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

Mo.B.1 129 - Mo.B.I 133

Monday, July 8, 1996

Conclusions: A significant reduction in VL (>1.4 log) was achieved in 37.5% of patients at a
3 month interval.The CD4 cell counts and percentages increased slightly during this period.
The long term follow up of this cohort will provide valuable information to determine
which surrogate marker (VL or CD4) will be more useful for predicting clinical outcome.
Angela lbinez, Retrovirology Lab. IRSI-Caixa. Hospital Universitar Germans Trias i Fuojol.
08916, Badalona, Spain TEL [phone] EXT 430 or 426 FAX. [phone]
Mo.B. I 129
SAFETY AND EFFICACY OF ZALCITABINE (ddC) AND ZIDOVUDINE (ZDV)
COMBINATION IN HIV-POSITIVE PERSONS WITH CD4 CELL COUNTS _300/MM3:
AN INTERNATION OPEN LABEL EVALUATION (ROCHE STUDY M50002).
WalkeriM, Moyle GJ#, Harri Rs R*,Warburg M*. on behalf of the M50002 co-ordinating
committee. F Hoffmann La Roche, Basel Switzerland; *Parexel International UK and USA;:
#Kobler Centre, UK
Objective.This study was initiated prior to the commercial availability of ddC to both provide ddc in countries where access was limited (Spain, Italy, Mexico, South America,
Benelux) and to collect well-controlled safety data in populations in which ddC had not
previously been investigated. Although not the primary objective of the study assessment
was made of patient outcome, CD4 count and Karnofsky index.
Methodology. An open label, single arm, multicentre study of combination ZDV (600mg/
day in divided doses) with ddC (0.75m tid) in HIV- I positive adult patients with advanced
disease and CD4 cell counts <300/mm. Both patients commencing therapy and patients
previously commenced on ZDV mnonotherapy were included in the study
Results. A total of 561 patients entered the study with 353 patients completing 12 months
of treatment. In the 492 ZDV experienced patients the mean duration of prior treatment
was 18.5 months (median 16 months, range 1-80 months). Adverse events (HIV or drugrelated) were the cause of treatment discontinuation in 60 of 218 (27.5%) discontinuations.
At least I adverse event was experienced by 76.6% of patients during the study with 53.8%
being assessed by investigators as unrelated to study drugs. Peripheral neuropathy (PN) was
reported in 59 patients (10.9%), being more common in patients with baseline CD4
<100/mm3 (16. 1%) than those with higher CD4 cell counts (8.9%).The mean time to
development of PN was 126 days (range 6-337). Neutropenia and anaemia were also
more common in patients with lower CD4 counts, being reported in 22.7% and 24.7% of
those with baseline CD4 <100/mm3 and 10. I% and 11.5% of those > 100 cells/mm3,
respectively Similarly a history of an AIDS defining event at baseline was associated with
higher rates of PN, neutropenia and anaemia. Median CD4 cell counts rose during the
study from 141.5/mm3 to a peak of 174/mm3 at week 12 and 148/mm3 at 12 months.
Additional safety and efficacy data will be presented.
Conclusions. Zalcitabine can be safely administered with ZDV in persons with advanced
HIV infection both as initial therapy and in ZDV experienced patients. Both safety and efficacy appear maximised by use in persons with CD4> 100 and no prior AIDS-defining
events.
Dr Marianne Walker F Hoffmanr La Roche, Basel CH 4002 Switzerland.
FAX [phone] Tel [phone]
Mo.B.1 I 130
ZIDOVUDINE PROPHYLAXIS FOR THE PREVENTION OF HIV VERTICAL
TRANSMISSION IN THE HOSPITAL CLINIC OF BARCELONA
Martinez Tejada B*, Coll O*, Zamora L*, Fortuny C*, Ravenau W*, Lonca M*, L6pez A*. *
Hospital Clinic of Barcelona, Spain.
Objective: To assess the effic icy.eval uate the acceptability and monitor the compliance and
side effects of zidovudine (ZDV) prophylaxis in HIV infected pregnant women.
Methods: Since June 1994, all HIV infected pregnant women have been offered ZDV prophylaxis for the prevention of HIV vertical transmission. All women were treated according
to ACT C076 guideline, and most of the patients met ACTG 076 criteria (17/25, 68%).
