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Zhao Y, Wang Y, Wang A, McGoogan JM, Wu Z. Median Time to Antiretroviral Therapy Initiation in a Cohort of Chinese Infants Born With HIV. JAMA Pediatr. 2018;172(1):90–92. doi:10.1001/jamapediatrics.2017.3920
A delayed start to antiretroviral therapy (ART) endangers the survival of HIV-infected infants and is a particular concern in resource-limited settings. In China, the health care system has dramatically scaled up its response to HIV, and as of 2012, immediate initiation of ART was recommended for all perinatally infected infants younger than 2 years.1 This study aimed to assess outcomes for infants diagnosed with HIV from 2011 to 2015.
The present study involves a nationwide cohort of infants reported to China’s HIV/AIDS Comprehensive Response Information Management System (CRIMS), which contains information about all HIV cases in China.2 However, CRIMS does not collect information on infant HIV testing dates, whether the tests were via serological vs virological methods, and CD4 percentage, because these data points fall under separate, specialized programs aimed at the prevention of mother-to-child transmission.2,3 The study protocol was approved by the institutional review board of the National Center for AIDS/STD Control and Prevention at the Chinese Center for Disease Control and Prevention. This study was exempt from informed consent procedures, because it is a secondary analysis of existing program data. (Parents and guardians of minor patients entering the National Pediatric ART Program sign informed consents at time of enrollment.)
Infants included in our cohort were reported to CRIMS between January 1, 2011, and December 31, 2015, and were younger than 2 years at CRIMS entry. The study endpoint was March 31, 2016. Primary outcomes were the time from birth to CRIMS reporting, the time from CRIMS reporting to initiation of ART, and all-cause mortality. Secondary outcomes were the determinants of ART initiation and determinants of death; these were assessed by Cox proportional hazards regression. All analyses were performed with R statistical package, version 3.3.0 (R Development Core Team).
The cohort included 689 infants. Most were of the Han Chinese ethnicity (n = 427; 62.0%), and most were residents of rural areas (n = 629; 91.3%) (Table 1). The overall median time from birth to CRIMS reporting was 601 days (interquartile range [IQR], 556-659), which decreased by 59.5 days from 2011 to 2015 (median, 630; IQR, 585-679, in 2011; and median, 570.5; IQR, 232-640, in 2015). A total of 390 infants (56.6%) began ART during the study. Overall median time from CRIMS reporting to ART initiation was 133 days (IQR, 29-352), which decreased by 333 days from 2011 to 2015 (median, 378; IQR, 133-704 in 2011; median, 45; IQR, 17-113 in 2015). We found increased odds of ART initiation for those with Han ethnicity (adjusted hazard ratio [aHR], 1.48; 95% CI, 1.20-1.83) and CRIMS entry between 2012 and 2015 (aHR, 1.41; 95% CI, 1.11-1.81), and decreased odds for rural residents (aHR, 0.70; 95% CI, 0.49-0.99) and those with missing CD4 counts (aHR, 0.12; 95% CI, 0.07-0.20). Overall all-cause mortality was 15.2%, but this was substantially lower among treated infants (4.9%) vs untreated infants (28.8%). Use of ART was protective (aHR, 0.24; 95% CI, 0.14-0.41), as was CRIMS entry between 2012 and 2015 (aHR, 0.59; 95% CI, 0.37-0.93), while low CD4 count (aHR, 3.97; 95% CI, 2.01-7.85) and unknown CD4 count (aHR, 12.70; 95% CI, 6.39-25.22) were risk factors for death (Table 2).
We found a large and persistent delay in CRIMS entry. Since starting ART depends on information in CRIMS, entry into the system is the most crucial stage for Chinese infants. However, CRIMS reporting is dependent on diagnosis, and although exposed infants should receive early infant diagnosis (EID) via virological testing at age 6 weeks,4,5 a recent systematic review3 found that EID was not implemented nationwide in China. Rather, two-thirds of exposed infants received serological HIV testing at age 18 months, and one-third died or were lost to follow-up. We suspect that local Chinese health care workers do not carry out timely virological tests, but rather delay the testing and reporting of HIV-exposed infants until after maternal antibodies no longer interfere with serological tests.6
For infants who received ART, the median time from CRIMS reporting to ART initiation decreased substantially from 378 days in 2011 to 45 days in 2015. The initiation of ART was more likely for Han Chinese and less likely for rural residents, reflecting the continued influence of societal imbalances. As expected, ART was protective against death, while low and unknown CD4 counts were risk factors. Decreased risk of death among infants reported to CRIMS from 2012 to 2015 suggests a positive effect of the new policy of immediate ART initiation.
This study was limited to the information available in CRIMS, and there was potential for bias related to infant death and loss to follow-up prior to entry into CRIMS as well as unequal observed time for participants. However, we provide evidence of a long delay in CRIMS reporting was associated with profoundly reduced effect on survival. Policymakers should consider integrating follow-up, EID, and ART initiation into prevention of mother-to-child transmission programs to address programming gaps and serious flaws in HIV service delivery.
Corresponding Author: Zunyou Wu, PhD, National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and Prevention, 155 Changbai Rd, Beijing 102206, China (email@example.com or firstname.lastname@example.org).
Accepted for Publication: August 31, 2017.
Published Online: November 13, 2017. doi:10.1001/jamapediatrics.2017.3920
Open Access: This article is published under the JN-OA license and is free to read on the day of publication.
Author Contributions: Dr Wu had full access to all the data in the study and takes responsibility for the integrity of the data and accuracy of the data analysis. Dr Zhao and Ms Wang contributed equally as joint first authors.
Study concept and design: Zhao, Wu.
Acquisition, analysis, or interpretation of data: All authors.
Drafting of the manuscript: Zhao, Y. Wang, McGoogan, Wu.
Critical revision of the manuscript for important intellectual content: All authors.
Statistical analysis: Zhao, Y. Wang.
Obtained funding: Zhao, Wu.
Administrative, technical, or material support: Zhao, A. Wang, Wu.
Study supervision: Zhao, Wu.
Conflict of Interest Disclosures: None reported.
Funding/Support: This study was supported by the National Science and Technology Major Project on Prevention and Treatment of Major Infectious Diseases including AIDS and Viral Hepatitis (grants 2015ZX10001001 and 2012ZX10001-007).
Role of the Funder/Sponsor: The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Disclaimer: The opinions expressed herein reflect the collective views of the co-authors and do not necessarily represent the official position of the National Center for AIDS/STD Control and Prevention of the Chinese Center for Disease Control and Prevention, nor the National Center for Women and Children’s Health of the Chinese Center for Disease Control and Prevention.
Additional Contributions: We thank local health workers for their contributions in providing HIV diagnosis and treatment services for HIV-infected infants and in data entry to CRIMS.
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