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237
A Pilot Study of Switch to Lopinavir/Ritonavir
(LPV/r) Monotherapy from Nonnucleoside Reverse
Transcriptase Inhibitor–Based Therapy
Gerald Pierone, Jr., MD,1,2 Jeffrey Mieras, RN,2 Dorothy Bulgin-Coleman, ARNP,1
Chandra Kantor, ARNP,1 James Shearer, PA,1 Lunie Fontaine, MT (ASCP),3
Michael Fath, PhD,3 and Michael Norton, PA3
1AIDS Research and Treatment Center of the Treasure Coast, Ft. Pierce, Florida;
2Treasure Coast Infectious Disease Consultants, Vero Beach, Florida;
3Abbott Laboratories, Abbott Park, Illinois, USA
For correspondence or reprints contact: Gerald Pierone, Jr., MD,
Treasure Coast Infectious Disease Consultants, 3715 7th Ter-
race, Vero Beach, FL 32960 USA. Email: pieroneg@bellsouth.net
HIV Clin Trials 2006;7(5):237–245
© 2006 Thomas Land Publishers, Inc.
www.thomasland.com
doi:10.1310/hct0705-237
Purpose: This study evaluated the safety and efficacy of switching HIV-infected
patients with stable viral suppression on nonnucleoside reverse transcriptase
inhibitor/nucleoside reverse transcriptase inhibitor (NNRTI/NRTI) therapy to
lopinavir/ritonavir (LPV/r) monotherapy. Method: Eligible patients discontinued
NNRTI and started LPV/r. Two weeks later NRTIs were stopped and LPV/r
monotherapy was continued. Patients were seen every 4 weeks throughout the 48-
week study. Results: Twelve of 18 (66%) participants met the primary endpoint with
HIV RNA <75 copies/mL at week 48. Thirteen (72%) participants completed 48
weeks of LPV/r monotherapy, and 12 of 13 (92%) participants on treatment at week
48 had HIV RNA <75 copies/mL. Ten (55%) of 18 patients maintained HIV RNA <75
copies/mL at all time points. Two patients were withdrawn with virologic failure but
demonstrated no evidence of virologic resistance. Three (17%) patients withdrew
due to diarrhea, 2 with hyperglycemia at baseline developed diabetes mellitus, 7
(54%) required addition of or increase in lipid-lowering agents, but none had grade 3
or 4 hyperlipidemia. Conclusion: Results from this pilot study suggest that LPV/r
monotherapy may be an option for management of HIV infection. Larger,
randomized trials are warranted to evaluate the safety, efficacy, and patient
population who might benefit from LPV/r monotherapy. Key words: HAART, highly
active antiretroviral therapy, lopinavir/ritonavir, LPV/r, NNRTIs, nonnucleoside
reverse transcriptase inhibitors, NRTIs, nucleoside reverse transcriptase inhibitors,
PIs, protease inhibitors
T
he US Department of Health and Human
Services (DHHS) guidelines for treatment of
HIV infection in adults and adolescents list
two preferred highly active antiretroviral therapy
(HAART) regimens. Both options comprise three
drugs, including two nucleoside or nucleotide
reverse transcriptase inhibitors (NRTIs), together
with either the protease inhibitor (PI) lopinavir/
ritonavir (LPV/r) or the nonnucleoside reverse
transcriptase inhibitor (NNRTI) efavirenz.1
Despite remarkable advances in management of
HIV2 since the advent of HAART, standard therapy
has several disadvantages. Clinically significant
side effects may be seen with all classes of
antiretroviral agents. NRTIs have been associated
with mitochondrial toxicity,1,3–5 which may mani-
fest as lactic acidosis, hepatic failure, neuropathy,
pancreatitis, and lipoatrophy. NNRTIs have been
associated with hepatotoxicity, hyperlipidemia,
and neuro-cognitive dysfunction. In addition, cur-
rently available NNRTIs demonstrate a low barrier
to the development of resistance, requiring the se-
lection of only a single mutant population to ren-
der loss of antiviral activity and cross-resistance to
other NNRTIs.6 PIs are associated with varying de-
grees of gastrointestinal side effects and metabolic
disturbances.1 Although the overall cost of care for
238 HIV CLINICAL TRIALS • 7/5 • SEPT-OCT 2006
adult HIV patients since the introduction of suc-
cessful combination therapy has declined, the an-
nual cost for the antiretrovirals that make up
HAART has increased.7 Hence, the identification of
an effective antiretroviral therapy that avoids long-
term exposure to three different agents and is less
expensive could be a useful option for the manage-
ment of HIV infection.
