Diagnosis of HIV infection

A diagnosis of HIV infction can usually be made by demonstrating anti-HIV antibodies in the
patients serum. However, the serogical diagnosis of HIV infection can sometimes be
problematic.
A small minority of individuals who are not infected by HIV hav soe serum antibodies which
are reactive with some HIV proteins, and give false-positive results with some enzym-linked
immunoabsorbent assays (ELISA). Many laboratories use to different types of ELISA to
identify such sera. To ensure that HIV infection not incorrectly diagnosed, an antibody test
should only be considered positive if antibody is also detected according to defined criteria,
using a confirmatory antibody test such as a western blot immunoassay.
Anti-HIV antibodies may be absent from the serum of patient with acute HIV infections.
They are usually detectable by 2-6 weeks after infection, and almost always detectable by 12
weeks. After this time, absence of HIV antibodies exclude HIV infection in all but the most
advanced case of AIDS, or in a patient with an antibody deficiency disease. Sera from
pastients with acute HIV infection which do not contain anti-HIV antibodies may be positive
foe p24 antigen ( a component of the HIV core protein) or HIV RNA.
The serological diagnosis of infection with HIVs originating from west africa can b
particulary problematic. Antibodies againts HIV-2 may not be detecteed by assays for HIV-1
antibodies, and it is therefore essential to use an HIV-2 spesific antibodies assay if HIV-2
infection is a possibility. Furthemore, a subtype of HIV-1, known as subtype O, which is also
present in west africa, may not be detected by ELISAs for HIV-1 or HIV-2 antibodies. Such
situations are very uncommon in Australia, Europe, and the USA, but infection with HIV-2
or HIV-1 subtype O must be considered in patients from west africa and their sexual partner.
If HIV induced immunodeficiency is suspected in a patient with a negative HIV antibody
test, or in a patient in whom an HIV antibody test cannot be performed, demonstration of a
low blood CD4+ T-cell count is highly suggestive of HIV infection. However, a rare acquired
celluler immunodeficiecy syndrome characterized by very low CD4+ T-Cell count may also
occur in patient without HIV infection.
Monitoring of HIV disease
Imunodeficiency and neurogical disease caused by HIV infection usually develop gradually
over month to years. It is important to monitor their severity to determine when to commenc
therapy and when the patient is susceptible to various disease manifestation.
Measurement of the blood HIV load is a means of demonstrating to severity of HIV
infection. This can be done most practically by quantiting HIV RNA in plas,a. The blood
CD4+ T-cell count or prcntage is the best indicator of the severity of HIV-induced
immunodficiency, and the type of infection which is likely to develop, even though the
immunodeficiency is not solely caused by CD4+ T-cell depletion. Measurement of the blood
CD4+ T-cell count or percentage is therefore very valuable in determining if the symptoms of
an HIV-infected patient are likely to be caused by an opportunistic infection, and if so, what
type of infection.
Other in investigations provide additional information provide additional information about
the severity of HIV-induced immunopathology. HIV infection causes activation of the imune
syste, the severity of which can be assesed by measuring serum concentrations of 2-
microglobulin (lymphocite activation). Immunoglobulin A ( IgA, ; B-cell activation). And
neopterin (macrophage activation). Measurement of cutaneus delayed-type hypersensitivity
(DTH) responses is a means of measuring cellulare imune fungtion, and also has clinical
utility in some circumstanses.
Treatment of HIV infection
Suppresion oh HIV replication is currently the most effective way to preventing or reversing
HIV disease. Whilst augmentation of Anti-HIV immunity by vaccination holds promise for
the future, the most effective way of doing this at present is to use drugs which impede HIV
replication. Two classes of antretroviral drugs are currently in use reverse transcrptase
inhibtors and protease inhibitors. Reverse transcriptase inhibitors are two types. Nucleoside
analouges act by subtituting for natural nucleoside during HIV replication, thereby inhibiting
DNA chain elongation and the effect s of the reverse transcriptase enzyme. Non-nucleoside
reverse transcriptase inhibitors (NNRTIs) inhibi the reverse transcriptase enzyme by a
different mechaism.
All antiretroviral drugs have a limited time of efficacy because the HIV eventually develop
resistence to them. Th use of drug combinations appers to be more effective than single
drugs, partly because drug resistance develops more slowly.
