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

12th World AIDS Conference

Abstracts 12264-12268 65

children received the proper treatment for opportunistic infections when it was
needed.
441*/12264 Mortality and health care costs for 6,297 AIDS
patients in California before and after protease
inhibitors
Mi Chen', J. Rains1, G. Hiehlel, R. Hun', J. Colford2. 1Dept. of Health Services,
Office of AIDS 830 S Street, Sacramento, CA, 95814; 2U.C. Berkeley School of
Public Health, Berkeley, CA, USA
Background and Objectives: Clinical trials have demonstrated reductions in
morbidity and mortality among AIDS patients receiving protease inhibitors (PIs).
Clinical trials are conducted on relatively small numbers of patients; those who
volunteer to enroll may differ from the broader population. This study examines
mortality rates and health care costs before and after the introduction of PIs in a
large cohort of AIDS patients.
Methods: We defined a cohort of 6,297 patients alive on 07/01/94 and present
in both Medi-Cal (California's medical public assistance program) records and the
California AIDS Case Registry. For each month beginning in 07/94, we determined
mortality rates and health care costs for these patients.
Results: For selected months:

Month/Year
Number of patients in cohort
Number of patients receiving Pis
Mortality rate (per 100 person-years)
Hospitalization days (per 100 person-days)
Costs/patient/month (US$): Inpatient
Outpatient
Pharmacy
Other

07/94 12/94 07/95 12/95 07/96 12/96

6,297 5,166
0 0
42.8 44.9
2.9 2.6
$727 $726
$472 $394
$543 $557
$217 $187
$1,959 $1,864

4,095 3,538 2,995 2,787
0 75 1,151 1,374
31.2 34.5 17.8 10.6
2.3 1.8 1.5 1.0
$521 $468 $324 $156
$390 $329 $294 $198
$600 $580 $800 $779
$167 $131 $166 $128
$1,678 $1,508 $1,584 $1,261

Total

Conclusions: Prior to the availability of PIs, mortality rates and health care
costs were declining for California AIDS patients receiving public assistance.
Coincident with the explosion in the use of Pi's in 1996, the decline became
more dramatic. Our current research employs individual level analysis to examine
the extent to which PIs (and other new therapies) were responsible for these
improvements.
S12265 Clinical trial comparing a ritonavir-saquinavir versus an
indinavir containing triple combination regimen
Robert Colebunders', P. Desmet1, A. De Roo', J. Boelaert2, P. Simons3,
B. Vandercam4. 1Institute of Tropical Medicine, Nationalestraat, Antwerp; 2St
Janziekenhuis, Brugge; 3VUB-ARC, Brussels; 4UCL ST-LUC, Brussels, Belgium
Objective: To compare the efficacy and tolerance of ritonavir-saquinavir (RITSAQ) + 1 nucleoside analogue reverse transcriptase inhibitor (NRTI) with indinavir
(IND) + 2 NRTIs.
Methods: An open randomised multicentre clinical trial among patients with
HIV infection meeting the Belgian criteria for starting with a protease inhibitor.
Antiretroviral naive patients received either RIT (400 mg bid) + SAQ (400 mg bid)
+ D4T (30-40 mg bid) or IND (800 mg bid) + D4T (30-40 mg bid) + 3TC (150
mg bid). Efficacy parameters: viral load (VL), CD4 cells, AIDS events. Intention
to treat analysis of the first 60 patients.
Results: So far no significant differences were observed concerning laboratory
or clinical outcome parameters.

