Background:  We previously described the stable medical outcomes of a cohort of HIV-infected children who underwent a partial treatment interruption of the protease inhibitor (PI) component of their combination ART. In this retrospective study, we examined the genotypic drug-resistance profiles of the subjects prior to and during the partial treatment interruption period. We elaborate on the unexpected finding that many of these patients maintained significant PI resistance despite the prolonged absence of PI drug pressure.

Methods:  We identified 40 perinatally HIV-infected children and adolescents among our clinic population who met the following inclusion criteria:  detectable viremia (>1000 copies/mL) at baseline; receipt of a stable PI-containing regimen for at least 3 months before baseline; stopping the PI either because of poor adherence, reluctance to continue PI therapy, or toxicity; completed at least 6 months on partial treatment interruption; and genotypic resistance testing had been obtained before and throughout the partial treatment interruption period. We catalogued mutational patterns affecting nucleoside, non-nucleoside, and PI drug susceptibilities. We explored the number, type, degree of persistence, and relationship between PI and RT resistance mutations; and speculate about the influence of these mutations on viral fitness and disease progression.

Results:  Gender and race distribution were 22 males and 18 females, 15 African Americans, 11 Latinos, 4 Caucasians. Median age at initiation of partial treatment interruption was 9.7 years (range 3 to 18 years). Median duration of partial treatment interruption was 45 months (range 8 to 79 months). All patients had evidence of genotypic RT and PI resistance at baseline. Despite detectable viremia (median 4.05 log₁₀ copies/mL) in all subjects throughout the study period, accumulation of further RT resistance was infrequent, while 80% of the cohort maintained 3 or more primary PI resistance mutations. PI resistance waned predominantly in those children who continued their partial treatment interruption beyond 40 months.

Conclusions:  Significant genotypic PI resistance persisted for an extensive time in this group of children who underwent partial treatment interruption. Because PI and RT resistance mutations can be linked on the same viral genome, this cohort demonstrated that maintenance of triple-class-resistant viruses can be achieved with simplified, RT inhibitor-based treatments. The reduced fitness of these resistant strains of HIV may contribute to the overall disease stability characteristic of these patients.