General approach to the assessment of gastrointestinal symptoms in HIV patients
Gastrointestinal symptoms and illnesses are extremely common in the general population and also in patients with human immunodeficiency virus (HIV) infection. When assessing this, we need to take into account:
- Detailed history including: Onset, frequency and progression, site/location Duration and severity Triggering and relieving factors Associated features such as fevers and weight loss
- Risk behaviour and activities: Injecting drug use – increased risk of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection and bacterial sepsis Substance abuse – including alcohol Sexual history including men who have sex with men – risk of enteric pathogens, particularly salmonellosis Recent travel – risk of parasitic infections, hepatitis A virus infection and typhoid Recent contacts Dietary habits
- Degree of immunodeficiency CD4 T- lymphocyte (CD4) cell count - opportunistic infections, such as cytomegalovirus (CMV) colitis, occur in advanced immunodeficiency Duration of CD4 cell depletion Additional immunosuppressive factors (e.g. corticosteroids, immunosuppressant therapy)
- Use of primary and secondary prophylactic therapy for gastrointestinal tract pathogens Azithromycin for Mycobacterium avium complex (MAC) Valganciclovir for CMV (including dose and adherence)
- Medications: Prescribed including antibiotics and opiates Over-the-counter including aspirin
- Previous serological tests for infection by gastrointestinal tract pathogens
- CMV antibodies HBV and HCV antibodies
- Previous abdominal surgery
- Gynaecological history in women
Common symptoms and signs reported in patients with HIV and the more common causes are presented in Table 1 along with a number of associated features and differential diagnoses that are particularly important to consider in patients with HIV.
Concerning associated features
Investigations to consider
Solid vs. liquid
|Oesophagitis – Candida, CMV, HSV||
Oesophagoscopy with biopsy and/or culture of brushings
Right upper quadrant or epigastric abdominal pain
Acute viral Hepatitis
FBE, LFT, U+E, Calcium
Targeted: Ultrasound of liver
Ultrasound of renal tract
Voluminous watery diarrhoea
Bacterial enterocolitis, including salmonellosis
Clostridium difficile colitis
Inflammatory bowel disease
Irritable bowel syndrome
HIV protease inhibitors
FBE, CRP, LFT, U+E, Blood cultures, including for MAC
Plasma CMV viral load
Stool cultures and microscopy
Clostridium difficile toxin
Colonoscopy and colonic biopsy
|Constipation||Bleeding per rectum (PR)||Haemorrhoids Poor diet Opiates||
Serum carcinoembryonic antigen
Acute vs. chronic
Bleeding PR Ascites
Inflammatory bowel disease
Irritable bowel syndrome
HIV protease inhibitors
|CT scan of abdomen||
Clarify location of pain to target investigations.
Gynaecological history and examination in women.
Painful vs. painless
Excessive alcohol use
LFT, INR, LDH Ultrasound of liver
CT scan of abdomen Ca 19.9
|ERCP/MRCP may be required|
CMV: cytomegalovirus; CRP: C-reactive protein; CT: computerised tomographic; ERCP: endoscopic retrograde cholangiopancreatography; FBE: full blood examination; GORD: gastroesophageal reflux disease; HSV: herpes simplex virus; INR: international normalised ratio for prothrombin time; LFT: liver function test; LDH: lactate dehydrogenase; MAC: Mycobacterium avium complex; MRCP: magnetic retrograde cholangiopancreatography; U+E: urea and electrolytes
Specific gastrointestinal and oral infections associated with HIV infection
The following section will discuss the diagnosis and management of a number of common bacterial, viral and parasitic gastrointestinal infections and also non-infectious diarrhoea. A number of important HIV-associated conditions are covered elsewhere in the monograph - oesophageal candidiasis, CMV infections, Kaposi sarcoma and HBV and HCV infection. Readers are referred to other text for management of common illnesses such as gastroesophageal reflux disease and the Australian antibiotic guidelines  and Sanford Guides for specific treatment advice.
Dental hygiene is important in all patients with HIV infection, but particularly challenging in those patients with social, financial and housing difficulties. Smoking, high sugar diets and excessive alcohol intake are risk factors for poor dental hygiene. The common form of gingivitis, linear gingival erythema characterised by a 1-3 mm erythematous band along the gingival margin, periodontitis and oral aphthous ulceration are common in patients with HIV and also the general population. Clinical features include halitosis, spontaneous bleeding and pain. These conditions are usually self-limiting and respond to dental attention and mouth washes. Severe gum disease seen previously in advanced HIV-associated immunodeficiency, such as necrotising ulcerative gingivitis and periodontitis, is now rare.
The case definitions of oropharyngeal candidiasis and other oral diseases have been updated by the Oral HIV/AIDS Research Alliance and expertly discussed in Shiboski et al:
- Pseudo-membranous candidiasis presents as white or yellow plaques, which may be located in any part of the oral cavity and easily rubbed off. Underlying mucosa may be erythematous and bleed. These are usually painful.
- Erythematous candidiasis presents as red areas on the palate, the dorsum of the tongue, and occasionally on the buccal mucosa. This is usually asymptomatic.
- Angular chelitis presents as ﬁssuring at the corners of the mouth.
