Diagnosis & Management:
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HIV: Essential facts
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HIV: Management guidelines
Case
definitions of AIDS-defining illnesses
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|
HIV infection
Patients
presenting for HIV serology should be
assessed by a medical officer for STD and
HIV risk,
which requires taking a detailed sexual and blood exposure history. In
addition to routine risk assessment (see Chapter 1), it is useful to
determine if the patient has had a previous HIV test, and ask why the
patient believes they need a test.
Infection with an STD at the time of exposure increases the risk of
HIV acquisition.
Therefore, all patients who are at risk of HIV
should be advised of the risk of other STDs and be offered testing.
Clinical
presentation
Clinical
presentations of HIV vary depending on the stage of infection, which
includes the following.
Acute
infection (seroconversion)
50-70%
of patients experience a mononucleosis-like illness including fever,
lethargy, myalgia, arthralgia, headache, maculopapular rash,
lymphadenopathy, splenomegaly 3-6 weeks after infection.
Asymptomatic
infection
Following
seroconversion patients may remain asymptomatic for many years.
Symptomatic
infection
Persistent
generalised lymphadenopathy (nodes ³
1 cm diameter, at 2 extrainguinal sites for 3 months) occurs commonly but
is not of prognostic significance.
The
degree of immune suppression ( measured as the CD4 cell count) predisposes
to the development of certain illnesses.
|
CD4
Cell Count
|
Common
Clinical Features
|
|
150-500/mL
|
Oral
and vaginal candidiasis, oral hairy leukoplakia, sinusitis,
gingivitis, seborrheic dermatitis, psoriasis, warts, molluscum
contagiosum, recurrent varicella-zoster and herpes simplex
infection, cervical dysplasia, tuberculosis, fever, sweats, weight
loss
|
|
<
150/mL
|
Pneumocystis
jiroveci pneumonia,
Kaposi’s sarcoma, oesophageal candidiasis, cerebral
toxoplasmosis, lymphoma, HIV dementia, cryptococcal meningitis
|
|
<
50/mL
|
Cytomegalovirus
retinitis, cerebral lymphoma, Mycobacterium
avium complex infection
|
Pre
test counselling should be performed and informed consent obtained prior
to testing. HIV testing is
performed by a screening ELISA which detects both HIV p24 antigen and HIV
antibodies. A positive
screening ELISA is confirmed on a Western Blot assay
If the Western Blot is negative, the ELISA result is considered to
be a false positive, indicating the patient is not infected with HIV.
Repeat testing is only indicated if the patient has been at risk in the
three month period prior to the test.
If
the Western Blot yields an indeterminate result, the patient may have been
recently infected with HIV and may be in the process of seroconverting. HIV
screening ELISA testing should be repeated at 2 weekly
intervals to determine whether the Western Blot assay becomes positive .
If
the Western Blot is positive, a report is returned with a “confirmed
positive” statement. These
patients require specific post test counselling and appropriate medical
assessment. Further assessment
should be conducted at 3-6 monthly intervals.
The
following table outlines the
clinical features of the above infections
|
Infectious
agent
|
Diagnosis
|
Clinical
features
|
|
Pneumocystis
jiroveci
|
Pneumocystis
jiroveci pneumonia
|
Dry
cough
Dyspnoea
Fever
Night
sweats
|
|
Candida
species
|
Oral
candidiasis (thrush)
|
White
mucosal plaques or erythema in oral cavity
|
|
|
Oesophageal
candidiasis
|
Dysphagia
+/-
chest pain
|
|
|
Vaginal
candidiasis
|
Vaginal
discharge, erythema, itching
|
|
Herpes
simplex virus
(HSV)
|
Oral,
genital and anal HSV genital and
anal vesicular dermatitis
|
Clusters
of painful vesicular lesions or shallow ulcers
|
|
Varicella
zoster virus (VZV)
|
Shingles/Herpes zoster
|
Dermatomal
pain
Vesicular
lesions in dermatomal distribution
|
|
Mycobacterium
tuberculosis
|
Pulmonary
tuberculosis
|
Cough
Fever
Weight
loss
Fatigue
|
|
|
Extrapulmonary
tuberculosis
|
Enlarged
lymph nodes or spleen
|
|
Cryptococcus
neoformans
|
Cryptococcal
meningitis
|
Headaches
Neurologic
abnormalities
+/-
meningism
+/-
fever
|
|
Cytomegalovirus
(CMV)
|
Retinitis
|
Visual
disturbance
|
|
|
Enterocolitis
|
Diarrhoea
Abdominal
tenderness
Bloating
|
|
Mycobacterium
avium complex
(MAC)
|
MAC
bacteraemia, wasting
|
Chronic
or recurrent fever
Weight
loss
Fatigue
|
|
Toxoplasma
gondii
|
Toxoplasma
encephalitis
|
Headache
Drowsiness
Fever
Focal
neurologic abnormality
Seizures
|
|
Cryptosporidium
|
Cryptosporidial
enteritis
+/- cholangitis |
Chronic
diarrhoea —may resolve spontaneously in early HIV infection
Right
upper quadrant pain
|
|
Microsporidia
(several organisms)
|
Microsporidial
enteritis
+/- cholangitis |
Chronic
diarrhoea
May
be asymptomatic
|
|
Malignancies
|
Clinical
features
|
|
Kaposi’s
sarcoma
|
Red/purple
skin and mucosal lesions
Bleeding
oral lesions
Gastrointestinal
obstruction causing nausea/vomiting
Pulmonary
disease—dyspnoea
Lymphatic
system involvement—swelling of extremities
|
|
Non-Hodgkins
lymphoma
|
Splenomegaly
Focal
neurologic abnormality
Increasing
asymmetrical lymphadenopathy
|
|
Primary
lymphoma brain
|
Headache
Focal
neurologic abnormality
|
|
Cervical
dysplasia/cancer
|
Post-coital
bleeding, intermenstrual bleeding
Abnormal
Pap smear
|
|
Anogenital
cancer
|
Mucosal
lesion—non-healing
Abnormal
biopsy
|
The
case definition of AIDS-defining illnesses used in Australia and the
United States is shown in Appendix 3.
