Abstracts Vol. 1 [International Conference on AIDS (11th: 1996: Vancouver, Canada)]

Tu.B.21 19 - Tu.B.2124

Tuesday July 9, 1996

Therapy with CD4 >50/mmc N. Survival (mths) Therapy with CD4<50/mmc N. Survival (mths)

YES

46 255*
24 158*

YES
NO
YES
NO

29
17
6
18

28,6*
20.2
18,8
14,8*

Conclusions: In these years many reports show a greater amount of pts with very low
CD+in count, most probably due to antiretroviral therapy and O.. therapy and profilaxis.
Our preliminary data suggest that antiretroviral therapy increases the survival especially if it
continued when CD4+ counts are very low. Unluckily often we must stop such therapy
due to their side effects and/or other adverse events. Nevertheless the chance to use more
different drugs will allow us to implement longer treatment.We also think that better care
organization and suppresive drugs with higher comphliance will decrease hospitalization and
impruve quality of life.
Lo CAPUTO SERGIO Infectious Disease Unit, S.M. Annunziata Hosp Vie Dell'antella 58,
500u Antella, FIRENZE ITALYTel. 39+556449445 FAX 39+556449234
Tu.B.21 19
TOLERABILITY OF AZT+DDI AND AZT+DDI+NEVIRAPINE AMONG
ANTIRETROVIRAL-NAIVE PATIENTS WITH ADVANCED HIV INFECTION
(AIDS OR CD4+ <200/mm3). PRELIMINARY RESULTS.
Tomino Carlo, Fragola V, Bucciardini R, Weimer LE, Ricciardulli D, Chiesi A, Floridia M,Vella S.
Laboratory of Virology Istituto Superiore di Sanita, Rome, Italy
Objective: to assess the safety profile of AZT+ddl and AZT+ddl+nevirapine in a population or patients with advanced HIV infection (AIDS OR CD4+ <200/mm3) and no previous antiretroviral treatment.
Methods: Phase II, double blind, centrally randomized multicenter trial. All patients received
open AZT (600 mg/day) + open ddl (400 mg/day) plus blinded trial treatment (nevirapine
or placebo). Nevirapine was administered at a daily dosage of 400 mg/day after a fourweek
run-in period at 200 mg/dayThe study is ongoing and data refer to cumulative events
observed. In no case trial treatment was unblinded.
Results: As of January 15. I1996, 54 patients were randomized. During follow up, an
improvement in general status was observed, with good CD4 response. With respect to
tolerability although gastrointestinal symptoms (nausea, vomiting and diarrhea) were relatively frequent, these and others at least possibly treatment-related adverse events were
generally mild (including rash, with no grade III or IV rash observed as of January 15, 1996),
and only in a few cases requiring discontinuation of treatment.
Conclusions: This trial is the first evaluating a triple combination including nevirapine in this
population.The preliminary results, although still blinded, suggest a good tolerability of both
AZT+ ddl and AZT+ddl+ nevirapine among antiretroviral-naive patients with advanced HIV
infection. Further follow up and unblinding of the data is however needed to draw definitive
conclusions. Definitive results, including an extensive virological evaluation, are expected in
about one year
C.Tomino, Laboratory of Virology, Istituto Superiore di SanitaViale Regina Elena, 299 00161
Rome Italy Fax [phone] Phone [phone]
Tu.B.2120
SWITCH OR ADD:A RANDOMISED TRIAL OF AZT/DDI COMBINATION VS DDI
ALONE AMONG PATIENTS PRE-TREATED WITH AZT
dre Philipe', Chave JP2, Ruef C3, Iten A2, Gabriel V I,Von Overbeck j2, Battegay M4,
Furrer HJS,Vernazza P6, Ceserani N7, Bernasconi E8, Hirschel B, the Swiss HIV Cohort
Study U niversity Hospitals, Genev, 2Lausanne, 3Zrich, 4Basel, 5Bern, 6St Gallen,
8Lugano Switzerland and 7Hop. San Raffaele, Milano, Italy
Objective: To compare the clinical efficacy and tolerance of Zidovudine/Didanosine
(AZT/ddl) therapy with ddl monotherapy among HIV-infected patients previously treated
with AZT.
Methods: Multicentric randomised controlled trial of AZT/ddl 300/200 mg daily vs ddl 400
mg daily and intention to treat analysis of CD4 cell count, AIDS-defining clinical events,
death, and toxicity Inclusion criteria: CD4 cell count <350 per mm3 & prior AZT treatment
for at least 16 weeks.
Results: Fifty-seven patients received ddl monotherapy and 65 combined treatment. Of I 22
patients, 26 were females and 96 males. Patients were similar in age, gender distribution,
transmission category HIV clinical stage (26% with prior AIDS-defining opportunistic infections [Ols]),. duration of AZT pre-treatment (mean: 20.9 months) as well as baseline laboratory values for hemoglobin, leukocytes, p24 antigenemia and CD4 cell count (mean 154 per
mm3). Median duration of follow up was 17.2 months. In the ddl group, 20 patients (35.1%)
discontinued treatment because of toxicity or severe intolerance compared to I 8 (27.8%)
in the AZT/ddl group (p = 0.38).There was no statistically significant difference in CD4
change between the two groups. In the ddl group, I 6 patients (28.1%) developed a clinical
endpoint -death or AIDS defining Ols- and 32 (49.2%) in the combined therapy group
(Relative risk: I1.75; 95% Confidence interval: 1.08-2.84).
Conclusions: This study indicates that the tolerance of AZT/ddl 300/200 mg daily and ddl
400 mg are similar For fairly advanced AZT pre-treated HIV-patients, monotherapy with ddl
was clinically and statistically superior to lowdose AZT/ddl combination in preventing AIDS
defining illness and death.
Ph Sudre, University Hospital, CH 1 21 Geneva 14, Switzerland Tel +4 I 22 372 98 12 Fax
[phone] emal: sudredminov I.hcuge.ch
Tu.B.2121
HYPERICIN: SAFETY AND ANTIRETROVIRAL ACTIVITY IN THAI HIV POSITIVE
VOLUNTEERS
Pitisuttithum P. Migasena S. Suntharasamai P Sutthan R*, Perathamanond P**,Wasi C*,
Shikan U.I Peeters P)-,Tobia AJ.+ Faculty of Troprcal Medicine, Mahidot University **
*Faculty of Medicine, Siriraj Hospital Mahidol U., Bangkok Thailand ** Dermatology Institute,
BangkokThailand -K Pharma Bio-Research, Netherland VIMRx Pharmaceutical Inc. USA
Objective: To determine the maximum tolerated effective oral dose of hypericin which
demonstrates antiviral activity with minimal phototoxic effects in Thai HIV positive volunteers.

