Paper # 879 
Safety and Efficacy of NRTI-only Antiretroviral Regimens in HIV-infected Children
Michael Neely*1, R Rutstein2, G del Bianco3, G Heresi3, T Barton4, J Wheeling5, R Wiegand6, B Bohannon6, K Dominguez6, A Wiznia7, and the LEGACY Consortium
1Univ of Southern California, Keck Sch of Med, Los Angeles, US; 2Children’s Hosp of Philadelphia, PA, US; 3Univ of Texas Hlth Sci Ctr at Houston, US; 4Univ of Texas Southwestern Med Ctr, Dallas, US; 5Northrup Grummon, Inc, Atlanta, GA, US; 6CDC, Atlanta, GA, US; and 7Jacobi Med Ctr, Bronx, NY, US
Background: In adults, NRTI-only Antiretroviral
Regimens (NOAR) (i.e., ≥3 NRTI) are less potent than regimens combining
multiple antiretroviral classes. Published experience with NOAR in children is
more limited.
Methods: We analyzed demographic and clinical data
from NOAR-treated patients in LEGACY, a multicenter observational cohort study
of HIV-infected children and adolescents. We defined NOAR duration based
on prescribed start and stop dates. We applied US Department of Health
and Human Services criteria for virologic failure (VF), immunologic decline
(ID) and adverse event (AE) grading. NRTI mutations were defined according to
the Stanford database. We calculated the VF hazard ratio (HR)
associated with specific ARV-containing NOAR regimens using Cox proportional hazards
regression.
Results: Of 575 patients with data from time of HIV
diagnosis through 2006, 92 (16%) received NOARs in 25 different NRTI
combinations; most (46%) received the fixed dose combination of zidovudine,
lamivudine and abacavir. NOAR use peaked in 2001 to 2002. Patients starting
NOAR had a median age of 15 years (interquartile range [IQR] 11 to 19); were
57% female, 61% black, 28% Hispanic, and 53% treatment-naïve. Neither race nor
gender differed significantly compared with children who did not receive NOARs.
Median NOAR duration was 2.0 years (IQR 0.9 to 4.4). Of 72 patients with
available virologic data, 56 (78%) had >1 log10 decrease in viral
load at week 12. However, by week 48, 63 (88%) had VF (>400 copies/mL), and
22 (32%) of 70 with immunologic data had ID (>5% CD4 cell count
decline from baseline). VF and ID prevalences did not differ significantly
among pre-NOAR treatment-naïve or -experienced patients. Tenofovir
(TDF)-containing NOAR, used in 9 (13%) of the 72, were significantly associated
with VF (HR 2.1; 95% confidence interval 1.0 to 4.4; P =0.04). AEs
(all grades) occurred in 63 (68%) patients, including anemia (59%), leukopenia
(43%), hepatitis (18%), rash (10%) and pancreatitis (9%). Among 49 patients who
were treatment-naïve at NOAR initiation, we detected NRTI mutations in 21 (95%)
of 22 tested after VF.
Conclusions: In LEGACY, NOAR users experienced high
rates of VF, adverse events, and NRTI mutations. VF was notably associated with
use of TDF-based NOAR. Immunologic decline was more moderate. NOAR should be
avoided, when possible, in HIV-infected children and adolescents.
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