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Early multitherapy including a protease inhibitor for human immunodeficiency virus type 1-infected infants
Albert Faye1, Catherine Bertone, Jean Paul Teglas
1Service d'Hémato-immunologie, Hĵpital R. Debré, Paris, France. albert.faye@rdb.ap-hop-paris.fr
Insights
Early antiretroviral therapy in infants with HIV showed no clinical progression but frequent virologic failure and resistance. Suboptimal protease inhibitor dosing may contribute to these challenges in pediatric HIV treatment.
Area of Science:
- Pediatric Infectious Diseases
- HIV/AIDS Research
- Antiretroviral Therapy
Background:
- Assessing the tolerance and efficacy of early combination antiretroviral therapy (cART) in infants with perinatally acquired human immunodeficiency virus (HIV).
- Evaluating the impact of protease inhibitor-based multitherapy initiated before one year of age.
Purpose of the Study:
- To evaluate the tolerance and clinical and immunovirologic outcomes of early multitherapy in HIV-infected infants.
- To identify factors influencing treatment response and resistance development.
Main Methods:
- An observational study within the French Perinatal Study cohort.
- Inclusion of 31 HIV-infected infants treated with multitherapy before age one.
- Monitoring of clinical status, immunologic markers (CD4 percentage), and HIV RNA viral load over a median of 27 months.
Main Results:
- No infant experienced clinical or immunologic progression. Mild to moderate adverse events occurred in 15 infants.
- Median viral load reduction observed, but the proportion of infants with viral load <500 copies/ml decreased over time.
- Virologic failure after 6 months was associated with antiretroviral resistance mutations; early viral load decrease slope predicted response.
Conclusions:
- Early cART in infants did not prevent clinical progression but was associated with high rates of virologic failure and emergent drug resistance.
- Suboptimal protease inhibitor dosing is a potential factor contributing to treatment failure in this pediatric population.
- Challenges remain in implementing effective long-term antiretroviral therapy for infants with HIV.
Background:
To assess tolerance and efficacy of early multitherapy including a protease inhibitor for infants perinatally infected with HIV.
Methods:
Observational study of tolerance and clinical and immunovirologic evolution in HIV-infected infants treated before the age of 1 year in the French Perinatal Study.
Results:
Thirty-one infants were included. The median age was 3.7 months at initiation of multitherapy. Clinical stage was C (n = 8), B (n = 5) or A/N (n = 18). The median HIV RNA viral load was 5.8 log copies/ml, and the median CD4 cell percentage was 29%. Median follow-up of treatment was 27 months. Of 31 infants 15 experienced mild to moderate adverse events. No infant had clinical or immunologic progression. The median change in viral load was -2.7 log copies/ml after 3 months, -2.0 log after 12 months and -1.7 log after 24 months of treatment. The proportion of infants with a viral load below 500 copies/ml decreased from 53% at 6 months to 18% at 24 months of treatment. The virologic response was not correlated with viral load at baseline. However, the slope of the viral load decrease during the first month of treatment was predictive of the virologic response at 3 and 6 months. Fourteen infants with a viral load of >500 copies/ml after 6 months of treatment displayed viruses with antiretroviral resistance mutations in reverse transcriptase and/or protease genes.
Conclusions:
Despite the absence of clinical or immunologic progression, the high frequency of virologic failure associated with genotypic resistance reveals the difficulties associated with implementing antiretroviral multitherapy in infants. Suboptimal doses of protease inhibitor could be a factor contributing to treatment failure.