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

54 Abstracts WePeB5894-WePeB5897

XIV International AIDS Conference

Presenting author: Jayant Deodhar, Deodhar Children's Clinic, 39/25 Erandawane, Karve Road, Pune 411004, India, Tel.: [phone], Fax: +91 20
5890694, E-mail: [email protected]
WePeB5894I Residual HIV-1 disease eradication (rhide) trial: an
HIV-1 reservoir eradication approach in humans
using stimulatory and novel intensification therapy
R.J. Pomerantz1, M. Otero1, G. Nunnari1, A. Malin1, C. Coates1, C. Dascenzo1,
J. DeSimone', T.J. Babinchak', H. Zhang', G. Dornadulal, D. Culnan',
J. Sullivan', Y Xu', J. Stern2, W. Cavert3, A.T. Haase3, J. Kulkosky4. 1Thomas
Jefferson University Division of Infectious Diseases, 1 Philadelphia, PA, United
States; 2Pennsylvania Hospital, Infectious Disease Section, Philadelphia, PA,
United States; 3 University of Minnesota Medical School, Minneapolis, MN,
United States; Thomas Jefferson University Philadelphia, PA, United States
Background: HAART has led to significant changes in mortality and morbidity.
Nevertheless, due to two main molecular mechanisms of viral persistence, cryptic
viral replication and proviral latency in resting T-cells, HAART does not eradicate
HIV-1. These mechanisms of residual reservoir disease in vivo were approached
with a rationally-designed combination therapeutic protocol.
Methods: Three patients with HIV-1 infection on HAART, with less than 50
copies/ml of plasma viral RNA, were enrolled. They continued their baseline
HAART, and DDI plus hydroxyurea (HU) were added as novel intensification to
attack cryptic viral replication. The patients were then treated in our bone marrow
transplant unit with low dose OKT3, followed by a two week course of subcutaneous IL-2 to stimulate latent provirus. Plasma viral RNA and 2-LTR DNA circles
were analyzed via quantitative RT and DNA-PCR respectively, with PBMC cocultures to detect replication-competent virus.
Results: All treated patients had only modest side effects. Replication-competent
virus was undetectable after treatment and plasma viral RNA also became undetectable in each of these patients, using an ultrasensitive laboratory RT-PCR assay which quantitates to 5 copies/mi. Tonsillar biopsies were performed and no in
situ hybridization for HIV-1-specific RNA was detected. HIV-1 2-LTR DNA circles,
which suggest on-going viral replication, also disappeared after treatment. The
first two patients have already been given trials off all anti-retroviral therapy, with
one patient having no viral rebound for several months.
Conclusions: This represents the first translational research protocol to combine both novel intensification and stimulatory therapeutics to deplete residual
viral reservoirs in vivo. This trial demonstrates that intensification and stimulatory
therapy in eradication protocols, when properly designed and at precise doses,
can be given safely to patients.
Presenting author: Roger Pomerantz, Thomas Jefferson University, Division of
Infectious Diseases, 1020 Locust St., Suite 329 JAH, Philadelphia, PA 19107,
United States, Tel.: [phone], Fax: [phone], E-mail: roger.j.
[email protected]
WePeB5895I Treatment with a combination of Efavirenz,
Nevirapine and NRTIs in HIV patients
J.A. Arranz-Caso', M. Gorgolas2, V. Estrada3, J.D. Garcia-Diaz4. ' Unidad de
Enfermedades Infecciosas, Hospital Principe de Asturias, Madrid, Spain;
2Unidad de Enfermedades Infecciosas, Fundacion Jimenez Diaz, Madrid, Spain;
3 Unidad de HIV Hospital Clinico., Madrid, Spain; 4Unidad de Investigacion
Clinica, Hospital Principe de Asturias, Alcala de Henares, Spain
Background: NNRTIs are increasingly used in PI-sparing regimens. Due to high
cross resistance, loss of sensitivity to one NNRTI almost always implies a reduced sensitivity to other drugs of this group. In this setting, the addition of a second NNRTI, otherwise lost if genotypic resistance appears to one of them, could
provide more durability and better viral suppression. On the other hand adverse
effects could also be increased.
This pilot study investigate both tolerance and efficacy of the combination of two
NNRTIs plus NRTIs in patients with P-based regimens that are failing or as a
simplification regimen.
Methods: Thirty patients were enrolled and distributed in two groups: I) naive patients (3) and patients were NNRTIs were introduced as a simplification regimen
(16) and II) patient with failing PI based regimen (11). All patients were treated
with nevirapine (400 mg BID) plus efavirenz (800 mg QD). In 21 patients DDI (qd)
was added and in 9 patients AZT/d4T plus 3TC, at standard doses.
Results: Severe adverse effects that led to treatment interruption, patients with
<50 copies/mL and CD4 changes of the two groups at 6th month of follow-up are
shown in the table. Nine patients (30%) had severe adverse effects: 2 hepatitis, 2
SNC disturbances, 2 gastric intolerance and 3 skin rash.
Group I Group II p value
Severe adverse effects (patients number/total[%]) 6/19 [31.6] 3/11 [27.3] 1
Patients ith VL <50 copies/mL at 6~ month 12/12 [100] 2/7 [28.5] 0.002
(Patients number/total [%])

CD4 changes at 60 month (mean [SD]) 142.6 [139.9] 46.8 [68.1] 0.06
Conclusions: In this pilot study a double NNRTI therapy in combination with DDI
or 2 NRTIs were associated to a higher than expected incidence of adverse effects although it was an effective PI-sparing therapy in naive patients or as a
simplification regimen.

