarrhea and to correlate the occurrence of such pathogens with stool characters, HIV seropositivity status, and CD4 counts. Stools from 154 HIV seropositive subjects and 50 HIV negative controls were examined by direct microscopy, fecal cultures, and serological tests (Clostridium difficile Toxin A, Cryptosporidium antigen, and Entamoeba histolytica antigen ELISA). CD4 T cell enumeration was done using FACS count (Becton Dickinson). The study showed a male preponderance (112 males and 42 females). Weakness, abdominal pain, and anorexia were the most common symptoms. Coccidian parasites were the most common cause of diarrhea in HIV seropositive cases. C. parvum was seen in 60.42% while Isospora belli in 9.03%. Amongst the bacterial pathogens C. difficile was detected in 18.06%, diarrheagenic Escherichia coli in 11.11%, and Shigella spp. in 2.78%. Pathogen isolation rates were more in HIV seropositive cases and subjects with low CD4 T lymphocyte counts. Regular monitoring of CD4 T lymphocyte counts and screening for enteric pathogens will help improve the quality of life for PLWHA.

The aim of the study was to identify possible causes of pancreatic insufficiency in patients with HIV infection.

A retrospective analysis of 233 HIV-positive patients for whom faecal elastase measurement was available was performed to investigate potential associations with core demographic data, HIV infection characteristics, degree of immunosuppresion, exposure to antiretroviral therapy (ART), alcohol misuse, diabetes, hepatitis C virus (HCV) infection, triglyceride and cholesterol levels and symptomatology. The response to pancreatic enzyme replacement for patients with evidence of insufficiency was also evaluated.

Of 233 patients, 104 (45%) had evidence of pancreatic exocrine insufficiency (faecal elastase < 200 mcg/g). A positive association with exocrine pancreatic insufficiency was found for HCV infection (P = 0.007), previous or current HCV treatment (P = 0.003), alcohol misuse history (P = 0.006) and the presence of steatorrhoea (P = 0.03). There was no demonstrated association between exocrine pancreatic insufficiency and didanosine (ddI) exposure (P = 0.43) or stavudine (d4T) exposure (P = 0.62). Seventy-seven per cent of patients who were treated with pancreatic enzymatic supplementation reported a subjective improvement in symptoms.

Faecal elastase sampling should form part of the routine work-up for HIV-positive patients with chronic diarrhoea even in the absence of 'traditional' risk factors such as ddI exposure. In particular, if the patient has steatorrhoea, a history of alcohol exposure or their HCV serology is positive, they should be considered for investigation. Treatment with pancreatic enzyme supplementation appears to be effective in the treatment of chronic diarrhoea caused by pancreatic insufficiency in the majority of patients.

The number of patients with chronic gastrointestinal (GI) symptoms after cancer therapies which have a moderate or severe impact on quality of life is similar to the number diagnosed with inflammatory bowel disease annually. However, in contrast to patients with inflammatory bowel disease, most of these patients are not referred for gastroenterological assessment. Clinicians who do see these patients are often unaware of the benefits of targeted investigation (which differ from those required to exclude recurrent cancer), the range of available treatments and how the pathological processes underlying side effects of cancer treatment differ from those in benign GI disorders. This paper aims to help clinicians become aware of the problem and suggests ways in which the panoply of syndromes can be managed.

A multidisciplinary literature review was performed to develop guidance to facilitate clinical management of GI side effects of cancer treatments.

Different pathological processes within the GI tract may produce identical symptoms. Optimal management requires appropriate investigations and coordinated multidisciplinary working. Lactose intolerance, small bowel bacterial overgrowth and bile acid malabsorption frequently develop during or after chemotherapy. Toxin-negative Clostridium difficile and cytomegalovirus infection may be fulminant in immunosuppressed patients and require rapid diagnosis and treatment. Hepatic side effects include reactivation of viral hepatitis, sinusoidal obstruction syndrome, steatosis and steatohepatitis. Anticancer biological agents have multiple interactions with conventional drugs. Colonoscopy is contraindicated in neutropenic enterocolitis but endoscopy may be life-saving in other patients with GI bleeding. After cancer treatment, simple questions can identify patients who need referral for specialist management of GI symptoms. Other troublesome pelvic problems (eg, urinary, sexual, nutritional) are frequent and may also require specialist input. The largest group of patients affected by chronic GI symptoms are those who have been treated with pelvic radiotherapy. Their complex symptoms, often caused by more than one diagnosis, need systematic investigation by gastroenterologists when empirical treatments fail. All endoscopic and surgical interventions after radiotherapy are potentially hazardous as radiotherapy may induce significant local ischaemia. The best current evidence for effective treatment of radiation-induced GI bleeding is with sucralfate enemas and hyperbaric oxygen therapy.

All cancer units must develop simple methods to identify the many patients who need help and establish routine referral pathways to specialist gastroenterologists where patients can receive safe and effective treatment. Early contact with oncologists and/or specialist surgeons with input from the patient's family and friends often helps the gastroenterologist to refine management strategies. Increased training in the late effects of cancer treatment is required.

