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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