Bridging the Gap: Conference Record [Abstract book, International Conference on AIDS (12th: 1998: Geneva, Switzerland)]

72 Abstracts 12296-12300

12th World AIDS Conference

12296 Combination antiretroviral therapy with ritonavir in
pediatric HIV infection
M. Isabel De Jose', R. Bastero2, J.T. Ramos-Amador2, C. Fortuny3,
J.M. Bertran4, R. Gonzalez-Montero5. Spanish Pediatric-AIDS Collaborative
Group; 'Servicio De Pediatria. Hospital La Paz Paseo De La Castellana
261-Madrid 28046; 2Pediatician. Hospital 12 De Octubre. DPTO. De Pediatia.
Madrid; 3Pediatrician. Hospital De san Juan De Dios Barcelona; 4Pediatrician.
Hospital Valle De Hebron Barcelona; 5Pediatrician. Hospital Universitario De
San Juan Alicante, Spain
Objective: To review the safety tolerance and efficacy of ritonavir (R) in combination antiretroviral therapy (ART) with other nucleoside retrotranscriptase inhibitors
(NRI) in children.
Methods: Retrospective chart review of ART with R in the setting of 11 pediatric hospitals fron december 1996 to november 1997. Ritonavir (dosis range =
150-430 mg/m2/12 h) and 2 NRI was iniciated in 63 inhibitor protease naive HIV
infected children (6% NRI naive), mostly with advanced disease (30% clinical
category B, and 60% C). Blood count, biochemical analysis, CD4 count and
viral load were carried out at baseline, 4-8 week, 12-16 weeks and 6 months.
Tolerance and adverse events were collected.
Results: Median age of the patient was 55 month (mean 62 ~ 41). There was
an important weight gain in the first 3 months in most of patients. Inmunological
and virological results are listed below:
Baseline Mean change Mean change Mean change
at 4-8 w at 12-16 w at 6 m
N 63 39 38 29
CD4 count 526 ~778 +210 ~ 413 +235 ~ 385 +486 ~ 929
CD4% 15.2 ~ 12.6 f+1.6 ~ 5 +3.4 ~ 6.1 +6.2 ~ 6.6
Viral load (log10) 5.36 ~ 0.71 -1.35 + 1.14 -1.43 ~ 1.73 -0.96 ~ 1.54
Intolerance to R (vomiting or diarrhea) occurred in 23 children (37%), and in 15
of them (24%) R was withdrawn. In 3 other patients R was discontinued due to 1
retinopathy and 2 MAC infection (drug interaction with rifampin), respectively.
Conclusions: Combination antiretroviral therapy with ritonavir was associated
with substantial short-term clinical, virologic and inmunologic improvement in
this heavily pretreated group of children. Intolerance, frequently transient, was
common and was an important adverse event limiting therapy. Ritonavir in combination with other NRI antiretrovirals may be useful in HIV-infected children, but
further options are required in the pediatric age group.
S12297 Virological follow-up of HIV infected patients treated by a
triple combination therapy with protease inhibitor
Narjis Boukli, M.C. Meyohas, O. Picard, J.C. Petit, L. Morand-Joubert. Hopital
Saint-Antoine Sce Virologie 184 Rue Fg Saint-Antoine 75012 Paris, France
Objective: To describe the evolution of HIV viral load and CD4 T cells count in
a cohort of 334 patients treated with a triple combination therapy with protease
inhibitor (indinavir).
Methods: Between March 1996 and March 1997, a total of 334 HIV infected patients received two combinations prescribed with a greatest frequency
in Saint-Antoine Hospital (Paris, France): ZDV/3TC/IDV (1) and D4T/3TC/IDV
(2). Virological and immunological follow-up was performed through respectively
plasma RNA measurement (bDNA, Chiron) and by CD4 T cells count. A positive
immunological response was determined by a increase of over 50% of baseline
CD4 count. The median viral load at baseline was 80010 copies/ml for (1) and
59670 copies/ml for (2). The median CD4 T cells count at baseline was 111/mm3
and 99/mm3 for (1) and (2) respectively. The median follow-up was 329 days for
(1) and 347 days for (2).
Results: Four patterns of virological response were observed: (A) Sustained
response with undetectable viral load (<500 copies/ml): 45% of individuals for (1)
and 53% for (2); (B) Sustained response with significant decrease, yet remaining
detectable: 21% for (1) and 22% for (2); (C) Virological failure with significant
decrease (>0.5 log) but return at the baseline: 17% for (1) and 13% for (2); (D)
Absence of virological significant response: 17% for (1) and 12% for (2). Sixty one
percent of patients for (1) and 71% for (2) had a undetectable viral load immediatly
after initiation of therapy but this phenomenon persisted in only 45% and 53%
with a median time of 300 days for (1) and of 306 days for (2). Around 35%
of patients have shown a discrepancy between virological and immunological
responses, whatever the prescribed combination.
Conclusion: There were no significant difference in virological and immunological responses between these two combinations including indinavir. Results of
extended follow-up will be presented.
S12298 Adherence to proteinase inhibitor based highly effective
antiretroviral therapy (HEART)
John Walsh1, M. Dalton2, J. Gill1, D. Wilkinson1, A.P. Burgess3, B.G. Gazzard1.
'St. Stephen's Centre, 369 Fulham Road; 2HIV Care Team, Glaxo Wellcome UK

Ltd.; 3lmperial College, London, UK
Background: The longterm success of HEART is likely to depend on the degree
of adherence to the chosen regimen. However the prevalence of non-adherence
with HEART is largely undocumented.
Objectives: To determine the prevalence of non-adherence with proteinase
inhibitor (PI) based HEART, and elucidate demographic and lifestyle factors and
health beliefs which may be predictive of poor adherence.

