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

12th World AIDS Conference

Abstracts 12245-12249 61

tuberculosis (1). The median reduction in VL is -2.2log10 at W4 (n = 34), -2.85
logio at W12 (n = 34), -3.3 loglo at W24 (n = 23). The percentage of patients
with HIV RNA < 200 copies and <20 copies/ml were respectively: 7/34 (20%)
and 2/7 (30%) at W4; 23/34 (67%) and 6/23 (27%) at W12; 17/23 (73%) and 8/17
(47%) at W24. Median HIV RNA VL was 622 copies at W4, 154 copies/ml at W12
and 65 copies/ml at W24. Median increase in CD4 lymphocytes were +95 cells
(W4), +74 (W12), +66 (W24). Cellular HIV DNA measurements are ongoing.
Adverse events were: delayed sensitive neuropathy (5), loose stool (8),
transaminases elevation (4), increase in CPK (4).
Conclusion: Saquinavir SGC in combination with 2 nucleosides analogues is
a highly potent suppressive therapy with a median reduction of viral load of -3.3
logio leading to 73% of patients below <200 copies and 100% < 3 000 copies
after 6 months. Tolerance of Saquinavir SGC was excellent. However, peripheral neuro-toxicity due to D4T/DDC is not in favor of this nucleoside analogues
combination.
12245 Double or triple therapy anti-HIV: A Brazilian dillema
Jorge Casseb1, L. Brigido2, A.P. Veigal, A. d'Anbrosio-Ferreiral, R. Olivieral,
R.S. Schwanza, A.J.S. Duarte1. 'Lab. Imuno. Exp. Transplantation, Sao Paulo;
2lInstitute Adolfo Lutz, Sao Paulo, SP, Brazil
Introduction: Since November 1996, Brazilian Government has been providing
HAART for all HIV/AIDS patients who are eligible for therapy, based on clinical status, CD4+ count and, more recently, RNA plasma viral load. It is recommendated
the use of double therapy with two nucleoside analogues (NA) for asymptomatic
patients with CD4 > 200 mm3, and triple therapy (2 NA plus 1 PI) in AIDS ou
CD4 < 200 cells/mm3.
Objective: We compared double versus triple therapy by measuring the viral
(results in means log 10 with standard desviation).
Study Design: Retrospective cohort study
Subjects and Methods: 107 HIV-1-infected patients divided in two groups:
CD4 count <200 and CD4 > 200 mm.
Results: 106 (mean of age = 36 year-old) patientes were evaluated by RNA
plasma viral load (VL by NASBA (Organon) or PCR (Roche). Forty-four cases
had CD4 count <199 cells/mm3 and 59 had >200 at entry in the study.
TCD4 < 199 N. VL Pre-treatment VL post-treatment (1st) VL post-treatment (2nd)

Double 20 4.68 ~ 0.18
Triple 28 3.79 ~ 1.42

3.79 ~ 1.42
3.76 ~ 1.31

TCD4 - 200 N. VL Pre-treatment (1st) VL post-treatment (2nd)
Double 40 4.74 ~ 0.84 3.81 ~ 1.25
Triple 19 5.19 A 0.41 3.90 ~ 1.22