Earlier studies of HAART induction followed by
simplification to unboosted PI monotherapy were
unsuccessful.8–10 However, as a result of recent ob-
servations made with ritonavir (r)-boosted PI
therapy,11–14 an interest in the investigation of
boosted PIs as monotherapy for HIV treatment has
emerged.
LPV/r is currently the only co-formulated
boosted PI available. LPV/r is considered to be a
single antiretroviral agent because the levels of
ritonavir achieved in plasma are subinhibitory and
therefore the antiretroviral effect of the combina-
tion is based on the activity of lopinavir alone.15
When LPV/r is dosed twice daily, trough lopinavir
plasma levels are a median 84-fold higher than the
protein binding–adjusted 50% inhibitory concen-
tration (IC50) of lopinavir against wild-type HIV-
1.15 This high inhibitory quotient (IQ = trough
lopinavir concentration/IC50) may partially ex-
plain the clinical observation that primary PI resis-
tance has rarely been seen in patients who have
received LPV/r as part of their first HAART regi-
men.16,17 Due to the potency of LPV/r, the low fre-
quency of selection for resistance to LPV/r, and the
potential for cost savings, a 48-week pilot study of
switching to LPV/r monotherapy was conducted
and the results are reported herein.
METHOD
Study Design
This was a 48-week prospective pilot study in
which HIV-1–infected patients with viral suppres-
sion to <75 copies/mL on an NNRTI-based regi-
men were switched to LPV/r monotherapy. A
planned target of 15 patients was chosen to provide
preliminary data on the safety and efficacy of LPV/r
monotherapy. The study was approved by the
Western Institutional Review Board, and written
informed consent was obtained from each patient
prior to any study procedures being performed. At
baseline, patients were instructed to discontinue
the NNRTI and substitute LPV/r 400/100 mg soft
gel capsules (three capsules twice a day). NRTIs
were continued for 2 weeks to provide an overlap
of antiretroviral coverage in case LPV plasma lev-
els were excessively lowered from the known drug
interaction with NNRTIs. At day 14, the NRTIs
were stopped and LPV/r was continued as
monotherapy. Study visits were scheduled every 4
weeks throughout the 48-week study period. At
each visit, a self-administered adherence question-
naire was completed and pill count was per-
formed.18 Vital sign measurements, abbreviated
physical examination, and assessment for adverse
events (AEs) were also performed at each visit.
Concomitant medications including the use of
lipid-lowering agents (LLAs) were recorded. Tele-
phone contact from the study team to each patient
was attempted between study visits to monitor
changes in the patient’s status and to reinforce the
importance of adherence to treatment.
Blood samples for CD4+ lymphocyte counts,
HIV RNA levels, hematology, and chemistry test-
ing were collected every 4 weeks for the first 24
weeks and every 8 weeks thereafter. Fasting
plasma lipid levels were collected at baseline and
at weeks 8, 24, and 48. A plasma sample was stored
for each patient at weeks 2 and 24 for ascertaining
LPV levels in cases of virologic failure (VF). Addi-
tionally, whenever a patient was found to have
viral load >400 copies/mL, a blood sample was
scheduled for collection at the succeeding visit for
resistance testing.
HIV RNA levels were determined by bDNA
technology (Bayer Diagnostics, Tarrytown, New
York, USA). Genotyping was performed as needed
using a Virco HIV-1 Virtual Phenotype.
Phenotyping was performed using Virologic
Phenosense GT.
Inclusion/Exclusion Criteria
Participants were recruited from two affiliated
HIV treatment clinics in Florida: the AIDS Research
and Treatment Center of the Treasure Coast in Ft.
Pierce, and Treasure Coast Infectious Disease Con-
sultants in Vero Beach. Patients were eligible for
enrollment if they were over 18 years of age, naïve
to PIs, and on a stable NNRTI-based antiretroviral
regimen for more than 6 months with two consecu-
tive viral load determinations <75 copies/mL. Pa-
tients not receiving their first HAART treatment
SWITCH TO LPV/R MONOTHERAPY •PIERONE ET AL.239
regimen could be enrolled if prior regimens were
successful and if (a) changes made to prior regi-
mens were due only to lack of tolerability or to
achieve simplification or (b) the prior regimen had
been interrupted for any reason other than VF but
then restarted.