Method: Confidential patient completed questionnaires and semi-structured
interviews with HIV seropositive patients taking PI based HEART for greater than
1 month. Adherence over the preceding month was assessed by patient self
report and estimates by the interviewer, the patient's HIV physician and pharmacy
records.
Results: Of 114 patients, 86% were gay males; 81% took triple combination
therapy (19% quadruple therapy). The commonest antiretrovirals prescribed were
indinavir (43%), stavudine (79%) and lamivudine (76%). Mean daily pill burden
was 18.3 (range 10-41). Full adherence over the preceding month was reported
by 41%; 23% claimed never to have missed a dose of HEART. Of the 59% admitting less than full adherence over the preceding month 8% missed a dose on the
day of interview, 15% on the day before and 41% in the preceding fortnight. Mean
self reported adherence in this group over the preceding month was 87% (range
60-99%) and 25% of patients admitted adherence of 80% or less. Pharmacy
records indicated mean adherence with HEART of 96% (range 80-100%); 19%
collected <90% of medication expected. Physicians estimated full adherence in
41% of cases; there was a significant correlation between physician and patient
estimates of adherence (p = 0.03) and interviewer and patient estimates (p <
0.01).
Conclusion: In our population there was a high degree of self reported nonadherence with proteinase inhibitor based HEART and a significant minority of
patients have missed more than one fifth of doses. Interventions aimed at identifying such individuals and improving adherence are urgently required to ensure
the longterm success of HEART.
S12299 1 Associated lipodystrophy metabolic disorders due to
protease inhibitor containing regimens
Eric Bonnet', L. Cuzin', L. Sailler', M. Obadia', B. Marchoul, Ph. Caron2,
P. Massip1. 'Service Des Maladies Infectieuses Hopitaln Purpan Place Baylac
Toulouse; 2Service D'Endocrinologie Toulouse, France
Background: Physical symptoms compatible with aquired lypodystrophia of lower
limbs and face occurred in 12% of our protease inhibitors treated patients.
Methods: 12 patients have been evaluated for metabolic disorders able to
explain this side effect. To date, results are available for 8 of them.
Results: There were 5 males and 3 females, aged 40 years ~ 4, with a body
mass index of 22.72 ~ 1.12 kg/m2, treated with indinavir (n = 7) or ritonavir and
saquinavir (n = 1), for 14.8 months ~ 0.8. All patients experienced a progressive
loss of subcutaneous fat tissue of the lower limbs and sometimes of the face (n
= 5) confirmed by CT scan and determined by the body composition measured
by dual X-ray absorptiometry: rate of fat mass in lower limbs was 10.4% ~ 2;
in trunc, 16.1% ~ 2.1; in body, 13.9% ~ 2.1 (normal range = 18 to 30%). On
metabolic evaluation we observed lipid abnormalities: hypertriglyceridemia (mean
level before treatment with PI = 1.36 mmol/l ~ 0.2; mean level during treatment
with PI = 2.75 mmol/1 ~ 0.8); a decreased HDL cholesterol level (0.36 g/l ~
0.04, N > 0.43 g/l), associated with basal hyperinsulinemia: fasting insulin = 23.8
mU/ml ~ 7.4, N < 20 mU/ml; fasting C peptid = 3.65 ng/ml ~ 0.39, N < 3;
abnormal oral glucose tolerance best (2 hours insulin level 128.8 mU/ml ~ 40,
2 h C peptid level 12.7 ng/ml ~ 1.6. The urinary C peptid was high: 84 uU/24 h
~ 21.7 (N < 58 uU/24 h). All patients had a very low plasma cortisol level but
inchanged nycthemeral cycle. TSH, freeT4, IGF1, testosterone, DHA and DEA
were in normal ranges.
Conclusion: Acquired lipodystrophy during PI treatment is associated with
hyperinsulinemia, hypertriglceridemia and low cortisolemia. Further studies are
needed to explain PI related lypodystrophia mechanism. Cortisol binding globulin
and leptine dosages. are in process.
S12300 Viral load levels during treatment with Viracept
combination treatment as predictor of response and
guidance for treatment choice strategy
George Yu, N.J. Clendeninn, B. Quart, L. Greenberg, Y. Chang. Agouron
Pharmaceuticals, Inc., 10350 N. Torrey Pines Rd., La Jolla, CA, USA
Design: Double-blind, randomized clinical trial.
Objective: Investigated the relationship and influence of HIV-RNA, up to the
time of response, on the duration of response.
Methods: A number of potent anti-HIV treatments are currently available in
suppressing the viral load in patients infected with HIV. Strategy is needed in order
to provide guidance in treatment choices to ensure the patient can maintain the
longest possible viral load suppression. Viracept (nelfinavir mesylate-NFV) has
been established as a potent suppresser of HIV-RNA when used in combination
with nucleoside analogues. Based on the data from the study AG 1343-511, NFV
in combination with AZT and 3TC, we have investigated the relationship and
influence of HIV-RNA, up to the time of response, on the duration of response
utilizing the two dose (500 mg TID and 750 mg TID) of NFV studied in the trial.
Response in this case is defined as, for a given assay (either PCR Amplicor-PCR
with Limit of Detection-LOD of 400 copies/mi or UltraSensitive-Ultra LOD of 50
copies/ml, two consecutive viral load determinations below the LOD and replapse

as two consecutive determinations above the LOD. The duration of response is
the time interval between the first response qualifying determination and the first
relapse qualifying determination.
Results: Treatment responders according to PCR were partitioned into two
categories: Those who also qualify as responders according to Ultra and those
who did not. Total number of NFV treated patients = 196, PCR responders =
144, Ultra responders = 105. Duration of response for Ultra responders were