Presenting author: Jose Alberto Arranz-Caso, Unidad de Enfermedades Infecciosas., Hospital Principe de Asturias, Cra de Alcala-Meco, SN, 28805. Madrid,
Spain, Tel.: [phone], Fax: [phone], E-mail: [email protected]
WePeB5896 Long-term follow-up of 21 subjects carrying
multinucleoside-resistant genotypes (0151 M,
67/69 inserts, deletion 67)
0. Gallego. C/Sinesio Delagado 10, 28029, Madrid, Spain
Background: Multiple resistance to nucleoside analogs represents an increasing
problem among HIV-infected persons since a growing number of subjects is being
on sequential therapy for long time.
Methods: All plasma samples collected from HIV+ subjects failing their current
antiretroviral therapy and referred for HIV genotyping to our institution were examined, using an automatic sequencer.
Results: Multinucleoside-resistance (MNR) genotypes were recognized in 21
(3%) subjects. Eleven of them (1.6%) carried the Q151M complex, 9 (1.2%)
showed different 67/69 inserts, and 1 carried a deletion at codon 67 in the RT
gene. All these patients had been exposed to AZT, ddl and/or ddC during almost
2 years. The mean plasma HIV-RNA at the time MNR was first identified was
141,231 cop/ml and the mean CD4 count was 242 cells/Il.
Five individuals whose samples wee collected before 1996, when PI were firstly
available, developed AIDS opportunistic infections, and one of them died within
3 months. In contrast, all 16 patients experiencing a favorable clinical outcome
after MNR was firstly recognized received triple combinations based on potent
PIs (lopinavir, 5 cases). Eight subjects showed a reduction in plasma HIV-RNA
>2 logs, and 7 of them reached <50 cop/mI. Undetectable viremia has been
maintained for a mean of 13.2 months (range, 8-48 months) in all these patients.
Of note, in all remaining subjects with detectable viremia, MNR genotypes have
persisted in further samples collected over time.
Conclusion: The prevalence of multinucleoside resistance genotypes (Q151M,
67/69 inserts and deletion 67) is low (3%) among pre-treated patients in Spain. In
all subjects experiencing a favorable virological and clinical outcome, the rescue
regimen was based on potent PI combinations (boosted PI) with/without NNRTI.
Therefore, rescue interventions based on potent PI combinations may overcome
the expected poor prognosis of subjects harboring MNR viruses.
Presenting author: Oscar Gallego, C/ Sinesio Delagado 10, 28029, Madrid,
Spain, Tel.: [phone], Fax: [phone], E-mail: [email protected]
WePeB5897 Youth and Survival: Developing a life-skills
curriculum to assist HIV affected, infected and
at-risk youth with transitional process into
adulthood
K.C. Sanchez. University of Miami School of Medicine Department of Pediatrics,
4420 nw 197street, miami, fl, 33055, United States
Issues: Adolescents (thirteen through twenty-one years of age) should be guided
through their developmental passage into adulthood as young as possible. Little
attention is given to the fact that youth are actively engaged in adult behaviorand
practices (e.g. drug use, employment, sexual activity, childbearing, etc.). The lack
of poor role-modeling and the absence of adult support enhances their vulnerablility. Through youth-focused interventions, many adolescents can have the opportunity to develop healthier, more productive lifestyles. Poverty, hunger, poor
education, violence in the neighborhood and home, and single-parent households
are some of the variables that may contribute to a young adults' obstacles towards
establishing themselves as a productive member of society.
Description: At the University of Miami School of Medicine Special Adolescent
Clinic (for HIV infected and at-rsk youth) the social workers developed a 10-week
program targetting adolescents living in the Miami-Dade County community. This
ten week course is holistic in nature focusing on an enriched didactic, experiential two hour intervention session with an unlimited number of participants, that
allows them to put into practice what they have learned. The topics include communication and problem-solving skills, job-readiness, human sexuality, health, nutrition, and independent living. A Manual contains lesson plans that help guide the
facilliatators through classroom activities and homework assignments. At the successful completion of the 10-week series, all participants receive a certificate of
completion upon "graduation".
Lessons learned: The key to the success of this model is in the high engagement of client participation, providing token incentives, and keeping the lesson
plan simple.
Recommendation: This low-cost/high-return intervention model can be easily
replicated by any organization for use with urban/inner city youth.
Presenting author: kenia sanchez, 4420 nw 197 street, miami, fl, 33055, United
States, Tel.: +[phone], Fax: +[phone], E-mail: ksanchez@med.
miami.edu