Aside from bacterial infections, viral, fungal, and parasitic infections are important differential diagnoses in inflammatory disorders of the colorectum. In contrast to bacterial infections, in which the causative organism can hardly ever be detected histologically, in non bacterial infections the germs can often be verified by either histology, immunohistochemistry, or at least by molecular pathology. This manuscript will give an overview of the spectrum of pathogenic germs, the clinical symptoms, and pathological findings of the most important infections.

Diarrhoea is a common presentation throughout the course of HIV disease.

To review the literature relating to aetiology, investigation and management of diarrhoea in the HIV-infected adult.

The PubMed database was searched using major subject headings 'AIDS' or 'HIV' and 'diarrhoea' or 'intestinal parasite'. The search was limited to adults and to studies with >10 patients.

Diarrhoea affects 40-80% of HIV-infected adults untreated with antiretroviral therapy (ART). First-line investigation is by stool microbiology. Reported yield varies with geography and methodology. Molecular and immunological methods and special stains have improved diagnostic yield. Endoscopy is diagnostic in 30-70% of cases of pathogen-negative diarrhoea and evidence supports flexible sigmoidoscopy as a first line screening procedure (80-95% sensitive for CMV colitis), followed by colonoscopy and terminal ileoscopy. Radiology is useful to assess severity, distribution, complications and to diagnose HIV-related malignancies. Side effects and compliance with ART are important considerations in assessment. There is a good evidence base for many specific therapies, but optimal treatment of cryptosporidiosis is unclear and only limited data support symptomatic treatments.

The immunological response to HIV infection and Antiretroviral therapy remains incompletely understood. Antiretroviral therapy regimens need to be optimised to suppress HIV while minimising side effects. Effective agents for management of cryptosporidiosis are lacking. There is an urgent need for enhanced regional diagnostic facilities in countries with a high prevalence of HIV. The ongoing roll-out of Antiretroviral therapy in low-resource settings will continue to change the aetiology and management of this problem, necessitating ongoing surveillance and study.

Diarrhea is a common clinical manifestation of HIV infection regardless of whether the patients have AIDS. HIV and malnutrition tend to occur in the same populations, the underprivileged and resource-poor. Malnutrition increases severity and mortality of infection. Occurrence of chronic diarrhea in HIV-infected patients, gut status and pathogenic agents, nutritional status and the crucial role of nutrition are reviewed. Bovine colostrum-based food can be useful for managing chronic diarrhea in HIV-infected patients, enhancing both nutritional and immunological status.

The gastrointestinal mucosa is a target of many sexually transmitted infections, and major advances have increased our understanding of the consequences of such infections within the gastrointestinal system. HIV-1 is associated with a marked loss of mucosal CD4(+) T cells that express CC-chemokine receptor 5. This process seems to be more rapid and more severe in mucosa-associated lymphoid tissue than in the peripheral blood. Mechanistic insights into the underlying cause of acute and chronic gastrointestinal damage with HIV infection-microbial translocation, defects in intestinal epithelial barrier function and activation of a systemic immune response-have also been achieved. Increased understanding of the pathogenesis of mucosal HIV-1 infection may identify therapeutic targets to restore immunological function and the integrity of the intestinal mucosal epithelial barrier. The increasing prevalence of lymphogranuloma venereum in Europe, mostly in HIV-positive men who have sex with men, suggests a change in the epidemiology of what was previously considered to be a 'tropical' disease. The increasing incidence of acute HCV infection transmitted via sexual contact has also been fueled by high-risk sexual behaviors among men who have sex with men, many of whom are also HIV-positive. The first part of this Review discusses the pathogenesis and gastrointestinal complications of HIV infection, and the second part summarizes advances in our understanding of other sexually transmitted infections of the gastrointestinal system.

Diarrhea in seropositive human immunodeficiency virus patients is one of the most important and disabling symptoms, and often decreases their quality of life. Cytomegalovirus colitis is among the principal causes of this symptom and colonoscopy is the gold standard examination to diagnose it.

To define the main endoscopic findings in seropositive human immunodeficiency virus patients with cytomegalovirus colitis.

Two hundred and forty-three colonoscopies were performed in 200 seropositive human immunodeficiency virus patients with diarrhea associated or not to abdominal pain or gastrointestinal bleeding, over 10-year period, whom 51 patients were diagnosed with cytomegalovirus colitis. Full length colonoscopy with ileum intubation was always tried and multiple biopsies of all segments examined, including endoscopically normal segments, were attempted. All diagnoses were confirmed by histologic and immunohistochemical studies.

Total colonoscopy was possible in 98.03% and ileum intubation in 88.23% of these cytomegalovirus colitis patients. At colonoscopy, a heterogeneous ulcerative pattern was presented in 72.54%, an inflammatory process of the mucosa in 21.56% and 5.88% of the patients mucosa was endoscopically normal.

Full length colonoscopy with ileum intubation and multiples biopsies of all segments, even when they are endoscopically normal, have always to be attempted in cases of seropositive human immunodeficiency virus patient with diarrhea.

