The immune system
T-CELL, CD4+ COUNTS
There are two main types of T-cells that play an important role in our immune systems. The CD4+ T-cell has CD4+ molecules on its surface and is responsible for gearing up the body’s immune system to respond to microorganisms such as viruses. The CD8 T-cell has CD8 molecules on its surface and is responsible for destroying cells that are infected with organisms such as viruses. CD8 T-cells also produce antiviral substances.
HIV is able to attach itself to the CD4+ cell, allowing the virus to enter and infect these cells. The virus multiplies in the infected cell, producing many copies of the virus and destroying the CD4+ cell in the process. The body produces billions of new CD4+ cells to replace those that have been destroyed.
CD4+ cells are measured by the number of cells per cubic millimetre (mm3) of blood. This is referred to as the CD4+ count. A normal count is between 600–1200 CD4+ cells per mm3 of blood – but this may vary from person to person and may even vary from day to day and hour to hour. Younger individuals may have higher counts than older people. A further measurement is the percentage of CD4+ cells of the total, white immune cell population. In HIV negative individuals, this is normally around 40% but in HIV positive individuals, can be lower. If the CD4+ percentage falls below 15% then there is a serious risk of opportunistic infection.
When a person is infected with HIV, the CD4+ count falls over a period of time, even though it may remain stable for a period of time. As a rough guide, the CD4+ count will drop by 40–80 cells/mm3 every year during the early stages of infection. It is important to monitor the CD4+ count on a regular basis, as this will assist the healthcare provider to determine when to start drug therapy, and to offer treatments to prevent opportunistic infections. If a patient is already on therapy, it is also used to measure the effectiveness of treatment.
When is drug therapy necessary?
The decision to start therapy should always be made in consultation with a doctor. There are various guidelines worldwide as to when to start therapy. However, a consistent CD4+ count below 350 is considered low and should be monitored on a regular basis. At levels of 200–250 an individual is at serious risk of opportunistic infection and a doctor may also recommend that antibiotics be taken to prevent PJP (pneumocystis Jiroveii pneumonia). Therapy should definitely be initiated at any CD4+ count below 350.
Once therapy is started, the CD4+ count may start to rise – which could reflect an improvement in immune function and the body’s ability to fight infection. Once the CD4+ count rises above 350 and is maintained above this level – patients with stage 3 or 4 continue to take prophylaxis irrespective of the (their) CD4 count.
Regular monitoring of CD4+ count and a rise in viral load helps determine whether the treatment is working. As long as the trend is upward or stable, then there is a positive indication of the effectiveness of the treatment. A consistent fall in CD4+ count may indicate that the treatment is becoming less effective. Importantly, any decision to change treatment should be taken in conjunction with a viral load test. Once therapy has started, it is normally recommended that CD4+ counts be done every 6 months (together with a viral load test).
A viral load test counts the number of HIV particles in a sample of blood. The result is expressed as the number of ‘copies’ of HIV RNA per ml (millilitre) of blood. It is now generally accepted that 10,000 copies per ml or less, is considered low – and 50,000 copies per ml and above, is considered high.
There are several tests that measure the amount of HIV particles present in the blood, although the tests become unreliable at low levels of infection. Originally this limit was less than 400 or 500 copies per ml. New ‘ultra-sensitive’ tests are now able to measure to a lower limit of 50 copies per ml – and these may become the tests that are more widely used. Depending on the test used, a measurement below the limit of detection may be referred to as ‘undetectable’.
The test for viral load is one of the monitoring tests that can indicate disease progression and may give an indication as to the likely course of HIV infection if left untreated. It is generally accepted that a higher viral load may lead to more rapid disease progression. Other indicators such as CD4+ count and symptoms should also be considered when deciding to take treatment.
When treatment is started, the viral load test gives an indication of how effective the anti-HIV regimen is. It is recommended that a baseline viral load test should be done prior to commencing treatment or switching from one treatment. A second test should follow a couple of months later, so as to monitor the effect of the drugs. It is then recommended to have repeat tests every six months, or even more frequently if there are indications that the regimen is not effective.
In some individuals, a drug combination can reduce the viral load to ‘undetectable’, even if the CD4+ count remains low. An ‘undetectable’ viral load normally means that the virus is less likely to develop resistance to the drugs and that viral replication is very slow. It is standard practice to try and reduce the viral load to ‘undetectable’ at the 50- copy level by around six months of treatment.
If an individual is taking the drugs correctly and viral load starts to rise again, it may mean that the drugs are becoming less effective (most probably due to viral resistance). It should be noted that the viral load only gives an indication of the amount of HIV in the blood – and does not measure the virus present in the brain and genital fluids where the effect of drugs may vary. The individual may therefore still be infectious to others.