Virologic response to first-line efavirenz- or nevirapine-based anti-retroviral therapy in HIV-infected African children

Journal article

Background

Poorer virologic response to nevirapine vs efavirenz-based antiretroviral therapy (ART) has been reported in adult systematic reviews and paediatric studies.

Methods

We compared drug discontinuation and viral load (VL) response in ART-naïve Ugandan/Zimbabwean children aged ≥3 years initiating ART with clinician-chosen nevirapine vs efavirenz in the ARROW trial. Predictors of suppression <80, <400 and <1000 copies/ml at 36, 48 and 144 weeks were identified using multivariable logistic regression with backwards elimination (p=0.1).

Results

445(53%) children received efavirenz and 391(47%) nevirapine. Children receiving efavirenz were older (median 8.6 years vs 7.5 nevirapine, p<0.001) and had higher CD4% (12% vs 10%, p=0.05) but similar pre-ART VL (p=0.17). The initial non-nucleoside-reverse-transcriptase-inhibitor (NNRTI) was permanently discontinued for adverse events in 7/445 (2%) children initiating efavirenz vs 9/391 (2%) initiating nevirapine (p=0.46); at switch to second-line in 17 vs 23, for tuberculosis in 0 vs 26, for pregnancy in 6 vs 0, and for other reasons in 15 vs 5. Early (36-48 week) virological suppression <80 copies/ml was superior with efavirenz, particularly in children with higher pre-ART VL (p=0.0004); longer-term suppression was superior with nevirapine in older children (p=0.05). Early suppression was poorer in the youngest and oldest children, regardless of NNRTI (p=0.02); longer-term suppression was poorer in those with higher pre-ART VL regardless of NNRTI (p=0.05). Results were broadly similar for <400 and <1000 copies/ml.

Conclusion

Short-term VL suppression favoured efavirenz, but long-term relative performance was age-dependent, with better suppression in older children with nevirapine, supporting WHO’s recommendation that nevirapine remain an alternative NNRTI.

Authors: Kekitiinwa, A; Szubert, A; Spyer, M; Katuramu, R; Musiime, V

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Lippincott, Williams and Wilkins
• Journal: Journal of Pediatric Infectious Diseases
• Volume: 36
• Issue: 6
• Pages: 588–594
• Publication date: 2017-06-01
• Acceptance date: 2016-09-12
• DOI: 10.1097/INF.0000000000001505
• ISSN: 1305-7707
• Keywords: HIV; viral load; children; NNRTI; antiretroviral therapy