Being Alive 1997 Apr 5: 1
The information emerging from this year's conference is mostly
a continuation of the good news that first started emerging
from last January's 3rd National Conference, where the data for
protease inhibitor therapy were first publicly released. There
are, however, some significant concerns, which are delineated
Some Protease Inhibitor Results
At last year's conference, Merck released data for about 20
participants in their now well-known study of individuals who
were 3TC and protease-naive but extensively AZT-experienced.
These people were treated with AZT, 3TC, and Crixivan.
Follow-up data extended only to 24 weeks. About 85% had
"undetectable" viral load with CD4 count increases of about 100
Abbott reported short-term (about 5 months) data indicating
clinical benefit in their study of individuals with advanced
aids treated with ritonavir (participants on average had about
25 or less CD4 cells prior to study entry). The early results
showed that survival was extended and progression of aids was
slowed. Since that time, there has been a steady flow of
generally positive news. Encouraging data for a new class of
drugs-non-nucleoside reverse transcriptase inhibitors
(NNRTIs)-have been emerging and is discussed below.
However, not all the news is exclusively positive. A number of
individuals either did not respond well to the new therapies or
initially responded well, but their viral load rebounded either
sooner or later. It is difficult to estimate how many
individuals have experienced this problem, but you are not
pleased if you are one of them.
A factor contributing to this problem is that in many cases
doctors and patients were not well prepared to know how to use
the drugs properly. In many instances, a potent protease
inhibitor was merely added on to therapy one may have been
taking for a while. Data from studies indicate clearly that to
maximize your benefit from protease inhibitor therapy or any
therapeutic regimen, you should begin if possible with at least
2 and preferably 3 drugs that you've never before taken.
Non-compliance is another problematic cause for the development
of resistance and failure. In order to benefit from the new
therapies, one must be prepared to commit to strict adherence
or compliance to the instructions for taking the
medications-dosing, hydration, eating, storage, etc. Other
factors may be relevant to why some individuals were not able
to benefit from protease inhibitor therapy, but at this point
they have not been identified.
For those who have responded well to the new therapeutic
regimens there is good news emerging from this conference. And,
for those of you who have not been able to respond well, there
is also hope from some of these newer promising drugs.
Viral Load in Other Body "Compartments"
Early in 1996, amidst the realization that we could render
viral load in peripheral blood to "undetectable" levels, it was
also realized that viral activity in other "compartments" would
now become of vital interest. The vast majority of virus in
humans is contained in peripheral blood, but it resides in
other parts of the body as well. Researchers started studying
viral activity in these other compartments and the effect of
the new potent antiretroviral regimens. It is crucial to
determine whether potent therapy can be effective in reducing
viral activity in these other compartments. Can the virus find
"sanctuary" in any of these compartments?
These other "compartments" include semen, lymph tissue and
spinal fluid. Preliminary results from ongoing small studies
reported at this conference indicate that reduction of
replicating virus in blood to "undetectable" levels was
accompanied by similar reductions in viral activity in the
cellular compartment (inside the cells) in the semen. This does
not by any means imply that these individuals are not fully
capable of transmitting hiv through unprotected sex. In fact,
provirus dna was detected in all these subjects, but it is
uncertain whether it is infectious or noninfectious.
HIV in Lymph Tissue
In lymph tissue studies, gut associated lymph tissue and
tonsillar lymph tissue were examined with similar results. When
blood plasma viral load is rendered "undetectable," the lymph
tissue samples display similar reductions in viral activity.
But, again, provirus dna was detected. After 6 months of
therapy for some individuals from whom lymph tissue samples
were taken, there was residual hiv rna virus detectable, but
there was a clear reduction in virus.
HIV in the Central Nervous System
Research exploring viral activity in the CNS (Central Nervous
System) was more mixed and uncertain. Preliminary information
was reported from several small studies indicating that the
course of disease progression appears to be complicated and not
yet well understood. For the participants in one small study,
investigators reported hiv rna load in blood plasma correlated
with hiv rna in CSF, but they also found no correlation between
the degree of neurocognitive decline and hiv rna load in CSF or
Some researchers suggest that there is a distinct course of
disease progression in the CNS, separate from that in the
peripheral blood. There may be a compartmentalization between
the blood and the brain. It appears possible that factors other
than viral load in the brain can affect neurocognitive
hiv-related disorder. This compartmentalization may be more
well-defined in advanced hiv than in earlier disease.
Although it has not been discerned just yet, there is some
concern that the brain can be a sanctuary for hiv. There are,
however, some suggestions for treatment. Early detection of a
neurological concern may be a key. Dr. Justin MacCarther, a
prominent neurology researcher at Johns Hopkins University,
said there is a reversible phase of impairment, and also an
irreversible phase. Therefore, early diagnosis and treatment is
imperative. It has also been suggested that if possible, when
designing a therapeutic regimen or drug combination, you should
consider combination therapy for the brain. That is, you should
consider including two drugs that are expected to penetrate the
CNS-these include AZT, d4T and nevirapine.