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

12th World AIDS Conference

Abstracts 11243-12103 31

the mouse model: groups of 4 mice were inoculated 1, 2 or 3 times with alvac-HIV
(vCP205) administered either by intramuscular route or by the intravenous route.
Injections were done at week WO, W3 and W6 and CTL response was measured
at W5 and W8.
Results: in macaques, we demonstrated a CTL response only when animals
are immunized by the intramuscular route. This response is detectable four weeks
after the second immunization in 5 out of 8 macaques and is not increased after
additional immunizations. The response is still present at least 5 months after
the second immunization. In mice, a CTL response is detected in all animals
after the first injection of alvac-HIV (vCP205) by both routes. However, the CTL
response increased with the second and third immunizations by intramuscular
route, whereas this response is maximal after the first injection by intravenous
route.
Conclusion: we have demonstrated that alvac HIV (vCP205) is able to induce
a specific CTL response, both in mice and macaques immunized by intramuscular
route. As this construct is also able to induce a CTL response in human beings,
we can postulate that these two animal models are relevant to evaluate CTL
response induced with alvac recombinant vectors.
11243 CTL induction in macaques using intravenous injection
of autologous PBMCs ex vivo infected with a
recombinant canarypox virus
Catherine Callet, T.M. Jourdier, J.C. Moulin, R. El Habib, E. Trannoy. Pasteur
Merieux Connaught 1541 Av. Marcel Merieux Marcyl'etoile 69280, France
Objectives: to analyze the capacity of autologous peripheral blood mononuclear
cells (PBMCs) expressing HIV antigens to raise specific CTL response in vivo.
Canarypox virus expressing gpl20MN-TM LAI, gag-LAI and pro-LAI antigens
was used to infect PBMCs ex vivo prior to intravenous reinjection.
Methods: Six cynomolgus macaques were injected intravenously with autologous alvac-HIV (vCP205) infected PBMCs whereas four other macaques were
injected with excipient treated PBMCs (placebo). Three alvac-HIV (vCP205) and
two placebo macaques were sacrificed six weeks after the last injection. Specific
CTLs were amplified in vitro by two consecutive stimulations of splenic or lymph
node lymphocytes with alvac-HIV (vCP205) infected antigen presenting cells.
Their specific lytic activities were then analyzed using autologous Herpes papio
transformed B cell lines infected with recombinant vaccinia viruses expressing
the different HIV antigens (gp120MN-TM LAI, gag-LAI, pro-LAI).
Results: showed that one macaque developed gag and pro specific CTL responses, an other one developed only a gag specific response whereas the third
one and the two placebos were completely negative. None of the macaques developed detectable gpl20-specific CTL responses. However, the level of response
suggests weak HIV-specific CTL precursor frequencies.
Conclusion: as this protocol should be used in HIV+ subjects to amplify their
CTL response, we can consider these results as very encouraging. This protocol
may be able to recall existing memory cells as well as to generate new CTL
precursors.
11244 AIDS induction in rhesus monkeys with a mutant SHIV by
systemic or mucosal inoculations
Yichen Lu1, D.C. Pauza2, N. Letvin3, J. Sodroski4, C.J. Miller5. 161 Moultonn
Street, Cambridge; 2lnstitute for International Vaccine Dev., Cambridge, MA;
3 Wisconsin Regional Primate Research Ctr, Madison, WI; 4Div. of Pathology,
Beth Israel Hospital, Boston, MA; 5California Regional Primate Research Ctr,
Davis, CA, USA
Objectives: To develop different SHIV challenge viruses with different infectivity
to macaque monkeys that can be used to test potential efficacy of HIV-1 vaccine
candidates.
Design: Characterizing the infectivity and pathogenesis of a group of different
SHIV in rhesus monkeys by intravenous, intravaginal or intrarectal inoculations.
Methods: By replacing the T-tropic HIV-1 env gene with that of a macrophagetropic virus, SHIV89.6 acquired the ability to intravaginally infect monkeys. By
passaging SHIV-89.6 in vivo, SHIV-89.6PD acquired pathogenicity that causes
AIDS in infected monkeys. By comparing the DNA sequence of SHIV-89.6 and
SHIV-89.6PD, a mutation was identified that may be associated with pathogenesis. Introduction of the mutation back into the SHIV-89.6 genome resulted in
SHIV-89.6PDMC1 which showed increased infectivity to monkeys. This virus can
now be used as the basis of a number of new SHIV strains derived from different
HIV-1 subtypes.
Results: SHIV-HXB can infect rhesus monkeys intravenously or intrarectally,
but not intravaginally. SHIV-89.6 can infect rhesus monkeys intravenously, intrarectally, andintravaginally, but can not cause AIDS. SHIV-89.6PD can cause
AIDS regardless the routes of inoculation. A deletion mutation in the HIV-89.6
env gene of SHIV-89.6PD results in a chimeric envelope glycoprotein with both
HIV-1 and SIV origins. New study shows that the introduction of this mutation
into SHIV-89.6 enhances the virus infectivity. The summary of using SHIV-HXB,
SHIV-MN, SHIV-89.6, and SHIV-89.6PD as the challenge viruses in HIV-1 vaccine

research will also be presented.
Conclusion: It is possible now to test most potential HIV-1 vaccines directly
in rhesus monkeys. The efficacy of vaccine candidates can be evaluated by
prevention of AIDS as well as by evaluation of virus infection that results from
SHIV challenge with different routes of inoculation.