Patients were ineligible if any of the following
conditions were present: pregnancy or nursing;
concomitant therapy with drugs contraindicated
for use with LPV/r; vaccination within 4 weeks of
screening; active AIDS-defining opportunistic in-
fection or condition; recurrent episodes of moder-
ate-to-severe diarrhea or vomiting lasting ≥4 days
within 12 weeks prior to dosing; clinically signifi-
cant laboratory findings obtained during screening
including serum creatinine >2.0 mg/dL, alanine
transaminase (ALT), aspartate transaminase (AST),
or alkaline phosphatase levels >5 x upper limit of
normal (ULN), total bilirubin >2 x ULN, hemoglo-
bin <10 g/dL for males, <9.0 g/dL for females,
platelets <75,000 cells/mm3, and absolute neutro-
phil count <750 cells/mm3.
Data Analysis
The primary efficacy variable was the percent-
age of participants with plasma HIV RNA <75 cop-
ies/mL at 48 weeks. Virologic failure was defined
as HIV RNA levels >400 copies/mL on two con-
secutive occasions at least 1 week apart. Due to the
small sample size of the study, the exact 95% confi-
dence interval (CI) for the proportion of partici-
pants with plasma HIV-1 RNA <75 copies/mL at
48 weeks was computed.
The secondary efficacy variables included: per-
centage of participants with HIV RNA levels <75
copies/mL at 24 weeks; percentage of participants
with HIV RNA level <400 copies/mL at 24 and 48
weeks; the mean change in CD4+ lymphocyte
count at week 48; the mean change in lipid levels at
24 and 48 weeks; the percentage of participants
who required addition of or an increase in LLAs at
24 and 48 weeks; and percentage of participants
who discontinued therapy due to adverse events.
RESULTS
Baseline Characteristics
Twenty patients were screened between July and
November 2003. One patient was a screen failure
due to exacerbation of a chronic psychiatric illness.
One patient withdrew consent prior to the baseline
visit.
Eighteen patients were enrolled (13 men and 5
women). Five patients were African American and
13 were Caucasian. The mean age was 46.8 years.
The median time on prior HAART regimens was
122 weeks (range, 21–257 weeks). The median
baseline CD4+ cell count was 272 cells/mm3
(range, 73–1174 cells/mm3), and median nadir CD4
count was 177 cells/mm3 (range, 5–519 cells/mm3).
Prior NNRTI-based therapy included efavirenz
(EFV) in 4 (22%) cases and nevirapine (NVP) in 14
(78%) cases.
Participant Disposition and Study Outcomes
Study outcomes are presented in Tables 1 and 2.
Twelve of 18 (66%) participants met the primary
study endpoint with HIV RNA <75 copies/mL at
week 48 (95% CI 41.0–86.7). One participant (Pa-
tient 18) met the definition of VF at week 8 during a
period of nonadherence. After adherence counsel-
ing, the patient demonstrated virologic
resuppression and maintained a VL of <75 copies/
mL from weeks 24–48. Of the 18 participants en-
rolled, 13 (72%) completed 48 weeks of LPV/r
monotherapy and 12 of these 13 (92%) participants
on treatment at week 48 had plasma HIV RNA <75
copies/mL (Figure 1, Table 1). Overall, 10 (55%) of
the 18 participants maintained continuous viral
suppression (<75 copies/mL) at all time points
throughout the 48-week study period.
Two participants (Patients 5 and 15) exhibited
breakthrough viremia not meeting the definition of
VF. Patient 5 demonstrated a one time viral eleva-
tion (blip) at week 40 and the VL returned to <75
copies/mL by week 48. Patient 15 demonstrated
intermittent low-level viremia between weeks 8
and 48 (Table 1).
Twelve (92%) of 13 participants who completed
the study demonstrated an increase in CD4+ cell
count at week 48 (Table 1). For participants com-
pleting the study, the absolute CD4+ lymphocyte
count was 371 cells/mm3 at baseline and 462 cells/
mm3 at week 48, a mean increase of 91 cells/mm3
(Table 1).
