Analysis of HIV- type 1 protease and reverse transcriptase in Brazilian children failing highly active antiretroviral therapy (HAART)

• Published in: Revista do Instituto de Medicina Tropical de São Paulo Vol. 47; no. 1; pp. 1 - 5
• Main Authors: Machado, Daisy Maria, Fernandes, Silvana Cláudia, Succi, Regina Célia de Menezes, Freire, Wilton Santos, Pannuti, Cláudio Sérgio, Gouveia, Aída Barbosa, Levi, José Eduardo, Diaz, Ricardo Sobie
• Format: Journal Article
• Language: English; Portuguese
• Published: Brazil Instituto de Medicina Tropical de Sao Paulo 2005; Instituto de Medicina Tropical
• Subjects: Adolescent; Adult; Anti-HIV Agents - therapeutic use; Antiretroviral Therapy, Highly Active; Brazil; Child; Child, Preschool; Drug Resistance, Viral - genetics; Genotype; HIV Infections - drug therapy; HIV Infections - virology; HIV Protease - genetics; HIV Reverse Transcriptase - genetics; HIV-1 - drug effects; HIV-1 - enzymology; HIV-1 - genetics; Humans; Infant; Mutation; Polymerase Chain Reaction; RNA, Viral - genetics; Treatment Failure; TROPICAL MEDICINE; Viral Load; Brazil; Treatment failure; Children; HIV resistance; Antiretroviral therapy
• ISSN: 0036-4665; 1678-9946; 1678-9946; 0036-4665
• DOI: 10.1590/s0036-46652005000100001

The aim of this study was to evaluate the genotypic resistance profiles of HIV-1 in children failing highly active antiretroviral therapy (HAART). Forty-one children (median age = 67 months) receiving HAART were submitted to genotypic testing when virological failure was detected. cDNA was extracted from PBMCs and amplified by nested PCR for the reverse transcriptase and protease regions of the pol gene. Drug resistance genotypes were determined from DNA sequencing. According to the genotypic analysis, 12/36 (33.3%) and 6/36 (16.6%) children showed resistance and possible resistance, respectively, to ZDV; 5/36 (14%) and 4/36 (11.1%), respectively, showed resistance and possible resistance to ddI; 4/36 (11.1%) showed resistance to 3TC and D4T; and 3/36 (8.3%) showed resistance to Abacavir. A high percentage (54%) of children exhibited mutations conferring resistance to NNRTI class drugs. Respective rates of resistance and possible resistance to PIs were: RTV (12.2%, 7.3%); APV (2.4%, 12.1%); SQV(0%, 12.1%); IDV (14.6%, 4.9%), NFV (22%, 4.9%), LPV/RTV (2.4%, 12.1%). Overall, 37/41 (90%) children exhibited virus with mutations related to drug resistance, while 9% exhibited resistance to all three antiretroviral drug classes.