Adverse effect of antiretroviral drugs are common, and are a cause of morbidity and even
mortality. Zidovudine may cause myelosuppresion. Particulary in severly immunodeficient
patiens, and a mithocondrial myopathy in patients who have taken therapy for long period of
time. Didanosine may can pacreatitis which can be fatal, tough this is uncommon with the
dose which are no used. Both zalcitabine and didanosine may cause a sensorimotor
neuropathy which can be severe. Hepatic steatosis with or without lactc acidosis is a rare but
potencially fatal complication of treatmen with all nucleoside analouges. It probably result
from inhibition of mithocondrial DNA function. The most common adverse effect of
NNRTIs is skin rash.
HIV-Induced immunodeficiency
Both CD4+ T-cell depletion and the effects of other poorly defined immune defect lead to
development of an immunodeficiency syndrome. This syndrome is characterized by impaired
celluler immunity and an increased propensity to opportunistic infection. In addition, some
patient have impaired antibody responses and phagocyte function, which reselut in infections
with encapsulated bacteria and systemic fungal infection.

Mild celluler immunodeficiency
Infectious complication of celluler immunodeficiency may occure when there is relative mild
impairment of celluler immune responses ( CD4+ T-cell counts of 200-500/l).
Mucocutaneus infections occur most commontly but infection with bacteria such as
camphylobacter jejuni, salmonella spp. or Shigella spp. are a cause of diarrhoea, and
occasionally bacteramia. Most of these infections are not restricted to patiens with HIV
infection, and are therefore not considered to be AIDS-defining opportunistic infections.
However, when they present atypically, are severe or are reccurent, they may be the first
indication of underlying HIV-induced immunodeficiency. In contras to the other infection,
oral hairy leukoplakia is almost always indicative of HIV infection.
Infection with Mycobacterium tuberculosis may also occur when there is mild
immunodeficiency, because virulence of thi microorganism. Most case of tuberculosis are the
result of reactivation of latent M. Tuberculosis infection, and therefore, the icidence of
tuberculosis in HIV infected patients is propotional to the rate of endemic infection. For this
reason, tuberculosis is particulary common in Africans, Asians and individuals from
underpriviledge groups in Europe and the USA. In patient with HIV induced
immunodeficiency tuberculosis often has an atypical presentation which includes
extrapulmonary disease.
Severe cellular immunodeficiency
cellular immunodeficiency which is severe enough to result in an icreased propensity to
systemic opportunistic infection is often present in patients with CD4+ T-cell count <200/l.
Such infections are considered to be indicative of the presence of AIDS. Infection with many
different microorganism may occur, including infection with unusual microorganism. Only
the most common are describe here.
Pneumocystis carinii pneumonia (PCP)
Infection of the lung by Pneumocystis carinii causes an interstitial pneumonitis. Patient with
this condition usually have a history of dyspnea, cough, fever, and weight loss. Examination
ofter reveals basal pulmonary crackles. Thes chest X-ray usually shows interstitial ifiltrates
but is occasionally normal. Other findings which would support diagnosis of PCP are
hypoxameia, and incrased serum lactic dehydrogenase (LDH) concentration, and diffuse
uptake of radiolabelled gallium into the lung on a gallium scan. A defintive diagnoses can be
made by dmonstrating. Pneumocystis cyst in a induced sputum specimen, broncoalveolar
lavage fluid or a transbroncial biopsy.
PCP is treated with co-trimoxazole (trimetrophin-sulfametoksazol), given orally or IV
depending on severity reaction, and alternative medications, including oral dapsone, and
PaO2 is < 7mmHg (9.3kPa)
Respiratory failure complication PCP is the most common reason for admitting on HIV-
infected patiet to an ICU. Survival following ventilation for PCP was poor in the early 1980s,
but improved later in the decade, probably as a result of improved treatment and selection of
patient. In recent years, survival has worsened again, particulary for patient with a CD4+ T-
cell count of <50/l and for those who develop pneumothorax as a result of barotrauma. The
poor outcome in recent years may reflect the fact that patient are living longer because of
improved therapy, and hence often more immunodeficient when PCP develops. Whetever
the cause, the cost effectiveness of treating patients with PCP is now being scrutinzed, and it
is important tto select patients for ventilatio carefully. A first episode of PCP, a CD4+ T-cell
count of >50/l, and no previous antiretrovoral theraphy are all favourable factors.
