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Review article: The aetiology, investigation and

management of diarrhoea in the HIV-positive
patient
ARTICLE in ALIMENTARY PHARMACOLOGY & THERAPEUTICS SEPTEMBER 2011
Impact Factor: 5.73 DOI: 10.1111/j.1365-2036.2011.04781.x Source: PubMed
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Alimentary Pharmacology and Therapeutics
Review article: the aetiology, investigation and management of

diarrhoea in the HIV-positive patient
N. A. Feasey*,, P. Healey & M. A. Gordon*
*Department of Gastroenterology,
University of Liverpool, Liverpool, UK.
Malawi-Liverpool-Wellcome Trust
Major Overseas Programme, Blantyre,
Malawi.
Department of Radiology, Royal Liverpool University Hospital, Liverpool,

UK.
Correspondence to:
Dr M. A. Gordon, University of Liverpool Gastroenterology Unit, Henry
Wellcome Laboratories, Nuffield Building, Crown Street, Liverpool L69 3GE,
UK.
E-mail: magordon@liv.ac.uk
Publication data
Submitted 2 February 2011
First decision 23 March 2011
Resubmitted 28 June 2011
Accepted 30 June 2011
EV Pub Online 20 July 2011
This commissioned review article was

subject to full peer-review.
SUMMARY
Background
Diarrhoea is a common presentation throughout the course of HIV disease.
Aim
To review the literature relating to aetiology, investigation and management of
diarrhoea in the HIV-infected adult.
Methods
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.
Results
Diarrhoea affects 4080% 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 3070% of
cases of pathogen-negative diarrhoea and evidence supports exible sigmoidoscopy
as a rst line screening procedure (8095% 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 specic therapies, but optimal treatment of cryptosporidiosis is unclear and only limited data support symptomatic treatments.
Conclusions
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.
Aliment Pharmacol Ther 2011; 34: 587603
2011 Blackwell Publishing Ltd

doi:10.1111/j.1365-2036.2011.04781.x
587
N. A. Feasey et al.
INTRODUCTION
Both acute and chronic diarrhoea have been recognised
as major complications of human immunodeciency
virus (HIV) infection and the acquired immunodeciency syndrome (AIDS) since the early days of the pandemic, being described as slim disease in Africa as a
result of the combination of watery diarrhoea and weight
loss that was characteristic.1 Denitions of chronic diarrhoea vary, but an accepted one is the abnormal passage
of three or more loose or liquid stools per day for more
than 4 weeks and or a daily stool weight greater than
200 g day.2 While acute bacterial gastroenteritis causes
blood stream invasion and death more frequently in
HIV-infected than in immune-competent patients,
chronic diarrhoea is also a massive problem for HIV
patients untreated with antiretroviral therapy (ART).
Case series from industrialised countries in the preantiretroviral (ARV) era (therefore involving untreated
patients) show that 4080% of HIV-infected patients will
experience diarrhoea.35
Human immunodeciency virus has an impact on
intestinal infection at all stages (by plasma CD4 count),
with additional aggregation of disease in individuals who
have increased susceptibility to diarrhoeal infection irrespective of CD4 count.6 While HIV associated diarrhoea
is most frequently caused by an opportunistic infection,
there are many non-infectious causes which should also
be considered. As the list of aetiological agents has
grown both with increased experience of HIV and as
powerful antiretroviral therapy (ART) has developed, so
too has the array of investigations and therapeutics available to manage diarrhoea in HIV infection.
THE IMPACT OF HIV ON THE GASTROINTESTINAL
TRACT
The Human Immunodeciency Virus (HIV) causes progressive immunosuppression as a consequence of its tropism for CD4+ T-lymphocytes which progressively
decline because of apoptosis. Following acute infection,
there is a sharp initial fall in the plasma CD4 count,
which is followed by recovery and then a progressive
deterioration in the plasma CD4 count. Monitoring this
deterioration in plasma CD4 count is the major surrogate marker of immune status and is often the principal
tool in guiding the timing of initiation of ART. Plasma
CD4 T-lymphocyte count is, however, an imperfect measure of immune status for a number of reasons; one of
these is that the majority of CD4+ T-cells do not reside
in plasma, but in mucosal surfaces, particularly the gut,
where they form a major target for HIV in early infec588
tion prior to the development of a CD8+ T-cell response.

Furthermore, the immunosuppression seen in HIV is
extremely complex and consequent on the effects of HIV
viraemia on multiple branches of the immune system.
The mucosal surface of the gut is a unique interface
through which water and nutrients are absorbed during
digestion, where multiple commensal bacteria thrive and
which forms a structural and immunological barrier
against infection. It is not surprising that HIV infection
causes profound changes in the GI mucosa and its functions, given the concentration of cells susceptible to HIV
infection found there, nor that the GI tract is consequently a major reservoir for HIV and also a focus of
viral reproduction from the earliest days of infection.79
AETIOLOGY OF DIARRHOEA
The aetiology of diarrhoea in HIV-infected patients is
multi-factorial. Although opportunistic infections are an
obvious cause to consider, there are also many noninfectious causes of diarrhoea in HIV. There is a lack of
high quality prospective studies of the aetiology of diarrhoea in countries with the highest prevalence of HIV
and some of the early studies, although of high quality,
were constrained by both the limits of understanding of
the range of opportunistic infections and the diagnostic
technology available early in the HIV epidemic. Table 1
summarises studies of the aetiology of diarrhoea in HIV
and Figure 1 schematically represents potential causes of
diarrhoea in HIV by disease stage.
INFECTIONS
Different claims have been made about the relative
importance of bacteria, viruses and protozoan parasites
in the aetiology of infectious diarrhoea complicating HIV
in different studies. A number of factors have affected
the results of these studies, including the stage of HIV
infection, the range of diagnostic tests available at the
time of the study and the geographical location of the
study. It is important to note that opportunistic infections may still be found in patients who are taking antiretroviral therapy, partly because of poor adherence.10
Bacterial infection
Human immunodeciency virus infected patients are at
risk of acute diarrhoea from the same bacterial agents of
enterocolitis as those who are HIV negative. They
are, however, at greater risk of prolonged infection
and of invasive disease, particularly from nontyphoid
Salmonellae11 and from Campylobacter jejuni.12, 13
Recurrent invasive nontyphoid Salmonella (NTS) disease
131
Cyclospora
cayetanensis
Chronic diarrhoea
Pathogen negative
diarrhoea
Blanshard et al.136
Blanshard and Gazzard137
Microsporidiosis
Chacin-Bonilla et al.135
134
Mortality: HIV
associated
diarrhoea
Dillingham et al.133
Chacin-Bonilla et al.
Causes of diarrhoea
case control study
Intestinal parasites
Subject
Goncalves et al.132
Saksirisampant et al.
Study
UK
UK
Venezuela
Venezuela
Haiti
Brazil
Thailand
Location
39 patients
155 patients
71 patients
103 patients
288 patients
40 patients with
diarrhoea, 60
without
90 stool samples
Cohort size
Table 1 | Summary of studies of aetiology of diarrhoea in HIV-infected adults
Follow-up of above
cohort
Examination of stools,
duodenal, jejunal
and rectal biopsy
specimens and
duodenal aspirate
for bacterial,
protozoal and viral
pathogens
Stool microscopy
Stool microscopy
Stool microscopy
Microscopy, culture
EIA & PCR
Microscopy & PCR
Technique
2 small bowel neoplasm, 3

