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Frequency of resistant virus and options for a second-line treatment for HIV-1 infected children under HAART in Mozambique

Article (PDF Available) inRetrovirology 6(Suppl 1) · July 2009with21 Reads
DOI: 10.1186/1742-4690-6-S1-O24 · Source: DOAJ
Abstract
Background: Resistance outcome for treated children in low resource countries is scarce. We aimed to describe the type and frequency of viral resistance in children with > 12 months of WHO advised highly active antiretroviral therapy (HAART) in a large access program in Mozambique. Methods: Between Dec 2003 and Dec 2006, 515 children (median age: 36.8 m) were included, 97% received a combination of d4T plus 3TC and nevirapine. HIV-1 RNA was transversally performed once using the Roche Amplicor v1.5 test. HIV-1 genotypic resistance tests were performed on available plasma samples when HIV-1 RNA was > 3 log10 copies/ml. Drug resistance was interpreted according to the 2007 French ANRS algorithm. Results: Viral load was available for 498 out of the 515 children. Among them, 134 had a viral load > 3 log10 copies/ml and genotypic resistance test could be performed for 87 children. The overall frequency of viruses showing genotypic resistance to at least 1 antiretroviral drug was 90%. The prevalences of children with ≥ 1 major mutation conferring drug resistance to NRTIs and NNRTIs were 85% and 90%, respectively. M184V was the most common NRTI mutation. Thymidine analogs mutations (TAMs) conferring resistance to ZDV or d4T were observed in 15%. Resistance to Tenofovir, Abacavir and ddI were described in 6%, 5% and 3.5% respectively. The NRTIs Multi Drug Resistance complex (Q151M) was found in 3 cases. Unexpectidely, five children (6%) had developed extensive resistance to NNRTIs inducing resitance to the new NNRTI etravirine. Conclusions: After experiencing failure with HAART containing 2 drugs with low genetic barrier, almost all children have at least lamivudine and NNRTI resistance. Broad spectrum resistances to second NRTIs line (ddI, ABC,TDF) concerned 6% of children. Multi drug resistance to all NRTIs was found in 3.5%.
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Retrovirology
Open Access
Oral presentation
Frequency of resistant virus and options for a second-line treatment
for HIV-1 infected children under HAART in Mozambique
Marie-Laure Chaix*1, Ilesh Jani2, Eugenia Macassa2, Dulce Bila2,
Adolfo Vubil2, Soren Andersson3, Christine Rouzioux1, Paula Vaz2 and
Stéphane Blanche1
Address: 1EA 3620 Université Paris Descartes, CHU Necker, Paris, France, 2Hospital Central de Maputo, Instituto Nacional de Saude, Mozambique
and 3Karolinska Institute Stockholm, Sweden
* Corresponding author
Background
Resistance outcome for treated children in low resource
countries is scarce. We aimed to describe the frequency
and the profile of resistant virus in children treated with at
least 12 months of WHO advised highly active antiretro-
viral therapy (HAART) in a large access program in
Mozambique.
Methods
Between December 2003 and December 2006, 515 chil-
dren (median age: 36.8 months) were included, 97%
received a combination of d4T plus 3TC and nevirapine.
HIV-1 RNA was transversally performed once using the
Roche Amplicor v1.5 test. HIV-1 genotypic resistance tests
were performed on available plasma samples when HIV-1
RNA was > 3 log10 copies/ml. Drug resistance was inter-
preted according to the 2007 French ANRS resistance algo-
rithm.
Results
Viral load was available for 498 out of the 515 children.
Among them, 134 (27%) had a viral load > 3 log10 cop-
ies/ml and genotypic resistance test could be performed
for 87 children. The overall frequency of viruses showing
genotypic resistance to at least 1 antiretroviral drug was
90%. The prevalence of children infected with virus with
1 major mutation conferring drug resistance to NRTIs
and NNRTIs were 85% and 90%, respectively. M184V
conferring resistance to lamivudine was the most com-
mon NRTI mutation. Thymidine analogs mutations
(TAMs) conferring resistance to ZDV or d4T were
observed in 15%. Resistance to Tenofovir, Abacavir and
ddI were described in 6%, 5% and 3.5% respectively. The
NRTIs Multi Drug Resistance complex (Q151M) was
found in 3 cases. Unexpectidely, five children (6%) had
developed extensive resistance to NNRTIs inducing resi-
tance to the new NNRTI etravirine (TMC 125). The only
factor identified by multivariate analysis as being associ-
ated with this broad spectrum resistance was the duration
of treatment: aOR: 10.15 [95% CI 1.59–64.94], p < 0.05
for treatment for longer than 24 months. The level of viral
replication at the time of genotyping was not predictive.
Conclusion
After experiencing failure with HAART containing two
drugs with low genetic barrier, almost all children have at
least lamivudine and NNRTI resistance. Broad spectrum
resistances to second NRTIs line (ddI, ABC, TDF) con-
cerned 6% of children. Multi drug resistance to all NRTIs
was found in 3.5%. Resistance to etravirine was descibed
in five children (6%).
from Fifth Dominique Dormont International Conference. Mother-to-child transmitted viral diseases: from transmission to children care
Paris, France. 26–28 March 2009
Published: 22 July 2009
Retrovirology 2009, 6(Suppl 1):O24 doi:10.1186/1742-4690-6-S1-O24
<supplement> <title> <p>Fifth Dominique Dormont International Conference. Host-Pathogen Interactions in Chronic Infections</p> </title> <note>Meeting abstracts – A single PDF containing all abstracts in this Supplement is available <a href="http://www.biomedcentral.com/content/files/pdf/1742-4690-6-S1-full.pdf">here</a>.</note> <url>http://www.biomedcentral.com/content/pdf/1742-4690-6-S1-info.pdf</url> </supplement>
This abstract is available from: http://www.retrovirology.com/content/6/S1/O24
© 2009 Chaix et al; licensee BioMed Central Ltd.
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