Furthemore, ventilation may be avoided by the use of continous positive airway preasure
(CPAP) or bilevel positive airway preasure, thereby reducing the risk of pneumothorax,
airway obstruction and nosocomial infection.
Pneumocystis infection can be prevented by prophylactic medication. All patienr with CD4+
T-cell count <200/l should be offered prophylaxis. Th most effective drugs is
cotrmoksazole. Alternative patient who are sensitive to cotrimoksazole include dapsone with
trimetrophim or pyremithamine, or inhaled pentamidine.
Oesophageal candidiasis
Candida infection of the oesophageal mucosa present with odynophagia and dysphagia. The
occurence of such symptoms in assosiation with oral candidiasis is usually sufficient to make
a presumptive diagnosis of oesophageal candidiasis and to start treatment. An azole such as
ketoconazole or fluconazole is usually used. If there is no response to treatment, endoscopy
should be performed to exclude other cause of odynophagia.
Chryptococal meningitis
Meningitis is the most common manifestation of infection with cryptococcus neoformans in
patient with AIDS. It usually presents with headache and fever, but sometimes confusion or
behavioural abnormalities. Neck stiffnes is often minimmal or absent. Cerebrospinal fluid
examination may reveall little evidence of inflamation, particulary in the most severe cases,
but cryptococcal antigen is virtually always present and cultures for cryptococci are positive.
Most patients also have cryptococcal antigen in their serum. IV amphotericin is the teratment
for choice., and must be followed by permanent suppressive theraphy for prevent relaps. Oral
fluconazole or, if that fails, intermitten IV ampfotericin are the most effective supressive
therapies.
Toxoplasma encephalitis
Reactivation of toxoplasma gondii infection most commonly presents as a focal encephalitis.
This may causes headache, fever, focal neurogical, deficits, convulsion, and ever coma. One
or more than brain lesions may be present. They usually produce ringenhancinglession with
surrounding oedema on a brain couted tomoghraphy (CT) scan, and can occure in many site,
with predilection for the basal ganglia. Evidence or previous toxoplasma infections is present
in virtually all patient, and absence of serum toxoplasma antbody essentially exclude the
diagnosis. Treatment is with IV sulphadiazine or clindamisin, and oral pyrimethamine.
Hypersensitivity reaction to sulphadizine and clindamycin are common, and an alternative
drug regimen may be necessary. A brain CT scan should be repeated after 2-3 weeks of
theraphy, and a alternative diagnosis considered if these has been no resolution of the lesion.
Cerebral lymphoma can produced very similiar lession to toxoplasma encephalitis. A brain
biopsy may be necessary to make the diagnosis
Very sevre cellule immunodeficincy
Other systemic infetion occur in patient with very severe immunodeficiency (CD4+ T-cell
count <50/l.
Cytomegalovirys (CMV) infection
The most common site for reactivation of CMV infection is the retina. CMV retinitis usually
presents with blurred visions, visual field loss or floater. Diagnosis is by funduscopy and
comfirmation by a ophtalmologist should be undertaken. Treatment is with IV Ganciclovir or
foscarnet, followed by lifelong suppresive theraphy to prevent relapses.
CMV infection less commonly presents with infection or other orgasm, particularly the
oesophagus, bile duct, colon or lunfs. Biopsy of affected tissue is necessary to make devitive
diagnosis, but presense of CMV antigen in blood leukocytes provids support for a diagnosis.,
whereas failure to culture CMV from urine argues againts it.
Cryptosporidiosis
Infection of the GI by Crystoporodium parvum causes a severe and intractable secretory
diarrhoea, which is often associated with a malabsorbtion syndrome. It can also cause
chlorangitis. Diagnosis is by demonstrating cryptosporidium oocyst in faeces and/or a rectal
or duodenal biopsy. There is o satisfactory teratment, but paromomycin is of use in some
patients.
Mycobacterium avium complex infection
Infection with mycobacterium avium complex (MAC) is usually disseminated and effect
blood leukocyte, liver, spleen and lymph nodes, and the gastrointestinal tract. This infection
often result in weight loss, fatigues, fever, anemia and diarrhoea. The diagnosis is usually
made by culturing MAC from blood, but sometimes stool microscopy and culture or biopsy
of affected tissue are necesary. Treatment with multiple drug theraphy is often sucsessful.
Commonly used drugs are clarithromycin, rifabutin, ethambutol.