CMV
83% had 1 pathogen: stool

analysis identified the
most pathogens (47%).
Rectal biopsy necessary
for the diagnosis of CMV
and adenovirus. Duodenal
biopsy was as helpful as
jejunal biopsy and
detected some treatable
pathogens missed by other
methods. Electron
microscopy, impression
smears and duodenal
aspirate yielded little extra
information.
Cyclospora oocysts were

found in 10%
Microsporidial infections
were detected in 14%
and 38% had other
parasitic pathogens.
33% had an enteric pathogen

identified: Cryptosporidium spp.,
Giardia spp., I. belli, C. cayetanensis, and E. histolytica.
Calicivirus, C. parvum & G.

lamblia significantly
associated with diarrhoea
46% positive for

parasites, of which: 30%
Cr.hominis, 4% Cr.
meleagridis, 6% E.
bieneusi 2% B. hominis,
1% C. cayetensis, 1% I.
belli
Major findings
Review: diarrhoea in HIV-positive patients
589
590
138, 139
Pathogen negative
diarrhoea
Connolly et al.34
Cytomegalovirus
Enteric infection
Greenson et al.143
Rene et al.144
Adenovirus colitis
Microsporidiosis
Janoff et al.142
Eeftinck Schattenkerk et al.
Cryptosporidiosis
141
Chacin-Bonilla et al.140
Risk factors for

Isosporiasis and
cryptosporidiosis
Enteric viruses
_ENREF_83
Subject
Grohmann et al.28
Sorvillo et al.
Study
Table 1 | (Continued)
France
UK
US
US
Holland
Venezuela
US
US
Location
18 HIV patients with

diarrhoea ante
mortum
33 patients with
diarrhoea
22 patients with
diarrhoea
51 patients with
diarrhoea
55 patients
with unexplained
diarrhoea
29 patients
222 stool samples
16,351 patients
Cohort size
Autopsy
Distal duodenal biopsy,

comprehensive barium
studies, microbiological
examination of six
further stool samples
and repeat rectal
histology
Stool negative, analysis

of endoscopic biopsies
using light and electron
microscopy, viral
culture,
TEM of tissue biospy
Upper GI endoscopy
3 stool samples patient
TEM, gel electrophoresis,

and EIA for rotaviruses,
adenoviruses,
caliciviruses,
picobirnaviruses, &
astroviruses
Data from AIDS

surveillance
analysed
Technique
7 had CMV colitis
Cryptosporidia were identified

on five occasions,
cytomegalovirus on four,
Giardia lamblia on two and
herpes simplex,
Campylobacter jejuni,
Salmonella enteritidis and
Entamoeba histolytica once
each.
Mycobacterium
avium-intracellulare and
microsporidia were the most
common occult agents in
study patients with diarrhoea
(5 each)
7% had adenovirus
27% had microsporidiosis
41% had cryptosporidosis
Viruses detected in 35%

percent of 109 faecal
specimens from patients
with diarrhoea and 12% of
113 specimens from those
without diarrhoea
(P < 0.001)
Isosporiasis was reported in

1%, linked to recent
travel or immigration.
Cotrimoxazole prevents.
Cryptosporidiosis was
reported in 4%
Major findings
N. A. Feasey et al.

Diarrhoea related to HIV seroconversion
1 000 000
Viral load without ART
Causes of diarrhoea as HIV disease progresses
CD4 count without ART
Causes of diarrhoea related to ART
CD4 count after commencing ART
HIV
seroconversion
ART side effects
1200
800
100 000
600
10 000
1 000
Bacterial infection
Tuberculosis
Isospora belli
400
Cyclospora cayatanensis
Strongyloides
Cryptosporidia
GI malignancies
microsporidia
200
06 weeks
MAC, CMV
CD 4 count
Viral load (copies/mL)
1000
10 years
Time since infection
Figure 1 | Scheme showing causes of diarrhoea at different stages of HIV disease: following HIV seroconversion, CD4
count recovers to a set point, then falls gradually over 50 years. The coloured boxes schematically indicate causes of
diarrhoea at different stages of HIV infection based on CD4+ T-lymphocyte count (blue line). The black dotted line
indicates the impact of starting ART on CD4 count and the overlap between different categories after starting ART
highlights the potential diagnostic difficulty at that time.
has been considered an AIDS dening illness since

1985,14, 15 and advanced HIV-disease is associated with a
198304-fold increased risk of invasive and multisite Salmonella infections.16 Diarrhoea may be a less prominent
feature of Salmonella infection in the setting of HIV.11
Campylobacter jejuni is another organism commonly
associated with diarrhoea in immunocompetent individuals which is an important cause of invasive disease and
morbidity and mortality in HIV-infected individuals. The
average incidence of Campylobacter among patients with
AIDS has been found to be 39 times higher than in noninfected people,13 furthermore HIV-infected individuals
are much more likely to have debilitating disease requiring prolonged courses of antimicrobials and in one series
the mortality of invasive disease was 33%.12 Other
species of this genus have also been implicated in diarrhoea in HIV. Other bacterial pathogens recognised to
cause diarrhoea more frequently in HIV-infected patients
include Escherichia coli, Shigella sp and Clostridium difcile. One study of trends in the aetiology of diarrhoea
proposed that C. difcile is the most common cause of
diarrhoea in HIV-infected adults in the US.17
Lymphogranuloma venereum (LGV), caused by serovars L1L3 of Chlamydia trachomatis, is endemic in
Africa and the Carribean, and was rare in industrialised