Small intestinal bacterial overgrowth (SIBO) syndrome is characterized in its florid form by diarrhoea and weight loss. The most common underlying factors are dysmotility, small intestinal obstruction, blind or afferent loops. Small intestinal bacterial overgrowth can be diagnosed by: 1) culture of jejunum aspirate for bacterial counts, 2) 14C-D-xylose breath testing, 3) non-invasive hydrogen breath testing using glucose or lactulose or 4) 14C-glycocholic acid breath testing. The treatment usually consists of the eradication of bacterial overgrowth with repeated course of antimicrobials, correction of associated nutritional deficiencies and, when possible, correction of the underlying predisposing conditions.

Although both human immunodeficiency virus (HIV) infection and diarrhea are considerable problems in Cambodia, there have not been any studies to determine the history, clinical presentation, and etiology of chronic diarrhea in patients with HIV infection in Cambodia. In this article, we present a case-control study involving 40 HIV-infected patients with chronic diarrhea and 40 HIV-infected patients without diarrhea.

Clinical, demographic, and laboratory data were collected. Stool samples were examined for parasites, including Cryptosporidium species (by partial acid-fast stain), bacterial pathogens, and rotavirus. Samples from 10 case patients and 10 control subjects were also analyzed for Cryptosporidium species by polymerase chain reaction-restriction fragment-length polymorphism.

The median CD4(+) cell count was 11.5 cells/mm(3). A potential pathogen was found in 30 case patients (75%) and 29 control subjects (72.5%). Cryptosporidium was the most common pathogen, present in 16 case patients (40%) and 20 control subjects (53.3%). The presence of Cryptosporidium was confirmed by polymerase chain reaction-restriction fragment-length polymorphism, with a prevalence of 40% in each of the 2 groups of 10 subjects who were enrolled for Cryptosporidium evaluation.

Subjects in this cohort had severe immunosuppression. The prevalence of pathogens, including Cryptosporidium, was extremely high but did not differ significantly between the case patients with diarrhea and the control subjects without diarrhea. Further studies are needed to examine factors associated with Cryptosporidium carriage and the natural history of asymptomatic infection.

Diarrhea in patients with AIDS is a worldwide problem that can have a devastating impact on quality of life for the patient. Chronic diarrhea, usually defined as at least 4 weeks' duration, is more common in patients with low CD4-positive T-lymphocyte counts, signaling advanced immunosuppression. Some organisms, such as Microsporidia, usually cause diarrhea only in the immunosuppressed; others, such as Cryptosporidium, Salmonella, Shigella, and Campylobacter, which are capable of causing diarrhea in the immunocompetent population, produce more severe or prolonged infections in people living with AIDS. Familiarity with the most common pathogens in the clinician's region will help with diagnosis and treatment. Because treatment options vary widely depending upon the infectious agent, thorough microbiologic evaluation is warranted. A stepped diagnostic approach of stool cultures and specialized microscopy and stains for protozoa, followed by sigmoidoscopy or colonoscopy and duodenoscopy with biopsies for histopathological examination is recommended in all patients with persistent, disabling diarrhea who have a CD4 count of less than 200/mm3, and should be considered for those with higher counts on an individual basis. Treatment, tailored to the specific pathogen, may need to be prolonged in the most severely immunocompromised patients to prevent relapse or recrudescence. For patients taking antiretroviral therapy (especially protease inhibitors) in whom no infectious agent can be found, diarrhea may be due to the medications. Nonspecific antidiarrheal agents should be tried until one that suits the patient is found. The most essential component of any therapeutic strategy for a patient with AIDS-associated diarrhea is restoration of the underlying immunologic defect using highly active antiretroviral therapy.

We describe the management of a cohort of eight HIV-positive patients on antiretroviral medication with evidence of pancreatic insufficiency consisting of chronic diarrhoea and a low faecal elastase measurement.

Twenty-two patients with chronic diarrhoea for whom a faecal elastase measurement was available were identified retrospectively. We compared baseline demographic characteristics, antiretroviral treatment and symptoms of steatorrhea between patients with evidence of pancreatic insufficiency, i.e. a low faecal elastase measurement of <200 microg/g (cases), and patients with evidence of normal pancreatic function, i.e. a normal faecal elastase measurement of >200 microg/g (controls). We describe the management of the patients with evidence of pancreatic insufficiency.

Of the 22 patients, eight had evidence of pancreatic insufficiency, i.e. a low faecal elastase measurement. Comparing cases with controls, cases were more likely to have symptoms of steatorrhea (P=0.03) or to have lost weight (P=0.02). Cases were also significantly more likely to have taken didanosine (ddI) as part of their antiretroviral treatment when their symptoms started. Seven cases were treated with oral pancreatic supplements and all had symptomatic improvement of their diarrhoea. One patient stopped treatment with oral pancreatic supplements because of side effects without a relapse of symptoms; he had also stopped zalcitabine (ddC).

We believe that measurement of faecal elastase to detect pancreatic insufficiency should be part of the standard investigation of HIV-positive patients with chronic diarrhoea alongside assessment for other causes of diarrhoea. Faecal elastase measurements should be requested, in particular, in all patients with diarrhoea and weight loss, or symptoms of steatorrhea, and in those on treatment with an antiretroviral regime containing ddI. If the faecal elastase level is low, a switch of antiretroviral medication to a nonddI/ddC-containing regime should be considered and treatment with oral pancreatic enzyme therapy should be instituted.