Two (11%) participants (Patients 10 and 11) dem-
onstrated VF and were withdrawn from the study
(Table 2). Patient 10 demonstrated VF at week 32,
was withdrawn at that time point, and subse-
240 HIV CLINICAL TRIALS • 7/5 • SEPT-OCT 2006
quently was lost to follow-up. Patient 11 demon-
strated VF at week 16; was changed back to the
original regimen of tenofovir, lamivudine, and
nevirapine; attained viral resuppression after 4
weeks; and has maintained long-term control of
viremia. Three (17%) participants (Patients 7, 8,
and 13) withdrew early (weeks 2, 4, and 8, respec-
tively) due to diarrhea, all of whom had HIV RNA
plasma levels <75 copies/mL at the time of with-
drawal.
Viral Resistance Results
Of the three participants who demonstrated VF,
genotypic amplification was successful in two (Pa-
tients 10 and 11) (Table 3). Patient 10 had VF at
week 32, and genotypic mutations L63P and V77I
were identified. The phenotypic fold change was
0.57 to LPV. LPV trough concentrations from fro-
zen plasma specimens at weeks 2, 24, and 32 dem-
onstrated levels of 0.67 µg/mL, 1.95 µg/mL, and
3.26 µg/mL respectively (therapeutic range, 3–10
µg/mL). Patient 11 was noted to have an M36I
mutation at week 16, 3 weeks after VF. The LPV
trough concentration for Patient 11 at week 16 was
6.07 µg/mL. Patient 18 experienced VF at week 8
during a period of low adherence and demon-
strated virologic resuppression at the subsequent
visits. Testing for viral resistance was inadvert-
ently omitted at the time of VF. An LPV trough
concentration from a frozen plasma specimen col-
lected at week 24 was 8.27 µg/mL.
Adherence Monitoring Results
Pill counts demonstrated that 9 (69%) of the 13
participants completing the study maintained at
least an 80% level of adherence throughout 48
weeks (Table 1). Three of the four participants (Pa-
tients 5, 15, and 18) who maintained less than 80%
adherence experienced viral breakthrough. The
two participants (Patients 10 and 11) who were
prematurely withdrawn due to VF had greater
than 85% adherence to LPV/r throughout their
participation in the study (Table 2).
Adverse Events and Laboratory Abnormalities
Fourteen (78%) of the 18 participants reported
diarrhea, and three participants (17%) withdrew
due to mild or moderate diarrhea (Table 2). Four
participants (22%) experienced transient mild diar-
rhea that began within the first 2 weeks of taking
LPV/r and resolved by week 6. Seven participants
(39%) continued to have persistent mild diarrhea
over the course of the study.
Two (11%) participants (Patients 9 and 16) with
elevated blood glucose determinations in the 110–
125 mg/dL range at study entry developed an in-
crease in fasting glucose readings to over 125 mg/
dL and were diagnosed with diabetes mellitus. Pa-
tient 9 had elevated blood glucose determinations
throughout the study, but the hemoglobin A1C
level was within normal limits at week 12 and
medication was not deemed necessary. After study
completion, Patient 9 was sequentially changed to
an atazanavir/ritonavir-based HAART regimen
followed by the original regimen of Combivir
(lamivudine/zidovudine) and nevirapine. Despite
these changes in therapy, there was continued el-
evation of serum glucose and diabetic medication
Figure 1. Disposition of the 18 participants enrolled
who were switched from nonnucleoside reverse tran-
scriptase inhibitor/nucleoside reverse transcriptase in-
hibitor (NNRTI/NRTI) regimens to lopinavir/ritonavir
(LPV/r) monotherapy and were followed for 48 weeks.
DC = discontinued; VF = virologic failure.
18
patients
enrolled
3 patients 13 patients 2 patients
D/C completed D/C with VF
diarrhea 48 weeks
1 patient with
VF at week 8
weeks 24-48
1 patient
12/13 with
HIV RNA <75 HIV RNA
at week 48 1047 copies
at week 48,
no VF
SWITCH TO LPV/R MONOTHERAPY •PIERONE ET AL.241
Table 1. Study results of participants switched to LPV/r monotherapy who completed 48 weeks
HIV RNA levels, CD4 change,
Patient no. copies/mL Adherence, % cells/mm3
01 <75 for entire 48 weeks 96–100 274
02 <75 for entire 48 weeks 80–102 52
03 <75 for entire 48 weeks 96–101 30
04 <75 for entire 48 weeks 85–113 99
05 3314 at week 40; 61 at week 40; 7
otherwise <75 74–101 at other time
points
06 <75 for entire 48 weeks 83–100 −50
09 <75 for entire 48 weeks 86–101 16
12 <75 for entire 48 weeks 81–101 114
14 <75 for entire 48 weeks 70–107 76
15 Intermittent viremia 37–100 52
16 <75 for entire 48 weeks 95–102 94
17 <75 for entire 48 weeks 83–102 189
18 10,068 at week 8 (VF); 81 and 58 at weeks 4 and 8; 233
<75 at weeks 24–48 59–76 at weeks 24–48
Note: LPV/r = lopinavir/ritonavir; VF = virologic failure.