Newborn infectious status was evaluated with PCR at 0, 3, and 6 months of age. Between
October I 1994 and January 20 1996, 26 pregnant women identified as HIV infected
(.5%) (2 seroconverted during pregnancy) delivered in our hospital. One of them was
identified after delivery and could not be reached after hospital discharge.The mean age of
the women was 28. I -+ 4 years. Seventeen women acquired HIV from contaminated needles (I 6 IVDU) and 8 acquired the virus through sexual contact. Clinical stage of HIV infection at delivery was as follows: A 17; B 7; and C- I. Seven patients were treated prior to gestation with ZDVThe mean gestational age at delivery was 38 weeks (range 31 I4 1).Vaginal
deliveries occurred in 24 cases and cesarean section in 2 cases.
Results: Sixteen women (61.5%) received ZDV during pregnancyThe mean gestational age
upon initiation of treatment was 21.6 weeks and the mean duration was 16.9 weeks.
Nineteen women (73. I%) were treated during labor (mean 317 min.), most received ZDV
before rupture of membranes.Twenty one newborns (80.7%) were treated with ZDV
Overall 13 mother infant pairs (50%o) received treatment at all three time points, and only 4
pairs did not receive treatment with ZDV Only one patient refused treatment with ZDV.
ZDV was tolerated well.Two women were transfused for severe anemia, and I mother discontinued therapy for GI symptoms prior to completing it. Of the evaluable newborns (> 6
months), only one (6.2%) has been shown to be infected (historical transmission rate: 20%).
Conclusions: ZDV is well accepted and tolerated by HIV infected women and is applicable
in a clinical setting Although these results are preliminary, ZDV seems to clearly reduce
HIV I vertical transmission
B.Martsinez-T-elada. 5620 Hobasit St., Apt#9, Pittsburgh,. PA I1521I7, USA
Teleph n 4 142104139 FAX [phone] email: teada+@pitt, edU
Mo.B.I 131
LAMIVUDINE (3TC) THERAPY FOR PATIENTS WITH ADVANCED AIDS AND < 50
CD4 CELLS
Sha BE, Pottage Jr JC. Benson CA, Agnoli MM, Haas A, Kessler HA. Rush Medical College,
Chicaigo, IL, USA
Objective: To characterize the clinical and virologic response and tolerability of 3TC in
patients with adv.nced AIDS.
Methods: From March I995 to December I995 patients with AIDS and CD4 < 50
cells/mn3 were enrolled, evaluated, and treated according to the 3TC compassionate treat
ment IND protocol. Data collected included baseline demographic character istics and
monthly targeted symptoms, weight, new HIV-related events, surwva, adverse reactons
CBC, chem panel, and amylase. Quarterly CD4 counts and quant tative HIV I RNA levels
were obtained.
Results: A total of 35 patients (30 men, 5 women) were enrolled The median ase was 40.5
yrs. Patients had been diagnosed with HIV infection a median of 62.5 months ( 14- 25) nd
had received antiretroviral therapy a median of 47 months ( I- 112) prior to study entr
The median baseline CD4 count was 13 cells/mrm3 (0-48) Median entry Karnofskyscore
was 90 (60-100). Patients received a median of 5.5 months of 3TC (- I0); 26 (74%)
received concurrent ZDV No improvement in CD4 cell count was noted. Cinicai improve
ment, defined as weight gain or improved Karnofsky score, was noted in 22 of 35 paients.
A total of 37 new or progression of prior HIV-related events occurred in 23 f (66%) pa ients
a median (Kaplan-Meier) of 3 months from entry These included PCP (4), CMV retints (3),
Kaposi's Sarcoma (2), disseminated MAC (2), wasting (2), oral thrush (7), penita HSV (4),
and cervical/vaginal dysplasia (2).Two patients have died. Adverse re actions occ urred in 12
patients (only one of which required discontinuation of drug) and included peripheral neu
ropathy (6), gastrointestinal intolerance (3), and pancreatitis (2). HIV-I RNA levels will be
presented.
Conclusions: Although HIV-related conditions continue to develop in patients with
advanced AIDS receiving salvage therapy with 3TC ~ ZDV, clinica limproverment does occur
and therapy is reasonably well tolerated.
