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

Tu.B.414 - Tu.B.522

Tuesday, July 9, 1996

malaria treatment regimens:. I) a 2-dose SP regimen (SP/SP); 2) a monthly SP regimen; and
3) a fever case management (CM) approach.The prevalence of placental malaria infection,
incidence of low birth weight (LBW), and incidence of adverse drug reactions (ADRs)
among HIV(+) were compared to that among HIV(-) women.
Results: Among 739 delivered women, the prevalence of placental parasitemia was highest
in the CM group (29%) and significantly lower in the SP/SP group (I 1%, p< 10-5) and the
monthly SP group (7%, p< 10- ). However when stratified by HIV serostatus (HIIV seroprevalence = 32%), the prevalence of placental parasitemia among HIV(+) women was
similar in the CM group (45%) compared to the SP/SP group (32%, p=0.32) but was significantly lower in the monthly-SP group (I 1%, p=0.02). LBW was most common in the CM
group (21%) and significantly less in the SP/SP group (10%, p-0.002) and the monthly-SP
group (10%, p=0.002); among HIV(+) women, LBW in the CM group (16%) was not significantly different frnm that in the SP/SP group ( 0%, p-0.24) or the monthly-SP group (7%,
p=0.09). A mild skin rash in 2.4% of women was the most commonly observed ADR.
Conclusions: Among HIV(-) women, regimens using intermittent SP had a similar and
marked impact in reducing the incidence of placental par-asitemia and LBW. Among HIV(+)
pregnant women, SP was well tolerated but had less efficacy, especially with less frequent
dosing. Reasons for the decreased efficacy of SP and alternate stategies to reduce placental
malaria infectiorn and associated LBW among HIV(+) women require further investigation.
Dr Bernard L. Nahlen. CDC Unit/CRC, Kenya Medical Research Institute, RO. Box 54840
Nairobi, Kenya Phone:[phone]-6142; Fax: [phone]:
Email: (lend c/o R. Steketee) at ri (a)cidhiv I.em.cdc.gov
Tu.B.414
COTRIMOXAZOLE (TMP-SMX) DESENSITIZATION USING ADJUNCTIVE STEROID
THERAPY IN HIV/AIDS PATIENTS
Beardsell, An D*, Coker K*,Woodfall B**, Conway B***. *Pharmacy, St.Paul's Hospital,
Vancouver, B.C., Canada;*Family Practice, St.Paul's Hospital,Vancouver, B.C., Canada;***B.C.
Centre for Excellence in HIV/AIDS,Vancouver, B.C., Canada.
Objectives: To determine efficacy safety and cost effectiveness of a protocol using adjunctive prednisone therapy with TMP-SMX liquid for desensitizing HIV positive patients previously allergic to TMP-SMX.
Methods: A protocol combining high risk exclusion criteria, increasing doses of TMP-SMX
suspension and tapering doses of prednisone was developed. A non-prednisone arm was
not attempted at this time due to current community practice. In a community practicebased setting, HIV positive patients who had previously experienced mild hypersensitivity
reactions to TMP-SMX were recruited. Prednisone 40mrg was started on the Sunday then
TMP-SMX 5rnl suspension was started the next day in the physician's office where the
patient was monitored for I hourThe TMP SMX was gradually increased over 10 days to
20ml daily and the prednisone was tapered off over 20 days. Physician contact was required
at least every 2 days with follow up visits at 30, 60 and 90 days post-initiation. Successful
desensitization was defined as ongoingTMP-SMX therapy without prednisone at 30 days
