Bergonzi, S.

Manfredi, R.

Sabbatani, S.

International Journal of Infectious Diseases

English

Elsevier - Publisher Connector 

13th International Congress on Infectious Diseases Abstracts, Poster Presentations e205
25.014
Cellular Antigen Stimulation Test (CAST) as a Novel,
Affordable Laboratory Technique to Assess Potential
Hypersensitivity to All Available Antiretroviral Com-
pounds
R. Manfredi1,∗, S. Sabbatani1, S. Bergonzi2
1 Department of Infectious Diseases, University of Bologna,
S. Orsola Hospital, Bologna, Italy
2 Department of Pathology, ‘Maggiore’ General Hospital,
Bologna, Italy
Introduction: Recently,novel allergometric techniques
allow to test inhalants,food,and also drugs by speciﬁc
in vitro assays. A ﬂow cytometry technique based on
the search of sulphidoleukotrienes LCT4, LTD4 and LTE4
released by basophils stimulated in vitro by IL-3 in
presence of the examined antigens (cellular antigen stim-
ulation test,or CAST), has a 80—90% sensitivity-speciﬁcity
rate,and becomes particularly useful when prick tests are
not applicable, and allergic reactions are not mediated
by allergen-speciﬁc IgE immunoglobulins.Methods-Results:
During the past three years, 13 HIV-infected subjects (eight
females and ﬁve males, aged 37—52 years),underwent a
standardized, speciﬁc in vitro cellular antigen stimulation
test (CAST),due to serious cutaneous (six cases),systemic
(two patients), and combined cutaneous-systemic hyper-
sensitivity reactions (ﬁve subjects),apparently not elicited
by the introduction of abacavir and nevirapine (which are
the antiretroviral agents burdened by the greatest fre-
quency of expected early allergic reactions,mediated by
already recognized pathogenetic mechanisms). Based on the
results of CAST testing, an allergic intolerance to ritonavir
(six cases), lopinavir,nelﬁnavir, and didanosine (three cases
each), saquinavir and lamivudine (two cases), and fosam-
prenavir,zidovudine, zalcitabine, stavudine, and efavirenz
(one case each), was documented: in 10 cases out of 13
(76.9.5%) multiple intolerances were detected. A perfect
relationship was documented between the results of CAST
testing and the panel of combined antiretroviral compounds
recently experienced by each allergic patient,and a CAST-
based elimination of in vitro allergenic molecules allowed a
rapid introduction of another effective antiretroviral com-
bination.
Conclusions: Adverse events to antiretroviral drugs are
quite frequent among HIV-infected patients, compared
with the general population. Further,controlled studies are
needed to implement in vitro allergometric testing in
patients treated for HIV infection,who are exposed to unpre-
dictable drug intolerance reactions. In fact,HIV-infected
subjects may suffer from frequent allergic drug reactions
which may be difﬁcult to be systematically recognized (due
to the frequent,multiple concurrent pharmacotherapy, and
the combined antiretroviral therapy itself).
doi:10.1016/j.ijid.2008.05.508
25.015
HIV Genotypes and Patterns of Drug Resistance in Patients
Failing HAART in a University Hospital Clinic
G. Revathi ∗, M. Bholla, P. Wangai, R. Harania, P. Ojwang
The Aga Khan University Hospital, Nairobi, Kenya
Background: HAART strategies yield excellent results in
drug na¨ıve patients starting ﬁrst-line treatment. Yet, data
from clinical cohorts indicate drug resistance emerging as
a consequence of toxicity, drug interactions or adherence
problems leading to sub-optimal serum drug concentrations.
The Aga Khan University Hospital, Nairobi, has compre-
hensive HIV care services since 2003 at the one stop clinic.
About 500 patients are on current follow-up by standard
international protocols.
Methods: Over one year, 38 patients failed ART and
were referred to the laboratory for resistance testing per-
formed by population sequencing technique using VIRASEQ
(Abbott) by manufacturer’s protocol. All clinical details
were recorded during sample collection.
Results: All patients belonged to a high socioeconomic
group with corporate health insurance cover and claimed
excellent drug adherence.
Patient age ranged from 6 to 57 years with a median
of 38 years. CD4 counts ranged from 12 to 450 with a
median of 135. Viral loads ranged from 2100 to 13 mil-
lion with a median of 140,000. 82% (31/38) of patients had
multiple hospital admissions indicating 2 to 5 episodes of
opportunistic infections of which TB (14 patients), PCP (11
patients), Cryptococcosis (10 patients) and Salmonellosis (8
patients) were most common. 4 patients had 3 simultane-
ous opportunistic infections. 6 patients had 2 simultaneous
opportunistic infections. Only 8 patients were on second-line
HAART which included boosted PI. 9 patients used ARVs for
over 10 years. A, D and CRFO1 were predominant subtypes.
Major NRTI/NNRTI mutations were seen in 80% of patients
while major PI mutations were seen in 8% of patients. High-
level resistance was seen to Tenofovir in 8% of patients,
Nevirapine, Efaverenz, 3TC & FTC in 80% of patients and
AZT in 29% of patients.
Conclusions: In the long run, high-level multiple resis-
tance is inevitable in patients on HAART, with serious
implications for national ARV programs and prophylactic reg-
imens.
doi:10.1016/j.ijid.2008.05.509
25.016
Multi-Pronged Strategy Greatly Enhances Enrollment of
HIV Positive Children Into HIV Care and Treatment: Expe-
rience from Uganda
E.M. Namagala ∗, H. Balidawa, E. Madraa
STD/AIDS Control Program, Ministry of Health, Kampala,
Uganda
Background: Although Uganda had successfully rolled out
Antiretroviral therapy (ART) in HIV-infected adults, enroll-
ment of children aged less than 15 years onto ART had
generally been very slow. However, the implementation of a
multi-pronged strategy for scaling-up pediatric HIV care has


