The following section will discuss the diagnosis and management of a number of common bacterial, viral and parasitic gastrointestinal infections that may be seen in people with HIV infection, and also non-infectious diarrhoea. A number of important HIV-associated conditions are covered elsewhere in the website – Kaposi’s sarcoma and HBV and HCV infections. Readers are referred to other texts for the management of common illnesses such as gastroesophageal reflux disease and the Australian Therapeutic Guidelines [1] and Sanford Guides [2] for specific treatment advice.
Dysphagia/ odynophagia
When assessing patients with dysphagia (difficulty swallowing with a sensation of food sticking), it is important to determine if their symptoms are due to an oropharyngeal or oesophageal cause. Patients with oropharyngeal dysphagia often have difficulty initiating a swallow, reporting a sensation that food gets stuck immediately on swallowing (usually localising/pointing to their neck) and may experience coughing, choking or nasal regurgitation during swallowing. Patients with oesophageal dysphagia usually report a sensation of food getting stuck soon after swallowing (they may localise/point to their neck or behind their sternum). Oesophageal dysphagia may be due to structural or motility disorders. A detailed history can give clues to the likely cause. The types of food that produce symptoms (solids, liquids or both), the changes over time (types of food at onset, intermittent or progressive nature) and associated symptoms (pain, heartburn, regurgitation, weight loss) should be ascertained. Previous interventions (surgery, radiotherapy), other diseases, such as atopy, asthma or eczema which are associated with eosinophilic oesophagitis, and other medications (tetracycline, bisphosphonates) may be relevant.
Oesophageal candidiasis is the most common cause of dysphagia in patients with HIV infection. Patients may also report odynophagia (pain on swallowing) and retrosternal discomfort. Most patients will have oropharyngeal candidiasis (oral thrush); however, its absence does not exclude the diagnosis [3]. An upper gastrointestinal endoscopy is generally not required for patients with HIV infection and oral candidiasis with oesophageal symptoms. Treatment consists of a loading dose of 200mg, then 100mg of oral fluconazole for 14 days [4]. Intravenous fluconazole can be administered to patients who are unable to tolerate oral therapy. For patients with a poor clinical response to oral fluconazole, an upper gastrointestinal endoscopy is necessary to exclude other diagnoses, such as CMV or HSV disease or oesophageal malignancy, and to obtain specimens to culture for fungal speciation and antifungal susceptibility testing [5].
HSV and CMV disease should be considered in patients presenting with odynophagia as this is the predominant complaint in patients with this type of oesophagitis. HSV oesophagitis usually has a severe and abrupt onset of intense pain (reviewed in Lavery et al. [6]). CMV oesophagitis is more subacute and generally associated with weight loss. The absence of oral lesions (herpes labialis) does not exclude the diagnosis of HSV oesophagitis. An endoscopy and biopsy is required to confidently distinguish these two conditions. HSV oesophagitis responds to aciclovir 5 mg/kg intravenously every 8 hours followed by famciclovir 500mg twice a day or valaciclovir 1g twice a day, when oral therapy is possible, to complete a 10-day course [7]. Maintenance therapy is usually reserved for frequent recurrences.
Diarrhoea
Diarrhoea is common amongst people with HIV infection. The differential diagnosis is strongly influenced by the risk factors, duration of symptoms (acute versus chronic) and the degree of immunodeficiency. A detailed clinical history and physical examination is essential. Investigations should include stool culture and microscopy and/or multiplex PCR. Additional investigations that may be required include mycobacterial blood cultures, endoscopy with biopsies and abdominal imaging with CT scan. Causes of acute and chronic diarrhoea that occur in patients without HIV infection should also be considered.
Enteric pathogens causing diarrhoea
Acute, infective diarrhoea is common in patients with HIV infection. Transmission may be food borne, waterborne, institutional or person-to-person via faecal-oral or sexual transmission. The patterns of infecting enteric pathogens vary based on patient and geographical epidemiology. In Australia, bacterial pathogens such as salmonella, shigella and campylobacter are common. Shigella sonnei is frequently sexually transmitted via the oro-faecal route with no history of overseas travel. Common viral infections such as norovirus and adenovirus are mostly self-limiting. A history of unprotected, receptive anal intercourse may suggest sexual transmission of organisms such as Neisseria gonorrhoeae or Chlamydia trachomatis. These organisms may cause anal discomfort and discharge. Clostridium difficile is most common after antibiotic usage. Parasitic infections are more common in returned travellers, although some parasites e.g. Giardia lamblia and Strongyloides stercoralis can be acquired in Australia (see Table 2).