The gut and its gut-associated lymphoid tissue serve as a preferential site for HIV1 entry, active viral replication, reservoir, and HIV-mediated CD4 cell apoptosis. The widespread use of highly active antiretroviral therapy (HAART) has resulted in a significant decrease in the incidence of opportunistic enteric pathogens as a consequence of immune recovery. Nonetheless, patients with advanced HIV1 disease who were recently diagnosed or have poor response to HAART can still suffer from opportunistic infections with pathogens such as Cryptosporidium, microsporidia, Isospora belli, Cyclospora cayetanensis, Mycobacterium avium complex, and cytomegalovirus, among others. This review describes the impact of HIV1 infection on gut immune function, the salient features of the most common opportunistic enteric pathogens and HIV-associated enteropathy, and the effects of immune reconstitution after introduction of HAART.

Octreotide has been used to treat HIV-associated diarrhea. We aimed to assess the effect of octreotide on small intestinal motility in a group of HIV infected individuals with chronic diarrhea. Small intestinal motility was measured continuously for 48 hr by ambulatory strain gauge manometry in 12 HIV seropositive subjects with chronic diarrhea. During the second 24-hr period, intravenous octreotide was administered (100 microg every 8 hr). Postprandial and nocturnal fasting motility data were compared before and during administration of octreotide. Octreotide was associated with increased numbers of migrating motor complexes (MMCs) (7.25 vs 4.92, P = 0.03), and a relative decrease in the duration of phase II (22% vs 49.8, P = 0.03) during nocturnal fasting activity. Postprandial activity was absent in half of the subjects and the duration significantly reduced in the remainder. In conclusion, octreotide has a significant effect on small intestinal motility in HIV-infected individuals with diarrhea, which may influence intestinal transit.

Microsporidiosis in AIDS patients has emerged as an important cause of morbidity, but diagnosis requires special stains, equipment and expertise. Here we describe a modification to an existing staining technique to allow more rapid preparation, without additional equipment, facilitating research in the tropics into these important pathogens.

Chronic HIV-associated diarrhea is currently a field in flux. Improved noninvasive diagnostic tests, improved pathogen-specific regimens, and better empiric therapies may change some of the assumptions used to select algorithms for diagnostic evaluation and management. Any shift in the cause of diarrhea from pathogen-associated to idiopathic or a reduction in the overall incidence of diarrhea would have considerable impact. It is unclear how significant the problem of pathogen relapse in previous responders will become. Existing studies reviewed in this article show that the high diagnostic yield of endoscopy when stool tests are negative, coupled with significantly better outcomes when pathogens are identified, support the current practice of routine endoscopic evaluation. There currently are scant data on the economic impact of HIV-associated diarrhea as it relates to pathogen-specific and empiric therapy in the era of protease inhibitors. Such data would be integral to future evaluation of the impact of diagnostic and therapeutic strategies.

To compare the primary diagnoses assigned by general surgical pathologists on a series of 103 consecutive colon biopsies from individuals infected with human immunodeficiency virus (HIV) with diagnoses rendered by a pathologist with extensive experience in gastrointestinal pathology in HIV/acquired immunodeficiency syndrome.

New sections were cut from paraffin blocks of 103 consecutive colon biopsies taken during colonoscopies of 82 different HIV-infected patients; all new sections were stained with hematoxylin-eosin. These individuals either had negative stool studies or had failed to respond to therapy and had chronic large bowel symptoms, such as frequent small volume-type diarrhea, tenesmus, and/or bright red blood per rectum. Immunohistochemistry for cytomegalovirus (CMV) was performed on 18 of 22 specimens originally diagnosed with CMV colitis.

The initial study yielded 70 (68%) negative or nonspecific diagnoses, 22 (21%) cases of CMV colitis, 5 (5%) Cryptosporidium diagnoses, 2 cases each of adenomatous polyps and Kaposi sarcoma, and 1 case each of spirochetosis and squamous cell carcinoma of the anorectum. Review of the recuts yielded 64 (62%) negative or nonspecific diagnoses, 12 (12%) new adenovirus infections (3 combined with CMV), and 11 (11%) lone CMV infections. Three attaching and effacing bacterial infections were diagnosed, 1 with adenovirus coinfection. A total of 4 spirochetosis cases were found on review. Seven (7%) of the biopsies showed at least 1 coinfection. Nine biopsies had features suggestive of inflammatory bowel disease.

Colonoscopy with biopsy after negative stool studies or failure to respond to therapy yielded a high proportion of negative or nonspecific diagnoses. Adenovirus and enteropathogenic bacterial infections had been totally overlooked on initial examination. It takes particular experience to evaluate gastrointestinal biopsies from HIV-infected patients.

