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

12th World AIDS Conference

Abstracts 12309-12313 75

S12309 Protease inhibitor therapy in 19 children with HIV 1
infection
Christian Courpotin1, J.C. Nicolas2, C. Dollfus3, Y. Reguerre3, P. Roques4,
G. Lasfargues3, G. Leverger3. ' Hpital d'Enfants A. Trousseau 26 Avenue du Dr
Arnold Netter 75571 PARIS cedex 12; 2Laboratory of Virology H6pital
ROTHSCHILD, Paris; 3Department of Hemato-Oncology H6pital Armand
Trousseau, Paris; 4CEA CRSSA, Fontenay Au Roses, France
Background: To evaluate the tolerance and efficacy of antiretroviral combinationtherapies: tritherapies (T3): 2 reverse transcriptase inhibitors (RTI) + 1 protease
inhibitor (PI) and quadritherapies (T4): 2 RTI + 2 PI, in 19 HIV 1 infected children
(15 vertical transmission). The median age at initiation of T3 was 110 months
(range, 54-182 months). 9 children had AIDS.
Methods: Clinical assessment, CD4+ lymphocyte count, viral load (VL), liver
transaminases (AST, ALT) and pancreatic enzymes (lipase) were evaluated at
Day 0, Month 1 and every 3 Months.
Results: Tritherapy (T3) was started because of clinical and/or biological progression in 19 children pretreated with an association of 2 RTI. In 8 children
quadritherapy was secondary initiated because of a clinical and/or biological
progression. Mean duration of T3 before the onset of T4 was: 6.5 months (range,
2-12 months). Mean duration of T4 on the 12/31/97 was 7 months (range, 1-13
months). Clinical and biological evolution was satisfactory in children with T4.
Tritherapy Quadritherapy
Time DO M1 M3 M6 M9 M12 M15 DO M1 M3 M6 M9
Mean increase 110 201 +195 +225 t208 +282 4161 +252 4346 t490
of CD4 (106/1)
Mean decrease 0.87 0.93 1.06 -0.75 1.04 -0.87 -1.35 -1.27 --1.25 1.73
of VL (loglo)
Number of 0/19 7/18 6/18 4/11 2/7 2/6 2/4 0/8 5/8 3/7 2/4 2/3
VL - 2.6 (logio)
Two adverse events were observed with T3: one 8 fold increase of ALT and one
grade 2 vomiting, both led to change in PI. New PI therapies were well tolerated.
No adverse event was observed with T4.
Conclusion: Tolerance and efficacy of T3 and T4 were good in children. When
PI were initiated with a complete change of RTI results were similar to those
observed in adults. Addition of PI without change of RTI for the first 6 children
treated with T3 resulted in moderate decrease of viral load. T4 led to clinical and
biological improvement without increased toxicity.
S12310 Ritonavir + saquinavir (RIT + SAQ) salvage therapy in
antiretroviral-experienced patients
Ernesto Scerpella, J.N. Moreno, M. Dashefsky, D.T. Jayaweera, C. Boulanger,
A.E. Rodriguez. University of Miami, 901 N.W. 17th Street, Suite D, Miami, FL
33136, USA
We describe the results obtained using the double protease combination of
Ritonavir plus Saquinavir (RIT + SAQ) as salvage therapy in 23 antiretroviralexperienced patients attending our outpatient clinic at Jackson Memorial Hospital,
Miami, Florida.
Patient Characteristics: Mean age 38 years (range: 21-65). Sex: 14 males,
9 females. Staging: 14 AIDS, 9 HIV-infection. Mean prior duration of therapy was
23 months (range: 2-91). All patients have been previously treated with most nucleosides available, and 17/23 had previously used protease inhibitors (indinavir,
saquinavir) for various periods of time. Median baseline CD4: 149 cells/mm3
(range: 7-609). Mean baseline viral load: 4.66 logs (45,708 copies/mL). Response to treatment with RIT + SAQ was defined as a viral load decrease >0.5
logs.
Results: Fifteen (65%) of the 23 patients that started RIT + SAQ responded
to treatment (viral load decrease >0.5 logs). Failures (8/23) were mostly due to
noncompliance and intolerance of medications. Eleven (73%) of the 15 responders became undetectable at one point. Eight of the 11 remain undetectable, for
periods of up to 17 months of follow-up. The mean decrease in viral load among
responders was more than 2 logs. We analyzed the characteristics that predict
response to RIT + SAQ in these patients.
Conclusion: Treatment with RIT + SAQ is a viable alternative for nucleosideexperienced and protease-experienced patients. The majority of responders in
this series reached undetectable levels of virus, and have remained undetectable
since.
I 12311 Indinavir (IDV) in combination with zidovudine (ZDV) and
lamivudine (3TC) in treatment-naive patients with >500
CD4 cells/mm3
Randi Leavitt1, Deborah McMahon2, A. Meibohm1, D. Aversa1, D. Goodwin3.
Merck Research Laboratories, 10 Sentry Parkway, Blue Bell, PA; 2University of
Pittsburgh, Pittsburgh, PA; 3Glaxo Wellcome, Inc. Res. Triangle Prk. NC, USA

