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HIV-1 DIVERSITY AND DRUG RESISTANCE IN TREATMENT-NAÏVE CHILDREN AND ADOLESCENTS FROM RIO DE JANEIRO, BRAZIL
Author
Affilliation
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de AIDS e Imunologia Molecular. Rio de Janeiro, RJ, Brasil.
Universidade Federal do Espírito Santo—UFES. Centro de Ciências Exatas, Naturais e da Saúde. Departamento de Biologia. Vitória. ES, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de AIDS e Imunologia Molecular. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de AIDS e Imunologia Molecular. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de AIDS e Imunologia Molecular. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de AIDS e Imunologia Molecular. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de AIDS e Imunologia Molecular. Rio de Janeiro, RJ, Brasil.
Universidade Federal do Espírito Santo—UFES. Centro de Ciências Exatas, Naturais e da Saúde. Departamento de Biologia. Vitória. ES, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de AIDS e Imunologia Molecular. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de AIDS e Imunologia Molecular. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de AIDS e Imunologia Molecular. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de AIDS e Imunologia Molecular. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de AIDS e Imunologia Molecular. Rio de Janeiro, RJ, Brasil.
Abstract
The human immunodeficiency virus type 1 (HIV-1) can be transmitted via parenteral,
sexual, or vertical exposure routes. The number of HIV-1 cases detected yearly in children and
adolescents in Brazil did not decrease over the last decade, representing ~5% of total cases described
in the country. In recent years, the HIV-1 diversity and the prevalence of transmitted drug resistance
mutations (TDRM) are moving toward a marked increase. In this study, we retrospectively evaluated
the diversity of HIV-1 subtypes and the TDRM prevalence in 135 treatment-naïve HIV-1 vertically
infected children and adolescents born in between 1993 and 2012. These children were assessed
in either 2001–2007 or 2008–2012 when they were 0 to 17 years old. The individuals assessed in
2001–2007 (n = 38) had median CD4+ T cell counts of 1218 cells/mm3 (IQR: 738–2.084) and median
HIV-1 plasma viral load of 4.18 log10 copies/mL (IQR: 3.88–4.08). The individuals (n = 97) evaluated
in 2008–2012 showed median CD4+ T cell counts of 898.5 cells/mm3 (IQR: 591.3–1.821) and median
HIV-1 plasma viral load of 4.69 log10 copies/mL (IQR: 4.26–5.33). A steady decrease in the median
CD4 T+ cell counts was observed with age progression, as expected. The majority HIV-1 pol sequences
(87%) were classified as pure HIV-1 subtypes (77% subtype B, 9% subtype F1 and 1.5% subtype C),
while 13% of sequences were classified as recombinants (CRF45_cpx, n = 4; CRF28/29_BF1, n = 2;
CRF02_AG, n = 1; CRF40_BF1, n = 1, CRF99_BF1, n = 1, URF_BF1, n = 8). The overall prevalence
of TDRM was 14% (19/135), conferring resistance to the nucleoside reverse transcriptase inhibitors
(NRTI, 13/135–9.6%), non-nucleoside reverse transcriptase inhibitors (NNRTI, 8/135–5.9%), and
protease inhibitors (PI, 2/135–1.5%). The main TDRM observed for NNRTI was the K103N (n = 8),
while the mutations T215I/Y/D/E (n = 7) and M184V (n = 4) were the main TDRM for NRTI. Only
two TDRM were observed for PI in one individual each (M46I and V82A). Most TDRM were found in
the HIV-1 subtype B (84%) sequences. This study reveals an HIV-1 epidemic with high diversity and
moderate prevalence of TDRM in the pediatric population of Rio de Janeiro, indicating the existence
of possible problems in the clinical management of prophylactic therapy to prevent mother-to-child
transmission and future treatment options for the affected children.
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