4.17 1.5
3.41 ~ 1.81
4.10~ 1.32
3.60 1.18

114*/12247 Immune reconstitution and role of thymus during
potent antiretroviral therapy in vertically
HIV-infected children
Alessandra Vigan6o, M. Clerici2, D. Bricalli', M. Saresella3, S. Difabio4,
N. Principi, S. Vella4. 1 Clinica Pediatrica IV Universita Milano Ospedalelsacco
ViaGBGrassi 20157 Milano; 2Cattedraimmunologia Universita Milano, Milano;
3Laboratorio Biologiafondazionedongnocchi, Milano; 4lstituto Superior Redi
Sanita V Regina Elena, Roma, Italy
Objectives: To analyze restoration of immune competence and viral suppression
in plasma in vertically HIV-infected children receiving potent antiretroviral therapy.
Methods: Nineteen HIV-infected, previously antiretroviral-experienced (ZVD,
ZVD+ddl) children (mean age 9.6, range 5.5-13.2 years), with clinical symptoms
(CDC class A n = 2, class B n = 6, class C n = 11) and evidence of immune
suppression (CDC class 2 n = 10, class 3 n = 9), were treated with a combination
of stavudine, lamivudine and indinavir. Immune competence was prospectively
assessed before and after 1, 3, 6, 9, 12 months of therapy by analysis of: T-cell
subset profiles, TCR P repertoire, lymphocyte proliferative response and DTH
skin test response. Plasma HIV-RNA and clinical parameters were concomitantly
evaluated. Thymus volume was measured at baseline and during antiretroviral
therapy by magnetic resonance imaging (MRI).
Results: CD4+ counts and percentages, CD4+/CD8+ ratio, CD4+ CD45RApercentage and CD4+ CD45RA/RO ratio were significantly increased under treatment, irrespective of immunologic and clinical stage at baseline. A positive
correlation was found between thymus volume at baseline and the increase in
CD4' cells, CD4+ CD45RA/RO ratio and the expansion of TCR / repertoire.
PBMCs proliferative response to Candida albicans and to Tetanus toxoid as well
as DTH skin test response increased significantly during treatment in the majority
of patients. Plasma HIV-RNA dropped below 400 copies/ml in all but one patient
during the 12 months of antiretroviral therapy. No child had progression of disease
or occurrence of opportunistic infections.
Conclusions: Our data suggest that thymus may play an important role in immune reconstitution in vertical HIV-infection. Therefore the goal of restoration of
immune competence during potent antiretroviral therapy could be better achieved
in children than in adults.
S12248 Saquinavir soft gelatin capsules (SQV-SGC) + nelfinavir
(NFV) + nucleoside reverse transcriptase inhibitors
(NRTIs) in HIV-infected children
Mark Kline1, C.V. Fletcher2, R.C. Brundage2, N.R. Calles3, E.L. Moreau3,
J.L. Steimer4, N.E. Buss5, F. Duff6, P. DeLora6, M. Eason6. I Texas Children's
Hospital MC1-3291 6621 Fannin Street Houston Texas 77030; 2University of
Minnesota, Minneapolis MN; 3Baylor College of Medicine Houston TX;
6Hoffmann-La Roche, Inc. Nutley NJ, US; 4F. Hoffmann La Roche Ltd. Basel,
Switzerland; 5Roche Products Ltd. Wewlyn, UK
Background: The addition of NFV (750 mg tid) to SQV-SGC (1200 mg single
dose) results in a 392% increase in SQV-SGC levels without increased incidence
of toxicity. This metabolic interaction may benefit children with intrinsically high
rates of metabolism in ways such as greater viral load suppression and delayed
development of resistance.
Methods: 14 children with HIV infection, age 3-16 years and able to swallow
adult capsules, are treated orally with SQV-SGC (33 mg/kg tid) + NFV (30 mg/kg
tid) + NRTIs of choice. Patients are followed for a minimum of 48 weeks with
intensive PK performed at day 0 (single dose profile), week 4 (steady state) and
as necessary thereafter. Sparse PK occurs at every study visit after week 4. CD4+
counts, plasma HIV RNA concentrations, and safety (adverse events and labs)
are assessed at each scheduled study visit.
Results: 9 patients enrolled to date: 67% female; 78% non-white; median
age of 4 years. Baseline CD4 and HIV RNA are 549 cells//iL, and 4.5 logio
copies/mL, respectively. PK data through week 4 are available from 8 children.
Week 4 PK parameters of SQV-SGC (median, range) were: oral clearance (CUF)
7.4 L/h/kg (1.9-55); elimination half-life, 1.7 h (1.6-2.4); AUC-24, 12300 ng*h/mL,
(1560-57700); and 8 hour concentration, 578 ng/mL (39-3280). No premature
study withdrawals or serious adverse events were reported. Preliminary 8 week
results show a 54 C134 cell increase and -1.97 logio HIV RNA decrease from
baseline using the Ultrasensitive assay. 67% and 50% of the children were below
the quantification limit of the Amplicor and Ultrasensitive assays, respectively.
Conclusions: Preliminary findings indicate that in combination with NFV, the
median CUF of SQV-SGC is approximately 3-fold less than that expected when
SQV-SGC is given without NFV. The combination of SQV-SGC + NFV + NRTIs
is generally well tolerated and safe in young children and is effective in reducing
viral load to unquantifiable levels.
1 12249 A randomised double blind trial of the addition of
lamivudine to current NRTI therapy in HIV infected
children - The PENTA 4 Trial

