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High Frequency of Mutations Associated to Antiretroviral Drug Resistance in Recently Diagnosed HIV-infected Children
Moira Vignoles*1, S González-Ayala2, G Barboni3, M R Agosti2, V Giraudi3, and H Salomón1
1Argentinian Natl Reference Ctr for AIDS, Buenos Aires; 2Superiora Sor María Ludovica Hosp, La Plata, Argentina; and 3“Dr. Pedro de Elizalde” Children Hosp, Buenos Aires, Argentina
Background: The
efficacy of ART to prevent mother-to-child transmission (MTCT) has been widely
proven. Since 1993, Argentina
has had the AIDS National Law that protects and guaranties universal and free
ART to every HIV-infected person. In spite of this, in Argentina, as
in many other under-developed countries, many children every year are infected
vertically. HIV treatment failure can have a variety of causes, including
limited drug potency, poor adherence to regimens, and variations in drug
metabolism. Yet, one of the most important factors associated with treatment
failure is the transmission of viral strains resistant to ART. The aim of our
study was to evaluate the presence of HIV variants susceptible or resistant to
ART in children with recent HIV diagnosis.
Methods: We evaluated 41 recently diagnosed HIV-infected children
(born to HIV-infected mothers). Patients were recruited from December 2004
until September 2005. Genotypic sequencing of pol
gene, with further Stanford
University
drug-resistance analysis, was performed. Plasma viral load and T lymphocytes
count were also measured.
Results:
Of 41 children, 4 (9.75%) had viral strains with at least 1 mutation
associated with ART resistance. These were:
L74V, K103N, V108I, Y181C, M184V, G190A, M46I, V118I, and T215I,
conferring resistance to almost all nucleoside reverse transcription inhibitors
(NRTI) and non-NRTI (NNRTI—didanosine, dideoxycytidine, abacavir, nevirapine, delavairdine, efavirenz, lamivudine, emtricitabine, zidovudine) and indinavir. Median
viral load was 5.7 log10, (range 3.34 to >5.7 copies/mL) and CD4 T
lymphocytes median percentage was 16.0%
(range 1 to 49%).
Conclusions: A high
percentage of children who have been infected with virus that have mutations
associated to ART resistance were found among the population studied. This will
certainly have serious implications in their progression to AIDS, as it may
reduce the choice of active antiretroviral drugs. These results demonstrate
that in developing countries, such as Argentina, where HIV MTCT is frequent,
monitoring of drug resistance in children prior to treatment should be
mandatory.
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