The gastrointestinal tract is a common site of infection in the opportunistic host. Pathogens range from highly virulent organisms, which infect people with well functioning immune systems as well as people with poorly functioning immune systems, to opportunistic organisms, which infect only those with impaired immune systems. Viruses, bacteria, fungi, and protozoa lead to disease that can be especially severe, debilitating, and difficult to treat in the immunocompromised host. Yet in this era of highly active antiretroviral therapy for HIV-infected patients and strategies to reduce immunosuppression in transplant and oncology patients, appropriate diagnostic tests and treatment can both improve the quality of life and decrease mortality. In this article, I review the changing pathogenesis, epidemiology, clinical presentation, diagnosis, and treatment of gastrointestinal infections in the immunocompromised host.

Incidence of opportunistic protozoal infections causing diarrheal illnesses in patients with HIV has decreased since the introduction of highly active antiretroviral therapy (HAART). The objective of this study was to determine whether the parasites, cryptosporidia, and microsporidia were effectively eradicated or only suppressed following treatment.

Six HIV-positive patients with diarrheal symptoms caused by cryptosporidia or microsporidia were prospectively followed up with stool samples and duodenal biopsies. Samples were taken before HAART, between 1 to 3 months, and 6 months post-HAART.

Duodenal samples were analyzed using routine histology and transmission electron microscopy. Stool samples were analyzed by both light microscopy and polymerase chain reaction (PCR) techniques.

Patients who responded successfully to HAART eradicated both cryptosporidial and microsporidial organisms. Symptoms improved within 1 month of therapy but complete eradication of the organisms was only observed after 6 months of treatment.

AIDs-related cryptosporidiosis and microsporidiosis can be cured following successful antiretroviral therapy.

HIV-related diarrhoea is an important cause of morbidity and mortality in HIV infection. Cytomegalovirus is a well-established cause of diarrhoea, but the role of other enteric viruses is less clear and will be discussed here. The clinical manifestations, disease mechanisms, diagnostic techniques and current treatments for the management of these infections are reviewed.

The purpose of this study was to evaluate the incidence and causes of chronic diarrhea in patients with AIDS over a period of time that included the pre-HAART (highly active antiretroviral therapy) era and the introduction of HAART.

The study cohort was comprised of patients receiving primary care at a university-associated outpatient HIV clinic from January 1, 1995 to December 31, 1997. Patients were identified retrospectively through a clinical database and were included in the study if their diarrhea had persisted for longer than two weeks and their CD4 cell count at time of symptoms was <200 cells/mm3. Further data were obtained by chart review.

Over the 36-month period, the occurrence of chronic diarrhea did not change significantly, ranging from 8 to 10.5% per year in patients with CD4 cell counts <200 cells/mm3. The percentage of patients diagnosed with opportunistic infectious etiologies decreased over the three-year period from 53% (1995) to 13% (1997). The percentage of patients diagnosed with noninfectious causes increased from 32% to 70% over this same time period.

Over the three years of the study, the incidence of chronic diarrhea in AIDS patients in our clinic did not change. The etiologies of diarrhea did change significantly, with an increased incidence of noninfectious causes and a decreased incidence of opportunistic infectious causes. This shift in etiologies coincides with the introduction and increased use of HAART in our clinic population (1996).

Incidence of opportunistic protozoal infections causing diarrheal illnesses in patients with HIV has decreased since the introduction of highly active antiretroviral therapy (HAART). The objective of this study was to determine whether the parasites, cryptosporidia, and microsporidia were effectively eradicated or only suppressed following treatment.

Six HIV-positive patients with diarrheal symptoms caused by cryptosporidia or microsporidia were prospectively followed up with stool samples and duodenal biopsies. Samples were taken before HAART, between 1 to 3 months, and 6 months post-HAART.

Duodenal samples were analyzed using routine histology and transmission electron microscopy. Stool samples were analyzed by both light microscopy and polymerase chain reaction (PCR) techniques.

Patients who responded successfully to HAART eradicated both cryptosporidial and microsporidial organisms. Symptoms improved within 1 month of therapy but complete eradication of the organisms was only observed after 6 months of treatment.

AIDs-related cryptosporidiosis and microsporidiosis can be cured following successful antiretroviral therapy.

Since the first reported case of HIV infection in 1981, many HIV-seropositive patients have died as a result of diarrhoea induced by opportunistic protozoal infections: pathogens that would normally cause only a transient illness in immunocompetent individuals. The introduction of highly active antiretroviral therapy (HAART) in 1996 has been associated with a significant decline in incidence and mortality arising from infections such as cryptosporidia and microsporidia. Previously, there were no chemotherapeutic agents known to be effective in eradicating these parasites, but since the availability of HAART, the memory of the emaciated terminally ill patient with advanced AIDS suffering from refractory diarrhoea will hopefully be a thing of the past. Significant advances in the knowledge of the pathogenesis of HIV disease, earlier detection and thus treatment of the virus, and availability of improved diagnostic techniques and HAART have transformed the way HIV-associated diarrhoea is managed. In this review, we look specifically at the management of protozoa-induced diarrhoea.

To determine whether diarrhea and intestinal malabsorption during HIV infection alter oral ganciclovir systemic exposure.

