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

346 Abstracts 22408-22412

12th World AIDS Conference

22408 1 Antiretroviral combination therapy in patients with low
CD4 cell counts
Dundu Malaki Dwili1, S.T. Datel2. 1Box 63355, Nairobi; 2MD Shah Hospital,
Nairobi, Kenya
Objectives: To monitor and access the clinical and laboratory responses to
antiretroviral therapy in HIV patients with low CD4 cell counts in Kenya.
Methods: 50 patients with an average of 50 CD4 cell counts were treated
at the Aga Khan and M.P. Shah Hospitals with a combination triple therapy of
Saquinavir 600 mg three times a day, zidovudine 200 mg three times a day and
lamivudine 150 mg twice a day between January 1997 and January 1998. All the
study patients were males aged between 35 and 54 years with symptoms caused
by different opportunistic infections of more that two years duration. Three of
the study patients had nodular kaposis sarcoma localized on the extremities and
in buccal mucosa. Majority of the patients had various opportunistic infections
ranging from Pulmonary Tuberculosis, Fungal infections to different types of skin
infections. Other symptoms observed included diarrhoea, loss of weight, night
sweats, fatigue and persistent fever. Before initiation of antiretroviral therapy,
baseline laboratory investigations including haemogram, CD4, CD8 cell counts
and viral load were carried out.
Results: 50 HIV positive patients treated with antiretroviral triple therapy using
two nucleoside reverse transcriptase and one protease inhibitor for 12 months
revealed that there was a significant increase in CD4 cell counts and marked
reduction in RNA copies. A steady increase of CD4 cell counts with the disappearance of opportunistic infection were observed. 20% of the patients had an
average increase of 200 CD cells within 3 to 6 months of triple therapy, 50% had
their viral load reduced and 10% had undetectable viral load.
Conclusion: Combination therapy with nucleoside analogues and protease
inhibitors has demonstrated in our study significant increase in CD4 cell counts,
viral load reduction and disappearance of the opportunistic infections. We also
observed the regression of kaposis sarcoma during the triple therapy. This study
has confirmed that patients with low CD4 cell counts can benefit from antiretroviral
therapy.
S22409 1 Efficacy and safety profile of antiretroviral treatment of
ritonavir in combination with zidovudine (ZDV/AZT) and
zalcitabine (ddC) for HIV/AIDS patients in San Lazaro
Hospital
Dominic Garcia, E.G. Santiago, M.A. Manalo, C.C. de la Cruz, E.D. de las Alas,
J.M. Maala. San Lazaro Hospital, 2515-C Tindalo Street, Sta. Cruz, Manila
1040, Philippines
Objective: To evaluate the clinical efficacy, safety profile, and antiviral activity of
Ritonavir in combination with ZDV and ddC in Filipino patients with HIV infections.
Design: Prospective, uncontrolled 24 week study.
Methods: A total of 10 HIV Filipinos were initially enrolled into the study that
met one of the three (3) following criteria: A single CD4+ cell count >50 and
<250 cells/uL within four weeks prior to initiation of study drug; single CD4+ cell
counts within 200-500 cells/ml associated with equivocal clinical symptoms and
viral RNA value >20,000 copies/mi. Virologic activity and immunologic activity
assessed at week 2 and every month beginning at week 4 therapy through
evaluation of HIV RNA level (viral load) and CD4-CD8 cell. The main parameter
of efficacy were CD4+ cell count, CD4/CD8 ratio and viral load.
Results: Mean baseline CD4+cell counts were 330 cells/mm3; mean baseline
plasma viral load level were 3.76 logs or 40,000 copies/ml of HIV RNA. Mean
CD4+ counts were 422 cells/mm3 after 2 weeks in 5 evaluable persons and 514
cells/mm3 after 24 weeks in 4 evaluable persons respectively, as compared to
330 cells/mm3 as baseline. All of the study population had undetectable levels of
HIV RNA (defined as below 200 copies/ml) in plasma after 24 weeks of therapy.
Conclusions: The triple therapy appeared to increase the CD4+ cell counts
and HIV RNA level were statistically significantly decreased compared to baseline. Ritonavir in combination with ZDV and ddC is well tolerated. Clinical benefits
from triple therapy has been shown. But, the feasibility of eradicating HIV from
the study population will require further evaluation.
22410 Experience with saquinavir zalcitabine zidovudine triple
combination
Denes Banhegyi, J. Szlavik, Z. Gerlei, A. Gyuris, J. MinRaacute;rovics. Saint
Laszlo Hospital, Budapest, Hungary
Background: The clinical investigations of new combination therapies with protease inhibitors (PI) as well as the introduction of the measurement of viral load
opened up new dimensions in the antiretroviral treatment. The long term effectivity
of saquinavir (SQV) zalcitabine (DDC) and zidovudine (ZDV) on the Hungarian
patient population is presented.
Patients and Methods: Nine symptomatic HIV infected patients with CD4 cell
counts <350/microL having given informed consent were included all treatment
naive. Mean CD4 count was 286/microL mean HIV-RNA copy/ml was 4.9 log.