The diagnosis is generally made on clinical appearance, but a plain swab or concentrated mouth rinse for microbiological culture may aid in confirming the diagnosis. In poorly resolving candidiasis, culture results assist in species identification and antifungal resistance profiling. Oral fluconazole 100-200 mg daily for 7-14 days is recommended therapy. A single dose of 750 mg fluconazole has also been shown to be equally effective as 150 mg daily for 14 days. Topical amphotericin B taken four times daily can be administered as a suspension, lozenge or tablet. Oral clotrimazole 10 mg troches/lozenges administered ﬁve times daily or nystatin oral drops (Nilstat®) 4-6 mL four times daily can successfully treat mild-to-moderate oropharyngeal candidiasis. Other azoles particularly posaconazole have also been shown to be successful (reviewed in Patton et al.), but are usually only required in fluconazole-refractory disease. Secondary prophylaxis targeted against candida is usually limited to those with recurrent disease and have a CD4 cell count of less than 50 cells/uL.
Oesophageal candidiasis, the most common cause of dysphagia (difficulty swallowing with a sensation of food sticking) in patients with HIV infection, is discussed in detail in the section on oesophageal candidiasis. This condition is usually treated with 200-400 mg of oral fluconazole for 14-21 days, and endoscopy is performed in the setting of poor clinical response, to rule out CMV and HSV disease.
HSV and CMV disease should be considered in patients presenting with odynophagia (pain on swallowing). HSV oesophagitis usually has a severe and abrupt onset of intense pain (reviewed in Lavery et al.). CMV oesophagitis is more subacute and 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 acyclovir 5 mg/kg intravenously every 8 hours followed by famciclovir or valaciclovir 500 mg twice a day when oral therapy is possible for 14-21 days. Maintenance therapy is usually commenced only after the ﬁrst relapse. CMV oesophagitis is discussed in the section on dermatological manifestations.
Enteric pathogens causing diarrhoea
Infective diarrhoea is common in patients with HIV infection. Transmission may be foodborne, waterborne, or person-to-person via faecal-oral or sexual routes, and institutional. The patterns of infecting enteric pathogens vary based on patient and geographical epidemiology. In resource-rich Australia, bacterial pathogens such as salmonella and campylobacter are common as is Clostridium difficile particularly after antibiotic usage, whereas parasitic infections are rare except in returning travellers. Common viral infections such as norovirus and adenovirus are mostly self-limiting (see Table 2).
MCS: microscopy culture sensitivities; spp: species
Salmonella spp.Abrupt onset of watery diarrhoea, nausea, abdominal pain and fevers occurring 6-48 hours post-contact Stool MC/ Blood culture(IV ceftriaxone if bacteraemic) then oral azithromycin or ciprofloxacin for total of 14 days Look for bacteraemia. Patients may be bacteraemic without diarrhoea
|Shigella spp.||Fever, non-bloody watery dysentery (usually 1-7 days post-contact) Tenesmus||Stool MCS Blood culture||Oral azithromycin or ciprofloxacin for 7-10 days||Strict rules for food handlers|
|Campylobacter spp.||Voluminous watery diarrhoea early, then proctocolitis with blood, mucous and tenesmus (usually 2-6 days post-contact)||Stool MCS Blood culture||Oral azithromycin or ciprofloxacin for 5-10 days||Look for bacteraemia. Patients may be bacteraemic without diarrhoea|
|Clostridium difficile||Diarrhoea, fever, abdominal pain Antibiotic exposure||Clostridium difficile toxin||Metronidazole 500 mg three times a day or alternatively oral vancomycin 125 mg three times a day for 10-14 days||Contact isolation in health services|
|Norovirus||Acute watery diarrhoea||-||Is usually self-limiting. No antiviral therapy required||Contact isolation in health services|
|Giardia||Non-bloody, chronic diarrhoea occurring 1-3 weeks post-exposure associated with nausea, vomiting, abdominal pain, belching, bloating and flatus. Fevers are rare||Red cells are rare. Cysts and trophozoites||Tinidazole 2 g single dose||-|
Chronic infective diarrhoea caused by unusual parasites such as Cryptosporidium parvum, microsporidia, Cyclospora cayetanensis and Cystoisospora belli are now rarely seen in resource-rich settings. These are associated with advanced immunodeficiency and patients present with profuse prolonged diarrhoea associated with anorexia, fatigue and weight loss and occasional fevers. Giardia is still occasionally encountered (Table 2). A travel history is helpful. Careful stool examination for ova, cysts and parasites may require special stains such as modified acid-fast and auramine-rhodamine fluorescent stains. Occasionally small intestinal biopsies may be necessary. Eosinophilia may be seen on full blood examination. Mycobacterium avium complex infection may also be associated with chronic diarrhoea – blood cultures are recommended.
While antiretroviral therapy (ART) has clearly reduced the incidence of diarrhoea due to opportunistic infections, up to a quarter of patients receiving ART are estimated to experience four or more loose motions a day. Non-infectious diarrhoea may be associated with ART, or HIV-infection itself (HIV enteropathy). Protease inhibitors have the highest rates of diarrhoea (13.3%) compared to nucleoside reverse transcriptase inhibitors (NRTIs) (10%, excluding stavudine and didanosine – no longer commonly used) and 2% in non-nucleoside reverse transcriptase inhibitors (NNRTIs). 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 has been proposed to be due to viral infection of enterocytes leasing to a loss of epithelial barrier and permeability, immune activation and loss of autonomic denervation.
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 increase in fibre consumption. Psyllium husk and oat bran, as bulking agents, and probiotics or bovine serum-derived immunoglobulin, to modulate and normalise enteric flora, have also been used. Pharmacological treatment includes adsorbents (e.g. bismuth), antimotility agents (e.g. loperamide) and antisecretory agents such as octreotide. 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.