We studied the oral disposition of ganciclovir in 42 HIV-infected patients stratified into three groups: A (n = 15), HIV (stage A and B); B (n = 13), AIDS (stage C); and C (n = 14), AIDS with chronic diarrhea and wasting syndrome (10% or more weight loss). Each patient was evaluated for nutritional (body mass index, serum albumin and transferrin), immunologic (CD4 count, plasma viral load) and intestinal status (D-xylose test, fecal fat and nitrogen excretion, and intestinal permeability). Following an overnight fast, 1 g oral ganciclovir was given to patients. Six blood samples were collected over 24 hours. Serum was analyzed for ganciclovir by high performance liquid chromatography. Drug disposition was characterized using a population pharmacokinetic approach.

Mean intestinal permeability increased as HIV disease progressed (0. 05, 0.1, and 0.2 for groups A, B, and C, respectively). Average weight-adjusted maximum concentration (Cmax) in group C was twofold more than that in group A and B patients (12.5 versus 6 and 6.4 ng/ml/kg), and average area under the curve (AUC0-infinity) was threefold greater in group C patients (193 versus 59 and 65 ng. hour/ml/kg in groups A and B, respectively). Mean oral clearance was threefold lower in group C (96 versus 258 and 212 L/hour in groups A and B, respectively).

Because systemic exposure of oral ganciclovir is enhanced in AIDS patients with diarrhea and wasting syndrome, oral ganciclovir therapy may benefit these patients.

The effect of protease inhibitors (PIs) on the outcome of AIDS-associated cytomegalovirus (CMV) colitis is unknown. The aim of this study was to determine the impact of PIs on the recurrence of CMV disease and long-term survival in a large cohort of acquired immunodeficiency syndrome (AIDS) patients with CMV colitis. We reviewed the medical records of 252 AIDS patients who were diagnosed with CMV colitis by colonoscopy between January 1992 and January 1997 at Bellevue Hospital (New York, NY, U.S.A.). Follow-up data were obtained from chart review and direct telephone contact. A complete response to ganciclovir and/or foscarnet therapy was seen in 87.0% of the patients. Recurrence of CMV colitis occurred in 53.1% of patients and was significantly less common in those who received maintenance therapy (36.1% vs. 56.7%; p = 0.03) and in those who were treated with PIs (22.8% vs. 71.9%; p < 0.001). During follow-up. 69.3% of patients died. Multivariate analysis using Cox regression showed that mortality was increased in patients with recurrent CMV colitis (relative risk [RR] of death, 1.7: 95% CI, 1.1-2.6; p = 0.02) and comorbid disease (RR, 1.5: 95% CI, 1.1-2.2; p = 0.02), and decreased in those who were treated with PIs (RR, 0.42; 95% CI, 0.3-0.7; p = 0.001). The median survival was 71 weeks and was significantly longer in patients who were treated with PIs than in those who did not receive these potent anti-retroviral medications (99 vs. 51 weeks; p < 0.001). PIs significantly improve the outcome of AIDS-associated CMV colitis.

Diarrhea is a frequent gastrointestinal symptom in patients with acquired immuno-deficiency syndrome (AIDS) and is a major source of morbidity and mortality. A stepwise diagnostic approach is often recommended to search for treatable causes. However, whether the stepwise diagnostic approach is adequate for planning treatment and whether specific treatment for infectious etiologies will affect the survival of patients with AIDS remain unknown.

From March 1996 to September 1997, endoscopy was performed in AIDS patients with diarrhea, the etiology of which was not identified by noninvasive methods. Specific treatment was given according to the identified etiologies and symptomatic treatment was given for those without definite diagnosis. The clinical symptoms, signs, and duration of follow-up were recorded and survival patterns were analyzed.

Etiologic diagnoses were made in 26 of 40 patients (65%) who underwent endoscopic studies. Amebic colitis and cytomegalovirus colitis were the 2 leading causes of prolonged diarrhea in patients with AIDS. Thirty-five patients (87.5%) recovered after treatment. The difference in survival time after diarrhea between patients whose symptoms resolved after treatment and those who continued to have diarrhea was statistically significant (p < 0.001).

Endoscopic studies were helpful for the diagnosis of prolonged diarrhea in AIDS patients who had negative stool studies and did not respond to 2 weeks of empiric treatment. Specific treatment according to the results of endoscopy may improve survival in these patients.

The effect of protease inhibitors on the outcome of chronic HIV-related diarrhea is unknown. The aim of this study was to compare the response to treatment of chronic HIV-related diarrhea, recurrence of diarrhea, and survival in a large cohort of individuals taking protease inhibitors to the outcome in similar patients not receiving protease inhibitors.

We reviewed the medical records of all patients referred between October 1993 and October 1996 at Bellevue Hospital for endoscopic evaluation of chronic HIV-related diarrhea after negative stool examination. Only patients presenting after December 1995 received protease inhibitor therapy. Follow-up data were obtained from chart review and direct telephone contact. The success of antidiarrheal therapy was compared between protease inhibitor and nonprotease inhibitor groups for patients receiving pathogen-specific therapy and for those with no pathogens found on endoscopy.

