Pooled HIV-1 RNA viral load testing for detection of antiretroviral treatment failure in Kenyan children.

BACKGROUND: Pooled viral load (VL) testing with 2 different testing strategies was evaluated as a potential cost saving method to monitor antiretroviral therapy (ART) in HIV-infected children receiving ART in a resource-limited setting. METHODS: Archived samples collected from 250 HIV-1-infected children on first-line ART at various time points post-ART initiation were evaluated for pooled VL testing using a minipool + algorithm strategy. Additionally, samples collected in real time from 125 children on ART were assessed for virologic failure using a minipool strategy for pooled VL testing. Virologic failure was determined as HIV-1 RNA VLs >1500 copies/mL. RESULTS: Minipool + algorithm strategy for pooled VL testing of archived samples had estimated viral failure of 13.6%, with a relative efficiency (RE) of 23.6% (95% CI: 18.5 to 29.4), and negative predictive value of 88%. This testing strategy would have resulted in 24% fewer assays needed for a cost savings of $1180 per 100 samples. The minipool strategy for pooled VL testing of samples obtained in real time yielded an estimated 23.2% of samples with viral failure and a RE of 8.0% (95% CI: 3.9 to 14.2); however, had a minipool + algorithm pooling strategy been used, the RE would have increased to 20%. CONCLUSIONS: The minipool + algorithm strategy for pooled VL testing to detect virologic failure in HIV-1-infected children on ART was determined to be relatively efficient in detecting virologic failure, have high negative predictive value, with substantial cost savings. Pooling strategies may be important components of cost-effect strategies to reduce rates of viral failure and resistance, thus, improving clinical outcomes.

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

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.