countries prior to 2003. It is currently re-emerging as a
sexually transmitted infection among men who have sex
with men (MSM), and HIV is a risk factor for susceptibility. WhilE genital LGV causes painful groin lymphadenopathy, gut mucosal infection can cause an ulcerative
rectocolitis, and adenopathy of the deep nodes which
drain the rectum may go unnoticed until they coalesce
to form a bubo, which may rupture and stulate. The
clinical picture and histology may both mimic Crohns
disease and clinicians must be alert to the potential for
misdiagnosis and mistreatment in this setting. It is likely
that depletion of mucosal CD4 cells plays a critical role
is susceptibility to LGV in HIV.18, 19
Mycobacterial infection
The likelihood of developing extra-pulmonary and disseminated infections with Mycobacterium tuberculosis
and nontuberculous mycobacteria increases as HIV-associated immunosuppression progresses. Gastrointestinal
infection with numerous species of Mycobacteria may
occur in HIV. Both Mycobacterium tuberculosis and nontuberculous mycobacterial infection may present with
diarrhoea.20, 21 While diarrhoea is a relatively uncom591
N. A. Feasey et al.
mon symptom of tuberculosis, it is more commonly a
feature of disseminated infection with members of the
Mycobacterium avium complex (MAC). Disseminated
MAC infection occurs in advanced HIV and is frequently
associated with diarrhoea, which was reported to be
symptom in 17% of cases in one series.22
Parasitic infection
Numerous parasitic infections are known to cause diarrhoea in association with HIV. These include parasites
previously described to have pathogenic potential in HIV
negative patients (Giardia lamblia, Entamoeba histolytica,
Blastocystis hominis, Strongyloides stercoralis and other
soil transmitted helminths) and a number of parasites
either newly discovered or not previously thought to
have signicant pathogenic potential, including Isospora
belli, Cryptosporidium parvum, Cyclospora cayetanensis,
and microsporidia particularly Enterocytozoon bienneusi
and Encephalocytozoon intestinalis. These organisms have
subsequently been identied as pathogens in otherwise
healthy people. The rst three are intestinal spore forming protozoa which cause intracellular infection and
which can lead to severe intestinal injury and prolonged
diarrhoea in advanced HIV,23 while microsporidia have
recently been reclassied as fungi. While some studies
have linked parasitic infection with progressive immunosuppression,24 others have questioned this association
and suggested that diarrhoeal infections aggregate in
HIV-infected individuals irrespective of CD4 count.6
Certainly risk factors for exposure to parasitic infection,
particularly socio-economic status and access to safe
water and adequate sanitary facilities need to be considered when assessing an HIV-infected patient with
diarrhoea.
Viral infection
A number of viruses have been implicated in the aetiology of diarrhoea in HIV-infected patients and the list
has grown and changed as advances have been made in
diagnostic virology. One of the rst viral OIs to be listed
as an AIDS dening illness was Cytomegalovirus
(CMV).25 CMV affects multiple organs in end stage HIV
and in the GIT can cause colitis. The hallmark is diarrhoea which may be bloody and accompanied by weight
loss, fever and abdominal pain. In early and pre-ART
cases series, CMV was a cause of approximately 15% of
HIV associated diarrhoea.26 The risk of CMV disease in
HIV is at its greatest as the CD4 count falls below
50 109 L, consequently CMV related disease has rapidly declined with the roll out of ART.27 As with proto592
zoal OIs, the list of viral infections associated with

diarrhoea has grown substantially and now includes
astrovirus, picobirnavirus, caliciviruses (both norovius
and sapovirus) and adenoviruses.28 While these viruses
have been found signicantly more frequently in the faeces of patients with both HIV and diarrhoea than in that
of patients with HIV alone, causality has yet to be proven for all of them, particularly picobirnavirus.28 Diarrhoea is also a well documented feature of HIV
seroconversion illness itself.29, 30 This is important to
recognise as a combined antibody antigen HIV test may
be negative during a seroconversion illness and if this
diagnosis is suspected, the HIV test should be repeated
12 weeks after the initial test.
Fungi
Candida species are frequently isolated from the stool of
HIV-infected patients31 and have been implicated in
antibiotic associated diarrhoea;32 however, their role in
the aetiology of diarrhoea remains unclear and further
studies are needed into the role of yeasts in HIV-associated diarrhoea. Systemic dimorphic fungal infection can
affect the gastrointestinal tract causing diarrhoea, for
example disseminated infection with Histoplasmosis.33
PATHOGEN-NEGATIVE DIARRHOEA
The concept of pathogen-negative diarrhoea has evolved
as the understanding of the breadth of OIs which cause
diarrhoea has evolved. One study of patients classied as
having pathogen-negative diarrhoea on entry to the
study observed that in the majority of the more severe
cases, an infectious cause was ultimately identied,34 furthermore this study preceded the rst reports of intestinal microsporidiosis as a cause of diarrhoea in HIV.35
The hunt for novel infectious causes of enteropathy in
HIV-infected patients continues.
The role of HIV itself
Despite this, it is clear that there are changes in the bowel
attributable to HIV disease itself, which have important
functional signicance. Massive and progressive depletion
of gastrointestinal effector memory CD4+ T lymphocytes
is seen early in the course of HIV disease, and the simian
model disease SIV.36 The suggested mechanisms are direct
infection of cells and bystander cell death. One of the most
important consequences of this loss of gut mucosal CD4
cells is a failure to maintain the epithelial barrier function
of the gut mucosa.37 This mucosal damage enables microbial products to translocate across the bowel. LPS levels in
both HIV and SIV have been found to be elevated and are

