Suppressing HIV

• Reducing viral load has been shown to reduce the risk of dying from AIDS. It has also been shown to improve the health of people with AIDS-related illnesses.

• Reducing viral load and keeping it down is the aim of anti-viral therapy.

• United Kingdom and United States guidelines say that the aim of treatment should be to achieve and maintain undetectable viral load, below 50 copies/ml. This is the cut off point for the ultrasensitive viral load test.

• If viral load has not gone below 50 copies/ml after four months on a new combination, many doctors are now advising 'intensification' - adding another drug to help get viral load down.

• Improvements in immune function are indicated by an increase in CD4 cell count. If treatment does not fully suppress HIV, you may still experience better immune function and improved health in the short-term.

• For people who have taken several anti-HIV regimens, the aim of treatment may be to boost CD4 cell counts rather than to achieve undetectable viral load. To strive for undetectable viral load may mean using many drugs which may in turn produce severe side-effects. In addition, it is unclear whether undetectable viral load necessarily signals improved health and prognosis for heavily pretreated individuals.

• Studies are now underway to see whether it is possible to achieve long-term viral load suppression by starting with three or four drugs and then reducing therapy to two or three drugs after viral load has been undetectable for around six months. This would make anti-viral therapy easier to take, less expensive and might cut the risk of long-term side-effects or cross-resistance to many drugs. However, the results of these studies have not been very promising so far.

Eradicating HIV

• Some researchers have investigated the elimination of HIV infection from the body with three, four or five drug combination therapy.

• Some researchers believe that treatment very early on, during the early weeks of infection ('primary' infection), is most likely to achieve this goal.

• Powerful therapy can reduce viral activity by 99.9% within eight to twelve weeks. This will leave low levels of virus production from cells which were infected before therapy began. These cells might remain dormant for many months before being triggered to produce virus particles.

• Anti-HIV drugs cannot kill these cells, so researchers are waiting to see how long it takes for these cells to die out in people who are taking triple therapy. Estimates range from 18 months to 80 years. This makes eradication of HIV unlikely.

• In the meantime, these cells will always provide the basis for a rebound in viral load if treatment stops.

• Virus production also has to be stopped in the brain, nerve cells, immune cells in the gut and the spleen, and in the male genital tract. Some currently used drugs cannot shut down HIV replication in all of these tissues.

Treatment approaches

• Once you have started to take an anti-HIV drug regimen, you will probably have to take it continuously until it stops working.

• Other approaches to HIV treatment remain experimental. Their effectiveness and safety have not been proven in clinical trials.

• These approaches include induction and maintenance therapy, when treatment is started with a large number of drugs during the induction phase, before the maintenance phase, when fewer drugs are used. Another experimental approach is to change between two or more regimens repeatedly. This may prolong the effectiveness of the drug regimens by delaying the development of resistance and side-effects.

• Structured treatment interruptions or drug 'holidays' are discussed in a separate section.

Treating HIV in the brain and other compartments

• The brain and central nervous system are important targets for anti-HIV therapy because they house HIV-infected cells which are very long-lived. Measuring levels of HIV and anti-HIV drugs in these places is difficult.

• Nucleoside reverse transcriptase inhibitors (NRTIs), especially AZT (zidovudine, Retrovir) and d4T (stavudine, Zerit), are more likely to pass into the brain and central nervous system than other types of anti-HIV drugs, but research is still going on to see whether boosting protease inhibitor levels means higher drug levels in the brain.

• Undetectable viral load in blood may not mean that virus is also undetectable elsewhere in the body.

• Some doctors believe that pushing down viral load will reduce the risk of passing on HIV to another person, but this is not proven. If you have undetectable viral load you may still be able to pass on HIV to another person during sex.