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

• Published in: Journal of clinical virology 2004-05, Vol.30 (1), p.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: Article
• Language: English
• 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
• ISSN: 1386-6532; 1873-5967
• DOI: 10.1016/j.jcv.2003.08.001

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.