temporarily reduced following neomycin treatment.38
Translocated microbial products such as LPS, peptidoglycan and viral genomes may cause chronic gastrointestinal
and systemic immune activation through stimulation of
the innate immune system via Toll-like receptors. The
resultant activated T-cells in turn are a further target for
HIV, thus driving a vicious circle in the immunopathogenesis of HIV disease.39, 40 The impact of HIV infection of
the gut mucosa may therefore extend to inuence overall
progression of the disease systemically. These changes,
however, also have signicant functional consequences for
the gut itself and also may be linked to the longstanding
observations that there is a jejunal enteropathy termed
HIV enteropathy, associated with mild villous atrophy
and crypt hyperplasia.4143 Increased permeability and
decreased absorption for sugars, vitamin B12 and bile have
been described, even in the absence of detectable opportunistic infections, associated with chronic diarrhoea and
malnutrition in HIV.4448 A third subset of T-lymphocytes
has recently been discovered and characterised, which act
through IL-17 to coordinate gut mucosal protection
against infection. The loss of the TH17 subset of CD4 cells
from the gut mucosa is thought to be particularly important during HIV49 and in addition to the consequences for
HIV disease progression described above, the loss of IL17-producing T cells has been shown to permit invasion
and dissemination of nontyphoidal Salmonella from the
gut in an SIV model.50
Another suggested mechanism for HIV-related diarrhoea has been rapid intestinal transit due to damage to
the autonomic nervous system; HIV is known to be neurotropic and a generalised autonomic neuropathy in
advanced HIV is well described.51 Increased transit time,
however, does not correlate well with symptomatic diarrhoea.45 HIV-associated inammatory bowel disease,
which has been dened as a non-infectious colitis refractory to standard treatment for inammatory bowel disease is characterised by colitis52 or caecitis (typhlitis)53
and may also cause pathogen-negative diarrhoea.
HIV-associated malignancy
Human immunodeciency virus-associated gastrointestinal malignancies may also present with pathogen-negative
diarrhoea.4 Non-Hodgkin B-cell lymphoma and Kaposi
sarcoma are both AIDS-dening and are considered noninfectious, although their pathogenesis is ultimately related
to oncogenic herpes viruses such as EBV and HHV8.
Non-Hodgkin lymphomas (NHL) are 60200-fold
increased among HIV-infected patients, commonly EBVrelated, and the categories most likely to affect the GI tract
are Burkitt and Burkitt-like lymphomas54, 55 and diffuse

large B-cell lymphomas (DLBCL), which frequently present with extra-nodal involvement including of the GI tract,
reected by a predominance of gastrointestinal symptoms
including diarrhoea.56 Primary effusion lymphoma (PEL)
is known to be HIV-related and an extracavitary, solid variant has recently been described which commonly affects
the gastrointestinal tract and is HHV8-associated, with frequent EBV co-infection.57
Hodgkin lymphoma is also 10-fold over-represented in
HIV, although it is not AIDS-dening and its incidence
in HIV has a nonlinear relationship with CD4 count and
disease stage.58 Cases present with advanced disease, extranodal disease and B symptoms, but not typically with
diarrhoea or luminal GI disease.57 The importance of the
GI-related non-AIDS dening malignancies Hodgkin
Lymphoma and anal carcinoma is increasing with the
advent of HAART as patients are living longer.
Kaposi sarcoma, caused by HHV8, is AIDS-dening
and is a multifocal disease which very frequently involves
the GI sub-mucosa. While GI involvement is often
asymptomatic, Kaposis may present with diarrhoea,59, 60
GI bleeding (since it is a very vascular tumour), perforation, intussusception or obstruction.
Pancreatic disease
Human immunodeciency virus infection may have multiple effects impairing exocrine pancreatic action, which
in turn may contribute to chronic diarrhoea through
impaired fat absorption. Factors associated with pancreatic disease include OIs, viral hepatits, HIV itself and
ART,61 although the principal culprit, didanosine, is
rarely used now. One study found measurement of faecal
elastase to assess pancreatic exocrine insufciency to
enable treatment with oral pancreatic enzyme therapy to
be useful in the management of chronic diarrhoea.62
Antiretroviral therapy as a cause of diarrhoea
In 1987, Zidovudine (AZT) became the rst pharmacological agent with proven efcacy against HIV.63 In the
late 1990s, combination ART became the standard of
care to combat the rapid emergence of drug-resistance
and it has been so successful that patients diagnosed
early in the course of HIV infection can expect a near
normal lifespan.64 Multiple classes of ARVs are now
available; however, these agents are not without side
effect and diarrhoea is a common consequence of ART
which may be severe enough to lead to discontinuation
of ARVs.65 While diarrhoea has been associated with all
three main classes of ARVs; nucleoside reverse transcrip593
N. A. Feasey et al.
tase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs),
perhaps the most problematic agents are the PIs, particularly ritonavir,66 which is used to boost levels of other
PIs.67 The dosage of ritonavir and dosing schedules of
PIs is a subject of major interest.68
INVESTIGATION
An algorithmic approach to investigation and management of chronic diarrhoea in HIV is shown in Figure 2.
To guide management, an accurate history concerning
the patients HIV, their treatment history and their professional and recreational exposure to pathogens and their
travel history should be sought. All of the pathogens listed
are transmitted by the faecal-oral route and are all potentially sexually transmitted. This information is equally
important for clinicians and medical scientists consider-
ing which tests to perform. Additional features of the history and examination may help distinguish between small
or large-bowel diarrhoea, and the possibility of complications. Although molecular diagnostics are predicted to
enhance the sensitivity of investigations in the future, the
majority of rst-line clinical diagnostic tests routinely
available are still based on microscopy and culture.
Microbiological investigation
Upon making a diagnosis of HIV, the most basic investigations necessary are a plasma CD4 count and HIV viral
load (see Figure 2). The CD4 count will help to assess
the degree of immunosuppression and thus clarify the
spectrum of OIs to which the patient susceptible. The
viral load is the most useful parameter of response to
ARVs and in early treatment failure will increase before
the CD4 count starts to decline.
Initial clinical assessment including:

Severity
Drug history
CD4 count and HIV Viral Load
Stool examination:
3 samples over 10 different days
Microscopy for ova, cysts & parasites
(ZN stain, trichrome stain)
Bacterial culture
C. difficile screen
Specific virology and protozoal PCR
Empirical or specific treatment for:

Infectious agents
Start or optimise ARVs to:

control VL, minimise drug side effect
Review all other drugs, withdraw suspect drugs
Pathogen negative diarrhoea?
Flexible sigmoidoscopy:
Biopsies for histology, standard and mycobacterial
culture and CMV PCR
Colonoscopy with terminal ileoscopy

(or consider gastroscopy)
Cross sectional imaging (malignancy, disease extent,
complications, tissue biopsy)
consider : double contrast upper GI barium study
consider : complete TB diagnostic work-up
Specific treatment for:

