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

12th World AIDS Conference

Abstracts 22393-22397 343

Conclusions: The advanced HIV infection, implies high economic costs, however the recent introduction of the new antiviral drugs, in spite of a not optimum
fulfillment of treatments and without increasing significantly the global costs, it
has improved the quality of life of the patient advanced HIV.

223931

Plasma viral load reduction in an open-label randomized
study of Rescriptor in combination with zidovudine and
two dose levels of indinavir compared to zidovudine,
lamivudine, and indinavir in HIV-1 infected individuals

Susie Sargent1, L.K. Wathen2, M.F. Para3, S.R. Cox2, W.W. Freimuth2,
C.A. Teugh2, D.C. Huang2. Adult Special Care Clinic Suite 5B01, 880 Madison
Avenue Memphis TN 38103; 2Pharmacia and Upjohn, Kalamazoo, MI; 3Ohio
State University Hospitals, Columbus, OH, USA
Objective: To compare the safety and efficacy of the three triple drug regimens,
Rescriptor + indinavir (400 mg q8h) + zidovudine, Rescriptor + indinavir (600 mg
q8h) + zidovudine, and zidovudine + lamivudine + indinavir (800 mg q8h) in the
treatment of HIV-1 infected individuals.
Design: Open-label, randomized
Methods: The safety and efficacy of three triple drug regimens, Rescriptor
+ indinavir (400 mg q8h) + zidovudine, Rescriptor + indinavir (600 mg q8h) +
zidovudine, or zidovudine + lamivudine + indinavir (800 mg q8h) was investigated
in HIV-1 infected individuals (n = 13) who were NNRTI, PI and 3TC naive. Prior
to therapy, the mean CD4 cell count was 377 cells/mm3 (range 142-675) and the
mean plasma viral burden was 5.3 log copies/mL.
Results: After 4 weeks on therapy, the groups treated with the Rescriptor +
indinavir (600 mg q8h) + zidovudine, Rescriptor + indinavir (400 mg q8h) + zidovudine, and zidovudine + lamivudine + indinavir combinations experienced 2.2,
2.6 and 1.1 log decreases in viral burden respectively. In the first two months of
therapy, these treatment regimens were well tolerated with no reported incidence
of nephrolithiasis. Pharmacokinetic data for both delavirdine and indinavir will be
presented along with available updated data from this on-going 24 week study.
Conclusion: All three treatment regimens provided over a 1 log decrease in
viral burden within 1 month of initiating therapy. The interaction of these drugs
has not demonstrated any significant adverse events to date.
22394 Changing patterns in use of antiretroviral combination
therapy are the most likely cause of falling AIDS cases
and deaths in Scotland
Gwen Allardice1, J.J. McMenamin2, G. Codere1, T. Parpia3, L. Shaw1,
D.J. Goldberg1, W. Smyth1. 1SCIEH, Clifton House, Clifton Place Glasgow, G3
7LN; 2Glasgow University Glasgow; 3Napier University Edinburgh, Scotland
Background: We examine the changing use of antiretroviral therapy in Scotland at a population level using surveillance data on HIV+ people undergoing
immunological monitoring in Scotland between 1993-1997.
Methods: The Scottish Centre for Infection and Environmental Health (SCIEH)
co-ordinates a surveillance scheme designed to capture both immunological
and treatment data on HIV+ people in Scotland. This scheme is estimated to
cover 90% of all HIV+ people being monitored in Scotland. Data collected includes details of antiretrovirals taken in the month preceding the test request and
immunological markers such as CD4 count.
Results: The table shows the number of people monitored each year, the
number and proportion of them who subsequently developed AIDS or died that
same year, and the maximum therapy received during that year.