post-initiation with follow up review at 60 and 90 days. Pharmacoeconomic analysis was
based on direct health care costs for the drugs and administration comparing the protocol
to maintenance aerosolized pentamidine.The "break even" point, with respect to direct
costs, was calculated.
Results: Thirty-six patients entered the trial. At the 30-day followup, 28/36 (77.8%) patients
were successfully taking TMP-SMX. At the 60 and 90 day followups, I more patient withdrew
and I patient was lost to followup. All failures were easily managed with adjunctive therapy
and withdrawal ofTMP SMX.There was no predictive factor for protocol failureThe direct
cost "break even point was calculated to be 28% successful desensitization to TMP-SMX.
Conclusions: Pnerrumncystis cirnnii pneumonia (PCP) continues to be a major cause of mrnorbidity and mortality HIV positive patients.TMP-SMX s generally felt to be the drug of
choice for PCP prophylaxis but the high incidence ofTMP-SMX intolerance in this population hinders its use. This desensitizing protocol is easy for patients to follow, is inexpensive
and shows good success (77.8%). Failures were easily managed without any lasting sequelae.
Prednisone use did not present any problems to patients and appears to be helpful in the
desensitization process although a comparative trial is required to confirm this. Optimal
PCP prophylaxis results in not only direct health care cost savings but, more importantly, in
indirect health care and social costs due to longer disease-free time and improved survival.
Ann D. Beardsell, Pharmacy Department, St.Paul's Hospital, 1081 Burrard Street,Vancouver,
B.C., Canada V6Z I Y6 Tel:(604)63 I-5 15I FAX:[phone]
Tu.B.415
COST-EFFECTIVENESS OF PREVENTING AIDS-RELATED OPPORTUNISTIC
INFECTIONS
Kenneth A. Freedberg, JL Alpher: GR Seage, E Losina, MC Weinstein, DE Craven, AD Paltiel
Boston City Hospital. Boston University School of Medicine, and Harvard School of Public
Health, Boston, MA, USA.
Objectives: To determine the cost-effectiveness of strategies to prevent the major opportunistic infections (Ol's) associated with AIDS.
Methods: We developed a decision analytic simulation model of advanced HIV disease to
project costs, clinical outcomes including primary cases of Ol's prevented (I cases prevented), life expectancy and cost-effectiveness (C-E) in dollars per year of life saved ($/YLS).We
utilized natural history data from the Multicenter AIDS Cohort Study; efficacy and toxicity
data from controlled clinical trhals of prophylaxis for Pneumocystis corinii Pneumonia (PCP),
toxoplasmosis, Mycobrcterium irvium complex (MAC), fungal infections, and cytomegalovirus
(CMV); and cost data from the national AIDS Cost and Services Utilization Survey The
model permitted timing of prophylaxis to be stratified by CD4 count into four groups (>
200/ms.O13200mm. 5 I- I00/ m3 and <50/rm3), and allowed combinations of prophylax s, crossover to second arsd third-line agents for toxicity and consideration of resistance and quality of life. Input data included the monthly risk of dropping from one CD4
stratum to another (2.5%-12.9%), prophylaxis efficacy (50%-95%), and yearly prophylaxis
costs ($i2 $15,600).
Results: For a cohort of if1,000 patients beginning with CD4 counts > 200/rm3 and
recenvirg zidovudinc', esults were