Additional infectious agents identified
HIV-associated malignancies
Mycobacterial disease
Supportive management
Antimotility agents, adsorbents, cholestyramine,
octreotide, etc
Figure 2 | Algorithm showing the management approach to the HIV patient with diarrhoea.
594


Investigation of faeces
Microbiological investigation of faeces should be the rst
investigation of diarrhoea. Different specimens provide
different challenges to a diagnostic microbiology laboratory; faecal culture is made challenging by the difculty
of ensuring that the pathogen or pathogens among a
diverse array of bacteria is identied. A faecal sample
should be collected and submitted soon as possible after
the onset of symptoms. While a 12 g specimen is sufcient for routine culture, more is required for the array
of tests which may be necessary in the context of HIV
and diarrhoea. Specimens of faeces should be transported
to the laboratory and processed as soon as possible,
because a number of important pathogens such as Shigella species may not survive the pH changes that occur
in faeces specimens which are not promptly delivered to
the laboratory, even if refrigerated.69 Three samples over
no more than a 10 day period are recommended for
detection of parasites, although more may be necessary,
especially if Giardia is suspected. No more than one
specimen per day should be submitted as shedding of
ova and cysts tends to be intermittent.70
Once received by a diagnostic laboratory, specimen
processing depends on the clinical context, but should
include culture on a media which favours selection of
Salmonella sp and Shigella sp and a second which selects
for Campylobacter sp. Consideration should be given to
testing for Clostridium difcile toxins A and B. Recovery
of mycobacteria from stool is uncommon therefore
mycobacterial stool culture is not recommended.69
Stool should be examined using direct microscopy for
the ova and cysts of protozoal parasites; however, a screen
for Cryptosporidia, Cyclospora, Isospora and microsporidia
requires a specic request as these organisms require specic stains. A modied acid fast stain is used to look for
the oocysts of cryptosporidia, isospora and cyclospora,
although the sensitivity is unknown and operator dependant. Examining multiple specimens increases sensitivity.23 Diagnosis of microsporidia is also challenging, in
part because their size (12 lm) makes them difcult to
differentiate from faecal debris by light microscopy.71
Improved methods include microscopy following staining
with modied trichrome stain72 with or without a chemouorescence brightener such as calcoour white; however,
the gold standard test remains transmission electron
microscopy (TEM) on small bowel biopsy specimens.
Other methods include antigen and antibody based detection methods and nucleic acid amplication techniques.71
Nucleic acid amplication tests are increasingly used
in the diagnosis of sexually acquired infection. Since
2005 several such tests have become available for the

diagnosis of LGV from anal swabs. The clinician must
consider the diagnosis of LGV to make the diagnosis.
Virology
Diagnosis of the viral infections which cause diarrhoea is
complex and species specic. While TEM (performed on
tissue) and viral culture enable the identication of new
viruses and viruses not expected in a given clinical context (i.e. non-enteric adenoviruses causing diarrhoea in
HIV positive patients), the skills required for these techniques are rarely used outside of reference laboratories.
Increasingly, viral infections are diagnosed using
enzyme-immunoassay (EIA), latex agglutination kits or
polymerase chain reaction (PCR) performed on stool,
blood or tissue. In the context of CMV, assays for CMV
DNA or antigen in blood are superior to culture for documenting viraemia73 and few UK laboratories use CMV
culture. Further prospective studies are required to determine whether PCR of blood or tissue is the most sensitive assay for diagnosing intestinal CMV,74 however
histology gives the best indication of disease severity.
The rapid reduction in the cost of whole genome
sequencing may make mass sequencing a viable diagnostic option in the near future. This approach will also
enable the discovery of novel viruses.
Other microbiology
In addition to stool samples, blood should be taken for
culture from febrile or septic patients and consideration
should be given to mycobacterial blood culture. If TB is
suspected, alternative microbiological specimens should
be sought including mucosal biopsy, lymph node tissue
or ascites for histology and culture, combined with
radiological evidence of TB, including a chest X-Ray in
all patients (http://www.nice.org.uk/CG033NICEguideline). The role of rapid PCR-based diagnostic tests for
TB is likely to expand. Blood for specic serology, antigen testing or PCR may be useful; however, patients with
advanced HIV may lose the ability to mount an antibody
response to the point where serology is negative.
Endoscopy
There has been much debate about the usefulness or
necessity for pan-endoscopy to investigate stoolnegative diarrhoea in HIV. Not all studies are directly
comparable, since sensitivity clearly depends not only
on the extent of examination, but on the associated
microbiological methods used for both stool and
biopsy material, which have improved over time. Geo595
N. A. Feasey et al.
graphical location, disease stage, the underlying risk
factor for HIV and the advent of HAART may also
be confounders in these studies. Endoscopy yields an
additional diagnosis in 3070% of stool-negative cases,
depending on methods and the completeness of study.
Unsurprisingly, diagnostic yield is highest when there
are worse symptoms, and at lower CD4 count. The
commonest additional or new diagnoses uncovered by
endoscopy are CMV colitis, microsporidiosis and giardia infection. There is a general consensus that 85
90% of cases of CMV colitis will be detected using
exible sigmoidoscopy and biopsy alone4, 34, 7577 and
exible sigmoidoscopy is generally considered a necessary and adequate rst-line assessment in stool-negative
diarrhoea. There are, however, a smaller number of
studies suggesting that proximally distributed CMV
colitis or other colonic diagnoses may be missed and
full colonoscopy (preferably with terminal ileoscopy) is
warranted if severe or functionally debilitating symptoms persist.26, 78 Although some studies have suggested that biopsy of the small bowel, either at
duodenoscopy or terminal ileoscopy, is necessary to
reliably diagnose microsporidiosis,76 improved microbiological stool methods such as PCR or trichrome stain
mean that the necessity for small bowel biopsy is now
reduced. The high pick-up rate for microsporidiosis in
the terminal ileum, combined with the detection of
proximally distributed CMV colitis, means that colonoscopy with terminal ileoscopy is a logical second-line
investigation and may obviate the need for upper GI
endoscopy. The decreasing utility of upper GI endoscopy to diagnose pathogens in HIV is conrmed in
other recent studies.79
Radiology
Radiology of opportunistic infections and inflammatory
disease. Interpretation of diagnostic imaging of the
HIV-infected patient presenting with diarrhoea can be
challenging as the appearances are usually nonspecic.80
The most common ndings in infectious diarrhoea are
of oedematous and ulcerated mucosa. The distribution
and type of ulcers and the extent of disease when correlated with the degree of immunosupression can aid in
narrowing the wide differential diagnosis of the various
infectious pathogens, but endoscopic samples need to be
obtained for histopathological or microbiological investigation to make a denitive diagnosis.81, 82
Literature on the appearances of the bowel in patients
with diarrhoea and HIV is sparse. Imaging of mucosal
detail, such as the pattern and distribution of ulcers and
596
oedema, is best seen in barium studies. Mucosal detail is

