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Genotypic resistance and HIV-1 subtype in Brazilian children on dual and triple combination therapy.
J Clin Virol. 2004 May; 30(1):24-31.JC

Abstract

BACKGROUND

Antiretroviral therapy is provided by the Brazilian Ministry of Health to eligible HIV-infected individuals. Based on clinical and immunological classification, the Brazilian guidelines recommend dual or triple therapy for children. However, the development of drug-resistant strains or poor adherence to therapy could impact the efficacy of this approach.

OBJECTIVES

We examined relationships between RNA levels, CD4+ T-cell counts, treatment history, and the prevalence of drug-resistant variants in a cohort of HIV-1-infected children in Rio de Janeiro, Brazil.

STUDY DESIGN

Direct sequencing of reverse transcriptase and protease genes from plasma was performed. Virologic and CD4+ T-cell counts responses to therapy were assessed by changes in HIV-1 RNA levels and CD4+ T-cell counts from baseline.

RESULTS

Thirty-seven patients were receiving dual therapy and 38 were on triple therapy at enrollment, segregated by antiretroviral history. Both groups had a higher increase in CD4+ T cell counts and a lower viral load in pre-treatment antiretroviral-naïve subjects. Notably, there was a direct correlation between the higher frequencies of drug-resistance mutations and cross-resistance with previous usage of antiretroviral (ARV) therapy in both groups. Non-B subtypes isolates were found in 21.3% of samples. A smaller increase in CD4+ T cell counts was found between non-B subtypes when compared to B-subtypes.

CONCLUSIONS

These results suggest that less immunological recovery and a higher number of mutations related to drug resistance were associated with previous usage of ARV and consequent higher time under drug selective pressure in these HIV-infected Brazilian children. These facts suggest the preferential use of triple drug combination as first line regimen in children.

Authors+Show Affiliations

Serviço de Doenças Infecciosas e Parasitárias, Hospital Universitário Clementino Fraga Filho, Rio de Janeiro, Brazil. emachado@biologia.ufrj.brNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15072750

Citation

Machado, Elizabeth S., et al. "Genotypic Resistance and HIV-1 Subtype in Brazilian Children On Dual and Triple Combination Therapy." Journal of Clinical Virology : the Official Publication of the Pan American Society for Clinical Virology, vol. 30, no. 1, 2004, pp. 24-31.
Machado ES, Lambert JS, Watson DC, et al. Genotypic resistance and HIV-1 subtype in Brazilian children on dual and triple combination therapy. J Clin Virol. 2004;30(1):24-31.
Machado, E. S., Lambert, J. S., Watson, D. C., Afonso, A. O., da Cunha, S. M., Nogueira, S. A., Caride, E., Oliveira, R. H., Sill, A. M., DeVico, A., & Tanuri, A. (2004). Genotypic resistance and HIV-1 subtype in Brazilian children on dual and triple combination therapy. Journal of Clinical Virology : the Official Publication of the Pan American Society for Clinical Virology, 30(1), 24-31.
Machado ES, et al. Genotypic Resistance and HIV-1 Subtype in Brazilian Children On Dual and Triple Combination Therapy. J Clin Virol. 2004;30(1):24-31. PubMed PMID: 15072750.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Genotypic resistance and HIV-1 subtype in Brazilian children on dual and triple combination therapy. AU - Machado,Elizabeth S, AU - Lambert,John S, AU - Watson,Douglas C, AU - Afonso,Adriana O, AU - da Cunha,Silvia M, AU - Nogueira,Susie A, AU - Caride,Elena, AU - Oliveira,Ricardo H, AU - Sill,Anne M, AU - DeVico,Anthony, AU - Tanuri,Amilcar, PY - 2003/03/20/received PY - 2003/08/07/revised PY - 2003/08/15/accepted PY - 2004/4/10/pubmed PY - 2004/8/6/medline PY - 2004/4/10/entrez SP - 24 EP - 31 JF - Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology JO - J Clin Virol VL - 30 IS - 1 N2 - BACKGROUND: Antiretroviral therapy is provided by the Brazilian Ministry of Health to eligible HIV-infected individuals. Based on clinical and immunological classification, the Brazilian guidelines recommend dual or triple therapy for children. However, the development of drug-resistant strains or poor adherence to therapy could impact the efficacy of this approach. OBJECTIVES: We examined relationships between RNA levels, CD4+ T-cell counts, treatment history, and the prevalence of drug-resistant variants in a cohort of HIV-1-infected children in Rio de Janeiro, Brazil. STUDY DESIGN: Direct sequencing of reverse transcriptase and protease genes from plasma was performed. Virologic and CD4+ T-cell counts responses to therapy were assessed by changes in HIV-1 RNA levels and CD4+ T-cell counts from baseline. RESULTS: Thirty-seven patients were receiving dual therapy and 38 were on triple therapy at enrollment, segregated by antiretroviral history. Both groups had a higher increase in CD4+ T cell counts and a lower viral load in pre-treatment antiretroviral-naïve subjects. Notably, there was a direct correlation between the higher frequencies of drug-resistance mutations and cross-resistance with previous usage of antiretroviral (ARV) therapy in both groups. Non-B subtypes isolates were found in 21.3% of samples. A smaller increase in CD4+ T cell counts was found between non-B subtypes when compared to B-subtypes. CONCLUSIONS: These results suggest that less immunological recovery and a higher number of mutations related to drug resistance were associated with previous usage of ARV and consequent higher time under drug selective pressure in these HIV-infected Brazilian children. These facts suggest the preferential use of triple drug combination as first line regimen in children. SN - 1386-6532 UR - https://www.unboundmedicine.com/medline/citation/15072750/Genotypic_resistance_and_HIV_1_subtype_in_Brazilian_children_on_dual_and_triple_combination_therapy_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1386653203002300 DB - PRIME DP - Unbound Medicine ER -