TY - JOUR
T1 - Long-term virological outcomes, failure and acquired resistance in a large cohort of Ugandan children
AU - Huibers, M. H. W.
AU - Kityo, C.
AU - Boerma, R. S.
AU - Kaudha, E.
AU - Sigaloff, K. C. E.
AU - Balinda, S. N.
AU - Bertagnolio, S.
AU - Nakanjako, R.
AU - Mugyenyi, P.
AU - Calis, J. C. J.
AU - Boele van Hensbroek, M.
AU - Rinke de Wit, T. F.
PY - 2019/10/1
Y1 - 2019/10/1
N2 - OBJECTIVES: To evaluate long-term virological failure (VF) and drug resistance among HIV-infected Ugandan children on first-line ART. METHODS: In a multicentre prospective cohort study, viral load (VL) and drug resistance mutations (DRMs) were investigated at baseline and 6 monthly intervals in children (age ≤ 12 years). VF (two consecutive VLs >1000 copies/mL or death after 6 months of ART) was defined as early VF (0-24 months of ART) or late VF (25-48 months of ART). An active regimen was defined as partially active if the genotypic susceptibility score (GSS) was <3. RESULTS: Between 2010 and 2011, 316 children were enrolled. Viral suppression was achieved in 75.8%, 71.5%, 72.6% and 69.2% at 12, 24, 36 and 48 months. VF occurred in 111/286 (38.8%), of which 67.6% was early and 32.4% late VF. Early VF was associated with a partially active regimen at baseline (OR 6.0, 95% CI 1.9-18.5), poor adherence (OR 3.1, 95% CI 1.3-7.4) and immunodeficiency (OR 3.3, 95% CI 1.1-10.2). Late VF was associated with age >3 years (OR 2.5, 95% CI 1.0-6.6) and WHO stage 3/4 (OR 4.2, 95% CI 1.4-13.4). Acquired DRMs were detected in 27.0% before 24 months, versus 14.4% after 24 months (P < 0.001). A total of 92.2% of the children with early VF, versus 56.2% with late VF, had a partially active regimen (P < 0.001). CONCLUSIONS: VF rates were high, occurred predominantly in the first 24 months and appeared to increase again in year four. Risk factors and patterns of early VF/DRMs were different from those of late VF/DRMs. Virological control may improve by close monitoring and prompt switching to second-line therapy in the first 24 months. Late VF may be prevented by early start of ART.
AB - OBJECTIVES: To evaluate long-term virological failure (VF) and drug resistance among HIV-infected Ugandan children on first-line ART. METHODS: In a multicentre prospective cohort study, viral load (VL) and drug resistance mutations (DRMs) were investigated at baseline and 6 monthly intervals in children (age ≤ 12 years). VF (two consecutive VLs >1000 copies/mL or death after 6 months of ART) was defined as early VF (0-24 months of ART) or late VF (25-48 months of ART). An active regimen was defined as partially active if the genotypic susceptibility score (GSS) was <3. RESULTS: Between 2010 and 2011, 316 children were enrolled. Viral suppression was achieved in 75.8%, 71.5%, 72.6% and 69.2% at 12, 24, 36 and 48 months. VF occurred in 111/286 (38.8%), of which 67.6% was early and 32.4% late VF. Early VF was associated with a partially active regimen at baseline (OR 6.0, 95% CI 1.9-18.5), poor adherence (OR 3.1, 95% CI 1.3-7.4) and immunodeficiency (OR 3.3, 95% CI 1.1-10.2). Late VF was associated with age >3 years (OR 2.5, 95% CI 1.0-6.6) and WHO stage 3/4 (OR 4.2, 95% CI 1.4-13.4). Acquired DRMs were detected in 27.0% before 24 months, versus 14.4% after 24 months (P < 0.001). A total of 92.2% of the children with early VF, versus 56.2% with late VF, had a partially active regimen (P < 0.001). CONCLUSIONS: VF rates were high, occurred predominantly in the first 24 months and appeared to increase again in year four. Risk factors and patterns of early VF/DRMs were different from those of late VF/DRMs. Virological control may improve by close monitoring and prompt switching to second-line therapy in the first 24 months. Late VF may be prevented by early start of ART.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85072508388&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/31289811
U2 - https://doi.org/10.1093/jac/dkz266
DO - https://doi.org/10.1093/jac/dkz266
M3 - Article
C2 - 31289811
SN - 0305-7453
VL - 74
SP - 3035
EP - 3043
JO - The Journal of antimicrobial chemotherapy
JF - The Journal of antimicrobial chemotherapy
IS - 10
ER -