Since
the advent of HAART in the mid-1990s,
there has been controversy regarding the best time to start antiretroviral therapy.
While some experts have favored a “hit early, hit hard” approach, others -- concerned
about long-term side
effects -- have advised waiting until disease progression occurs.
Current
U.S. federal treatment guidelines recommend
that HIV positive individuals should start combination
therapy when their CD4 cell counts fall below 350 cells/mm3. But a
new study published in the June 1, 2007 Journal
of Acquired Immune Deficiency Syndromessuggests that patients may
have better outcomes if they start
treatment when their CD4 count is 350 cells/mm3 or higher.
In
this study, Dutch researchers analyzed data from treatment-naive patients starting
HAART in the ATHENA cohort. The investigators looked at 3 end-points:
·Time to
≥ 800 CD4 cells/mm3 in 5299 treatment-naive patients starting
HAART;
·CD4 cell
count changes during 7 years of uninterrupted HAART in a subset of 544 patients;
·Reaching
a plateau in CD4 cell restoration after 5 years of HAART in 366 virologically
suppressed patients.
Results
·Within 7
years after starting HAART, the following proportions of subjects attained CD4
counts of 800 cells/mm3 or higher according to baseline CD4 count:
o20% who
started treatment with 50 or fewer cells/mm3;
o26% who
started with 50-200 cells/mm3;
o46% who
started with 200-350 cells/mm3;
o73% who
started with 350-500 cells/mm3;
o87% who
started with 500 or more cells/mm3.
·While even
patients who started treatment with very low CD4 cell counts experienced good
immunological response, their recovery was slower and did not reach the same level
as those who started earlier.
·Patients
age 50 years or older and those with periods of HIV RNA levels above 500 copies/mL
had smaller increases in CD4 cell counts between 6 months and 7 years.
·Having reached
≥ 800 CD4 cells/mm3 at 5 years, older age and having 1 or more
HIV RNA measurements above 1000 copies/mL between 5 and 7 years were associated
with a plateau in CD4 cell restoration.
Conclusion
“Restoration
to CD4 cell counts ≥ 800 cells/mm3 is feasible within 7 years
of HAART in most HIV-infected patients starting with ≥ 350 cells/mm3
and achieving sufficient suppression of viral replication,” the authors concluded.
“Particularly in patients ≥ 50 years of age, it may be beneficial to start
earlier than current guidelines recommend.”
In
an accompanying editorial, Evan Wood,
PhD, and Julio Montaner, MD, of the British Columbia Centre for Excellence in
HIV/AIDS wrote that with the availability of newer antiretroviral regimens that
are simpler and safer, it may be time to re-evaluate the ideal time to start therapy,
incorporating outcomes besides survival, such as extent of immune reconstitution
and potential for HIV transmission.
HIV
Monitoring Foundation, Amsterdam, Netherlands; Imperial College School of Medicine,
London, UK; London School of Hygiene and Tropical Medicine, London, UK; University
Medical Centre, Utrecht, Netherlands; Academic Medical Centre of the University
of Amsterdam, Amsterdam, Netherlands.
06/22/07
References
L
Gras, AM Kesselring, JT Griffin, and others. CD4 Cell Counts of 800 Cells/mm3
or Greater After 7 Years of Highly Active Antiretroviral Therapy Are Feasible
in Most Patients Starting With 350 Cells/mm3 or Greater. JAIDS 45(2): 183-192.
June 1, 2007.
E
Wood and JSG Montaner. When to initiate HIV antiretroviral therapy: do benefits
other than survival deserve greater attention? JAIDS 45(2): 131-132. June
1, 2007.
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