Second-line TAF-based ART improves viral suppression in pediatric HIV

1. In this randomized controlled trial (CHAPAS-4), tenofovir alafenamide fumarate (TAF) with emtricitabine showed superior viral suppression at 96 weeks compared to standard care (abacavir or zidovudine with lamivudine) in children living with human immunodeficiency virus (HIV) in Africa.

2. Dolutegravir as an anchor drug outperformed ritonavir-boosted lopinavir and atazanavir, with a higher rate of viral suppression and fewer severe adverse events.

Evidence Rating Level: 1 (Excellent)

Study Rundown: The mainstay of treatment for HIV in both children and adults is antiretroviral therapy (ART). Access to HIV care is improving on a global scale, with non-nucleoside reverse transcriptase inhibitor (NNRTI)–based treatment recommended as first-line. When first-line therapy fails, it is unclear which drugs have the best safety in efficacy outcomes in the pediatric population. Accordingly, this randomized controlled trial evaluated second-line antiretroviral therapy in African children with HIV who had failed first-line NNRTI–based treatment. Children were randomized to receive either TAF with emtricitabine or standard care with abacavir or zidovudine plus lamivudine, along with one of four anchor drugs: dolutegravir, ritonavir-boosted darunavir, ritonavir-boosted atazanavir, or ritonavir-boosted lopinavir. TAF and dolutegravir led to better viral suppression and growth outcomes. Strengths included a large sample size and high retention. Limitations included limited availability of pediatric TAF and regional generalizability. In summary, this study demonstrated that TAF-based ART is an effective and safe second-line HIV treatment in the pediatric population.

Click to read the study in NEJM

Relevant Reading: Assessment of Second-Line Antiretroviral Regimens for HIV Therapy in Africa Leukodystrophy

In-Depth [randomized controlled trial]: This open-label, randomized controlled trial (CHAPAS-4) assessed second-line ART options in 919 African children aged 3 to 15 years living with HIV who experienced virologic failure on first-line NNRTI–based regimens. Participants were randomized in a two-by-four factorial design to receive either TAF-emtricitabine or standard care (abacavir–lamivudine or zidovudine–lamivudine) as the nucleoside reverse transcriptase inhibitor (NRTI) backbone. Additionally, they were assigned one of four anchor drugs: dolutegravir, ritonavir-boosted darunavir, ritonavir-boosted atazanavir, or ritonavir-boosted lopinavir. The primary outcome was achieving viral suppression, defined as HIV RNA <400 copies/mL, at 96 weeks. Viral suppression was observed in 89.4% of participants receiving TAF–emtricitabine versus 83.3% in the standard care group (adjusted difference, 6.3 percentage points; 95% Confidence Interval [CI], 2.0–10.6; p=0.004), meeting criteria for both noninferiority and superiority. Among anchor drugs, dolutegravir led to the highest suppression rate at 92.0%, compared to 80.7% with ritonavir-boosted lopinavir and 84.3% with ritonavir-boosted atazanavir. Dolutegravir was significantly superior to the combined comparator group of lopinavir and atazanavir (adjusted difference, 9.7 percentage points; 95% CI, 4.8–14.5; p<0.001). Ritonavir-boosted darunavir showed moderate benefit (88.3%) but did not meet the pre-specified threshold for superiority (p=0.04). Growth outcomes also favored TAF–emtricitabine, with modest but statistically significant improvements in weight-for-age, height-for-age, and BMI-for-age z scores. Adverse event rates were similar across groups: grade 3 or 4 events occurred in 13.8% of participants overall, and serious adverse events in 3.2%. One participant died, though the cause was unrelated to treatment. These results support the use of TAF–emtricitabine and dolutegravir as preferred second-line options in pediatric HIV care, offering effective viral suppression and acceptable safety profiles.

Image: PD

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