Triple-drug therapy provides hope in the fight against the immune deficiency syndrome
OVER the last 16 years, AIDS has become the most important challenge for medical scientists. It has already destroyed or
is in the process of decimating the
immune systems of over 8 million people the world over. Close to half of them have perished due to opportunistic
infections such as tuberculosis, and
many more are waging a grim battle. An
estimated 20 million have the virus in
their system and, with 10,000 cases
added every day, another 11 million will
be infected by the turn of the century.
But there appears to be hope of arresting the trend as, for the first time, the number of deaths in the West has actually come down. AIDS-related deaths in early 1996 have witnessed a drop of 13 per cent as compared to the corresponding period in 1995. In European countries like France, the decline has been as steep as 25 per cent. This is attributed to two factors. First, the message that AIDS is a deadly disease and, therefore, one is better off taking precautions against infection, seems to have firmly sunk in. More importantly, as compared to the earlier average life expectancy among AIDS patients of about 11 months, new drugs and treat ment protocols have increased that time to 20 months or more.
Till date, drugs had only succeeded in delaying the progression from HIV to AIDS by about eight years. New research by Ashley Haase and his colleagues from the University of Minnesota Medical School, Minneapolis, us, suggests that with a new regimen of drug therapy it should now be possible to cure patients with HIV infection (Science Vol 276, No 5314).
The new strategy, called triple-drug therapy, has shown unusual promise. It relies on a combination of a protease inhibitor, which blocks the action of an enzyme needed by the virus to make some of the new components of its replica, and two reverse transcriptase inhibitors (RTIS). RTI is block the copying of viral genes into a form that can enter a host cell's nucleus through a process known as reverse transcription. With the virus making thousands of copies of itself daily in the HIV host's body, it would need a lot of protein molecules and enzymes for its survival and progression. Proteases just break down proteins into amino acids. The viral genes cannot make new clones as it cannot be read by the host cell's genetic machinery without these agents.
The tremendous success of this triple-drug therapy was initially reported earlier this year. Christened ACTG320, it was tried out in over 1,000 people with advanced HIV infection. Patients who were administered this therapy received a protease inhibitor called indinavir and two RTIS called AZT and 3TC. Analysis of the early results showed that patients who received ACTG320 were half as likely to develop a new AIDS-related complication or to die of the acquired disease, as compared to those who received only the two RTIS. But triple- drug therapy did not benefit all the patients. Six per cent did not respond as the viruses infecting them had developed resistance to one or both of the RTIs as a result of previous treatment.
This is hardly surprising as the basic objective of the combination therapy is tb counter the virus from developing a drug- resistant strain. The virus develops drug resistance by undergoing genetic change through mutation. Scientists are of the opinion that the chances of the Virus acquiring three different mutations simultaneously are minimal when three different drugs are simultaneously let loose. Also, the wild propagation of the virus starts in organs like the lymph nodes and then spills out into the blood. With the triple-drug assault, it was found that the viral load can fall from thousands per milliliter at the height of infection to a nearly undetectable level within a few weeks of treatment.
However, researchers were unsure of the effectiveness of the triple-drug therapy in flushing out the two per cent of viral load still lurking inside the body, which could lead to a resurgence of the virus. Haase's study suggests that it can. His team has shown that triple-drug therapy can sweep HIV out of the tonsils, one of the favourite haunts of the virus. After six months of continuous treat- ment with dozens of pills a day, there were no signs of HIV in immune system cells, called T-lymphocytes, and white blood cells, called macrophages, which the virus normally inhabits.
While the results of the research have generated understandable euphoria, there are still some grey areas. For one, there is the possibility, albeit remote, that some leftover parts of the viral DNA in the patient's body could resurrect the infection. The success of the experiments needs to be cross-checked after some time to determine the presence of the virus. More important, even if the therapy succeeds, it can hardly provide a solution to the AIDS crisis. Nine out Of 10 HIV infected people live in the poorer parts of the world. At US $16,000 a year for triple-drug therapy, it would be impossible to take care of the 26 million people from the developing countries who would be infected by AD 2000. Effective preventive strategies remain the best bet.
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