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Table 2. Common causes of infectious diarrhoea in patients with HIV infection in Australia – clinical presentation, diagnosis and management [8,9] |
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Infection |
Clinical presentation |
Diagnosis |
Management |
Comments |
|
Salmonella spp. |
Abrupt onset of watery diarrhoea, nausea, abdominal pain and fevers occurring 6-48 hours post-contact |
Stool culture, microscopy and multiplex PCR Blood culture |
IV ceftriaxone if bacteraemic, then oral azithromycin or ciprofloxacin for 5 to 7 days as guided by susceptibility testing |
Patients may be bacteraemic without diarrhoea |
|
Shigella spp. |
Fever and watery diarrhoea (dysentery), with or without blood, usually, 1-7 days post-contact Tenesmus |
Stool culture, microscopy and multiplex PCR Blood culture |
Oral ciprofloxacin for 5 days if susceptible May need IV ceftriaxone for resistant isolates [10] |
Strict rules for food handlers |
|
Campylobacter spp. |
Voluminous watery diarrhoea followed by proctocolitis with blood, mucous and tenesmus (usually 2-6 days post-contact) |
Stool culture, microscopy and multiplex PCR Blood culture |
Uncomplicated diarrhoea - oral azithromycin or ciprofloxacin for 3 days if symptoms persist. Resistant strains are emerging [11] |
Patients may be bacteraemic without diarrhoea |
|
Clostridium difficile |
Diarrhoea, fever, abdominal pain Antibiotic exposure |
Clostridium difficile toxin |
Metronidazole 400 mg three times a day OR Oral vancomycin 125 mg four times a day for 10-14 days |
Contact isolation in health services |
|
Norovirus |
Acute watery diarrhoea |
Faecal multiplex PCR |
Is usually self-limiting. No antiviral therapy available. |
Contact isolation in health services |
|
Giardia lamblia |
Non-bloody, chronic diarrhoea occurring 1-3 weeks post-exposure associated with nausea, vomiting, abdominal pain, belching, bloating and flatus. Fevers are rare |
Faeces microscopy to demonstrate cysts and trophozoites; erythrocytes are rare. Multiplex PCR |
Tinidazole 2g as a single dose or oral metronidazole 2g daily for 3 days |
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Chronic infective diarrhoea caused by unusual organisms such as Cryptosporidium parvum, microsporidia, Cyclospora cayetanensis and Cystoisospora belli are now uncommon in resource-rich settings, although occupational exposure may occur. These are often associated with advanced immunodeficiency and patients present with profuse prolonged diarrhoea associated with anorexia, fatigue, weight loss and occasional fevers. Travel, animal exposure and occupational histories are helpful. Careful stool examination for ova, cysts and parasites should be undertaken and may require the addition of special stains such as modified acid-fast and auramine-rhodamine fluorescent stains. Some multiplex PCR assays will detect unusual organisms such as microsporidia and cryptosporidium. Although rare in Australia, Mycobacterium avium complex (MAC) infection should be considered in patients with advanced immunodeficiency and appropriate blood cultures obtained. Endoscopy with biopsies may be required, particularly for the diagnosis of CMV colitis.
Non-infectious diarrhoea
While antiretroviral therapy ART has clearly reduced the incidence of diarrhoea due to opportunistic infections in people with HIV infection, up to a quarter of patients receiving ART are estimated to experience four or more loose motions a day.[12] Non-infectious diarrhoea may be associated with ART, or HIV-infection itself (HIV enteropathy). Protease inhibitors have the highest rates of diarrhoea (13.3%) when compared with nucleoside reverse transcriptase inhibitors (NRTIs) (10%, and 2% in non-nucleoside reverse transcriptase inhibitors (NNRTIs).[13] ART-associated diarrhoea has been postulated to be due to damage to the intestinal epithelial barrier and altered secretion of calcium-dependent chloride ions. HIV enteropathy is caused by viral infection of enterocytes leading to a loss of epithelial barrier and permeability, immune activation and autonomic dysfunction [12].
Dietary, non-pharmacological and pharmacological approaches should be attempted before switching ART from a successful regimen. Clinical trials in this area are limited. Proposed modifications include: reduction in caffeine, fat and lactose intake and an increase in fibre consumption. Psyllium husk and oat bran, as bulking agent, and probiotics or bovine serum-derived immunoglobulin to modulate and normalise enteric flora have been investigated. Pharmacological treatment includes adsorbents (e.g. bismuth), anti-motility agents (e.g. loperamide) and anti-secretory agents such as octreotide.[12,13,14] Crofelemer, a novel dual inhibitor of cAMP-stimulated CFTR (cystic fibrosis transmembrane conductance regulator) chloride channel and CaCC (calcium-activated chloride channel) has shown promising results.[15] While the only current indication for faecal microbiome transfer (FMT) is Clostridium difficile infection [16], FMT may become a novel therapy for other indications in the future.