TY - JOUR
T1 - Predictors of virologic and clinical response to nevirapine versus lopinavir/ritonavir-based antiretroviral therapy in young children with and without prior nevirapine exposure for the prevention of mother-to-child HIV transmission
AU - Lindsey, Jane C.
AU - Hughes, Michael D.
AU - Violari, Avy
AU - Eshleman, Susan H.
AU - Abrams, Elaine J.
AU - Bwakura-Dangarembizi, Mutsa
AU - Barlow-Mosha, Linda
AU - Kamthunzi, Portia
AU - Sambo, Pauline M.
AU - Cotton, Mark F.
AU - Moultrie, Harry
AU - Khadse, Sandhya
AU - Schimana, Werner
AU - Bobat, Raziya
AU - Zimmer, Bonnie
AU - Petzold, Elizabeth
AU - Mofenson, Lynne M.
AU - Jean-Philippe, Patrick
AU - Palumbo, Paul
PY - 2014/8
Y1 - 2014/8
N2 - Background: In a randomized trial comparing nevirapine (NVP)-based versus lopinavir/ritonavir (LPV/r)-based antiretroviral therapy (ART) in HIV-infected children [primary endpoint discontinuation of study treatment for any reason or virologic failure by week 24] aged 2 months to 3 years, we assessed whether clinical, virologic, immunologic and safety outcomes varied by prior single-dose NVP exposure (PrNVP) for prevention of motherto- child HIV transmission and other covariates. Methods: Efficacy was assessed by time to ART discontinuation or virologic failure, virologic failure/death and death; safety by time to ART discontinuation because of a protocol-defined toxicity and first ≥ grade 3 adverse event; immunology and growth by changes in CD4%, weight/height World Health Organization z-scores from entry to week 48. Cox proportional hazards and linear regression models were used to test whether treatment differences depended on PrNVP exposure and other covariates. Results: Over a median follow up of 48 (PrNVP) and 72 (no PrNVP) weeks, there was no evidence of differential treatment effects by PrNVP exposure or any other covariates. LPV/r-based ART was superior to NVPbased ART for efficacy and safety outcomes; however, those on NVP had larger improvements in CD4%, weight and height z-scores. Lower pretreatment CD4% and higher HIV-1 RNA levels were associated with reduced efficacy, lower pretreatment CD4% with shorter time to ART discontinuation because of a protocol-defined toxicity, and no PrNVP with shorter time to first grade ≥3 adverse event. Conclusions: Differences between LPV/r and NVP ART in efficacy, safety, immunologic and growth outcomes did not depend on PrNVP exposure, prior breast-feeding, sex, HIV-1 subtype, age, pretreatment CD4%, HIV-1 RNA or World Health Organization disease stage. This finding should be considered when selecting an ART regimen for young children.
AB - Background: In a randomized trial comparing nevirapine (NVP)-based versus lopinavir/ritonavir (LPV/r)-based antiretroviral therapy (ART) in HIV-infected children [primary endpoint discontinuation of study treatment for any reason or virologic failure by week 24] aged 2 months to 3 years, we assessed whether clinical, virologic, immunologic and safety outcomes varied by prior single-dose NVP exposure (PrNVP) for prevention of motherto- child HIV transmission and other covariates. Methods: Efficacy was assessed by time to ART discontinuation or virologic failure, virologic failure/death and death; safety by time to ART discontinuation because of a protocol-defined toxicity and first ≥ grade 3 adverse event; immunology and growth by changes in CD4%, weight/height World Health Organization z-scores from entry to week 48. Cox proportional hazards and linear regression models were used to test whether treatment differences depended on PrNVP exposure and other covariates. Results: Over a median follow up of 48 (PrNVP) and 72 (no PrNVP) weeks, there was no evidence of differential treatment effects by PrNVP exposure or any other covariates. LPV/r-based ART was superior to NVPbased ART for efficacy and safety outcomes; however, those on NVP had larger improvements in CD4%, weight and height z-scores. Lower pretreatment CD4% and higher HIV-1 RNA levels were associated with reduced efficacy, lower pretreatment CD4% with shorter time to ART discontinuation because of a protocol-defined toxicity, and no PrNVP with shorter time to first grade ≥3 adverse event. Conclusions: Differences between LPV/r and NVP ART in efficacy, safety, immunologic and growth outcomes did not depend on PrNVP exposure, prior breast-feeding, sex, HIV-1 subtype, age, pretreatment CD4%, HIV-1 RNA or World Health Organization disease stage. This finding should be considered when selecting an ART regimen for young children.
KW - Africa
KW - Antiretroviral therapy
KW - Clinical trials
KW - Pediatrics
KW - Prevention of mother-to-child transmission
UR - http://www.scopus.com/inward/record.url?scp=84905814677&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84905814677&partnerID=8YFLogxK
U2 - 10.1097/INF.0000000000000337
DO - 10.1097/INF.0000000000000337
M3 - Article
C2 - 25222305
AN - SCOPUS:84905814677
SN - 0891-3668
VL - 33
SP - 846
EP - 854
JO - Pediatric Infectious Disease Journal
JF - Pediatric Infectious Disease Journal
IS - 8
ER -