Opportunistic infections in HIV positive patients
Opportunistic infections in HIV positive patients |
|
Key words: HIV; opportunistic infections; anti-retroviral therapy; immune supression
Since the widespread introduction of highly active anti-retroviral therapy (HAART) in 1996 the role of the HIV Physician has greatly changed. Pre HAART, great detail was paid to slowing the natural history of the disease and as the CD4 declined being watchful for development of AIDS indicator disease and AIDS defining infections (ADI). However, since 1996 the natural history of the disease has dramatically altered and there is now the ability to maintain and even reconstitute the immune system. The major used marker of immune health is the CD4 cell which accounts for 60% of all circulating lymphocytes and in immune competent individuals, numbers -800cells/mm . CD4 numbers decline on average by 40-80 cells/year but acceleration in decline heralds disease progression. CD4 levels are reduced below 500cells/mm3 and British HIV Association (BHIVA) guidelines recommend initiation of HAART if levels are consistently below 350 cells/mm3. Below 200 cells/mm3 indicates significant immune suppression and potential development of opportunistic infections (OI). Certain ADI such as recurrent bacterial infections, tuberculosis, Kaposi’s sarcoma, herpes zoster, oesophageal candida occur with CD4 cells greater than 200 cells/mm3. The majority of ADI are opportunistic infections and occur with CD4 cells below 200 cells/mm3. Opportunistic infection become more common as the CD4 numbers fall and indeed most infections including PCP occur as CD4 cells fall below 50 cells/mm3.
Pneumocystitis carinii pneumonia
The majority of infections in HIV positive patients affect the pulmonary system
with pulmonary tuberculosis, recurrent bacterial pneumonia and pneumocystis
carinii pneumonia (PCP) being ADI. Pneumocystitis carinii pneumonia was the most
common serious infectious complication of HIV infection although CD4 monitoring
and introduction of cotrimoxazole prophylaxis successfully prevented the
majority of cases. However, PCP still too commonly is the presenting illness in
patients denying or not considering themselves to be at risk of HIV. This
condition classically presents with a 3 week history of worsening dyspnoea
associated with a dry unproductive cough. Often there are little clinical signs
on chest examination, however hypoxaemia is often profound and the patient
desaturates on exercise. Confirmatory diagnosis is provided on transbronchial
biopsy with histology confirming invasive pneumocystis. However this is rarely
performed as there is an appreciable risk of inducing a pneumothorax. Induced
sputum with hypertonic (3%) saline administered via an ultrasonic nebuliser or
specimens retrieved following bronchial alveolar lavage is most commonly used.
Therapy with high flow oxygen and high dose cotrimoxazole (100-120mg/kg/day) in
divided doses is the treatment of choice with the addition of prednisolone
(40-60mg/day) in severely hypoxic patients.
Pulmonary Tuberculosis
Mycobacterium tuberculosis world-wide remains an extremely important
co-infection in the context of HIV infection. The natural history of both
infections are deleteriously affected by the presence of the other. The
presentation of tuberculosis is altered in the severely immunocompromised
individual due to reduction in the cellular and macrophage immune systems. Chest
x-ray examination in patients with pulmonary tuberculosis often lack the
classical changes of apical cavitation produced by lung destruction and
caseation, and often the only radiological sign is the presence of pleural
effusion. Routine sputum and urine specimens should be collected for tubercle
examination. However, in co-existing HIV infection tubercle can also be cultured
from blood in special culture media. It is important to obtain the appropriate
mycobacterial specimens before initiation of therapy as tubercle in HIV
infection is associated with multi drug resistance. Infection control procedures
should be undertaken. Patients are nursed in negative pressure rooms and staff
and visitors should be masked when in contact with the patient. With global
travel and many cases of imported HIV infection occurring as well as increasing
numbers of refugees the number of HIV/tuberculosis co-infections may be expected
to increase.
Central Nervous System
Central nervous system infection commonly affects HIV positive patients with
late disease (CD4, 50 cells/mm3). Pre HAART, cytomegalovirus retinitis,
cryptococcal meningitis, toxoplasmosis, AIDS dementia and progressive multifocal
leucoencephalopathy were all difficult to treat, impossible to eradicate and
indicated the later stage of the disease. Many therapies involved intravenous
administration and were life long. The frequency of these infections has been
dramatically reduced after the introduction of HAART.
Gastrointestinal tract
Gastrointestinal tract may be infected from mouth to anus, with viruses (herpes,
CMV), bacteria (salmonellosis), fungi (candida) and parasites (cryptosporidiosis
and related organisms). These infections aggravate the ill health of patients by
leading to weight loss and malnutrition and indeed weight loss was a leading
marker of disease progression and death. A reasonably common scenario in HIV
clinics is for patients to be diagnosed with HIV after a number of month’s
investigation (including invasive procedures) for weight loss and diarrhoea.
Hepatitis C virus (HCV) often co-infects patients who have acquired HIV through
blood products or injecting drug use. HCV in immunocompetent individual lead to
cirrhosis in 20 years in 20% of patients. In those co-infected with HIV the
condition is accelerated. CDC in Atlanta have now defined hepatitis C
co-infection as an ADI and indeed liver disease is the most common reason for
admission of HIV patients to the John Hopkins Centre, Baltimore.
Malignancy
As science progresses other HIV associated disease have been found to have an
infecting agent basis. Kaposi’s sarcoma is associated with gamma herpes virus,
human herpes virus 8. HHV8 is also responsible for development of lymphomatous-like
conditions such as Primary Effusion Lymphoma and Castleman’s disease.
Castleman’s disease is a monoclonal proliferation of B cells within the lymph
node and in 20% transforms into plasmablastic lymphoma. Unfortunately HIV viral
suppression and restoration of CD4 number does not appear to affect the progress
of Castleman’s disease.
Summary
Highly active anti-retroviral therapy has transformed the management of HIV
infection, however the HIV Physician has to remain vigilant to detect the
development of opportunistic infection due to late presentation/diagnosis or
drug failure.
AIDS INDICATOR CONDITIONS
Infections
Recurrent bacterial infections <13yo
Invasive candidiasis*
Extra-pulmonary coccidioimycosis
Crytococcosis*
Cryptosporidiosis > 1 month
Non RES CMV*
Invasive HSV*
Extra pulmonary histoplasmosis
Isoporiaisis > 1 month
Disseminated mycobacteriosis*
PTB*
PCP*
KSV8 or HSV8 related diseases*
PML*
Recurrent pneumonia
Recurrent salmonella septicaemia
Cerebral toxoplasmosis*
Non infections
Cervical carcinoma
HIV encephalopathy
LIP <13 years
Lymphoma
Wasting >10% baseline weight
©2000 Sexual Health Matters. Published Quarterly by Express Print Works, Middlesbrough,
UK
ISSN 1469-7556
http://www.sexualhealthmatters.com