Cellular Antigen Stimulation Test (CAST) as a Novel, Affordable Laboratory Technique to Assess Potential Hypersensitivity to All Available Antiretroviral Compounds 

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13th International Congress on Infectious Diseases Abstracts, Poster Presentations e20525.014Cellular Antigen Stimulation Test (CAST) as a Novel,Affordable Laboratory Technique to Assess PotentialHypersensitivity to All Available Antiretroviral Com-poundsR. Manfredi1,∗, S. Sabbatani1, S. Bergonzi21 Department of Infectious Diseases, University of Bologna,S. Orsola Hospital, Bologna, Italy2 Department of Pathology, ‘Maggiore’ General Hospital,Bologna, ItalyIntroduction: Recently,novel allergometric techniquesallow to test inhalants,food,and also drugs by specificin vitro assays. A flow cytometry technique based onthe search of sulphidoleukotrienes LCT4, LTD4 and LTE4released by basophils stimulated in vitro by IL-3 inpresence of the examined antigens (cellular antigen stim-ulation test,or CAST), has a 80—90% sensitivity-specificityrate,and becomes particularly useful when prick tests arenot applicable, and allergic reactions are not mediatedby allergen-specific IgE immunoglobulins.Methods-Results:During the past three years, 13 HIV-infected subjects (eightfemales and five males, aged 37—52 years),underwent astandardized, specific in vitro cellular antigen stimulationtest (CAST),due to serious cutaneous (six cases),systemic(two patients), and combined cutaneous-systemic hyper-sensitivity reactions (five subjects),apparently not elicitedby the introduction of abacavir and nevirapine (which arethe antiretroviral agents burdened by the greatest fre-quency of expected early allergic reactions,mediated byalready recognized pathogenetic mechanisms). Based on theresults of CAST testing, an allergic intolerance to ritonavir(six cases), lopinavir,nelfinavir, and didanosine (three caseseach), saquinavir and lamivudine (two cases), and fosam-prenavir,zidovudine, zalcitabine, stavudine, and efavirenz(one case each), was documented: in 10 cases out of 13(76.9.5%) multiple intolerances were detected. A perfectrelationship was documented between the results of CASTtesting and the panel of combined antiretroviral compoundsrecently experienced by each allergic patient,and a CAST-based elimination of in vitro allergenic molecules allowed arapid introduction of another effective antiretroviral com-bination.Conclusions: Adverse events to antiretroviral drugs arequite frequent among HIV-infected patients, comparedwith the general population. Further,controlled studies areneeded to implement in vitro allergometric testing inpatients treated for HIV infection,who are exposed to unpre-dictable drug intolerance reactions. In fact,HIV-infectedsubjects may suffer from frequent allergic drug reactionswhich may be difficult to be systematically recognized (dueto the frequent,multiple concurrent pharmacotherapy, andthe combined antiretroviral therapy itself).doi:10.1016/j.ijid.2008.05.50825.015HIV Genotypes and Patterns of Drug Resistance in PatientsFailing HAART