The Washington Blade, January 7, 2000
Once again, a group of researchers has emerged with some
evidence to argue that early intervention with a triple-drug
therapy can have "a major effect on the outcome of HIV
infection" and "provide[s] the highest chance of normalization"
of the immune system.
The latest to weigh in is a team led by renowned Italian
researcher Franco Lori, working at the Research Institute for
Genetic and Human Therapy in Washington, D.C. Lori's team gave
10 patients hydroxyurea-ddi-indinavir before their immune
systems had begun developing antibodies.
Hydroxyurea (a cancer drug) and ddi (a nucleoside analog) have
demonstrated strong ability against the AIDS virus in immune
cells where the virus tends to lie dormant. Indinavir (a
protease inhibitor) has demonstrated effectiveness against the
virus in cells that are actively replicating. Thus, Lori's
group wanted to see whether the three drugs together could have
any significant effect on preserving the immune system if given
so soon after initial infection that the immune system has yet
to develop HIV antibodies.
The team concluded that such a combination given at such a time
"leads to normalization of immunologic defects" caused by HIV
infection and that it "limits the establishment of HIV
As with other triple-drug combinations, the patients taking
hydroxyruea-ddi-indinavir saw their viral loads drop
dramatically, below 50 viral particles per milliliter. But the
10 taking the combination before they had developed antibodies
also experienced a much slower progression to that point of
testing positive (one patient took more than a year, versus the
usual two to six weeks). Most of the 10 also had "vigorous" CD4
immune responses and only the most sophisticated of tests could
detect any replication-competent virus in the patients. In one
patient, no replication-competent virus could be found.
"Although these results confirm recent studies that early
treatment does not prevent the establishment of latent cellular
reservoirs for HIV," wrote the researchers in the December
issue of the Journal of Infectious Diseases, "our data show
that treatment before seroconversion with hydroxyurea,
didanosine, and indinavir is associated with an unusually low
frequency of latently infected cells."
"Our findings provide evidence that the earliest treatment
leads to the fastest recovery of the naive cell repertoire,"
concluded the team. "Furthermore, early treatment might be the
only chance to limit the establishment and expansion of latent
"[A]lthough recovery of immune functions and normalization of
some immune parameters have been demonstrated when treatment is
initiated during chronic HIV infection," noted the doctors,
"recovery was incomplete and did not occur in all patients. Our
data suggest that the time before complete seroconversion might
provide an important window for therapeutic intervention to
prevent irreversible immune damage. Limiting the number of
resting infected cells very early after infection might also
have implications in the control of HIV replication."
The combination of hydroxyurea-ddi-indinavir was the same used
by the so-called "Berlin patient," who has been able to keep
his viral load down for more than two years after having gone
off that combination twice. The patient had taken the
hydroxyurea-ddi-indinavir before his body had begun developing
antibodies to the AIDS virus, and experts have speculated that
going on and off the combination might have "taught" his immune
system how to fight HIV on its own. Lori's team's research
seems to suggest that the Berlin patient's success might also
be due to his initiating therapy before his body began
producing HIV antibodies.
In brief ...
RITONAVIR WORRY: The use of the protease inhibitor ritanovir
(Norvir, by Abbott) appears to increase the chances for severe
liver problems, according to a study out this week from Johns
Hopkins University. The study, in the Jan. 5 issue of the
Journal of the American Medical Association, notes that doctors
followed 298 patients taking either a three-drug protease
inhibitor combination or a two-drug nucleoside combination.
About half had co-infection with hepatitis B and hepatitis C.
While some increase in liver toxicity was associated with each
combination, those using ritonavir accounted for five times the
number of cases the others did.
HOME TEST CONCERN: The U.S. Federal Trade Commission last month
charged a firm doing business on the Internet with "falsely
representing that his HIV tests accurately detected HIV."
According to the FTC, the company, Medimax Inc., was selling
tests that "provided false negative results" nine times out of
10, and that "the 10th test did not work at all." In November,
the FTC settled a similar complaint with another Internet
marking company, Cyberlinx. The company agreed to stop
marketing any HIV test kits and to pay back the money it
received from the sale of tests previously sold.
D.C. CLINICAL TRIALS: The National Cancer Institute's HIV and
AIDS Malignancy Branch (HAMB) is enrolling volunteers for a
variety of HIV-related trials. The new 800-number to call for
information is 800-243-2732, then choose No. 4. To check for
trials on the Web, use www-dcs.nci.nih.gov/aidstrials.