Format

Send to

Choose Destination
Clin Infect Dis. 2016 Oct 15;63(8):1113-1121. doi: 10.1093/cid/ciw488. Epub 2016 Jul 20.

Nevirapine- Versus Lopinavir/Ritonavir-Based Antiretroviral Therapy in HIV-Infected Infants and Young Children: Long-term Follow-up of the IMPAACT P1060 Randomized Trial.

Author information

1
Makerere University-Johns Hopkins University Research Collaboration, Kampala, Uganda.
2
Harvard T. H. Chan School of Public Health, Boston, Massachusetts.
3
University of KwaZulu-Natal, Durban.
4
Stellenbosch University, Tygerberg.
5
Perinatal HIV Research Unit.
6
Wits Reproductive Health and HIV Institute, Johannesburg, South Africa.
7
UNC Project-Malawi, Lilongwe.
8
B. J. Government Medical College, Pune, India.
9
University of Zimbabwe-University of California, San Francisco Collaborative Research Programme, Harare, Zimbabwe.
10
Kilimanjaro Christian Medical College, Moshi, Tanzania.
11
University Teaching Hospital, Lusaka, Zambia.
12
Children's Hospital Colorado, Aurora.
13
HJF-DAIDS, Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, Maryland.
14
Elizabeth Glaser Pediatric AIDS Foundation, Washington, District of Columbia.
15
Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire.
16
University of North Carolina at Chapel Hill.

Abstract

BACKGROUND:

The International Maternal Pediatric Adolescent AIDS Clinical Trials Network (IMPAACT) P1060 study demonstrated short-term superiority of lopinavir/ritonavir (LPV/r) over nevirapine (NVP) in antiretroviral therapy (ART), regardless of prior NVP exposure. However, NVP-based ART had a marginal benefit in CD4 percentage (CD4%) and growth. We compared 5-year outcomes from this clinical trial.

METHODS:

Human immunodeficiency virus (HIV)-infected, ART-eligible children were enrolled into 2 cohorts based on prior NVP exposure and randomized to NVP- or LPV/r-based ART. The data safety monitoring board recommended unblinding results in both cohorts due to superiority of LPV/r for the primary endpoint: stopping randomized treatment, virologic failure (VF), or death by 6 months. Participants were offered a switch in regimens (if on NVP) and continued observational follow-up. We compared time to VF or death, death, and CD4% and growth changes using intention-to-treat analyses. Additionally, inverse probability weights were used to account for treatment switching and censoring.

RESULTS:

As of September 2014, 329 of the 451 (73%) enrolled participants were still in follow-up (median, 5.3 years; interquartile range [IQR], 4.3-6.4), with 52% on NVP and 88% on LPV/r as originally randomized. NVP arm participants had significantly higher risk of VF or death (adjusted hazard ratio [aHR], 1.90; 95% confidence interval [CI], 1.37-2.65) but not death alone (aHR, 1.65; 95% CI, .72-3.76) compared with participants randomized to LPV/r. Mean CD4% was significantly higher in the NVP arm up to 1 year after ART initiation, but not beyond. Mean weight-for-age z scores were marginally higher in the NVP arm, but height-for-age z scores did not differ. Similar trends were observed in sensitivity analyses.

CONCLUSIONS:

These findings support the current World Health Organization recommendation of LPV/r in first-line ART regimens for HIV-infected children.

CLINICAL TRIALS REGISTRATION:

NCT00307151.

KEYWORDS:

HIV/AIDS; antiretroviral therapy; long-term follow-up; pediatrics

PMID:
27439527
PMCID:
PMC5036919
DOI:
10.1093/cid/ciw488
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Silverchair Information Systems Icon for PubMed Central
Loading ...
Support Center