27th June 2023

Gastrointestinal complications of HIV/AIDS

Oral and oesophageal presentations

Oral lesions are early indicators of infection and can predict progression to AIDS. There are numerous lesions seen in HIV affecting the oral cavity, including:

• Oral hairy leukoplakia
• Pseudomembranous candidiasis
• Herpes simplex infection
• Kaposi’s sarcoma
• Ulcers, including aphthous ulcers

Oral candidiasis is usually caused by Candida albicans and is very common in HIV-l, affecting 80-90% of patients. ~15 species cause candidiasis, and in HIV is caused more commonly by C. dubliniensis relative to other patients. Oral candidiasis infection usually starts on the dorsum of the tongue. Pseudomembranous candidiasis is the common ‘thrush’ pattern of Candida infection. It features white-yellow plaques in the oral mucosa, which show an erythematous base when scraped off. Other risk factors for candidiasis include steroids, smoking, dentures, and poor saliva production. Management of oral candidiasis in HIV is with oral fluconazole, advice on hygiene and smoking cessation.

Oesophageal candida infection is more specific for HIV, affecting 10% of patients with HIV, usually at CD4+ T cell counts <100/μL. Symptoms include:

• Painful swallowing
• Difficulty swallowing
• Retrosternal pain
• Abdominal pain
• Asymptomatic finding

Differentials include viral oesophagitis, and so diagnosis requires visualisation (i.e. endoscopy) and histology (biopsy or brushing the oesophageal mucosa). An alternative is radiological examination with barium swallow – a ‘double swallow’ is needed and is about 90% sensitive. Management involves antifungal therapy with fluconazole PO or IV if swallowing is not possible, it is taken for 2-3 weeks.

Oral hairy leukoplakia is more specifically associated with immunosuppression, usually by HIV. It is caused by Epstein-Barr virus (EBV) and characteristically causes a white lesion on one side of the tongue. It is ‘shaggy’ in appearance, usually unilateral, and cannot be rubbed off. Over 90% of the adult population has EBV. It is treated with topical antiviral agents, which are generally effective and safe. Treatment options include:

• Combined 25% podophyllin and 5% acyclovir cream
• Gentain violet 2%
• Surgical excision
• Cryotherapy

Overall, the clinical significance of oral hairy leukoplakia is primarily as an indicator of progression towards AIDS, and its development should prompt testing if there is no HIV diagnosis.

Biliary and pancreatic presentations

HIV causes inflammation of the liver parenchyma and biliary tree. HIV additionally causes biliary tree damage by opportunistic infections, resulting in the formation of biliary strictures, which is termed ‘AIDS cholangiopathy’ and tends to develop with a CD4+ T-cell count <100/μL. The most common organisms causing AIDS cholangiopathy are:

• Cryptosporidium parvum
• Cytomegalovirus
• Microsporidia (usually Enterocytozoon bieneusi)

The presentation of AIDS cholangiopathy includes:

• Right upper quadrant pain
• Fever
• Jaundice
• Nausea and vomiting

Abdominal tenderness and hepatomegaly may be seen on examination. Blood tests demonstrate raised liver function tests with obstructive pattern. Imaging is often useful for establishing the cause of biliary symptoms in HIV:

• Ultrasonography is abnormal in ~75%, showing dilated intrahepatic and extrahepatic ducts and/or dilated CBD
• CT is not the preferred imaging modality but may demonstrate intrahepatic and extrahepatic dilatation
• Magnetic resonance cholangiopancreatography (MRCP) is preferred to ERCP due to lower risk of perforation and pancreatitis

AIDS cholangiopathy management involves:

• Endoscopic sphincterotomy
• Analgesia, e.g. a CT-guided coeliac plexus block
• Ursodeoxycholic acid improves deranged liver function
• Screening for cholangiocarcinoma

The liver parenchymal cells are injured by numerous mechanisms, including:

• Oxidative stress
• Lipotoxicity
• Metabolite accumulation
• Translocation of the gut microbiota
• The accumulation of toxic metabolites

Additionally, there may be indirect mechanisms which result in HIV causing liver injury or a higher risk of liver injury. These include:

• Hepatitis co-infection
• HIV-associated neoplasm
• Hepatotoxic antiretroviral therapy

Overall, these mechanisms and confounding factors (e.g. non-alcoholic fatty liver disease) mean that people with HIV are ~10 times more likely to die from liver infection than the population as a whole.

Transient elastography can determine the degree of liver fibrosis. Patients with higher viral load usually have higher levels of fibrosis. Despite hepatotoxicity associated with some antiretroviral agents, better controlled HIV and higher antiretroviral use is associated with a lower risk of fibrosis overall.