Genotypic resistance and HIV-1 subtype in Brazilian children on dual and triple combination therapy

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 p...

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Published in:	Journal of clinical virology Vol. 30; no. 1; pp. 24 - 31
Main Authors:	Machado, Elizabeth S, Lambert, John S, Watson, Douglas C, Afonso, Adriana O, da Cunha, Silvia M, Nogueira, Susie A, Caride, Elena, Oliveira, Ricardo H, Sill, Anne M, DeVico, Anthony, Tanuri, Amilcar
Format:	Journal Article
Language:	English
Published:	Amsterdam Elsevier B.V 01-05-2004 Elsevier Science
Subjects:	Adolescent Anti-HIV Agents - pharmacology Anti-HIV Agents - therapeutic use Biological and medical sciences Brazil CD4 Lymphocyte Count Child Child, Preschool Combination therapy DNA, Complementary - chemistry DNA, Complementary - isolation & purification Drug Resistance, Viral - genetics Drug Therapy, Combination Evolution, Molecular Female Fundamental and applied biological sciences. Psychology Genotypic resistance HIV Infections - drug therapy HIV Infections - immunology HIV Infections - virology HIV Protease - genetics HIV Reverse Transcriptase - genetics HIV-1 - drug effects HIV-1 - genetics HIV-1 - isolation & purification HIV-1 subtype Human immunodeficiency virus Human immunodeficiency virus 1 Human viral diseases Humans Infant Infectious diseases Male Medical sciences Microbiology Miscellaneous Molecular Sequence Data Mutation, Missense RNA, Viral - blood RNA, Viral - isolation & purification Selection, Genetic Sequence Analysis, DNA Viral diseases Viral diseases of the lymphoid tissue and the blood. Aids Viral Load Viremia Virology South America Brazil America Combination therapy Genotypic resistance HIV-1 subtype Human Immunopathology Drug combination Typing Microbiology HIV-1 virus Retroviridae Genotype AIDS Immune deficiency Lentivirus Virology Infection Virus Resistance Microbiological investigation Viral disease Combined treatment Human immunodeficiency virus Child Subtype
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Summary:	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-naı̈ve 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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1386-6532 1873-5967
DOI:	10.1016/j.jcv.2003.08.001