was started. Patient 16 was started on diabetic
medication that led to blood glucose control, and
the patient completed 48 weeks of therapy. After
study completion, Patient 16 was changed back to
NNRTI-based therapy, glucose readings returned
to baseline, and antiglycemic medication was dis-
continued.
The National Cholesterol Education Program
(NCEP) guidelines were used for management of
lipid levels. Six (33%) of the 18 participants en-
rolled were receiving LLAs at study entry. Of the
13 participants who completed the trial, 7 (54%)
required the addition of or an increase in LLAs.
The mean cholesterol measurements in fasting
plasma samples for those seven participants were
225 mg/dL at baseline and 219 mg/dL at week 48
(change -6 mg/dL from baseline). The mean fast-
ing triglyceride measurements were 203 mg/dL at
baseline and 249 mg/dL at week 48 (change +46
mg/dL from baseline).
Six (46%) of the 13 participants completing the
trial had no change in LLAs. The mean fasting
cholesterol determinations were 183 mg/dL at
baseline and week 48 (+0 mg/dL). The mean fast-
ing triglyceride determinations at baseline were
136 mg/dL and 157 mg/dL at week 48 (change +21
mg/dL from baseline). None of the 13 participants
completing the trial experienced a grade 3 or 4
cholesterol or triglyceride elevation.
DISCUSSION
The appeal of PI monotherapy stems from a de-
sire to find a simple approach to HIV management
242 HIV CLINICAL TRIALS • 7/5 • SEPT-OCT 2006
that might avoid cumulative toxicities associated
with other antiretroviral classes. PI monotherapy
also has the potential to reduce the cost of long-
term therapy in certain settings. To that end, other
investigators have also conducted pilot studies to
evaluate the safety and efficacy of LPV/r
monotherapy. One study examined patients who
were receiving HAART but were naïve to PIs.19
Others looked at patients who were receiving
LPV/r-containing HAART20,21 and were simplified
to monotherapy. Yet another enrolled patients who
were naïve to HIV treatment.22 Finally, another
Table 2. Study outcomes of participants switched to LPV/r who did not complete 48 weeks
Patient Study HIV RNA levels, Adherence, CD4 change,
no. outcome copies/mL % cells/mm3
07 DC at week 4, <75 at week 4 100 14 at week 4
moderate diarrhea
08 DC at week 2 <75 at week 2 70 26 at week 2,
moderate diarrhea
10 VF at week 32, 6156 at week 28; 89–100 through 36 at week 32
LTFU 18,734 at week 32 week 28
11 VF at week 16, 1067 at week 12; 90–100 −13 at week 12
resuppressed on 2278 at week 16;
previous regimen DC at week 16
13 DC at week 8, <75 at week 8 100 through week 4 151 at week 8
mild diarrhea
Note: LPV/r = lopinavir/ritonavir; DC = discontinued; VF = virologic failure; LTFU = lost to follow-up.
Table 3. Viral resistance results in participants with virologic failure (VF)
Weeks on VF LPV trough
Patient Week therapy with VF phenotype concentration,
no. of VF ongoing viremia genotype (LPV FC) µg/mL Study status
10 32 8 L63P, V77I 0.57 0.67 at week 2, LTFU at
1.95 at week 24, week 32
3.26 at week 32
11 12 3 M36I 0.8 (virtual) 6.07 at week 16 DC at
week 16
18 8 4 NA NA 8.27 at week 24 Resuppressed
Note: LPV FC = lopinavir fold change; LTFU = lost to follow-up; DC = discontinued; NA = not available.
