HIV/AIDS


DEFINITION

An acquired deficiency in a particular facet of the body’s immune system (hence the term Aquired Immune Deficiency Syndrome/AIDS), resulting in an increased risk of contracting a variety of otherwise rare fungal, parasitic and viral infections, caused by infection with the human immunodeficiency virus (HIV).

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INCIDENCE

Uncertain, but infection rates are in the region of 50-60 million worldwide.
Only about 5% of cases have occurred in Europe.
There are just over 1000 known HIV-infected people in New Zealand.
HIV infection in children occurs via vertical transmission transplacentally, perinatal ingestion of mother’s vaginal secretions, breastfeeding.
In the past, unscreened blood transfusions accounted for most paediatric infection.
AIDS in NZ is predominantly a disease of homosexual men.
IV drug users and homosexual men make up the bulk of HIV infections in the Western world.
In Sub-Saharan Africa the infection is endemic amongst the heterosexual population as well.

Risk Factors
Anal sex.
Illicit IV drug use.
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AETIOLOGY

Infection with HIV-1 (aka HTLV-III), a retrovirus.
The virus infects T helper cells in the blood, interfering with cell-mediated immunity (see biological behaviour).

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BIOLOGICAL BEHAVIOUR

Virology
HIV is an enveloped RNA retrovirus, with genetic material coding for a reverse transcriptase enzyme.
Following the entry of HIV into a cell (most commonly a T lymphocyte, but other tissues can be infected), the virus creates a complementary DNA strand of its genetic material and this is inserted into the host cell’s genome.
The cell then acts to replicate the virus, until the body’s cell mediated immunity acts to destroy the infected T cell.
This process is thought to continue until the immune system of the body becomes exhausted.
There are two major variants of HIV: HIV-1, which is the more common, and HIV-2, which has been identified in patients in West Africa and is similar to simian immunodeficiency virus (SIV).

Transmission

Can occur through homosexual or heterosexual sexual contact (including oral sex), through infected blood products or needles, or via vertical transmission.
Transmission rates vary according to method:
Blood transfusion = approximately 80%
Vertical transmission = 20-40% from mother to child, with breastfeeding adding an undetermined risk
Unprotected man-man sex = 0.1-5%
Unprotected heterosexual sex = 0.1-1% (woman to man transmission is possibly more likely)
Sharing infected injecting equipment = 1%
Needle-stick injury = 0.3%

Natural History
After infection, the virus multiplies in the blood, initially without detection by the immune system.
After 4-8 weeks post-infection, a seroconversion illness may be noted during which antibodies to HIV are produced.
After this initial illness, sufferers are usually asymptomatic for many years, the duration of which varies from individual to individual.
During this time, the virus infects and multiplies within CD4 T lymphocytes, stimulating an immune response and the gradual (but varying rates of) depletion of T-cells as T-cell production fails to keep pace with destruction.
Infection leading to production of T-cells can result in immunodeficiency occurring sooner, due possibly to extra material for the virus to infect.

Complications
As CD4 counts are gradually depleted, otherwise rare opportunistic infections are seen in sufferers.
Any infection fought using predominantly cell-mediated immunity will be worsened or not cleared effectively.

A CD4 count below 200 X 10 6/L or presence of these AIDS-defining illnesses with a low CD4 count (<400 x 10 6/L)is the AIDS complex:
Multiple or recurrent bacterial infections in a child <13 years old;

Candidiasis
;
Recurrent bacterial pneumonia (>1/year) or one episode of Pneumocystis carinii pneumonia (PCP);
Viral infections, including CMV retinitis, atypical herpes simplex infection;
Neoplasm such as Kaposi’s sarcoma, lymphoma or cervical carcinoma;
Any encephalopathy with no other cause in a child;
Cerebral toxoplasmosis or progressive multifocal encephalopathy;
disseminated or pulmonary TB;
wasting syndrome of weight loss, fever >30 days and diarrhoea.
Shingles and molluscum contagiosum are also common, and can occur at low normal CD4 counts.
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MANIFESTATIONS

SYMPTOMS
Ask about risk behaviours eg unprotected man-man sex, unprotected sex with people from risk areas, IV drug use.
[Systemic] –
A seroconversion illness, with glandular fever-like features, may occur ~4 weeks post-infection.
Other than this, there are few signs of HIV infection per se.
Most symptoms occur due to one or more of the AIDS-defining illnesses mentioned in Biological Behaviour, or are due to the side effects of one of the antiretroviral agents.

SIGNS
[Observe] –
Often wasting/cachexia in a patient with full-blown AIDS.
Signs of opportunistic infections.
Infections such as pneumonia may be misleadingly mild clinically due to ineffective immune response.
[Palpate]
Generalised lymphadenopathy is often seen in symptomatic or soon-to-be symptomatic patients.
Peripheral neuropathy or myelopathy can be seen with drug toxicity, or occasionally with HIV itself.
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INVESTIGATIONS
[Haematology]
An absolute lymphocytosis may be seen.
Misleadingly low white cell counts may be seen in acute infections.
[Microbiology]
Viral load is an expensive test (NZD$500), and is a rough guide to future CD4 behaviour but is not as important as previously thought.
[Immunology]
Diagnosis is made using ELISA techniques for HIV antibodies, which is extremely sensitive (99.5%) and very specific (~95%).
Positive ELISAs go on to have a Western blot test. This is almost 100% specific.
The test will be positive approximately 10-12 weeks post-infection, prior to this a ‘window’ period exists in which false-negative results can occur.
Requires consent
CD4
The CD4 count is by far the most useful way to monitor disease progress and gauge the risk of opportunistic infections (normal 500-1500 x 10 6/L).
[Histopathology]
Biopsy of lymphadenopathy shows a reactive histiocytosis.
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MANAGEMENT
In New Zealand, HIV is managed by a specialist infectious diseases physician.
[Conservative] –
Counselling pre- and post-testing.
Education as to safe sex, the likely course of the disease and regular follow-up from the time of diagnosis.
Look closely for opportunistic infections, but remember HIV-infected patients get ‘normal’ infections as well.

[Medical] –
Because of the difficulty with compliance with the complicated drug regimen and the risk of viral drug resistance, treatment should not start until CD4 count dips below 300 x 10 6/L.
Treatment is highly active antiretroviral therapy (HAART), and all other regimens (such as can be found in the 14th edition of Harrison’s) are far less effective.
HAART involves a backbone of two nucleoside analogues, AZT and 3TC (in one tablet, Combivir) combined with either a protease inhibitor such as saquinavir or non-nucleoside reverse transcriptase inhibitor (NNRTI) such as nevirapine.
It is unclear whether 4 drugs is better than the current guideline of three.
The aim of treatment is to keep the viral load undetectable; if the virus is not completely suppressed while on drug therapy, resistance can develop.
Some recently acquired infections in the States are already multi-drug resistant.
This means 100% (not 99%) compliance with the regimen is necessary.
Side effects of the drugs include liver and nerve toxicity, lipodystrophy with ‘buffalo hump.’

Co-trimoxazole is good primary prophylaxis for PCP.
The efficacy of other prophylaxis is much less established.

The risk of vertical transmission from an infected mother can be reduced to 1-2% by administration of AZT to the mother in the 3rd trimester of pregnancy and the neonate for 4 weeks post-partum.
The efficacy of caesarean section on top of this is unclear.

The risk of transmission of needle-stick injuries from infected patients can be reduced by ~80% by 4 weeks of Combivir.
In either situation where new HIV infection is possible, discussion with an infectious diseases physician should be the first action.

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