Two hundred eighty-two of 307 patients evaluated for chronic diarrhea were followed for a mean of 69.9+/-34.1 weeks. Patients receiving protease inhibitors had a significantly higher rate of successful response to antidiarrheal therapy (62.0% vs 33.5%, p < 0.001). Protease inhibitors were associated with a significant decrease in stool frequency (4.8+/-4.5 vs 3.4+/-4.6 bowel movements per day, p = 0.01), an increase in weight (2.4+/-5.9 vs -1.6+/-6.2 kg, p < 0.001), a decrease in recurrence of diarrhea (34.8% vs 15.3%, p = 0.02), and a longer mean survival (148 vs 118 weeks, p = 0.002).

Protease inhibitors significantly improve the outcome of antidiarrheal therapy and survival in patients with chronic HIV-associated diarrhea.

The role of non-cytomegalovirus (CMV) enteric viral infection in causing diarrhoea in patients with human immunodeficiency virus (HIV) is poorly understood. We aimed to investigate the prevalence of these infections in acute and chronic diarrhoea.

Stool specimens from 377 HIV-infected patients presenting with diarrhoea were studied prospectively for evidence of non-CMV enteric viral infection. Patients with diarrhoea underwent investigation for gastrointestinal pathogens, including electron microscopic examination of stool for enteric viruses. We collected data on patients in whom enteric virus was identified and examined the association of enteric virus infection with diarrhoeal symptomatology.

Eighty-nine (10.3%) stool specimens from 60 (15.9%) HIV+ individuals were positive for coronavirus (n = 13, 22%), rotavirus (n = 11, 18%), adenovirus (n = 30, 50%) and small round structured viruses (n = 5, 8%) or dual infection (n = 2, 3%). Thirty-four of 52 (65%) patients available for analysis had acute diarrhoea, and 18/52 (35%) had chronic diarrhoea. Twenty-three of 52 (44%) patients had a concurrent gut pathogen. After exclusion of concurrent pathogens enteric viral infections were found to be significantly associated with acute as opposed to chronic diarrhoea (P = 0.004). The presence of adenovirus colitis was significantly more likely to be associated with chronic diarrhoea (15/21 cases) than adenovirus isolated from stool alone (9/23 cases) (P = 0.03). There was a trend towards an association between adenovirus colitis and colonic cytomegalovirus infection (P = 0.06).

Enteric viral infection is strongly associated with acute diarrhoea in patients with HIV. Light microscopic examination of large bowel biopsies can identify adenovirus colitis which is significantly associated with chronic diarrhoea, and in addition may facilitate gastrointestinal co-infection with CMV.

To determine the prevalence of intestinal parasites and risk factors for infection associated with diarrhea in HIV-infected patients in Harare, Zimbabwe.

Prospective observational study.

Single stool samples were collected from 88 HIV-infected individuals presenting with diarrhea of greater than 1 week duration. Stools were examined for intestinal parasites using modified acid fast stain, fluorescence- labeled monoclonal antibody for Cryptosporidium parvum, as well as a modified trichrome stain and a PCR-based protocol for Enterocytozoon bieneusi.

C. parvum was detected in 9% (seven out of 82) of samples evaluated, but no Cyclospora was detected. E. bieneusi was detected in 18% (10 out of 55) of stool by trichrome staining and in 51% (28 out of 55) of stool examined by PCR. Risk factors for E. bieneusi infection were: living in rural areas, consumption of nonpiped water, contact with cow dung and household contact with an individual with diarrhea.

E. bieneusi infection was common in HIV-infected patients with diarrhea in Zimbabwe and may be acquired through person-to-person and fecal-oral transmission.

Conclusive studies of small bowel bacterial overgrowth in patients with HIV-1 infection are limited. The relation was therefore determined between the quantity and species of bacteria in the proximal small intestine of HIV-1 infected patients and the presence of diarrhoea, gastric acidity, severity of immune deficiency, and clinical outcome.

Bacteria in the duodenal fluids obtained endoscopically from 32 HIV-1 infected patients, 21 of whom had diarrhoea, and seven control subjects without HIV-1 risk factors were quantified and speciated. Gastric pH was determined at the time of endoscopy. Clinical follow up was performed to assess outcome.

Oropharyngeal Gram positive cocci were present in fluids from 28 patients (88%). Gram negative aerobic or facultatively anaerobic bacteria were present in fluids from 12 patients (38%), and strict anaerobes were detected in six patients (19%), but for both groups colony counts infrequently exceeded 10(4) colony forming units/ml. The number and species of bacteria did not correlate with the presence of diarrhoea, gastric pH, or CD4 lymphocyte count.

Small bowel bacterial overgrowth is not common in HIV-1 infected patients, regardless of the presence of diarrhoea, and is not associated with hypochlorhydria

Gastrointestinal infections are a frequent and important complication of immunodeficiency diseases and immunosuppressive therapy. Such infections may be severe, prolonged, or even fatal, whereas the same infections are typically mild and transient in immunocompetent persons. In this regard, the strong association between HIV-induced immunosuppression and the increased prevalence of severe enteric infections is strong evidence of the link between immune function and defense against enteric pathogens. Because gastrointestinal infections in immunocompromised persons are frequently severe and life-threatening, a vigorous approach to the diagnostic evaluation and therapeutic management is advocated by many clinical investigators. In this review, we summarize the important new developments, particularly during the past year, regarding gastrointestinal infections in immunocompromised persons.