Objectives: To study the effects of IDV 800 mg q8h plus ZDV 300 mg q12h plus
3TC 150 mg q12h on long term suppression of serum viral RNA in treatment-naive
patients with early HIV-1 infection defined as CD4 cell counts >500 cells/mm3,
serum viral RNA (vRNA) >1000 copies/mL, and no history of HIV associated
conditions.
Methods: This is an ongoing 192 week study. Currently 159 of a planned 250
patients have been enrolled with enrollment ongoing. Preliminary antiretroviral

activity was assessed by changes in vRNA obtained every 4 weeks using both
the Roche Amplicor and Ultra Sensitive assays. All samples reported as <400
copies/mL, using the Amplicor assay were reassayed using the Ultra Sensitive
assay.
Results: Median entry vRNA was 7682 copies/mL. At week 4, 76% of 147 patients had vRNA below the Amplicor assay level of quantification (400 copies/mL)
and at week 24, 98% of 55 patients had vRNA < 400 copies/mL. At week 4 and
week 24 respectively, 14% of 91 patients and 97% of 39 patients with vRNA <
400 copies/mL also had vRNA < 50 copies/mL using the Ultra Sensitive assay.
Therapy has been generally well tolerated with a low rate of discontinuation.
Conclusions: In patients with early HIV-1 infection, IDV plus ZDV plus 3TC
resulted in suppression of vRNA below 400 copies/mL in 98% of patients by week
24 and <50 copies/mL in 97% of those patients who were <400 copies/mL.

12312|

Long-term efficacy and toxicity of antiretroviral
combination treatment: Data on 4230 patients in the
Italian cohort of persons on antiretroviral therapy
(ART-IC)