Methods: An open -label sequential dose escalation tolerance study which proceeds
sequentially in a group of cfour HIV positive volunteers.The first group (Gr I) will receive an
oral dose of 0.05 mgkg one: daily for 28 days. If no toxicity after 14 days is observed then
the second group will receir a dose of half log higher (0.16 mg/kg) for 28 days.
Subsequent treatment rorups will receive either increases or decreases in dosage of 0.5 log
10 unit until the maximum tolerated dose has been identified.
Results: Group I consists of 2 females and 2 males with HIV positivity confirmed by
Western blots and ELISA with mean age of 25 and mean weight of 57.7 kg. Mean base line
CD4 count in group I was 330 (range 217 -423). All of them have received hypericn at
the dose of 0.05 mg/kg. 3 have completed 28 days treatment and one had received the
drug for only 17 days. Three out of four have mild complaint of photosensitive reaction for
a short duration on exposive to sunlight. So the second group (I male and 3 females) was
decided to give the next higher dose of 0.1 6 mg/kg.The mean age and weight in this group
were 30.75 years and 57.2 kg respectively. Mean CD4 was 199.5 (rang 24 -406).Two developed intolerable symptoms of photosensitivity reaction, so much so the drug is discontinued.The other two developed mild tolerable photosensitivity symptoms, for which the drug
was decreased to 0.05 mg/kg after 7-10 days of treatment. Next group are recruited now
to give the dose of 0.05 mg/kg to confirm the maximum tolerated dose which has maximum antiretroviral effect.
Punnee Pitisuttithum,Vaccine Trial Centre, Faculty of Tropical Medicine, Mahidol University
420/6 Rajvithi Rd., Rajthevi, Bangkok 10400,Thailand Telephone: [phone] Fax [phone] email: [email protected]
Tu.B.2122
TRANSMISSION OF DRUG-RESISTANT HIV-I IN AMSTERDAM,THE NETHERLANDS:
INCIDENCE, PERSISTENCE,AND RELATIVE FITNESS
De Ronde, Anthony*, De Rooij E*, Coutinho RA**, Goudsmit J.*. *Department of Human
Retrovirology Academic Medical Center, University of Amsterdam, the Netherlands;
**Municipal Health Service, Amsterdam, the Netherlands
Objective: To determine the incidence of new infections with drug resistant HIV- I in the
Amsterdam cohorts of homosexual men and intravenous drug users, and to assess the persistence and evolution of drug-resistant viruses and its consequences for therapy
Methods: Serum RNA was isolated of the first antibody or antigen positive sample of
prospectively surveyed participants of the Amsterdam cohort studies who seroconverted in
the years 1992-1995.The sequence of the aminoterminal 250 amino acids of reverse transcriptase was determined by using a nested RT-PCR and automated DNA sequencing.
Results: Drug resistance conferring mutations were found in none of four (0/4) seroconverting intravenous drug users (IVD) and in none of two (0/2) homosexual men (H) in
1992, in I/4 IVD and 0/4 H in 1993, in 0/10 IVD and 0/2 H in 1994, and in 2/5 IVD and I/4
H in 1995.Thus, in 35 seroconversions 4 were found with viruses conferring drug resistance. All four carried zidovudine resistant HIV- I: three had the M4 IL and T2 15Y mutations,
and one the D69N and K70R combination.The infection of I1993 (with M4 IL and T215Y)
