Diarrhoea remains common in people with
HIV and usually has a non-infectious cause, according to a review article
published in the online edition of Clinical
Infectious Diseases. The authors stress that diarrhoea can have a severe
impact on quality of life, necessitate changes to HIV therapy and
contribute to poor adherence to treatment. The article sets out a matrix for
the diagnosis and management of diarrhoea, considers possible therapies and
sets out some priorities for future research.
Up to 60% of people living with HIV report
diarrhoea. The condition is usually defined as three or more loose or liquid
bowel movements per day and its prevalence is significantly higher among
HIV-positive people when compared to matched controls.
A large corpus of research shows that
diarrhoea has a severe impact on the quality of life of people living with HIV. In one study, 40% of participants indicated that diarrhoea adversely
affected their social life. This involved restricting schedules or staying close
to home because of concerns about the possibility of urgent bowel movements.
Diarrhoea was also associated with feelings of shame.
Gastrointestinal opportunistic infections
are a cause of diarrhoea in people with immune suppression. However, diarrhoea can affect people at all stages of HIV disease and is often
unrelated to an infection. Possible non-infectious causes include the
side-effects of antiretroviral drugs, the effects of HIV on the
gastrointestinal tract and, more unusually, malignancies and pancreatitis.
A meta-analysis showed that approximately a
fifth of people taking HIV therapy experienced moderate to severe diarrhoea.
The condition has been associated with drugs in all three of the major classes
of antiretrovirals. However, ritonavir-boosted protease inhibitors appear to
involve the biggest risk of diarrhoea.
There are a number of possible reasons why
antiretrovirals cause diarrhoea. These include damage to the intestinal
epithelial barrier, leading to “leaky-flux” diarrhoea. However, much of the
data for this explanation were obtained from animal models using large doses of
medication. An alternative explanation is that anti-HIV drugs may alter chloride ion secretion
causing so-called “secretory diarrhoea”.
HIV itself is also a potential cause of
diarrhoea. The virus can infect the cells in the gastrointestinal tract and
cause immune damage in this compartment, especially to gut-associated lymphoid
tissue (GALT). Such damage may not be repaired with antiretroviral therapy and
there is some evidence that HIV continues to replicate in gut tissue even in
the presence of virologically suppressive antiretroviral therapy.
Another possible explanation is the
autonomic damage that HIV can cause. Damage to autonomic nerves in the
gastrointestinal tract has been observed in HIV-positive people.
More unusual causes of diarrhoea include
the lesions associated with certain malignancies, as well as pancreatitis.
The authors present an algorithm for the
diagnosis and management of diarrhoea in people with HIV.
They note that definitions of diarrhoea can
differ, and therefore propose that it should be defined as three or more daily
bowel movements of unformed or liquid stool of large volume. They further
propose that diarrhoea lasting four or more weeks should be defined as chronic.
Assessment of someone with diarrhoea
should involve a consideration of physical examination, a detailed medical
history and a review of HIV treatment history. Potential
infectious causes should be considered, especially for people with a low CD4
A stool sample should be obtained for
microbiologic examination. The authors anticipate that this will yield a
diagnosis for 50% of people. If no infectious cause is identified, then people with especially severe diarrhoea (ten or more bowel movements per day)
should have an endoscopy.
HIV therapy should be reviewed to consider
if this is the potential cause. Radiological examination is recommended if a
malignancy is suspected.
Appropriate therapy should be provided for people with infection-related diarrhoea.
The authors stress that there is currently
no recommended therapy for non-infectious forms of diarrhoea in HIV-positive
people. The use of medication such as Imodium
to control symptoms should be considered purely supportive, and it should be
noted that this can cause side-effects, most notably constipation. Crofelemer, an agent designed to address HIV-associated diarrhoea, is currently being reviewed by the US Food and Drug Administration and a decision is expected by September 2012.
Dietary changes, such as the use of fibre
supplements, have been shown to have some impact on protease inhibitor-related
Three research priorities are identified by
- Better definition of the causes
of diarrhoea in people taking HIV therapy.
- An evaluation of the safety and
efficacy of anti-diarrhoea therapies.
- Exploration of how current HIV
treatment can be refined so as to reduce the risk of gastrointestinal
complications and improve immune responses in this compartment.