Methods: Prospective multicentre cohort of 451 patients started on PI between
March and May 1996, in 13 French AIDS centers. Clinical and therapeutic data,
CD4+ cell counts, plasma HIV-RNA were collected at day 0 of PI, Month (M) 1,
M3 and every 3M thereafter. Proportional hazards models were used to estimate
the independent effect of potential prognostic factors.
Results: At entry, 63% had AIDS, median CD4 cell count was 22/mm3 (range
= 0-444), median plasma HIV-RNA was 5.1 loglo copies/ml (range = 2.4-6.7),
mean previous antiretroviral Rx was 33 M (92% non naive). The PI used were:
ritonavir (n = 199), indinavir (n = 149), saquinavir (n = 103). The mean follow-up
time was 9 months. The cumulative probability at one year of developing a new
AIDS-defining event was 21%, it was 9% for death, 44% for AE and 47% for
PI interruption. AIDS incidence was associated with: AIDS prior to PI (RR = 3.4
vs non AIDS, p < 0.001) and CD4+ (RR = 1.1 for each 10-cells decrease, p =
0.003). Incidence of AE was associated with AIDS prior to PI (RR = 1.4 vs non
AIDS, p = 0.04), CD4+ < 20/mm3 (RR = 1.8 vs CD4 > 20, p = 0.001), indinavir
(RR = 2.6 vs saquinavir, p = 0.001), or ritonavir (RR = 2.9 vs saquinavir, p <
0.001). Interruption was more frequent when saquinavir (70%) or ritonavir (51%)
was prescribed as first PI than indinavir (27%), (p < 0.001).
Conclusion: In these pts with advanced immunodeficiency started on PI, clinical stage and CD4+ cell count remain the most prognostic informations regarding
the progression of disease, while plasma HIV RNA is not a major prognostic
marker. The high rate of AE and of interruption of PI has to be balanced with the
favorable clinical effect and the high survival rate, even at this stage of disease.
292*/12267 Long-term evaluation of
saquinavir-soft-gel-capsule or indinavir as part of
combination triple therapy (CHEESE study)
Charles A.B. Boucher, Jan Borleffs. On behalf of the CHEESE Study Group;
University Hospital Utrecht, Dep. Virology, Heidelberg Laan 100, 3584 CX UTRE
CHT Netherlands
Objectives: Saquinavir-soft-gel-capsule (SGV-SGC) provides 10 times greater
plasma levels of saquinavir vs. hard-capsule formulation. In this study the efficacy
and safety of SQV-SGC given in combination with AZT and 3TC is evaluated and
compared with those of triple therapy with indinavir (IDV), AZT and 3TC.
Methods: Antiretroviral naive (or previous AZT < 12 months) HIV infected
patients with CD4 cells <500/mm3, HIV-RNA load >10.000 copies/mL (Roche
Amplicor), and/or HIV-related symptoms were randomized for either SQV-SGC
1200 mg tid, AZT 200 mg tid and 3TC 150 mg bid ("SQV-SGC group") or IDV
800 mg tid, AZT 200 mg tid and 3TC 150 mg bid ("IDV group").
Results: During 1997 62 patients have been enrolled. Median baseline viral
load and CD4 cell count are 4.94 copies/mL and 301 cells/mm3 in the SQV-SGC
group. In the IDV group these figures are 4.97 copies/mL, and 337 cells/mm3. At
present, follow up data up to week 24 after the start of treatment are available.
Virological response is equal in both groups. In all patients viral load became
undetectable within 8-12 weeks. By applying an ultrasensitive assay (cut off
point of 20 copies/mL), about 50% of the patients has undetectable viral load,
irrespective the treatment. Interestingly, CD4 cell increase appears to be more
pronounced in the SQV-SGC group than in the IDV group. At weeks 12 and
16 median increases are, respectively, 139 and 163 cells/mm3 in the SQV-SGC
group; in the IDV group these figures are, respectively, 69 and 12 cells/mm3 (p <
0.05). Till now no major drug related adverse events have occurred.
Conclusions: Both treatment regimens have potent antiretroviral activity. A
possible better immunological response in favor of the SQV-SGC containing
triple therapy is of great interest and will be analyzed by additional immunology
research focussing on subtyping of T lymphocytes. This will be done during the
forthcoming months.
S12268 Can prophylaxis for PCP and cerebral toxoplasmosis be
safely discontinued in HIV-infected patients successfully
treated with HAART? The EuroSIDA Study
Peter Reiss1, G.J. Weverling1, A. Mocroft2, B. Ledergerber3, J.D. Lundgren4,
A. d'Arminio Monforte5, T.L. Benfield4. INatec Academic Medical Centre, F5. 166
Meibergdreef 9 1105 AZ, Amsterdam, Netherlands; 2Dept. of Primary Care and
Population Sciences Royal Free Hospital, London, United Kingdom; 3Div. of
Infect. Dis. University Hospital ZOrich, ZOrich, Switzerland; 4]Div. of Infect. Dis
Mvdovre Hospital, Copenhagen, Denmark; 5Clinica Malattie Infettive Ospedale L
Sacco, Milan, Italy
Background: The proportion of patients who stop primary or secondary prophylaxis for HIV-related opportunistic infections is currently unkown; of particular
interest are those patients who discontinue following sustained rises in CD4 cell
counts, following the initiation of highly active antiretroviral therapy (HAART).
Methods: The incidence of PCP and cerebral toxoplasmosis (both the first
occurrence and the first recurrence) was analysed after the permanent discontinuation of primary or secondary prophylaxis for these infections within the
EuroSIDA study. This is an ongoing prospective pan-European cohort study of
4,491 HIV-infected patients.

Results: The median date of last follow-up was June 1997, by this date 3275
patients (72.9%) had ever received prophylaxis and 990 patients (22.0%) had
permanently discontinued these treatments during follow-up. Among those patients who stopped treatment, the median duration of prophylaxis was 13 months
(IQR 7-22) and the most common drug used trimethoprim-sulfamethoxazole (n =
603, 60.9%). The median CD4 cell count at starting prophylaxis was 78 cells/mm3
(IQR 20-176) and at stopping was 50 cells/mm3 (IQR 10-201). In 68 patients

Baseline
Mean Mean
CD4 VL
IND 251 (28) 4.7 (28)
RIT-SAQ 187 (32) 4.8 (32)

Month 1
Mean Mean
CD4 \ VL \
105 (27) 1.9(22)
70(30) 1.5(27)

Month 3 Month 6
Mean Mean Mean Mean
CD4 \ VL \ CD4 \ VL \
137 (26) 1.7(25) 112(12) 1.3(12)
69(29) 1.9(29) 83(14) 1.6(15)

(N) = number of patients, VL in log copies/mL
Both treatment regimens were relatively well tolerated, the main side effect of
the RIT-SAQ association was diarrhoea, the main complaint of patients treated
with IND was the difficulty of taking the drugs 3x a day on an empty stomach.
Conclusions: Triple combination therapies including RIT-SAQ or IND are effective and well tolerated antiretroviral treatment regimens. Only when all patients
have been enrolled in the study and with longer follow-up we will be able to
determine whether one of the treatment arms is clinically more beneficial.
440*/ 12266 Clinical progression and adverse events in a
cohort of HIV-infected patients with advanced
immunodeficiency started on protease inhibitors
(PI) in March 1996
Genevieve Chene1, C. Katlama2, J.P. Coulaud3, R. Lasalle', J.M. Ragnaud4,
C. Leport3. Appit Study Group; 'Inserm Unit 330, 146 Rue Leo-Saignat 33076,
Bordeaux; 2Hopital Pitie Salpetriere, Paris; 3Hopital Bichat Claude Bernard,
Paris; 4 Hopital Pellegrin, Bordeaux, France
Objective: To identify prognostic factors associated with the incidence of new
AIDS-related clinical events and adverse events (AE) in HIV-infected patients
(pts) with advanced immunodeficiency started on PI.