Strategy
Medication
CD4 Stratum
I~ Cases Prevented
Total Cost/person
Life Expect /person
C-E ($/YLS)

Nc Prophylaxis PCP/Toxo MAC
TMP-SrX Rifbuti n
<200/mm3 /
1,519 120,'0 $ 54.235 $ 59.1 0
4 689 4.730 yrrv6 r
Saves $ $210600

Fungal CMV
Fluc n tz 'le S,, c -ov
39 7
$ 19.7=6 $ t,.023
S$4O 3 90.20

Sensitivity analysis showed that-while lower drug costs improved cost-effectiveness, a 10%
decrease in the risk of CD4 decline increased life expectancy without prophylaxis to 5.003
years, a greater impact than any OI prophylaxis.
Conclusions: Strategies for preventing Ol's vary widely in cost-effectiveness. Prophylaxis for
PCP and toxo saves money and has the greatest impact on life expectancy These results
can be used in sett ng priorities for HIV therapy and O prophylaxis.
Kenneth A. Freedberg, MD, MSc Boston City Hospital, 91 E. Concord St. 2nd F oor, Boston
MA 02118 USA phone: [phone] fax: [phone] email: [email protected]
Tu.B.520
ETHICAL ISSUES OF COMPASSIONATE ARM IN A CLINICAL TRIAL
Seaton, D.*, Roy D..**, Ruedy J.***.* HIV + Member of NERC, Canadian HIV Trials
Network,Vancouver, Canada; ** Director, Centre for Bioethics, IRCM, Montreal, Canada;
***Dean of Medicine, Dalhousie University Halifax, Canada
Issue: Does the lack of a compassionate release program for a new HIV drug renderi a randomized controlled trial unethical?
Project: The National Ethics Review Committee (NERC) asked if it should withhold
approval of a clinical trial on the basis that unrestricted compassionate access (like parallel
track) was not offered as part of the randomized access clinical trial. NERC was told that a
sufficient quantity of Saquinavir was not available. Patients who wished to use the experimental drug might be "forced" into the randomized clinical trial, which would vi olate the
principle of freely given consent. NERC listened to HIV + community groups for guidance.
Results: Compassicnate release program is ethically essential, provided that: there is initial
evidence of safety: compassionate release will not prevent chinical study of the drug; the
program offers fair access. For Saquinavic NERC adopted the HIV + group's method of
allocating the drug in the compassionate arm, based on the principle of sickest frst. Four
months later NERC listened to the group's assessment of how this worked, and heard criticism of the implementation, but not the main ethical position. Researchers remain concerned that compassionate release will seriously delay or cripple a clinical trial, preventing
knowledge about the new drug's harm or benefit, and ask if that is ethical.
Lessons Learned: Compassionate release programs are an ethically required part of a controlled clinical trial Limitations on the compassionate release require collaboration between
the drug company researchers and people with HIV disease.The Ethics Review Board
should ensure that people with HIV disease have a voice.There should be monitoring and
evaluation of the implementation of compassionate access as a part of the protocol.
D. Seaton, 3132 Madle Street,Vancouve, BC, Canada,V6J 4X3.Tel.: [phone]
Fax: [phone] email: [email protected]
Tu.B.52 I
PATIENT INITIATED RESEARCH;JEFF GETTY, PROJECT INFORM &THE BABOON
BONE MARROW TRANSPLANT
Thorne, Bill, Getty J. Sharp M, Parks V, Mahon D. ACT UP Golden Gate, San Francisco, CA, USA
Issue: Scientific research is a complicated. lengthy process. Patients with advanced AIDS are
offered few options by the research establishment. Fifty thousand late stage AIDS patients
die each year Promising research which coul d lead to treatments and potentially a cure can
be stifled by bureaucracies and fear of theoretical risks.
Project: Jeff Getty, a late stage AIDS patient and an AIDS activist of many years with ACT
UP Golden Gate, followed the animal model research of Dr Suzanne Ilstead of the
University of Pittsburgh which had been presented at a Project Inform Think Tank on
Immunology Dr: Ilistead's work centered on engrafting immune systems from one species
into another. Two years ago he began discussions with researchers, Institutional Review
Boards,The University of California, and the Food and Drug Administration regarding
Xenogeneic Baboon Bone Marrow Transplant. His involvement in the project continued
and he became personally interested in becoming the subject of the research about I and
1/2 years before the procedure. By employing his skills and contacts as an AIDS activist
Getty was able to speed up the process by several years. Use of contacts with Media,
researchers, community organizations, ethicists, and other AIDS patients enabled him to
accomplish this.
Results: Jeff Getty received the transplant on I 2-15-95 and continues to do well six weeks
later. His T-cell level is higher than before the procedure, his energy enthusiasm and commitment remain high. The safety issue of whether this has harmed Jeff appears to be
resolved; no evidence of harm to the subject has been found.
Lessons Learned: Aggressive patient involvement from the earliest stages of scientific investigation can aid cutting edge research; regulatory obstacles can be overcome and the
research process can be expedited. Patients can help move forward life saving, groundbreaking approaches which benefit AIDS research, basic science and all people iv ng with
AIDS and other life threatening diseases. Hypothetical fears of unknown risks must not
stop important medical research.
BThorne, 1460 Clayton St, San Francisco, CA. 94114 USA Tel/Fax: 4 5-626-9r42
E-mail: [email protected]
Tu.B.522
THE PERILS OF VISIT-DRIVEN ENDPOINTS IN ANTIRETROVIRAL TRIALS
Hogan Carlton Ht., Hodges JSt. Mugglin At, Peterson PM-, Abrams, D1, Saravolatz Li. the Terry
Beirn Community Programs for Clinical Research on AIDS. Division of Biostatisthc ners ty
of Minnesota University of California, San Francisco Medical School ( Henry Ford Hospital
Objectives: Powerful laboratory assays are increasingly important in AIDS care and
research. Measures such as CD4+ lymphocyte counts and HIV viral load (QC PtR oR
bDNA) have been used in lieu of clinical outcomes to approve new ant retroviral ther apies.
Debate continues as to whether treatment-induced hanges in these surrogates actua y

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