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 poor adherence to therapy could impact the efficacy of this approach.


OBJECTIVE
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.


METHODS
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.
Machado
Elizabeth S
ES
Serviço de Doenças Infecciosas e Parasitárias, Hospital Universitário Clementino Fraga Filho, Rio de Janeiro, Brazil. emachado@biologia.ufrj.br
Lambert
John S
JS
Watson
Douglas C
DC
Afonso
Adriana O
AO
da Cunha
Silvia M
SM
Nogueira
Susie A
SA
Caride
Elena
E
Oliveira
Ricardo H
RH
Sill
Anne M
AM
DeVico
Anthony
A
Tanuri
Amilcar
A
D000293:Adolescent; D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001938:Brazil; D018791:CD4 Lymphocyte Count; D002648:Child; D002675:Child, Preschool; D018076:DNA, Complementary / Q000737:chemistry / Q000302:isolation & purification; D024882:Drug Resistance, Viral / Q000235:genetics*; D004359:Drug Therapy, Combination; D019143:Evolution, Molecular; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology*; D016333:HIV Protease / Q000235:genetics; D054303:HIV Reverse Transcriptase / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D007223:Infant; D008297:Male; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D012367:RNA, Viral / Q000097:blood / Q000302:isolation & purification; D012641:Selection, Genetic; D017422:Sequence Analysis, DNA; D019562:Viral Load; D014766:Viremia
D019380:Anti-HIV Agents; D018076:DNA, Complementary; D012367:RNA, Viral; D054303:HIV Reverse Transcriptase; D016333:HIV Protease