Antonio Chiese, Stefano Vella, L.G. Dally, L.E. Waimer, A. Geraci. Istituto
Superiore Di Sanita'-Lab. Virology Viale Regina Elena, 299-Rome 00161, Italy
Background: The introduction of protease inhibitors (PI) as treatment for HIVpositive patients in clinical practice is a fairly recent event. Ritonavir, Saquinavir
and Indinavir were licensed for clinical use in Italy in December 1996. Very little is
known about the long term efficacy and toxicity of PI in combination with reverse
transcriptease inhibitors (RTI).
Objectives: ART-IC began in January 1997 with the aim of collecting and
analysing information on a large cohort of patients treated with combination therapy, including PI, and focusing on the long term efficacy and toxicity of their
prolonged use.
Patients and Methods: To date 4230 patients have been enrolled by 94 clinical centres throughout Italy. All patients were PI naive at enrolment. Data are
collected either on paper forms or entered directly onto a computer by the Clinical
Centre through a standardised software. Follow up is every six months. Data
include patients demographics, clinical condition, immunological and virological
information, antiretroviral treatment, adverse events, and details of death.
Results: Baseline characteristics of our cohort are the following: mean age
36 (+ 7.9) years, median CD4 count 134 cells/mm3, 73% males, 33.6% AIDS,
33.9% symptomatic not AIDS and 32.6% asymptomatics. The male population
consists mainly of IV drug users (56%), homosexuals (21%) and heterosexuals
(17%), whereas the female population consists mainly of heterosexuals (48%)
and IV drug users (45%). 24% of all patients had less than 50 cells/mm3, 41% had
between 50 and 199 cells/mm3, 30% had between 200 and 499 cells/mm3. 50%
of AIDS patients had less than 50 CD4 cells/mm3, 50% of symptomatic not AIDS
patients had between 50 and 199 cells/mm3 and 50% of asymptomatic patients
had between 200 to 499 cells/mm3. The overall median, among the 2787 patients
with HIV-RNA viral load measurement at enrolment, was 72,000 copies/ml. 83%
had over 5,000 copies/ml, including 43% with at least 100,000 copies/ml. 53% of
AIDS patients had at least 100,000 copies/mI. The most frequent AIDS defining
diseases presented at enrolment by AIDS patients were PCP (29%), candidiasis
(22%) and toxoplasmosis (10%). Most patients began PI treatment with Indinavir
or Saquinavir, the respective proportions being 47% and 38% (AIDS), 40% and
45% (symptomatic not AIDS), 42% and 44% (asymptomatic). At the start of PI
treatment, patients in all 3 clinical stages were similar with respect to the different
combinations of PI and RTI treatments, with the majority of patients taking a combination of one PI and two RTI, e.g., 86%, 90% and 81% of AIDS, symptomatic
not AIDS and asymptomatic patients, respectively. By the time of conference
presentation, analyses of the 1997 data, including 2 follow-up visits for most of
the patients, will be available.
Conclusions: Data on patients enrolled in 1997 show that PI treatment is
already being used by many HIV-positive patients in Italy, irrespective of their
clinical or virological status. Ritonavir appears to be the least preferred PI in clinical practice, Saquinavir and Indinavir being almost equally prescribed. Follow up
data will allow comparisons between single treatments and treatment strategies
to be made. Progression to new/first AIDS defining events, toxicity-free time, the
sustained effect of treatment on immunological and virological parameters, as
well as mortality rates, will be addressed in person-years based analyses.
S123131 Virologic long term results of a double protease inhibitor
therapy with saquinavir and ritonavir plus stavudine
Pietro Vernazza1, M. Battegay2, E. Bernasconi3, M. Flepp4, R. Malinverni5,
A. Tellenti6, S. Morgenthaler7, B. Hirschel8, F. Roth9. IDepartment of Medicine
Cantonal Hospital, 9007 St. Gallen; 2University 4031 Basel; 3Cant. Hosp.
Lugano 6900 Lugano; 4 University Hosp. Zurich 8091 Zurich; 5 University Hosp.
Bern 3011 Bern; 6University Hosp. Lausanne 1011 Lausanne; 7Roche Pharma
Ch 4153 Rheinach; 8University Hosp. 1211 Geneva; 91kmi St. Gallen 4001 St.
Gallen, Switzerland
Objectives: This open label study evaluated the efficacy and safety of the combination of saquinavir + ritonavir + d4T in HIV-1 infected patients with moderate
to severe immunosuppression. We assessed the virologic effect of this treatment
on cell-associated DNA, HIV-culture and HIV phenotype in blood.
Methods: Drug experienced, protease-inhibitor naive patients were treated in
this open label phase 11 study as described in a companion abstract where
effects on HIV-RNA and CD4 markers are reported. In addition, HIV culture