Treatment was as follows, ZDV 3 x 200 mg, DDC 3 x 0.75 mg, SQV 3 - 600
mg. Clinical examinations, blood count, blood biochemistry, CD4+ cell count, viral
load were determined.
Results: The nine treatment-naive patients received the triple combination for
more than 86 weeks. AIDS defining event was observed in one case. All patients'
CD4 cell counts were higher than the initial ones mean: 426/micoL.. HIV-RNA
copies' number were below detection levels but two (22000 and 11000 copy/ml)

at week 86. The treatment was well tolerated no serious adverse reaction was
registered.
Conclusions: Saquinavir, zalcitabine, zidovudine triple combination proved to
be more effective and have longer effect in the inhibition of HIV replication as
well as a more sustained raise in CD4 cell counts were observed. Combination
treatment was well tolerated.
S272*/22411 Immune reconstitution of HIV discordant
monozygotic twins: Insight into T cell dynamics
Chris Tsoukas1, H. Turner1, J. Goodhew2, D. Kilby3, C. Kovaks4,
J. Luetkehoelter4, S. Walmsley4, J.P. Routy5, N. Bernard1. 1The Montreal
General Hospital, Rm. A5-140 1650 Cedar Ave Montreal, Quebec, H3G 1A4;
2Toronto ON; 3Ottawa ON; 4 Toronto General Hospital Toronto ON; 5 The Royal
Victoria Hospital, Montreal, QU, Canada
Background: Little is known about CD4 cell replenishment and T cell trafficking in persons achieving maximal viral load suppression. Attempts at replacing
CD4 cell stores utilizing lymphocyte transfers from HIV positive identical twins
have previously failed, due to poor HIV control. Using potent anti HIV triple drug
combinations, HIV discordant monozygotic twins present a unique opportunity to
study true immune reconstitution by transferring syngeneic T cells from healthy
uninfected identically histocompatable siblings.
Methods: 5 sets of male monozygotic twins (mean age 40.2) enrolled in a
phase I study were treated with a protease inhibitor and 2 RT inhibitors. Upon
maximal viral load suppression in the HIV infected twin, repeated infusion cycles
of lymphocytes and ex vivo expanded CD8 T cells from the uninfected twin
were given with continuous IV infusions of IL-2 (9x10 iu/day). The clinical status,
viral load, immune phenotypes of function, activation and apoptosis, lymphocyte
proliferative responses and HIV specific CTL activity (env, gag, pol, nef) were
evaluated.
Results: In patients receiving more than one cycle of treatment an improvement in clinical status and quality of life was noted. AIDS related opportunistic
infections resolved in two with active infections. CD4 increases to normal levels
were noted in all patients in both percent and absolute numbers. Mean baseline
12% ~ 10, 49 cells/mm3 ~ 176 increased to 28% ~ 9, 836 cells/mm3 ~ 477. Long
term stability of CD4 cells (up to 8 months) was noted following cessation of the
infusions and normalizing trends in other phenotypes occurred. Two patients with
undetectable direct HIV specific cytotoxicity prior to therapy, developed responses
with treatment.
Conclusions: Under restricted HIV replication the use of syngeneic T cell
transfers in HIV discordant identical twins leads to immune reconstitution. Studies
of T cell survival and trafficking in these patients may provide insights as to the
true potential for immune restoration in HIV disease.
S345*/22412 Changes in lymphocyte subsets with interleukin-2
therapy in patients with advanced HIV disease on
highly active anti-retroviral therapy (HAART)
Daniel Berger1, B.E. Baker1, G. Bucher1, R. Bessinger3, P. Maroni1,
W.M. Reiter2. Center for Special Immunology - 12835 N Sheffield, Chicago IL,
2Ft Lauderdale, FL; 3Tulane University, New Orleans, LA, USA
Objective: To evaluate safety, immunologic markers (including CD4 naive &
memory cells) and virologic response to IL-2 in patients (pts) with advanced HIV
disease.
Methods: 12 pts with HIV/AIDS on HAART, were treated with IL-2; 11 pts
received subcutaneous and one pt received intravenous IL-2, at 9-18 million
IU QD for 5 days every 8 weeks. T lymphocyte subsets - CD4, CD4%, CD8,
CD45+RA+ (naive), CD45+RO+ (memory) and viral burden were measured prior
to receiving HAART, prior to IL-2 therapy and 4-8 weeks after each IL-2 cycle.
Final means with standard error (se) were calculated from the values after the
last IL-2 cycle; p values from non-parametric Wilcoxon signed-rank test.
Results: Prior to HAART, mean CD4 count (se) were 100 cells/mm3 (29.1),
CD4% 8 (1.45), n = 10; 6/12 pts had HIV-related complications: CMV retinitis 3;
PCP 1; KS 2; chronic HCV 1; cryptococcal memingitis 1; wasting syndrome 3;
bacterial pneumonia 1. A total number of 44 IL-2 cycles were completed. Prior
to IL2 therapy, mean cell counts in cells/mm3 (se) on HAART (mean duration
12.2 months) were: CD4, 249 (28.4); CD4%, 17 (1.24); CD8, 787 (97.0); HIV
RNA was undetectable in 80% (<500 copies/ml), mean 2.84 logio (n = 12); CD4
subsets measured included CD45+RA+, 98 (16.2) and CD45+RO+, 142 (17.7)
(n = 8);. To date, on IL-2 therapy, mean cell counts rose to: CD4, 470 (72.4, p <.001); CD4%, 24 (3.16, p <.05); CD8, 1127 (205.0, p < 05); HIV RNA remained
relatively unchanged, mean 2.96 log10o. CD4 lymphocyte subsets increased to:
CD45+RA+, 189 (18.3, p <.05) and CD45+RO+, 242 (26.5, p <.01); One pt
withdrew secondary to intolerance.
Conclusion: IL-2 therapy significantly increased CD4, CD4%, CD8,
CD45+RA+, and CD45+RO+ cells in pts with advanced HIV disease being
treated with HAART, without increasing viral burden. This suggests additional
immune reconstitution occurred with IL-2 therapy beyond that seen with HAART.

Additional studies to further evaluate immune recovery should be considered in
pts with advanced HIV disease.