not apparent on CT or MRI and the appearances of the
bowel are not pathogen specic. CT or MRI scanning is
undertaken in patients with more severe disease to assess
disease distribution, potential complications, for staging
tumours and to aid intervention. If these modalities are
unavailable, ultrasound may demonstrate small and large
bowel thickening.83
While a tissue or microbiological diagnosis must be
sought, imaging can suggest certain diagnoses. Tuberculosis commonly affects the ileocaecal region resulting in
mural thickening of the terminal ileum and caecum. Skip
areas in the small bowel may mimic Crohns disease with
luminal narrowing and proximal dilatation, but the presence of skip lesions with ileocaecal involvement is
strongly suggestive of TB. Necrotic mesenteric lymphadenopathy can be seen on CT and is also suggestive of TB
infection.84 Advanced disease results in the classic
appearance of a conical small caecum. Colonic involvement results in segmental ulcers, strictures and polypoid
hypertrophic lesions.
Mycobacterium avium affects the jejunum with thickening of the folds, but there is no ulcer as MAI is not
associated with tissue destruction. Normal appearances
are seen in 25% of infected patients undergoing CT.85
Cytomegalovirus infection most commonly affects the
colon and radiological appearances vary depending on
the severity. Bowel wall thickening, ulcers and irregular
folds are seen on barium studies and CT. With increasing severity of disease, large ulcers, nodular defects and
pseudo-membranes may develop. Tumour like lesions
may develop which may be indistinguishable from neoplasia.86 Thrombosis secondary to vasculitis with subsequent ischaemia may result in penetrating ulcers and
subsequent perforation.87 Histoplasmosis also affects the
colon, particularly the ascending colon. The thickening
of the bowel and pericolonic inammatory change can
mimic carcinoma.88
Human immunodeciency virus-related typhlitis (caecitis) is localised inammation of the caecum with symmetric wall thickening, pneumatosis and pericolonic
inammation. This can extend to involve the terminal
ileum and ascending colon.89 Diagnosis takes account of
and is based on the entire clinical picture, rather than by
imaging alone. CT imaging is particularly useful to
exclude a perforation or abscess and to guide
intervention.90
Radiology of neoplastic lesions. The lesions of Kaposi
sarcoma are submucosal in location and can affect any

part of the gastrointestinal tract, most commonly the
duodenum. Barium studies in the early stages may be
negative as the lesions are submucosal and diagnosis
may be more readily achieved endoscopically. When
advanced, both barium studies and CT may demonstrate
larger at or polypoid submucosal masses with or without ulcers and associated fold thickening. Enhancing
lymph nodes are seen commonly in patients with disseminated disease which may aid diagnosis. Otherwise,
the lesions may mimic other neoplastic lesions such as
carcinoma, metastases or lymphoma or infections.91
Acquired immunodeciency syndrome-related nonHodgkins lymphoma (NHL) in HIV has been found to
affect extra-nodal sites in 86% of abdominal CT scans,
the commonest being the GI tract.92 Primary B-cell lymphoma in HIV patients often affects the distal small
bowel. Thickening of the distal ileum, mass like lesions,
ulcers and aneurysmal dilatation may be seen on CT with
extension of tumour into the adjacent mesentery and
lymph nodes. Barium studies are nonspecic demonstrating polypoid mass lesions, ulcers and inltrative change
or nodularity. Intussusception and bowel obstruction may
occur and the appearances may be indistinguishable from
carcinoma.93 The patterns and distribution of intestinal
ndings on CT imaging of small bowel NHL are not distinguishable from those seen in HIV-uninfected cases.94
Other investigations
A diagnosis of Mycobacterium tuberculosis (MTB) complex can be inferred from a localised immune reaction to
intradermal injection of Mycobacterial puried protein
derivative (PPD, the tuberculin test). More sophisticated
ex-vivo tests based on detection of interferon gamma
release in response to two antigens specic to MTB (and
which are not found in the BCG vaccine) have recently
been introduced. Interferon gamma release assays (IGRAs)
may be more sensitive than intradermal PPD in HIVinfected adults.95 More work needs to be carried out to
dene the role of IGRAs in the diagnosis of extrapulmonary TB in HIV-infected adults and no studies have
focused on the use of IGRAs in intestinal tuberculosis.
Despite this, a positive tuberculin-test or IGRA may be of
value in supporting a diagnosis of MTB,96 while a negative
result should be interpreted with caution.
MANAGEMENT AND OUTCOMES

Treatment of infectious diarrhoea by aetiology
The rst steps in managing diarrhoea in the context of
HIV are the same as those taken in managing any acute
diarrhoea; to evaluate which pathogens the patient is at