therapy from 44 to 72 weeks. Since week 24 of treatment, monthly determinations
of HIV-1 plasma RNA (25 copy/ml limit of detection) has revealed undetectable
plasma levels >50% of the time in 11/12 NI subjects and 6/10 Cl subjects (P =.03). Similarly, 6/12 in the NI group and 3/10 Cl individuals are undetectable at
>75% monthly visits (P=.15). No subject in either cohort has maintained a steady
increase in the level of measurable HIV-RNA in plasma. To further detect active
virus replication, MS (multiply-spliced) and US (unspliced) 1-mRNA species in
the PBMC of 15 subjects (7 Cl, 8 NI) at the 12 month visit were measured. Three
patterns emerged: 3 NI and 1 Cl (-MS, -US), 5 NI and 4 Cl (-MS, +US) and
2 Cl (+MS, +US). The 2 individuals with +MS had undetectable HIV-RNA levels
less than 50% of the time, consistent with ongoing low-level virus replication. This
suggests that 11/12 NI and 6/10 Cl are durably suppressed with this regimen. The
significance of detectable US mRNA in PBMC in the absence of plasma viremia
remains unclear. Ongoing studies of peripheral blood and lymphoid tissue, using
CD8-depleted co-culture, PCR and in situ hybridization are being performed to
estimate the pool size of the residual replication competent HIV-1.
We conclude that intensive antiretroviral regimens employed within 90 days
of infection are more likely to completely and durably suppress virus replication.
However, effective and durable suppression can be achieved in the majority of
chronically infected subjects similarly treated.
22396 Prescriptions of protease inhibitor (PI) antiretroviral (AR)
drugs: Patterns in five large outpatients departments in
Rome, Italy
Orlando Armignacco1, P. Narciso1, V. Tozzi1, P. Settel, P. Franci', R. D'Urso,
F. Montella2. 1L Spallanzani Hosp Via Portuense 292 00149 Rome; 2S. Giovanni
Hosp Rome, Italy
Objective: To assess how and whether the recently published guidelines on AR
treatment of HIV infection have changed the attitude towards AR prescription of
the infectious disease phisicians operating in five large outpatients (OP) depts in
Rome with particular concern on the protease inhibitors (PI) drugs.
Design: Cross sectional study.
Patients and Methods: Clinical records of all HIV positive patients who sought
care during the month of december 1997 in the partecipating OP depts were
reviewed for type of AR therapy and stage of disease as part of a multicenter
study on the efficacy of AR treatment.
Results: Two thousands and one hundred patients were included in the analysis: 1.268 (60.4%) were receiving a triple AR therapy with at least one IP (only
4 patients were receiving RTV + SQV), of these 38.2% were PWA and 24%
were women. The PI more used was IDV (62.8%) followed by SQV (hard gel)
(26.9%), RTV (9.5%) and NFV (0.8%) - the last one is not yet registered in Italy.
Looking at the reverse transcriptase inhibitors (RTI) used in the combinations,
3TC was the more widely used (88.1% of the patients), followed by D4T (65.4%),
AZT (33.7%), DDI (10.4%) and DDC (3%). There was a certain variability in
the pattern of AR therapy among the five centres: IDV ranked first in 4 of the
centres, SQV was first in one and second in two others, RTV ranked second in
two and last in the remaining three. Lamivudine was the more used RTI in all the
5 centres, D4T ranked second in four centres while AZT ranked second in the
others.
Conclusions: Our sample represents nearly half of the HIV patients followed
ill Rome. PIs (IDV, RTV and SQV) were introduced in Italy between december
1996 and march 1997 and after less than a year they were administered as part
of a triple combination to almost two thirds of the patients followed in our centres.
Many of the RTIs widely used a only a year ago have become almost obsolete.
We believe that we should be careful in introducing new drugs without considering
the risk of running out of therapeutic options.
22397 Antiviral effect of a four-drug combination in plasma and
lymph node cells: The Quadri-96 Trial
Gillese Hittinger1, A. Lafeuillade2, C. Poggi3, L. Chollet3, N. Profizi3. 1Unite
Infectiologie, Hopital Chalucet, Toulon; 2Hopital Chalucet, Toulon; 3Hopital De
Toulon-La Seyne, La Seyne Sur Mer, France
Objectives: to evaluate the antiviral effect in blood and lymph nodes (LNs) of a
quadruple drug therapy administered in previously untreated patients.
Design: the "Quadri-96 trial" is a pilot study on 21 patients of a combination
of ZDV + ddl + 3TC + Saquinavir at standard doses administered during 12-18
months. Efficiency is evaluated on plasma and PBL in all cases and LN evaluation
proposed as optional.
Methods: HIV-1 RNA was quantitated in plasma using the Roche PCR kit.
LNs were biopsied surgically and mononuclear cells (LNMC) isolated by Ficoll
gradient centrifugation. LNMC RNA was measured using the Roche PCR kit with
a limit of detection of 20 copies/106 cells.
Results: 12 patients had a LN biopsy at baseline, 8 at 6 months, 13 at 12
months and 5 after 18 months of therapy. Mean plasma RNA was 5.06 ~ 0.24
copies/ml and mean LN RNA was 5.51 ~ 0.32 copies/106 LNMC at baseline in
the 12 patients who accepted a LN biopsy. Plasma RNA dropped <200 copies/mi

within 6 months in each case. LNMC-associated RNA was detected in each
patient at 6 months with mean levels of 2.69 ~ 0.26 copies/106 cells. LNMCassociated RNA was undetectable in 5 cases at 12 months, was 2.77 ~ 0.70
copies/106 cells in 5 patients with proper compliance and 4.81 ~ 0.25 copies/106
cells in 3 who admitted recent lack of compliance (and had plasma RNA between
210 and 4000 copies/ml). RNA was undetectable in 2 cases at 18 months and
found at 1.73 ~ 0.27 copies/106 cells in the 3 others.

Year All
persons
1993 1004
1994 996
1995 949
1996 902
1997 1025

AIDS Deaths Mono
Therapy
113 74 24%
97 82 20%
107 75 19%
59 59 19%
58 24 4%

Dual
Therapy
16%
12%
14%
16%
27%

Triple (or more)
Therapy
2%
1%
1%
5%
27%

None/Not Known
Therapy
58%
67%
66%
60%
42%

Footnote: Data for 1997 are based on reports received by 31/12/97 and are corrected for
reporting delay.
Conclusions: Our research shows that there has been a considerable fall in
the number of HIV+ people developing AIDS and dying in Scotland since 1995.
Data from our CD4 monitoring scheme show that these changes have occurred
as antiretroviral therapies have become more commonly administered. This population based data supports recent results from clinical trials that combination
therapy provides real clinical benefits.
22395 Durable suppression of virus replication with saquinavir
in combination with ritonavir and double nucleoside
inhibitor therapy
Martin Markowitzt, A. Talal1, M.S. Vesanen', Y. Caol, M. Salgo2,
M.R. Chaudhry1, C. Farthing3. 1Aaron Diamond AIDS Research Center, 455 1st
Avenue, 7th Floor, New York, NY; 2Hoffman-La Roche, Nutley NJ; 3AIDS Health
Care Foundation, Los Angeles, CA, USA
A pilot trial of a four-drug combination regimen; saquinavir (800-1200 mg/d) with
ritonavir (800-1200 mg/d), 3TC and AZT or D4T was begun in September 1996.
10/13 chronically infected (Cl) and 12/14 newly infected (NI) subjects remain on