Since the introduction of HAART the increasing recognition of drug-related toxicities and the development of more potent antivirals have stimulated exploration of alternative regimens and strategies for experienced patients including protease inhibitor

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Kaletra Monotherapy A Real-Life
Experience Laura Waters, Steve Balbeck, Brian
Gazzard Mark Nelson.
INTRODUCTION Since the introduction of HAART the
increasing recognition of drug-related toxicities
and the development of more potent antivirals
have stimulated exploration of alternative
regimens and strategies for experienced patients
including protease inhibitor (PI) monotherapy.
Limited data supporting the use of boosted
lopinavir (LPV/r) as a single agent (unlicensed)
has been presented (refs) and larger trials are
ongoing. We have a number of patients at our
unit who have been prescribed LPV/r therapy
outside a trial protocol. METHODS Using our
large, prospective database all individuals who
have ever received LPV/r monotherapy up until
October 2005 were identified all those taking
part in a clinical trial were excluded. Previous
treatment history, resistance and reason for
switch were defined and CD4, viral load (VL),
alanine transaminase (ALT), total cholesterol
(TC) and triglygeride (TG) levels were monitored
for up to 12 months.
Virological Outcomes log changes Of the 15
individuals with viraemia at the time of switch
to LPV/r monotherapy 11/15 (73) achieved a
greater than 1log reduction in viral
load. Immunological Outcomes The overall CD4 gain
in the 28 individuals with follow-up was 92
cells/mm3 (232 to 324) after a mean of 8.9
months. CD4 changes in the group achieving
undetectability are summarised in table 2.



Table 2 CD4 change up to 1 year (on treatment
virologically suppressed).
CD4 rises in those who did notreceive a viral
load less than 50 copies/ml are demonstrated in
table 3
Table 3 CD4 change up to 1 year (on treatment
detectable viraemia).
RESULTS 35 individuals, 8 women and 27 men,
received LPV/r monotherapy baseline
characteristics are illustrated in table 1.
Table 1 Baseline Characteristics
Treatment Failure The 8/28 subjects with
follow-up who changed or stopped therapy are
described below.
Table 4 Subjects switching therapy.
Reasons for switch 19 switched to LPV/r for
adherence difficulties, 4 secondary to
drug-related toxicity, 1 due to drug interaction
and 1 patient request. Reasons were not
documented for 10 subjects. 7 individuals had no
post-baseline results available for the following
reasons - 2 treatment interruption (prescribed
LPV/r to cover NNRTI cessation) - 3 lost to
follow-up - 2 for toxicity (1 gastrointestinal, 1
transaminitis ?cause) Virological Outcomes
Undetectability 14/28 (50) achieved an
undetectable viral load within 12 months (mean
follow-up 9.2 /-3.9 months) 10/14 had an
undetectable viral load at baseline (and 8/10 of
these simplified a LPV-based regimen). 11/14
remain on LPV/r monotherapy and 10/11 have viral
load lt50 copies/ml at a mean of 12.1 months
(range 3-34) 1 subject had a viral load of 129
copies/ml at 20 months. 3/14 changed therapy, 1
added tenofovir for blips, 1 added didanosine and
1 added two nucleosides (reasons unclear).
14/28 did not achieve an undetectable viral load
within 12 months, 3 of whom were undetectable at
baseline (2 on a LPV-containing regimen). 9/14
remain on LPV/r monotherapy 7/9 have a viral
load less than 400 copies/ml out to 1 year (mean
10 months). 1 has viral load of 1494 copies/ml
at 12 months (baseline 57693 1.5 log drop) and 1
has a viral load at 1878 copies/ml (from gt500,000
copies/ml gt2.4log decline) at 3 months. With
prolonged follow-up 2 are now undetectable after
16 and 24 months respectively. Of the other 5
subjects, 1 was switched to salvage therapy and
subsequently died, 2 were intensified with 2
nucleosides (results pending) and 2 switched to
atazanavir-based HAART and achieved viral loads
lt50 copies/ml.

Baseline Resistance 7 patients had a history of
major PI mutations (defined as per IAS
guidelines) 1 was lost to follow-up and 1
received 3 weeks of LPV/r only, the remaining 5
are described in Table 5.
Table 5 Treatment outcomes in subjects with
major PI mutations.
New Resistance 10 patients with viraemia
underwent genotyping on LPV/r monotherapy. 4/10
didnt amplify, 2/10 had no resistance test
recently prior to LPV/r for comparison, 1/10
exhibited no new mutations, 2/10 developed new
minor mutations/polymorphisms (63P and
63P/79A/93L respectively) and 1/10 developed
20R/46I/50V.
CONCLUSIONS 35 subjects in our cohort were
prescribed LPV/r monotherapy and we present
outcomes for 28. 2 individuals switched
primarily for toxicity however, the impact of
adverse events on compliance and subsequent
failure could not be elucidated fully from a
retrospective note review. The majority of
patients were switched to LPV/r for poor
compliance and all were treatment experienced.
50 achieved an undetectable viral load (less
than 50 copies/ml) and the majority attained a
greater than 1log reduction in viral load, an
independent prognostic factor. The majority of
subjects experienced a CD4 increase. LPV/r
therapy provided a safe, effective treatment
option in a highly experienced group of poorly
compliant individuals.