Beverly E. Sha, M.D. Section of Infectious Disease Rush Medical College, 600 S. Paulina, Sute
143, Chicago, IL 60612
Mo.B. I 132
A PHASE I TRIAL OF HIV PROTEASE INHIBITOR KNI-272 IN PATIENTS WITH AIDS
OR SYMPTOMATIC HIV INFECTION
Humphrey RW*, Nguyen B-Y*,Wyvill KM*, Shay LE*, Lietzau J*, Ueno T*, Fukasaiwa T'
Hayashi H**, Mitsuya H*, Yarchoan, Robert*. *National Cancer Institute, Bethesda, MD,.
USA; **Japan Energy Corp.,Tokyo, Japan
Objectives: KNI-272, a novel transition-state mimetic tripeptide HIV protease inhibitor, was
previously shown to have potent activity against HIV in vitro at concentrations of.008 - 2
pM and to have reasonable oral bioavailibility in animals (Kageyama et al, AAC I1994; 38:
I 107).The present study was undertaken to study its pharmacokinetics in humans, its toxi city profile, and its activity against HIV
Methods: Patients (pts) with AIDS or symptomatic HIV infection and 100-400 CD4
cells/mm3 were eligible. In an initial phase, 6 pts received a 3 day course to study pharmacokinetics.The second phase was a dose escalating study of KNI-272 administered orally for
4 - I12 wks. Groups of pts received doses ranging from 2 - 14 rmg/kg orally every 6 hr
Parameters followed include quantitative RNA PCR, and CDL count
Results: Results from the 6 pts entered onto the initial phase revealed that KNI-272 had an
oral bioavailibility of 25-35%.The Cmax of pts receiving a 4 mg/kg dose was 3 5~0.47 pM.
34 pts have now entered the second phase of the study Using the initial dosing schedule,
dose-limiting transient hepatic transaminase elevations were observed in pts receiving 6.6
mg/kg doses.This was partially ameliorated by escalating to the target KNI-272 dose over 4
wks, and pts are now being entered on the 14 mg/kg dose schedule. Other possible toxicties observed included a cutaneous eruption in one pt and m Id esophageal burnin at the
higher doses.There were no clear trends in the RNA PCR rneasurements in pts receiving
doses up to 4 mg/kg.There was a transient but non-significant i ncrese in the CD4 count at
4 weeks in pts receiving the 6.6 mg/kg dose. To date, 7 of 9 evaluable pts on the 6.6 a7/kg
dose schedule have had decreases in HIV virions by RNA PCR at the end of dosing or i
soon thereafter as compared to baseline; the average drop in HIV particle number it this
dose was 0.27 log10 (p <0.05).Also, 2 of t vauable ps to date on the 3 evluablpsteot0 mg/kg
dose schedule have had a decrease in the HIV viral load.
Conclusion: KNI-272 has reasonable oral bioavailability. Preliminary results suggest that aniHIV activity (assessed by RNA PCR) may be observed, but additional results wil be needed
for confirmation of this finding.The trial is ongoing, and updated results will be presented.
Dr RobertYarchoan Bldg. I0, Rm. I12N226, NIH, Bethesda MD 20892 -1906 USA
Tel: [phone] Fax [phone]
Mo.B.I 133
PERSISTENCE OF CD4 LYMPHOCYTE INCREASES AT 18 MONTHS OF TREATMENT
WITH LAMIVUDINE
Wiewora, Ronald I, Landvay K. Stratogen of the Palm Beaches, Palm Beach Gardens, FL, USA
Objective: Lamivudine has been shown to increase CD4 counts.This increase has been
shown to persist for at least 12 months.We sought to determine if this increase persists for
18 months.
Method: Seventy-seven patients in a community practice setting had received lamevudine
since it became available through compassionate use programs.Twenty-two people (1 7
men and 5 women) took the drug for at least 18 months. CDt counts were obtained at six
month intervals.
Results:The average increase in CD4 counts in all patients receiwng iamudine was 34
cells. When lamivudine was combined with zidovudine, the average CD4 increase was 77
cells.Those people with a baseline CD4 count above 200 had an average CD4 increase of
59 cells. Finally those who took combination lamivudine/zidovudine and had a basel ne CD4
count above 200 had an average CD4 increase of 93 cells.
Conclusion: Lamivudine induced a persistent increase in CD4 cel s when masuridrt
menths.The most striking increases were in people wbo had a hase no CD4 ount bovye
200 and used combination antivirals.
RJ Wiewora, 3345 Burns Rd, #302, Palm Beach Gardens, FL, USA. 33) 10
Phone [phone] Fax [phone] II

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