in a University Hospital ClinicG. Revathi ∗, M. Bholla, P. Wangai, R. Harania, P. OjwangThe Aga Khan University Hospital, Nairobi, KenyaBackground: HAART strategies yield excellent results indrug näıve patients starting first-line treatment. Yet, datafrom clinical cohorts indicate drug resistance emerging asa consequence of toxicity, drug interactions or adherenceproblems leading to sub-optimal serum drug concentrations.The Aga Khan University Hospital, Nairobi, has compre-hensive HIV care services since 2003 at the one stop clinic.About 500 patients are on current follow-up by standardinternational protocols.Methods: Over one year, 38 patients failed ART andwere referred to the laboratory for resistance testing per-formed by population sequencing technique using VIRASEQ(Abbott) by manufacturer’s protocol. All clinical detailswere recorded during sample collection.Results: All patients belonged to a high socioeconomicgroup with corporate health insurance cover and claimedexcellent drug adherence.Patient age ranged from 6 to 57 years with a medianof 38 years. CD4 counts ranged from 12 to 450 with amedian of 135. Viral loads ranged from 2100 to 13 mil-lion with a median of 140,000. 82% (31/38) of patients hadmultiple hospital admissions indicating 2 to 5 episodes ofopportunistic infections of which TB (14 patients), PCP (11patients), Cryptococcosis (10 patients) and Salmonellosis (8patients) were most common. 4 patients had 3 simultane-ous opportunistic infections. 6 patients had 2 simultaneousopportunistic infections. Only 8 patients were on second-lineHAART which included boosted PI. 9 patients used ARVs forover 10 years. A, D and CRFO1 were predominant subtypes.Major NRTI/NNRTI mutations were seen in 80% of patientswhile major PI mutations were seen in 8% of patients. High-level resistance was seen to Tenofovir in 8% of patients,Nevirapine, Efaverenz, 3TC & FTC in 80% of patients andAZT in 29% of patients.Conclusions: In the long run, high-level multiple resis-tance is inevitable in patients on HAART, with seriousimplications for national ARV programs and prophylactic reg-imens.doi:10.1016/j.ijid.2008.05.50925.016Multi-Pronged Strategy Greatly Enhances Enrollment ofHIV Positive Children Into HIV Care and Treatment: Expe-rience from UgandaE.M. Namagala ∗, H. Balidawa, E. MadraaSTD/AIDS Control Program, Ministry of Health, Kampala,UgandaBackground: Although Uganda had successfully rolled outAntiretroviral therapy (ART) in HIV-infected adults, enroll-ment of children aged less than 15 years onto ART hadgenerally been very slow. However, the implementation of amulti-pronged strategy for scaling-up pediatric HIV care has

Cellular Antigen Stimulation Test (CAST) as a Novel, Affordable Laboratory Technique to Assess Potential Hypersensitivity to All Available Antiretroviral Compounds

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Cellular Antigen Stimulation Test (CAST) as a Novel, Affordable Laboratory Technique to Assess Potential Hypersensitivity to All Available Antiretroviral Compounds

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