Long-term virologic response and genotypic resistance mutations in HIV-1 infected Kenyan children on combination antiretroviral therapy

Abstract

Background: HIV-infected children may require the use of combination antiretroviral treatment (cART) into adulthood. However, regimens are limited to first line and second line in many African settings. Therefore, understanding the long-term rate of virologic failure and drug resistance during prolonged antiretroviral treatment is important for establishing treatment strategies in African pediatric cohorts.

Methods: Children aged 18 months to 12 years initiated first-line cART and were followed every 1-3 months, for up to 5.5 years. Treatment was switched to second-line cART based on clinical and immunologic criteria according to national guidelines. Virologic failure was determined retrospectively as defined by ≥2 viral loads >5000 copies per milliliter. Drug resistance was assessed during viral failure by population-based sequencing.

Results: Among 100 children on first-line cART followed for a median of 49 months, 34% children experienced virologic failure. Twenty-three (68%) of the 34 children with viral failure had detectable resistance mutations, of whom 14 (61%) had multiclass resistance. Fourteen (14%) children were switched to second-line regimens and followed for a median of 28 months. Retrospective analysis revealed that virologic failure had occurred at a median of 12 months before switching to second line. During prolonged first-line treatment in the presence of viral failure, additional resistance mutations accumulated; however, only 1 (7%) of 14 children had persistent viremia during second-line treatment.

Discussion: Virologic suppression was maintained on first-line cART in two-thirds of HIV-infected children for up to 5 years. Switch to second line based on clinical/immunologic criteria occurred ∼1 year after viral failure, but the delay did not consistently compromise second-line treatment.

Figure 1. Viral load and CD4 kinetics during first-line cART

Changes in (A) log₁₀ viral load and (B) CD4 percent during first-line cART in the 100 children included in the study. The horizontal bar at the center of each box plot represents the median value, the top and bottom of each box are the 75^th and 25^th percentiles, respectively. The upper bound and lower bounds of the whiskers are the largest data point ≤ 75^th percentile + 1.5*IQR and the smallest data point ≥ 25^th percentile − 1.5*IQR, respectively. Observed data points beyond these bounds are plotted as filled circles.