Medical
history
At
the first appointment after diagnosis complete assessment includes a full
medical and sexual history, including current state of health and systems
review.
Examination
A
complete medical examination including:
-
the
patient’s weight and vital signs
-
lymphadenopathy:
cervical, axillary and inguinal
-
skin
lesions or rashes
-
oral
lesions
-
hepatosplenomegaly
-
genital,
including anorectal, lesions
-
any
neurologic abnormalities
-
inspection
of fundi (in patients with CD4 < 50/mL
review by an ophthalmologist should be performed 3 to 6 monthly)
Investigations
The
following investigations are conducted:
at
first visit after diagnosis
-
repeat
HIV ELISA for confirmation
-
HIV
viral load
-
liver
function tests (LFTs), electrolytes, renal function tests
-
amylase,
CK
-
full
blood examination (FBE)
-
CD4,
CD8 lymphocyte markers
-
serologic
tests for syphilis
-
Hepatitis
A serology
-
Hepatitis
B serology
-
Hepatitis
C serology
-
HSV
type 2, EBV, CMV, toxoplasmosis serology
-
G6PD
in case future use of sulphonamides is required.
Subsequent
routine 3-6 monthly follow up
-
FBE,
CD4/CD8 lymphocyte surface markers, HIV viral load, LFTs,
electrolytes, renal function tests.
-
amylase,
CK, lipase,to check for medication side effects if on HAART
-
when
the CD4 count falls below 100, regular screening for MAC should be
performed (Mycolytic F)
-
Pap
smear should be performed 6-12 monthly, more frequently as CD4 count
declines
-
STD
check should be included if relevant symptoms exist or if exposure has
occurred.
Antiretroviral
therapy
Combination
antiretroviral therapy has been demonstrated to significantly increase
life expectancy and delay the progression to AIDS in individuals with a
CD4 cell count below 500/mL.
As yet, there are no published data on the effect of combination therapy
in individuals with early infection and a normal CD4 cell count.
Patients
are usually prescribed a minimum of three drugs to include drugs from at
least two of the following categories.
Treatment
recommendations are constantly changing and a detailed description of
specific treatment of HIV infection is beyond the scope of these
guidelines . Antiretroviral therapy should only be initiated by
practitioners experienced in their use.
Currently,
the main antiretroviral agents for the management of HIV infection in
Australia include:
Nucleoside
analogue reverse transcriptase inhibitors
-
abacavir
(Ziagen)
-
didanosine
(ddI, dideoxyinosine, Videx)
-
didanosine
enteric coated (ddI EC, dideoxyinosine EC, Videx EC)
-
lamivudine
(3TC;)
-
stavudine
(d4T, Zerit)
-
zalcitabine
(ddC, dideoxycytidine, Hivid)
-
zidovudine
(ZDV, AZT, Retrovir;)
-
combine
formulations
-
abacavir,
lamivudine, zidovudine (Tizivir)
-
lamivudine,
zidovudine (Combivir)
Nucleotide
analogue reverse transcriptase inhibitors
Non-nucleoside
analogue reverse transcriptase inhibitors
-
delavirdine
(Rescriptor)
-
efavirenz
(Stocrin)
-
nevirapine
(Viramune)
Protease
inhibitors
-
atazanavir
(Reyataz)
-
indinavir
(Crixivan)
-
lopinavir
(combined formulation with ritonavir, Kaletra)
-
Fosamprenavir
(Telzir)
-
nelfinavir
(Viracept)
-
ritonavir
(Norvir)
-
saquinavir
(Invirase – hard-gel
capsule, Fortovase – soft
gel capsule)
Fusion
inhibitors
Management
of Opportunistic Infections
(less
likely to occur because of the efficacy of antiretroviral and preventive
therapy)
|
Infection
|
Management
|
Pneumocystis
jiroveci
|
|
Prophylaxis
CD4 < 200/mL |
Trimethoprim-sulfamethoxazole
(TMP-SMX)
1 DS tablet (160 mg/800 mg) daily
or
Dapsone
100 mg twice weekly
or
Pentamidine
300 mg by nebuliser once a month. Nebulised salbutamol may be used
as a premedication to reduce bronchospasm.