341*/12101 1Extended benefit of protease inhibitor-containing
combination therapy through a dissociated
viremia-CD4 T-cell response
Daniel Kaufmann, Giuseppe Pantaleo, Pascal Meylan, Philippe Sudre,
Patrick Francioli, Micheal P. Glauser, Amalio Telenti. Division of Infectious
Diseases University Hospital 1011 Lausanne, Switzerland
Background: The marked benefit of HAART has been attributed to its drastically
suppressing viral replication. The evolution of HIV-infected individuals who remain
viremic under HAART is unknown.
Methods: All individuals followed at a single HIV outpatient unit who initiated
HAART before February 1997 (n = 101) were included.
Findings: At 48 weeks, an increase in CD4 T cell counts was observed in
91 (92.9%) of 98 evaluable participants. Among 82 participants continuously
under HAART, average (95% CI) CD4 increase was 138 (98-178) for those with
undetectable viremia (group 1, n = 28), and 130 (77-182) cells/mm3 for those
with transient undectable viremia (n = 21). Unexpectedly, an increase of 105
(79-132) cells/mm3 CD4 T cells was also observed among participants with
persitent detectable viremia (n = 33) who took HAART continuously (p = 0.108
vs. group 1). Participants with documented non-adherence to treatment (n = 16)
presented a modest increase of 57 (30-84) cells/mm3 (p = 0.002 vs. group 1).
Interruption of HAART was associated with a rapid drop of CD4 independently of
prior level of viremia. Clinical endpoints were observed at CD4 counts below 200
cell/mm3.
Interpretation: HAART exerts an unexpected and prolonged benefit on CD4
counts even in the absence of suppression of viremia. These findings may have
major implications for the design of therapeutic strategies for individuals remaining
viremic under HAART.
S12102 Change in renal function associated with indinavir
Karim Boubaker, Frank Bally, Gerard Vogel, Jean Yves Meuwly, Michel
P. Glauser, Amalio Telenti. Division of Infectious Diseases University Hospital
1011 Lausanne, Switzeland
Objectives: To evaluate the association between treatment with indinavir (IND)
and change in renal function.
Methods: Retrospective cohort study of all adults (n = 106) from an HIV unit
who started IND after June 96.
Results: A mean CR increase from baseline of 13.6%/ was observed for the
whole cohort (95% CI, 9-18%). In total, 20 subjects (19%) presented an increase
of CR over normal ranges (mean increase from baseline 42%, 95% Cl 29-54).
Elevation of CR was associated with length of treatment (p =.006), low baseline
weight (p =.036), exposure to Bactrim (p =.004), low CD4 (p =.025), leukocyturia
(p <.001), and low urine specific gravity (p =.013), but not with baseline CR.
Lithiasis (n = 3), back pain without documented lithiasis (n = 6), and dysuria
without lithiasis (n = 4), occurred more frequently among individuals with elevated
CR (30% vs 8%, p =.016).
Conclusion: In our cohort, IND was associated with moderate elevation of
CR. This elevation is progressive, more frequent in advanced HIV-infection, and
associated with occurrence of clinical events. However, it is fully reversible upon
discontinuation.
12103 Evaluation of an orphan support programme in rural
Tanzania
Peris Lucas Urasa. Mawenzi Regional hospital PO Box 3054 Moshi, Tanzania
Objective: To determine the felt needs of AIDS orphans and asses. Community
response towards caring of the Orphans
Methodology: Focus group discussions with guardians, Community members
and older orphans, on their views and experiences on the needs and support
offered to the Orphans. The attitude of the Community towards offering support
and care to the orphans.
Results: The programme offers support to 297 AIDS orphans, and 95% are
below 15 years. 43% Care givers are grandparents either both or one, and in
most cases they are 60 years or above, 27% a present majority are unhealthy.
15% a member of the extended family; while 10% the older orphans and 5% the
community members. During the focus group discussion, the repeated concern
were, lack of resources, upon reduction family income and too many children to
take care of. The orphans needs were constant healthy care services, which is
now affected by cost sharing exercise. The pressing issue ahead of them, the
need of vocational training completing their primary school education. Widow's
and orphans properties were violated. Stigma still prevails among community
members to the extent of segregating the AIDS orphans.
Conclusion: The number of orphans without support is growing fast and we
are yet to address the orphans immediate need as they go beyond food and
school support. The AIDS orphans are vulnerable, stigma and misconceptions
hinder the community support to the orphans.
There is a great need of involving the older orphans/guardians in the planning

stage of their support programme.