risk of by taking a careful history and to assess and manage dehydration, although known HIV infection should
lower the threshold for using antimicrobial therapy.
There is increasing, but geographically heterogeneous
resistance to multiple antimicrobials among enteric
pathogens, making recommendation of an empirical
antimicrobial unrealistic, instead expert local advice
should be sought or local guidelines consulted in the
management of the critically ill patient. Ultimately, identication of specic organisms by culture will enable
antimicrobial susceptibility testing to be performed.
Lymphogranuloma venereum proctocolitis caused by
Chlamydia trachomatis requires a prolonged course of
therapy. Either doxycycline or a macrolide is recommended, although there are no clinical trials to guide the
use of macrolides. There is also interest in uoroquinolones, although again, trial data are lacking.
Mycobacterial infection
Gastrointestinal infection with M. tuberculosis is treated
in the same fashion as pulmonary tuberculosis, initially
using a four drug regimen involving rifampicin, isoniazid, pyrazinamide and ethambutol dosed according to
patient weight for 2 months followed by a further
4 months of rifampicin and isoniazid.97 Following culture of M. tuberculosis, sensitivity testing should be performed to rene the antituberculous regimen if
resistance is detected. Treatment of MAI consists of a
macrolide, rifamycin and ethambutol given three times
weekly for noncavitary disease and daily with or without
an aminoglycoside for cavitary disease.98 Antimycobacterial therapy for MAI should not be stopped until
immune reconstitution with ART has occurred.99
Protozoal and fungal infections
Despite a drive to diagnose HIV earlier and the introduction of ART, protozoal infections continue to cause diarrhoeal disease in HIV-infected patients and they frequently
present a therapeutic challenge. The drugs of choice for
Giardiasis are metronidazole (2 g day for 3 days) or tinidazole (2 g once), with a cure rate of 73100%.100 Nitazoxanide is an alternative with an 81% success rate.101 There
are inadequate and conicting trials of specic therapy
for cryptosporidiosis with both nitazoxanide and
paroromycin. A recent Cochrane meta-analysis of seven
trials including 130 adults with HIV concluded that
although nitaxozanide reduces the load of parasites and
may be useful in immunocompetent individuals, the effect
was not signicant for HIV-infected patients. Despite this,
597
N. A. Feasey et al.
the use of nitaxozanide should be considered in very sick
HIV-infected patients with Cryptosporidiosis.102 Trials of
paroromycin have included even fewer HIV-infected
patients and the same meta-analysis found no statistically
signicant effect. Further trials are unquestionably warranted; however, the mainstay of treatment is effective
immune reconstitution with ART.103105
The treatment of Isoporiasis and Cyclospora is more
straightforward. Both pathogens are susceptible to cotrimoxazole, which may resolve symptoms in up to
100% of patients.106 In the case of intolerance or allergy
to sulphonamides, ciprooxacin may be used, although it
is less effective, resolving only 87% cases.106
The main specic therapy for microsporidiosis is albendazole. While Encephalitozoon intestinalis responds well to
albendazole 400 mg b.d. for 3 weeks, which caused clinical
resolution and parasite clearance in 4 4 patients in one
study,107 Enterocytozoon bieneusi does not. Albendazole
should still be tried, but supportive therapy with uids and
early initiation of ART are crucial. As with cryptosporidiosis, immune reconstitution can lead to complete clearance
of microsporidia.103
Anti-viral therapy
Specic anti-viral therapy is available for CMV colitis
using IV ganciclovir or oral valganciclovir. Alternatively
foscarnet and cidofovir have been approved, but there
are no clinical trials to support a specic therapy for
CMV colitis. Immune reconstitution is an essential component of treating CMV disease.
Prophylactic therapy
Cotrimoxazole remains a useful prophylactic agent in
HIV-infected patients. While in the developed world, it is
primarily used to prophylax against PCP and toxoplasma
encephalitis in the profoundly immunosuppressed (plasma
CD4 count less than 200 109 L), it will also prevent isospora diarrhoea.108 Cotrimoxazole is used much earlier in
the course of HIV in developing countries (plasma CD4
count less than 500 109 L). This is in part due to its
prophylactic role against malaria, but it also prevents diarrhoea.109
Secondary prophylaxis is recommended by the CDC
for the prevention of recurrent nontyphoid Salmonella
sepsis, but not for other enteric bacterial pathogens.108
Antiretroviral therapy
The treatment of HIV was revolutionised initially by the
introduction of Zidovudine AZT and subsequently by
combination ART. Now multiple classes of ARVs are
598
available and what was once a terminal illness should

now be regarded as a chronic, treatable medical disorder.
Current regimens for ARV naive patients are well tolerated with low pill burdens. In the early days of HIV
therapy, the consensus was that treatment was unnecessary until the CD4 count fell to around 200 109 L.
This decision was based on the perceived risk of OIs at
CD4 counts of 200400 109 L or less, the severe side
effects of early regimens and the cost of ART. Current
guidelines recommend that ART should start before the
CD4 count falls below 350 109 L,110 with many experts
advocating even earlier treatment,111 although this
remains controversial.
Antiretroviral therapy rapidly reduces plasma HIV
viral load enabling the CD4+ T-lymphocyte population
to reconstitute and there is good evidence that this
reduces chronic diarrhoea in HIV-infected individuals,
often very rapidly.112 Sampling of gut tissue reveals a
rapid fall in viral load,112 which suggest that the virus
has a central role in HIV-associated diarrhoea. There is
robust evidence of both a general reduction in gastrointestinal OIs113 with the introduction of ART and of
improvement in the outcome from infection with specic
OIs. Infections caused by pathogens which have no specic treatment may resolve following the introduction of
ART including cryptosporidiosis and microsporidiosis,103
while the treatment of other OIs for which specic therapy is available (i.e. CMV colitis) is enhanced by the
introduction of ART.27 Lastly, recurrence of invasive bacterial infections such as Salmonellosis has been shown to
cease following introduction of ART.114
Despite the clinical improvement that is frequently
seen, the picture at a GI cellular level is more complex.
The completeness of gastrointestinal reconstitution is
controversial with some studies showing good CD4 Tcell repletion, while others have suggested that it is both
poor and much slower than the improvement in plasma
CD4 count40 and that in the long term, patients with
poor GI CD4 reconstitution have ongoing immune activation. One possible explanation for this is the
observation that some GI CD4 cells have been observed
to produce HIV years after initiation of ART.115, 116 A
second possibility is that brotic damage to GI lymphoid
tissue prior to initiation of ART may be such that the
ability to replace CD4 T-cells in the GIT is permanently
impaired40 and early initiation of ART certainly fosters a
more complete CD4 reconstitution in the GIT.115, 116
Although gut mucosal CD4 depletion does not completely reconstitute following antiretroviral therapy, possibly because of the deposition of collagen in GALT,117