was followed for 20 months, and appeared to maintain the 4 I mutation but the 2 15 tyrosine changed to a 50-50 mixture of aspartic acid and serine at 20 months.This indicated
that viruses with a 215 tyrosine in their reverse transcriptase have a reduced relative fitness.
Conclusion: Drug-resistant viruses are being transmitted in the population of intravenous
drug users and homosexual men of the Amsterdam cohort studies with 3 of the 9 tested
new infections in 1995 carrying zidovudine resistance conferring mutations. At least part of
these mutations appear to persist in a significant number of viable virus genomes for some
time following infection.Their persistence implies that effective therapy with anti-viral drugs
should be preceded by testing for the presence of resistance.
Anthony de Ronde, Department of Human Retrovirology Academic Medical Center:
University of Amsterdam, Meibergdreef 15, 1105 AZ Amsterdam, the Netherlands tel 3 1 -
20-5664853; fax [phone]
Tu.B.2123
SUSTAINED BENEFIT AFTER FOUR YEARS OF SAQUINAVIR MONOTHERAPY
Pym AS I, Churchill, Duncan RI, Galpin S I, Kaye S2, Loveday C2, Duncan IB3, Owen S4,
Weber JN. Imperial College School of Medicine (St Mary's), London, UK; 2UCLMS,
London; 3Roche Products Ltd.Welwyn Garden City UK; 4Roche ICRC, Lingolsheim, France.
Objective: To describe clinical progression and changes in surrogate markers in patients on
saquinavir monotherapy over four years.
Methods: 49 HIV-infected patients entered a single-centre phase I/1 study of saquinavir
between August 1991 and August 1992. Patients were drug-naive, asymptomatic or minimally symptomatic, and had CD4 counts below 500 x 106/I. 15 patients continued on
long-term saquinavir 600mg tid as monotherapy for a median of 46 months (range 36 49).
Patients were evaluated clinically by changes in CD4 count, plasma viraemia and by point
mutations in the viral protease gene.
Results: Of the I 5 patients on long-term saquinavir, 2 developed an AIDS diagnosis during
follow-up. Median CD4 count fall from baseline was 80 cells (I 6%) over a median period of
46 months. In 4 patients, regression plots of CD4 count over time were flat or had a positive slope, although 2 of these patients had an L90M mutation for almost 3 years. Median
viral load increase fl-om baseline was 0.53 log. 60% of patients so far studied had an L90M
mutation in the protease gene at 17-35 months.
Conclusions: No other group of patients worldwide have received saqurnavir monotherapy
for such an extended period. Progression of HIV disease in these patients has been slow.
Although this may be in part due to selection bias, the possibility is raised that long terrm
saquinavir therapy is of sustained clinical benefit, despite evidence of genotypic resistance.
Dr D R Churchill, St Mary's Hospital Medical School, Praed St. London W2 I NY UK Tel: 44
t7 I 725 6604 Fax: 44 17 I 725 6604 e-mail: [email protected]
Tu.B.2 124
LONG TERM TREATMENT WITH SAQUINAVIR (INVIRASE), DOES NOT LEAD TO A
SIGNIFICANT REDUCTION IN SENSITIVITY TO MK-639
Esther Race, SM Gilbert, PWTomlinson, L Whittaker A Moffat. R Jupp. IB Duncan NA
Roberts, | Charles Crai. Roche Products Ltd, UK.
Saquinavir (Invirase TM is the first inhibitor of HIV proteinase to be registered for the treatment of HIV infection. Although it has been suggested that treatment with saqunavc may

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