Improving the Management of HIV Disease Vol. 6, no. 5 [World Conference on AIDS (12th: 1998: Geneva)]

International AIDS Society-USA

indinavir. In a few cases, HIV proviral
DNA was not detected in the lymph node
cells of treated patients, and HIV could
not be cultured in vitro. However, given
the very limited data available and the
potential for toxic effects with such a
combination, more scientific information
is necessary before any recommendation
can be safely made about the use of
hydroxyurea in primary infection.
DR MONTANER: Several groups have
now conclusively demonstrated the ability of hydroxyurea to enhance the antiretroviral effect of nRTIs. This has been
most thoroughly documented for
didanosine, but it is at least possible that
the efficacy may extend to most if not all
nRTIs. This effect has been demonstrated
both in naive- and chronically nRTI-treated patients. A second consistent finding
across studies using hydroxyurea relates
to the decreased CD4+ cell response that
is associated with this treatment. As
pointed out by Dr Yeni, interesting
results were recently presented in the
form of a small case series or case reports
where patients treated with hydroxyureacontaining regimens during primary
infection did not demonstrate a rebound
viral replication after completing several
months of highly suppressive therapy.

Given the uncontrolled nature of these
observations, one should be extremely
careful in drawing any conclusions from
these data. At this time the possible role
of adjunctive hydroxyurea therapy in primary infection should be regarded as
experimental. This is a very important
and urgent question that needs to be
addressed in a prospective, randomized,
controlled trial.

2 to 5 months, and it is not clear that her
plasma virus titer has yet reached its
nadir. Once a virologic set-point is
reached, she should be reevaluated and
further therapeutic options should be
considered.
Had she been seen earlier, during
acute infection, I would have recommended aggressive antiretroviral treatment, on the possibility that such therapy could reduce the virus set-point,
diminish the likelihood of subsequent
viral heterogeneity and resistance, and
maintain optimal immune responsiveness. However, we are now beyond that
acute period, and the risks and
benefits of aggressive intervention are
less clear.

19-year-old woman was
IV-seronegative in f/97 and
1V-seropositive in 2/98 (she
ad no acute symptoms). In
arch 1998, her CD4+ cell
runt was 64o/L and plasa viral load was 64,000
)pies/mL. In April 1998, her
94+ cell count was 67o/pL
7d plasma viral load was,ooo copies/mL. Would you
commend initiating theraSat this point for this
atient? If so, what regimen
ould you suggest?

DR HI RSCH: I would recommend continued virologic and immunologic monitoring, but not immediate initiation of therapy. This individual has been infected for

I/ NTAL HEAPYI SA:LSE NETO

4. Combination didanosinel
hydroxyurea is being used in
sub-Saharan Africa. Please
comment on this approach.
DR KATZENSTEIN: I think we must recognize that the recommendations of the
IAS-USA panel, the US Public Health
Service, and others do not take into

account the economic and practical issue
of antiretroviral therapy in resource-limited countries. Even HIV-seropositive
individuals with the means to afford 3- or
4-drug regimens may find it very difficult
to access consistent supplies of the different drugs in much of the world. There
are demonstrated benefits to didanosine
monotherapy. Didanosine can be used as
a single daily dose of 400 mg and,

although resistance to didanosine will
eventually develop, prolonged didanosine therapy does not result in high-level
cross-resistance to other nRTIs.
Hydroxyurea enhances the activity of
didanosine, even after genotypic and
phenotypic evidence of viral resistance
to didanosine are demonstrated.
Depending on the urgency of treatment,
didanosine may be used alone as initial

IMPROVING THE MANAGEMENT OF HIV DISEASE

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