many of the functional consequences, including permeability defects, are measurably reversed.118
Symptomatic treatment of chronic diarrhoea
Chronic diarrhoea in Western populations is now
increasingly rare due to the introduction of ART early in
the course of HIV infection. Despite exhaustive investigation of diarrhoea and initiation of ART, diarrhoea may
persist or even result from HIV therapy and empirical
treatment may be required. Antimotility agents (loperamide, diphenoxylate and codeine) and adsorbents (bismuth subsalicylate, kaolin pectin and attapulgite) have
anecdotally been found to be useful. Antimotility agents
increase gut transit time, giving more time for uid reabsorption and while narcotic analgesics should be avoided
because of their addictive nature, loperamide and diphenoxylate may be useful, although studies are lacking.
A recent Cochrane review highlighted the lack of evidence for these agents and the need for further studies.119 Cholestyramine may be benecial if diarrhoea is
caused by malabsorption of bile salts.120 Other measures
studied include zinc or other micronutrient supplementation, mesalazine (mesalamine) and curcumin. Randomised controlled trials of zinc supplementation121 and
mesalazine122 in adults revealed no benet, while a small
study of the turmeric extract curcumin revealed a benet
in ve of six patients.123 A Cochrane review has concluded that micronutrient supplementation offers no
reduction in morbidity (including diarrhoea) or mortality
among HIV-infected adults.124 One more recent study of
broader micronutrient supplementation did not result in
signicant reduction in diarrhoea, although there was a
very modest reduction in severe infectious diarrhoea.125
Supplementation with vitamin A and zinc, however, has
failed to signicantly reduce gut permeability or markers
of microbial translocation.126 Although octreotide has
been used for symptomatic control of diarrhoea in HIV
enteropathy, the results of trials are inconsistent.127129
In the case of HIV-related colitis, thalidomide has been
used with success in individual patients,52 but randomised
controlled trials are lacking. Typhlitis or caecitis has been
successfully managed with bowel rest, IV uids and broad
spectrum antibiotics.130 Discussion of chemotherapy for
mitotic lesions is beyond the scope of this review, but the
expert opinion of an oncologist should be sought in
the case of discovery of an HIV-related malignancy as the
cause of diarrhoea and it should be remembered that tight
control of HIV viraemia forms an essential part of the
treatment of these cancers.

CONCLUSIONS
Human immunodeciency virus infection impacts upon
the gastrointestinal tract in a variety of ways and there is
an incomplete understanding of the mechanisms by which
it does this. The aetiology of diarrhoea in HIV infection is
diverse and includes the direct effects of the virus upon the
GIT, infection with both obligate and opportunistic enteropathogens, malignant and other non-infectious causes
and as a consequence of anti-viral therapy. In addition,
HIV-infected patients are still susceptible to unrelated but
common causes of diarrhoea including irritable bowel disease and drug side effects. A multidisciplinary approach to
diagnosis and management is therefore best practice and
in the best interests of the patient.
Faecal microbiology remains the principal and rstline investigation for diarrhoea in HIV-infected patients.
Tests typically available routinely include microscopy,
culture and enzyme immunoassays. In recent years, the
cost of genome sequencing technology has plummeted
and its increasing availability is revolutionising microbiology. Failure to detect pathogens by currently available
diagnostic microbiology may lead to a need for complex
radiology or the judicious use of endoscopy and tissue
biopsy.
Flexible sigmoidoscopy is generally acknowledged to
be an appropriate rst-line investigation in stool-negative
cases, and full colonoscopy with visualisation and biopsy
of the terminal ileum, rather than gastroduodenoscopy is
generally a reasonable second-line endoscopic investigation. Radiological ndings are often nonspecic but useful to detect disease severity, distribution and
complications, and some HIV-related malignancies.
While current research suggests that people diagnosed
with HIV infection today might expect to live a normal
life if adherent to their therapy, ARVs may themselves
cause diarrhoea and further research is needed to optimise drug dosage, particularly with protease inhibitors. A
good evidence-base for symptomatic management of
HIV-related diarrhoea is also lacking. The greatest burden of HIV infection falls on Sub-Saharan African countries where there are limited diagnostic facilities.
National and regional prevalence studies of enteropathogens are needed, both to inform regional and national
treatment strategies and to highlight the true burden of
disease attributable to neglected or newly discovered
pathogens. The intestinal parasites also number among
the neglected tropical diseases and new therapies for
these pathogens are urgently needed for both HIVinfected and uninfected patients.
599
N. A. Feasey et al.
ACKNOWLEDGEMENTS
Declaration of personal interests: None. Declaration of
funding interests: No nancial support was received for
the preparation of this manuscript. Dr Feasey is supported

by a Wellcome Trust Research Training Fellowship.
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Review article: The aetiology, investigation and

Liverpool School of Tropical Medicine

Royal Liverpool and Broadgreen University

30 PUBLICATIONS 341 CITATIONS

Available from: Melita A Gordon

Alimentary Pharmacology and Therapeutics

Review article: the aetiology, investigation and management of

Department of Radiology, Royal Liverpool University Hospital, Liverpool,

This commissioned review article was

Aliment Pharmacol Ther 2011; 34: 587603

2011 Blackwell Publishing Ltd

tion prior to the development of a CD8+ T-cell response.

2011 Blackwell Publishing Ltd

Aliment Pharmacol Ther 2011; 34: 587603

Blanshard and Gazzard137

Table 1 | Summary of studies of aetiology of diarrhoea in HIV-infected adults

Microscopy & PCR

2 small bowel neoplasm, 3

83% had 1 pathogen: stool

Cyclospora oocysts were

33% had an enteric pathogen

Calicivirus, C. parvum & G.

46% positive for

Review: diarrhoea in HIV-positive patients

Eeftinck Schattenkerk et al.

Risk factors for

18 HIV patients with

222 stool samples

Distal duodenal biopsy,

Stool negative, analysis

TEM of tissue biospy

3 stool samples patient

TEM, gel electrophoresis,

Data from AIDS

7 had CMV colitis

Cryptosporidia were identified

27% had microsporidiosis

41% had cryptosporidosis

Viruses detected in 35%

Isosporiasis was reported in

Aliment Pharmacol Ther 2011; 34: 587603

2011 Blackwell Publishing Ltd

Review: diarrhoea in HIV-positive patients

Viral load without ART

Causes of diarrhoea as HIV disease progresses

CD4 count without ART

Causes of diarrhoea related to ART

CD4 count after commencing ART

ART side effects

Viral load (copies/mL)

has been considered an AIDS dening illness since

Africa and the Carribean, and was rare in industrialised

zoal OIs, the list of viral infections associated with

Review: diarrhoea in HIV-positive patients

are Burkitt and Burkitt-like lymphomas54, 55 and diffuse

Initial clinical assessment including:

Empirical or specific treatment for:

Start or optimise ARVs to:

Pathogen negative diarrhoea?

Colonoscopy with terminal ileoscopy

Specific treatment for:

Aliment Pharmacol Ther 2011; 34: 587603

Review: diarrhoea in HIV-positive patients