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

QUESTIONS TO THE ANTIRETROVIRAL THERAPY AND RESISTANCE TESTING PANELS

9. A 34-year-old man was diagnosed approximately 3 years
ago with CD4+ count 10ooo00
cells/pL and plasma viral
load io,ooo copies/mL. He
now has a CD4+ count of
goocells/pL and viral load
of 30000 copies/mL (by
repeated testing 3 months
apart); he remains asymptomatic and has not started
antiretroviral therapy In
light of the laboratory variability of CD4+ cell counts,
do you think the oo cell/pL
decline in CD4+ count is due
to the HIV infection or simply explained by laboratory
variability? Would you recommend therapy for this
patient?
DR SAAG: While CD4+ counts at this
level (about 1000 cells/pL) may vary as
much as 100 cells/pL between timepoints
due to biologic variability, I think the
decrease in this case is most likely due
to the virus. In the Multicenter AIDS
Cohort Study (MACS), patients with
viral load levels below 5000 to 10,000
copies/mL had an average CD4+ cell loss
of 40/pL per year. Therefore, a decline of
100 cells/pL over a period of 3 years
would be expected in a patient with a
viral load of about 10,000 copies/mL.
The decision to treat or not is driven in
this case more by the current viral load
value, which has risen to 30,000
copies/mL. If the patient is willing to
start therapy and commit to taking medications routinely, I favor initiation of
therapy at this time. I would tend to recommend a protease inhibitor-sparing
regimen (eg, 2 nRTIs plus an NNRTI or a
triple nRTI regimen) that could be taken
once or twice daily. If the patient is not

IMPROVING THE MANAGEMENT OF HIV

committed to starting therapy at this
point, I would continue monitoring,
including viral load testing every 2 to 3
months and CD4+ counts every 4 to 6
months.
1o. Do you consider phenotyping for all initially diagnosed patients in areas
such as Newark, New
Jersey, where there are
high incidences of injection-drug- related and
heterosexual transmission,
and a lot of patients who
are on therapy but not
adherent to the antiretroviral regimens?
DR LOVE DAY: In our center in the
United Kingdom we have now decided
to screen all drug-naive patients to determine the individual and community
prevalence of viral resistance. This serves
two functions: first, to monitor the problem of resistance locally and its rate of
evolution, and second, to ensure that no
new patient now starts triple therapy
with drugs to which they may carry
pre-existing resistance-conferring viral
mutations.
The question specifically addresses
the use of phenotypic resistance in this
exercise. We have been impressed by the
data from our own collaborative trials
and others that show the good correlation between phenotypic and genotypic
results, and as such we have elected to
use genotyping from plasma HIV RNA,
derived from viral load quantification, by
automated sequencing to detect mutations that are known to be associated
with viral resistance. This is providing
very extensive data that will also contribute to scientific research.
Nonadherence to therapy is a separate
issue and must be urgently addressed.

17
DISEASE

DR YE N I: There is, at present, no definitive answer to this important question.
More data are needed about the epidemiology of lipodystrophy in treated HIVinfected patients, as well as about other
complications of therapy such as
increased levels of plasma triglycerides or
cholesterol levels. If a 10% risk of progression of HIV disease in 3 years is acceptable, such a risk is cumulative with time
and the level of individual acceptance is
variable. An appropriate solution would
be to treat this patient at an early stage of
HIV disease with a potent protease
inhibitor-sparing regimen. Unfortunately,
there is less information available on the
long-term activity and toxicity of protease
inhibitor-sparing than of protease
inhibitor-containing regimens. Clearly,
the decision to initiate therapy and the
choice of treatment are difficult in such
patients, and should be individualized; an
in-depth discussion with the patient,
including a thorough explanation of the
benefits, risks, and uncertainties of each
strategy, is a critical step.
DR HIRSCH: As Dr Yeni noted, the true
incidence of clinically significant lipodystrophy is unclear, as is its etiology and
VOLUME 6, OCTOBER 1998