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

Area of Science:

• Pediatric infectious diseases
• HIV/AIDS research
• Virology

Background:

• Antiretroviral therapy (ART) is crucial for HIV-infected individuals, with Brazilian guidelines recommending dual or triple therapy for children.
• Efficacy of ART can be compromised by drug-resistant strains and poor adherence.
• Understanding treatment history's impact on resistance and immune response is vital for optimizing pediatric HIV care.

Purpose of the Study:

• To investigate the relationship between RNA levels, CD4+ T-cell counts, treatment history, and drug-resistant variants in HIV-1-infected children in Rio de Janeiro.
• To assess virologic and immunological responses to ART based on treatment history and drug resistance.

Main Methods:

• Direct sequencing of reverse transcriptase and protease genes from plasma samples.
• Monitoring changes in HIV-1 RNA levels and CD4+ T-cell counts from baseline to assess treatment response.
• Categorizing patients based on dual or triple therapy regimens and antiretroviral history.

Main Results:

• Patients with prior antiretroviral (ARV) exposure showed higher frequencies of drug-resistance mutations and cross-resistance.
• Antiretroviral-naïve subjects exhibited greater increases in CD4+ T-cell counts and lower viral loads.
• Non-B HIV subtypes were associated with a smaller increase in CD4+ T-cell counts compared to B-subtypes.

Conclusions:

• Previous ARV use in HIV-infected Brazilian children is associated with reduced immunological recovery and increased drug resistance mutations due to prolonged drug selective pressure.
• These findings support the preferential use of triple drug combination therapy as a first-line regimen for children.
• Optimizing first-line ART regimens is critical for improving long-term outcomes in pediatric HIV infection.