study explored HAART-experienced patients with
multiple toxicities and treatment failures who were
placed on LPV/r monotherapy.23 Although the
numbers of patients studied in these initial pilot
trials were small, ranging from 6 to 21, the results
were encouraging; over 60% of participants by in-
tention-to-treat (ITT) analysis maintained viral
suppression from periods ranging from 24 to over
48 weeks. In these pilot trials, PI resistance was
rarely observed and few participants withdrew
due to treatment-related side effects.19–24
More recently, results from larger, randomized
SWITCH TO LPV/R MONOTHERAPY •PIERONE ET AL.243
comparative studies have been reported. These trials
include over 500 participants with follow-up ranging
from 48 to 96 weeks. Efficacy results again are similar
to the findings reported herein and the findings of the
aforementioned other small pilot trials (73%–89%
with HIV RNA levels <500 copies/mL).25–28
The results obtained from the current pilot study
of LPV/r monotherapy are encouraging and are
consistent with results reported by other investiga-
tors. Most of the participants maintained virologic
suppression and experienced an increase in CD4+
lymphocyte cell counts, and few withdrew due to
medication-related side effects.21,23,25,28 In the cur-
rent study, however, after switch to LPV/r, mild
diarrhea was commonly observed, increased blood
glucose occurred in two patients, and about half of
the participants needed the addition of or an in-
crease in lipid-lowering therapy. The costs for
management of these potential adverse effects
would need to be considered in any formal
pharmaco-economic analysis of LPV/r
monotherapy.
It is well known that resistance to LPV/r is very
rarely selected in PI-naïve patients who are started
on this agent,13,14,16,29,30 so it is not surprising that PI
resistance did not emerge during the study. The
mutations detected in the two patients with VF in
the current study have not been identified by the
International AIDS Society-USA as primary resis-
tance mutations for LPV.31 However, there have
been reports of LPV/r monotherapy leading to PI
genotypic resistance.24,32–35 The frequency of these
resistance cases among patients on LPV/r
monotherapy suggests that the barrier to PI resis-
tance may be lower with LPV/r monotherapy
when compared to LPV/r-based triple therapy.
Additionally, limited data suggest that mutations
in the Gag gene may influence resistance to some
PIs.36–38 The extent to which those findings may
relate to the VF of two participants (Patients 10 and
11) who maintained adherence of over 89% and
lacked evidence of significant genotypic or pheno-
typic resistance is unknown.
Another area of potential concern is the penetra-
tion of highly protein-bound LPV into the cere-
brospinal fluid (CSF).39 However, results of two
studies have shown that CSF levels of HIV RNA
decrease in patients receiving LPV/r as part of
HAART40 and LPV/r monotherapy.41 One study
using a highly sensitive assay with a lower limit of
detection of 3.7 µg/L level demonstrated that the
median CSF level of LPV/r in patients receiving
LPV/r-containing HAART exceeded the median
inhibitory concentration of HIV by 5-fold.42 Addi-
tional studies will be required to better understand
HIV central nervous system suppression in the
context of LPV/r monotherapy.
A comparison of costs between triple HAART
and LPV/r monotherapy reveals that LPV/r
monotherapy offers a potential cost savings in
some settings. The annual cost of one of the DHHS
recommended combination regimens purchased in
the United States1 for initial antiretroviral therapy
ranges from $12,323.88 to $15,935.88 compared
with $8,472 for LPV/r monotherapy. This repre-
sents a potential savings of between 31% and 47%
of drug acquisition costs,43 which is similar to the
findings of a pharmaco-economic analysis of LPV/r
monotherapy from Spain.44
This pilot trial was designed to provide prelimi-
nary data on the safety and efficacy of LPV/r
monotherapy rather than to support switching pa-
tients on successful NNRTI-based therapy to LPV/r
monotherapy. Our results suggest that LPV/r
monotherapy may offer a viable alternative for the
management of HIV infection. Future studies of
LPV/r monotherapy will utilize the LPV/r tablet
formulation (200 mg/50 mg) that reduces pill
count, does not require refrigeration, and may
have a lower incidence of diarrhea compared to the
soft gelatin capsule used in this trial.45 Results from
this pilot study and other trials reported to date
suggest that LPV/r monotherapy may be an option
for management of HIV infection. Larger, random-
ized trials will be required to define the patient
populations that might benefit most from LPV/r
monotherapy and to better understand the poten-
tial risks and benefits associated with this thera-
peutic strategy.
ACKNOWLEDGMENTS
Partial funding for this study was provided by
Abbott Laboratories, Abbott Park, Illinois, USA.
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