Abstract Book Vol. 2 [International Conference on AIDS (14th: 2002: Barcelona, Spain)]

396 Abstracts ThPeB7237-ThPeB7240

XIV International AIDS Conference

ThPeB7237 HIV-infected children receiving antiretroviral
therapy in Abidjan, Cote d'Ivoire: results from a
cohort study: le "Programme Enfant Yopougon"
P. Msellati', P Fassinou2, F Rouet3, R. Laguide4, N. Elenga4, A. Kouakoussui4,
S. Blanche5. 'Laboratoire Population Environnement/IRD, LPE, case 10, Centre
Saint Charles, 3 Place Victor Hugo, 13331 Marseille Cedex 3, France; 2Pediatric
Departement, Universitary Hospital of Yopougon, Abidjan, Cote d'voire;
3Cedres, PACCI, Abidjan, Cote d'voire; 4Programme Enfant Yopougon, PACCI,
Abidjan, Cote dIvoire; 5Hopital Necker Enfants Malades, Paris, France
No data are available on antiretroviral therapies (ART) in HIV-infected children in
Africa. A prospective cohort started in Cote d'Ivoire in october 2000.
Objectives: to describe pediatric HIV infection under antiretroviral drugs in Africa.
Methods: At baseline, there was a clinical and biological (blood cell count, CD4
lymphocyte count, viral load (VL)) examination and a chest X ray. A systematic
examination was then done quaterly. CD4 and VL were measured each 6 months.
We opened an outpatient clinic and all treatments and tests were free of charge.
Children had ART if needed, in the context of the Drug Access Initiative in Cote
d' Ivoire.
Results: 155 HIV-infected children were recruited from october 2000 to october
2001. The probability of survival for children under ART is 83% at 12 months. In
a multivariate analysis, 2 factors were associated to survival: % of CD4 Hazard
Ratio (HR)=0.05 (95%CI 0.006 - 0.38) and ART HR 0.28 (95%CI 0.1 - 0.9). At
baseline, 24 children received already ART, including 20 HAART. Ten were <250
cp/ml, 4 between 250 and 5,000, 6 between 5 and 100,000 cp and 4 >100,000.
All except 1 were under HAART after six months. For an average follow-up of 256
days, there has been a mean increase of 7.5% of %CD4 and mean decrease of
VL of 179000 cp/ml. One child stopped for neuropathies and 3 children died. During the follow-up, 40 others received HAART with on average 560,000 cp/ml at
baseline. Two were under 10000, 10 between 10,000 and 100,000, 20 between
100,000 and 500,000 and 8>500,000. A child stopped for a suspicion of pancreatitis and another for diarrhea with nelfinavir replaced by a combination including
efavirenz. VL average decrease was of 309000 cp/ml and mean increase of 4.8%
CD4 for a mean duration of 124 days of treatment, 18 children had a VL <250.
Six children died.
Conclusion: HAART are factors of survival in HIV infected children in Africa. Adverse effects are rare. The increase of CD4 and decrease of VL are significant.
Presenting author: Philippe Msellati, LPE, case 10, Centre Saint Charles, 3
Place Victor Hugo, 13331 Marseille Cedex 3, France, Tel.: [phone],
Fax: [phone], E-mail: [email protected]
ThPeB7238 Lymphoproliferative responses to p24 antigen in
HIV-1-infected children with high CD4+ T cell
counts
M. Hainaut', M. Ducarme2, L. Schandene2, C.A. Peltier', F. Mascart2, J. Levy1.
'Department of Paediatrics, Hdpital Saint-Pierre, Free University of Brussels,
Pddiatrie, H6pital Saint-Pierre, Rue haute, 322, 1000 Brussels, Belgium;
2Department of Immunology, H6pital Erasme, Free University of Brussels,
Brussels, Belgium
Background: The lack of immune control of HIV has been linked to a defect in
virus-specific T-helper-cell responses. The goal of this study was to test lymphoproliferative responses (LPR) to p24 and to recall antigens in 3 groups of children:
5 with non progressive disease who maintain a normal CD4+ T cell count and a
low plasma viral load without antiretroviral therapy (group 1), 9 treated with highly
active antiretroviral therapy (HAART) within their first 2 months of life (group 2),
and 8 treated later in life who experienced normalisation of their CD4+ T cell count
with HAART (group 3).
Method: Cross-sectional study.
Results: The characteristics of the patients are:

