[afro-nets] Do I have to take ARV all my life?

[Claudio Schuftan <claudio@hcmc.netnam.vn>]

Do I have to take ARV all my life?
----------------------------------

You may want to have the similar question as we have looking at
this study: "Then, should we continue to recommend CD4 count 200
as the indication for initiation of HAART?" Although - as
pointed by the authors - the study didn't follow up the patients
after they restart HAART, we can now start to hope that AIDS pa-
tients may not have to take ARV "every day for the rest of the
life".

************

HAART CAN BE SAFELY INTERRUPTED FOR OVER A YEAR BY PATIENTS WITH
LOWEST EVER CD4 CELL COUNT ABOVE 250 AND A SUSTAINED TREATMENT
CD4 CELL COUNTR OF 500 OR MORE

Michael Carter, Tuesday, March 08, 2005

Individuals who started HAART with a lowest ever CD4 cell count
above 250 cells/mm3 and achieved a sustained increase in CD4
cell count above 500 cells/mm3 appear to be able to safely in-
terrupt HIV therapy for over a year, according to an interna-
tional study published in the February 18th edition of AIDS. It
is likely that the investigators' findings will be viewed with
considerable interest by researchers involved in the SMART study
into the safety and efficacy of CD4 cell guided treatment inter-
ruptions.

The team of investigators from Italy and Sweden wished to deter-
mine the risks and benefits of CD4-guided treatment interrup-
tions using data obtained from observational cohorts. In par-
ticular, they wished to see which patients with higher CD4 cell
counts at the time of treatment interruption would be able to
remain off treatment for longer. They therefore identified pa-
tients whose nadir CD4 cell count was between 250 - 350
cells/mm3 and who had a CD4 cell count of at least 500 cells/mm3
at the time of discontinuing HAART in seven patient cohorts in
Italy and Sweden. Data were gathered on the duration of treat-
ment interruption, new clinical events and the effect of inter-
rupting treatment on fasting lipids. Study endpoints were a fall
in CD4 cell count to below 350 cells/mm3 or patient request to
recommence therapy.

A total of 139 patients were included in the investigators'
analysis. All were over 18 years of age, had been taking HAART
for at least twelve months. At the time HAART was commenced, the
patients had a median CD4 cell count of 417 cells/mm3, and at
the time of treatment interruption this had increased to a me-
dian of 800 cells/mm3. In total 43 individuals (31%) had a nadir
CD4 cell count between 250 - 350 cells/mm3.

When treatment was interrupted, HAART had been taken for a me-
dian of 3.5 years. Investigators included individuals who did
not have full HIV suppression in their analysis, and at baseline
only 63 patients (61%) had a viral load below 50 copies/ml.

In total, 63 patients resumed treatment or experienced a fall in
their CD4 cell count to below 350 cells/mm3 over a median of 75
weeks of therapy interruption. Of these 63 patients, 33 (52%)
experienced a fall in their CD4 cell count to below 350
cells/mm3, the remaining individuals recommencing treatment be-
fore their CD4 cell count fell to this level.

The investigators calculated that the rate of therapy resumption
or CD4 cell count decline below 350 cells/mm3 was significantly
lower in patients with a higher nadir CD4 cell count (p = 0.03),
with HIV suppression below 50 copies/ml for twelve months or
longer (p = 0.008), and for patients with higher viral loads at
the time of interruption (p = 0.008). The investigators believe
that patients with detectable HIV at baseline may have been non-
adherent patients and that non-adherent patients may have been
less likely to wish to resume therapy after interruption.

According to further calculations, the investigators estimated
patients with a nadir CD4 cell count between 2510 - 350
cells/mm3with a CD4 cell count above 500 cells/mm3 at the time
of treatment interruption would be able to interrupt therapy for
a median of 61 weeks.

Clinical events

One patients developed disseminated herpes simplex and PCP pneu-
monia when his CD4 cell count was 205 cells/mm3 at week 87 of
the study. In total 212 person years of follow-up were provided
by patients in the study, giving an incidence rate of new AIDS
events of 1 per 212 person years of follow-up. There were no
deaths. Six patients developed minor symptoms of HIV infection,
but non restarted HAART.

Lipids

At baseline 39 patients had elevated triglycerides and during
the interruption of treatment they returned to normal at least
once in 26 individuals (66%). Using the last available measure-
ment, 30% of individuals had normal triglycerides.

In total 13 patients had abnormally high cholesterol before in-
terruption HAART. During their break from treatment cholesterol
levels returned to normal in ten patients ((77%), and were still
normal in 61% when the investigators looked at the last avail-
able measures.

"Our analysis has shown that the duration of CD4 cell-guided in-
terruptions was longer in patients who had a higher nadir CD4
cell count", write the investigators, adding "most importantly,
our data demonstrate that people starting therapy with a CD4
cell count between 250 - 350 cells/mm3, the level recommended by
the current international treatment guidelines, can safely in-
terrupt therapy - maintaining CD4 cell counts above 350
cells/mm3 - for a reasonably long time if they had previously
attained a CD4 cell count above 500 cells/mm3 on therapy."

Reference

International Study Group on CD4-monitored Treatment Interrup-
tions. CD4 cell-monitored treatment interruption in patients
with a CD4 cell count above 500 cells/mm3. AIDS 19: 287 - 294,
2005.