Diana Gibb. On Behalf of The PENTA Steering Committee: MRC HIV CTC,
Mortimer Market Centre Capper Street, London WC1E GAU, UK
Background: Studies have shown that addition of lamivudine (3TC) to zidovudine
(ZDV) containing regimens slows progression of disease and improves survival
in adults with HIV-1 infection. There are few data on the use of 3TC in children
with HIV infection.

Conclusions: 1) Patients with double therapy presented good response in
both CD4 count stratum, but the VL increased after 6-12 months in the CD4 <
199 group, almost returning to the baseline copies number. 2) Patients with triple
therapy showed better response when started before immunossupression, with
a decresed VL at the second and third measurement. In spite of VL decreased
initially, it tends to increase few months later. Therefore, we concluded that double
therapy with NA should not be used. There is a failure in most treatment schemes
to achieve the goal of negative RNA viral load after 4-6 months after therapy.
173*/12246 First large US study of efficacy and tolerability of
ritonavir in HIV-infected children
Stephen Peltont, K. Stanley2, K. Mclntosh3, A. Wiznia4, S.A. Nachman5,
R. Yogev6. Boston Medical Center 818, Harrison Avenue, Boston MA 02118;
2Harvard University, Boston MA; 3Children's Hospital, Boston, MA; 4Bronx
Lebanon Hospital Center, Bronx, NY; 5Health Sciences Center, Stony Brook,
NY; 6The Children's Memorial Hospital, Chicago, IL, USA
Background: To evaluate zidovudine (ZDV) + lamivudine (3TC) versus stavudine
(d4T) + ritonavir (RTV) versus ZDV + 3TC + RTV with respect to plasma RNA,
safety and tolerance.
Methods: Pediatric AIDS Clinical Trials Group (PACTG) Protocol 338 is a
randomized, open label, Phase II study of 298 clinically stable, antiretroviral
experienced HIV-infected children 2-17 years of age.
Results: At baseline the median age was 7.1 years and the median loglo RNA
was 4.37. The proportion that reached undetectable (<400 copies) RNA at 12
weeks was 12% for the ZDV + 3TC group and 60%-63% for the ritonavir-containing arms (p < 0.001 for comparisons versus the ZDV + 3TC group). The median
drop in RNA from baseline to week 12 was 0.35 logs for the ZDV + 3TC group
and was to the limit of detection (more than 1.6 logs) for the other two treatment
groups. Of the 197 children on the ritonavir-containing arms, at 12 weeks 57%
were on full dose and 13% were permanently off ritonavir. All patients will have
reached 48 weeks of follow-up by May 1998. We will present the experience to
48 weeks for these three groups of children with durability of reduction in RNA,
changes in lymphocyte markers, safety and tolerance.
Conclusions: This first large study in children comparing reverse transcriptase
inhibitor therapy with and without a protease inhibitor showed that ritonavir-containing treatment arms achieved significantly lower RNA values at 12 weeks.
Durability of the RNA response, CD4, safety and long-term tolerability will be
presented.