Rabeprazole (LY307640, E3810) is a new, potent, proton pump inhibitor. A single daily 20 mg dose significantly decreases 24-h intragastric acidity. There are no data currently available directly comparing the effect of rabeprazole on 24-h acidity with established proton pump inhibitors.

To compare the effects of rabeprazole 20 mg o.m. and omeprazole 20 mg o.m. on 24-h intragastric acidity and plasma gastrin concentration in a randomized, double-blind, placebo-controlled trial, in healthy H. pylori-negative subjects.

Twenty-four healthy male volunteers, negative for H. pylori infection by serology and 13C-urea breath test, were studied on the 1st and 8th day of dosing with either placebo, rabeprazole 20 mg or omeprazole 20 mg, once each morning, in a crossover fashion. On days 1 and 8, hourly intragastric acidity was measured by gastric aspiration for 24 h from 08.00 hours. On day 8, plasma gastrin concentrations were also measured hourly from 08.00 to 24.00 hours, then every 2 h thereafter.

A single dose of both rabeprazole and omeprazole significantly decreased 24-h intragastric acidity compared with placebo. The 24-h acidity on day 1 was significantly decreased for rabeprazole compared with omeprazole (331 vs. 640 mmol.h/L, P < 0.001), resulting in a significantly higher median 24-h intragastric pH and longer times at which intragastric pH was > 3 and > 4. On day 8 of dosing, the decrease in 24-h intragastric acidity was greater with rabeprazole than with omeprazole, but the difference was not statistically significant (160 vs. 218 mmol.h/L, P = 0.1). However, 24-h plasma gastrin concentration (1687 vs. 1085 pmol.h/L. P < 0.01) and percentage time that intragastric pH was > 3 (69 vs. 59%, P = 0.008) and > 4 (60 vs. 51%, P = 0.03) were significantly greater.

Rabeprazole 20 mg once daily has a significantly faster onset of antisecretory activity than omeprazole 20 mg once daily. After 8 days the differences in intragastric pH > 3 and > 4 holding times persisted, but there was no significant difference in 24-h acidity.

Endoscopy is commonly performed in patients with chronic human immunodeficiency virus (HIV)-related diarrhea after negative stool studies. The aim of this study was to determine the diagnostic yield and cost-effectiveness of endoscopy in this setting.

Consecutive HIV-infected patients with chronic unexplained diarrhea who were referred for diagnostic endoscopy were identified. Patient charts, pathology reports, and endoscopy records were reviewed.

A total of 479 endoscopic procedures were performed in 307 patients. A pathogen was identified in 147 patients (47.9%); cytomegalovirus was the most frequent organism found (21.5%). The average cost of identifying a pathogen by endoscopy was $3822.94. Colonoscopy had a greater diagnostic yield than flexible sigmoidoscopy (38.7% vs. 22.4%, p = 0.009) and was more cost-effective. The yield of upper endoscopy was 29.6%. In patients with a CD4 count of less than 100/mm3, endoscopy had a higher diagnostic yield (62.8% vs. 8.3%, p < 0.0001) and a lower cost of identifying a pathogen ($2943.92 vs. $21,583.51) than in those with higher CD4 counts.

Endoscopy frequently identifies a pathogen in HIV-related chronic diarrhea. Colonoscopy is the most cost-effective procedure. Endoscopic evaluation has a significantly higher diagnostic yield and is considerably more cost-effective in patients with a CD4 count of less than 100/mm3 than in those with higher CD4 counts.

In human immunodeficiency virus (HIV)-infected patients with chronic unexplained diarrhea, upper endoscopy with small bowel biopsy and aspirate is often performed to identify treatable pathogens. The purpose of this study was to compare the diagnostic yield of duodenal with jejunal biopsy and aspirate.

All HIV-infected patients with chronic unexplained diarrhea who were evaluated by upper endoscopy at Bellevue Hospital Center between January 1992 and January 1997 were identified. Data were collected by reviewing patient charts, endoscopy reports, and pathology records.

During the 5-yr study period, 442 patients underwent upper endoscopy with sampling of the duodenum (N=173) or jejunum (N=269). A pathogen was identified in 123 patients (27.8%). Microsporidia was the most common organism detected (12.2%). The diagnostic yield of jejunal biopsy and aspirate was significantly higher than that obtained from the duodenum (32.3% vs 20.8%, p=0.009). Small bowel aspirates detected a pathogen in only 1.8% of patients evaluated, and there was no difference in the yield of duodenal and jejunal aspirates (1.3% vs 2.1%, p=0.7). Patients with a CD4 count of < 100 cells/mm3 were significantly more likely to have a pathogen identified than those with higher CD4 counts (38.8% vs 7.1%,p < 0.0001).

Upper endoscopy with small bowel biopsy and aspirate identifies a pathogen in 27.8% of individuals with HIV-related chronic unexplained diarrhea. In this patient population, jejunal biopsies acquired by enteroscopy are superior to those obtained from the duodenum. Small bowel aspirates are of little value in the workup of chronic HIV-related diarrhea.