Infectious complication of other immune defect
Some infection appear to develop as a concequence of impaired antibody-mediated
immunity of phagocyte defects. Acute infectio of the respiratory tract by Haemopilus
influenza and streptococcus pneumoniae occurs particulary in injecting drug users, eldery and
children. These infection s may occur long before the onsetof symptomatic celluler
immunodeficiency. In contrast, infection with pseudomonas aureginosa are most common in
patient with advanced HIV disease, particulary those with neutropenia. Infection of the
respiratory tract by Aspergillus spp. and some other uncommon fungimay also occurs in
patients who are neutopenic.
Chronic infections of the respiratory tract are a common and often difficult problem to
manage in patients with advanced HIV disease. Nasal sinusitis causes hadaches and fever,
and may be associated with chronic suppurative bronchitis or brochiectasis. Infection of the
sinuses by H. Influenzae, pneumococc or Pseudomonas is the most common cause, but
infecton with Aspergillusor other fungi also occurs. A CT scan of the sinuses is the most
sensitive radiological investigation. Treatment is with antibiotics or antifungal drugs and
nasal decongestants. Drainage of the sinuses and microbiological examination of the sinus
contents may be necessary if there is no response to therapy.

HIV-associated neoplasms
Certain neoplasms are a characteristic complication of cellular immunodeficiency disease,
including HIV-induced immunodeficiency. Uncontrolled replication of an additional
microorganism resulting from the immunodeficiency is probably involved in the pathogenesis
of all of these neoplasms.
Kaposis sarcoma (KS) is an angioproliferative tumour which originates from
vascular endothelium. There is much evidence implicating an infectious agent in the
pathogenesis of KS. This has recently been identified as a herpesvirus (Human Herpesvirus 8;
HHV 8). KS usually presents as skin lessions whichhave a reddish-brown colour. They very
in extent fromm one or two small papules to numerous bulbous lesions. The mucosal surface
of the gastrointestinal tract, lymph node, and rarely, internal organs may also be involved. A
clinical diagnosis of KS can be confirmed by biopsy of a lesions. KS may be a complication
of any degree of immunodeficiency (CD4+ T-Cell count < 500x 10
6/
l) but occurs most often
in patients with moderate to svere immunodeficiency.
Lympomas are also a complication of HIV induced immunodeficiency. The great majority
are B-cell lymphomas, and reactivation of Epstein-Barr virus infection is implicated in the
pathogenesis of many cases. Primary cerebral lymphoma or extracerebral lymphoma with
frequent extra nodal involvment are common in patient with severe immunodeficiency.
These lymphomas are usually high grade with poor prognosis. Low grade lymphomas occur
less commonly in patient with a better prognosis.
Cervical intraephitelial neoplasia (CIN) is more common than normal in woman with HIV
infection. This in presumably because human papiloma virus (HPV) infection is more likely
to be present in woman with HIV infection, and the cellulee immunodeficiency permits HPV
replication. As a consequense, the incidencee of cervical carcinoma appers to be incrased in
HIV-infected woman.
HIV-associated neurogical dissease
In addition to opportunistic infection of the nervous system in patient with AIDS, HIV
infection of macrophages and microglial cell in the nervous system often results in
neurogical disease by incompletely understood mechanism. Encphalopathy, myelopathy,
pripheral neuropathy or myopathy are all possible, and in a small number of patients, the
neurogical disease is more problematical than the imunodeficiency. The encephalopathy
usually devlops insidiously and eventually results in cog nitive, motor, and behavioural
abnormalities. Myelopathy results in an ataxic spastic parapresis, which is often associated
with bladdder dysfunction.
HIV infection and AIDS in the ICU
Although AIDS remains an incurable disease, the admission of a patient with AIDS to an
ICU is indicated in some circumtances. The most common indication are :
1. Respiratory failure complicating PCP
2. Coma or convulsions complicating opportunistic infections or tumours of the brain
3. Non-HIV-related conditions such as a self-poisoning
Selection of patients for intensive care is important. In the case of PCP and respiratory
failure, the blood CD4+ T-Cell count is valuable in predicting outcome. However, the only
indicator of outcome of coma or convulsions apears to be the severity of the neurogical
deficit.
Patients wit unrecognized HIV infection or AIDS may also be admitted to an ICU with the
firs manifestation of HIV disease. It is therefore iportant for all ICU staff to practise stringent
infection control procedures at all times.