ThPeB7239 Transmission of HIV-1 infection by a mechanism
involving via LFA-1-mediated T-cell contact
Trophoblast placental cells
M.A. Munoz Fernandez, L. Diaz Munoz, R. Alonso Arias. Hospital Gregorio
MaraFdn, Servicio de Inmunologia, Madrid, Spain
Background: Vertical transmission of HIV-1 is thought to mainly take place by
virus crossing the placental barrier. However, the mechanism by which HIV-1 infects placental cells remains to be elucidated.
Methods: Cytotrophoblast were further purified by negative selection with antiHLA antibodies by immunomagnetic separation. Cocultures of infected placental
cells with PBMC were carried out with the cells in close contact, or separated by
0.4mm pore size transwells. Cell surface expression of CD4,
CCR5 and CXCR4 and ICAM-1, in placental cells, was evaluated by direct flow
cytometry. To block viral entry, JEG-3 and JAR cultures were preincubated with
different antibodies.
Results: We have found that purified cytotrophoblasts as well as trophoblastic
cell lines are susceptible to infection by different HIV-1 isolates as detected by
DNA-PCR and release of infectious virus. Purified trophoblast or trophoblastic
cell lines express low levels of chemokine receptors CCR-5 and CXCR-4 but not
CD4 on the cell surface. None of those treatments inhibited HIV-1 infection. In
contrast, we have found that infection of placental cells by HIV-1 was increased
in cocultures of infected T cell blasts and placental cells. Antibodies to b2 integrins and to LFA-1 were able to significantly block infection of placental cells. Cell
surface expression of ICAM-1, an adhesion molecule involved in attachment of
leukocytes to placenta, was upregulated in HIV-1-infected placental cells.
Placental cells were able to transfer HIV-1 infection to T cell blasts. This transmission required cell to cell contact and was also inhibited by anti-LFA-1 antibodies.
Conclusions: Our results indicate that placental trophoblast could be infected by
HIV-1 by a mechanism involving direct
T-cell to placental contact. Moreover, placental infection enhanced ICAM-1 expression and leukocyte adherence, an event, which was required to transfer
HIV-1 infection to PBMC. This provides a mechanism to explain virus passing
through the placental barrier during "in utero" HIV-1 vertical transmission.
Presenting author: Ma Angeles MUNOZ-FERNANDEZ, Hospital Gregorio
Marahi6n, Servicio de Inmunologia, C/ Dr Esquero 46, 28007 Madrid, Spain, Tel.:
[phone], Fax: [phone], E-mail: [email protected]
ThPeB7240 Placental trophoblast could be infected by a
mechanism involving direct T-cell to placental
contact
L. Daz Muhoz, R. Alonso Arias, M. Muhoz-Fernindez. Hospital General Univ.
Gregorio MaraF7dn, Madrid, Spain
Background: Vertical transmission of HIV-1 is thought to mainly take place by
virus crossing the placental barrier. However, the mechanism remains to be elucidated.
Methods: Cytotrophoblast were further purified by negative selection with antiHLA antibodies by immunomagnetic separation. Cocultures of infected placental
cells with PBMC were carried out with the cells in close contact, or separated by
transwells. Cell surface expression of CD4, CCR5 and CXCR4 and ICAM-1, in
placental cells, was evaluated by direct flow cytometry. To block viral entry, JEG-3
and JAR cultures were preincubated with different antibodies.
Results: We have found that purified cytotrophoblasts as well as trophoblastic
cell lines are susceptible to infection by different HIV-1 isolates as detected by
DNA-PCR and release of infectious virus. Purified trophoblast or trophoblastic
cell lines express low levels of chemokine receptors CCR-5 and CXCR-4 but not
CD4 on the cell surface. None of those treatments inhibited HIV-1 infection. We
have found that infection of placental cells by HIV-1 was increased in cocultures
of infected T cell blasts and placental cells. Antibodies to &#61538;2 integrins and
to LFA-1 were able to significantly block infection of placental cells. Cell surface
expression of ICAM-1 was upregulated in HIV-1-infected placental cells. Placental cells were able to transfer HIV-1 infection to T cell blasts. This transmission
required cell to cell contact and was also inhibited by anti-LFA-1 antibodies.
Conclusions: Our results indicate that placental trophoblast could be infected by
HIV-1 by a mechanism involving direct T-cell to placental contact. Moreover, placental infection enhanced ICAM-1 expression and leukocyte adherence, an event,
which was required to transfer HIV-1 infection to PBMC. This provides a mechanism to explain virus passing through the placental barrier during "in utero" HIV-1
vertical transmission.
Presenting author: Ma Angeles MUNOZ-FERNANDEZ, Division of Immunology,
Hospital General Universitario "Gregorio Marah6n", C./Dr Esquerdo 46, 28007
Madrid, Spain, Tel.: [phone], Fax: [phone], E-mail: inmuno
@teleline.es

ThPeB7241I Syncytium inducing (SI) to non-syncytium inducing
(NSI) phenotype switch under HAART in pediatric
HIV-1 infection
J. Kopkal, M. Batalla', A. Mangano2, D. Mecivovsky', R. Bologna', L. Sen'.
'Hospital Nacional de Pediatria, Combate de Los Pozos 1881 (1245), Buenos
Aires, Argentina; 2Hospital Nacional de Pediatrd, Buenos Aires, Argentina
Background: NSI viral isolates predominate during the asymptomatic phase of

Median age (range),
years

Median HIV load (range),
copies/mL

Median CD4 (range),

Group 1 9.2 (7.4-10.2) 416 (206-19,200) 27(24-41)
Group 2 1.7 (1-5) <50 (<50-34,700) 34 (24-46)
Group 3 6 (3.2-11.7) <50 (all) 32 (21-46)
The 3 groups had comparable LPR to candida. All five children in group 1 had
vigorous LPR to p24, tetanus, and tuberculin antigens. Children in group 2 had
weak or absent LPR to tetanus, and only 1/9 had a barely detectable response to
p24 antigen. Children in group 3 had well present LPR to tuberculin antigen, no
response to tetanus (but this was present after re-immunisation) and 4/8 of them
had a LPR to p24 antigen.
Conclusion: HIV-specific CD4+ T-helper cell activity, measured as the LPR to
p24 antigen, is present in children with non progressive disease as described in
adults, and in some children treated in chronic infection. By contrast, early treatment in infants does not lead to detection of HIV-specific LPR.
Presenting author: Marc Hainaut, Pediatrie, H6pital Saint-Pierre, Rue haute,
322, 1000 Brussels, Belgium, Tel.: [phone], Fax: [phone], E-mail:
[email protected]