|
|
Pneumocystis
jiroveci
|
|
Acute
infection
|
Intravenous
therapy
if
acutely ill, unable to take oral medication, or pO2<60:
Trimethoprim
20 mg/kg/day and sulfamethoxazole 75-100 mg/kg/day in 4 divided
doses for 21 days
or
Pentamidine
3 mg/kg once daily
plus
Hydrocortisone
100 mg iv qid for 7 days
Oral
therapy
TMP-SMX
2 DS tablets tid for
14-21 days
or
Trimethoprim
200 mg qid and dapsone 100 mg daily for 14-21 days
plus
Prednisolone
50 mg/day orally for 7-14 days.
|
Candidiasis
|
|
|
|
Oral
(treat until symptoms resolve) |
Fluconazole
200 mg orally daily for 7 days
or
Nystatin
100,000 unit tablet dissolved in mouth 3-5 times daily
or
Amphotericin B
10 mg lozenges orally 3-5 times daily
|
|
Vulvovaginitis
|
See
Vulvovaginal
candidiasis diagnosis and management guidelines (Chapter
10 of this book)
|
|
|
|
|
Oesophagitis
|
Fluconazole
200 mg orally daily for 2 weeks, then 50-100 mg daily
Long
term secondary prophylaxis is recommended to prevent relapse.
|
|
Cryptococcal
meningitis
|
|
Acute
infection
|
Amphotericin
B 0.6-0.8 mg/kg/day iv plus
5-flucytosine 100 mg/kg/day orally qid for 2 weeks
followed
by
Fluconazole
400 mg daily for 6-10 weeks
|
|
Maintenance
|
Fluconazole
200 mg once daily
There
is a 60% recurrence rate if maintenance therapy is not taken.
|
Toxoplasma
encephalitis
|
|
Acute
Infection
|
Pyrimethamine
200 mg orally as a single dose then 50 mg orally daily plus folinic
acid 10 mg orally daily plus sulfadiazine 1 g orally qid for 6 weeks
or
Pyrimethamine,
folinic acid as above plus clindamycin 900 mg iv qid for 3 weeks,
then 450 mg orally qid for 3 weeks
|
|
Maintenance
Prophylaxis
|
Pyrimethamine,
folinic acid plus sulfadiazine 500 mg orally qid
or
Pyrimethamine,
folinic acid, plus clindamycin 300 mg orally qid
TMP-SMX
1 DS tablet daily
|
Mycobacterium
avium
complex
|
|
Treatment
|
Rifabutin
300 mg orally daily, plus
Ethambutol 400 mg orally bd, plus
Clarithromycin 500 mg orally bd.
The
required duration of treatment is uncertain, but should be at least
12 weeks. Indefinite maintenance therapy (with 2 agents) should
continue.
|
|
|
Prophylaxis:
CD4£100/mL
|
Azithromycin
1.2 g orally weekly
|
Herpes
simplex/zoster
|
|
Severe
|
Aciclovir
5 mg/kg iv tds for 7 days
|
|
Moderate
|
Valaciclovir
1 g orally tds for 7
days
|
|
Suppression
|
Valaciclovir
500 mg orally bd
|
Cytomegalovirus
retinitis
|
|
Initial
treatment
|
Ganciclovir
5 mg/kg iv bd for 2
weeks
or
Foscarnet
90 mg/kg iv bd for 2 weeks
|
|
Maintenance
|
Ganciclovir
10 mg/kg iv 3 days/week
or
Foscarnet
90 mg/kg iv 5 days/week
|
Cryptosporidium
enteritis
|
|
|
Anti
retroviral therapy with immune reconstitution controls persistent
cryptosporidiosis
Paromomycin
500 mg orally tds until resolution
|
Bacterial
pneumonia
|
|
|
Ceftriaxone
1 g iv daily for 10-14 days
followed
by
Augmentin
Duo 850 mg
orally bd until resolution
|
Prophylactic
therapy against opportunistic infections
|