Non-virologic Methods to Diagnose Treatment Eligibility in HIV-exposed Infants (IDX)

Tracking Information
First Submitted Date	October 14, 2010
First Posted Date	October 18, 2010
Last Update Posted Date	September 18, 2014
Study Start Date	July 2009
Actual Primary Completion Date	June 2011 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures; (submitted: October 14, 2010)	performance (i.e., sensitivity, specificity, negative and positive predictive value) of different algorithms in predicting virologically confirmed HIV infection [ Time Frame: within first 12 months of life ]
Original Primary Outcome Measures	Same as current
Change History	Complete list of historical versions of study NCT01222130 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures	Not Provided
Original Secondary Outcome Measures	Not Provided
Current Other Outcome Measures	Not Provided
Original Other Outcome Measures	Not Provided
Descriptive Information
Brief Title	Non-virologic Methods to Diagnose Treatment Eligibility in HIV-exposed Infants
Official Title	CIDRZ 1234 - Non-virologic Methods to Diagnose Treatment Eligibility in HIV-exposed Infants
Brief Summary	This study is designed to develop and evaluate a set of non-virologic diagnostic algorithms to monitor HIV-exposed children of unknown infection status for treatment eligibility during the first year of life. The results of this cross sectional study are expected to be used in development of a series of non-virologic algorithms to determining treatment eligibility among HIV-exposed children in settings where polymerase chain reaction (PCR) testing is not available and to guide the judicious use of PCR testing among HIV-exposed children in settings where PCR is available. These results will directly inform program implementation in Zambia.
Detailed Description	Despite recent scientific advances in prevention of mother-to-child transmission (PMTCT), substantial donor investment, and national commitments to PMTCT program roll-out, pediatric HIV/AIDS remains a largely uncontrolled epidemic. Unless some intervention is undertaken, more than half of children who become HIV-infected will die by their second birthday. Yet in sub-Saharan Africa, the majority of infected children die without ever having confirmation of their HIV status, having never had the chance to begin life-saving antiretroviral therapy (ART). Recognizing the need to provide children with greater access to care, the World Health Organization (WHO) has advised countries that at least 10% of patients receiving ART should be children. However, most programs fall well short of this target. Unlike diagnosis in adults, definitive diagnosis of HIV in children less than 18 months of age requires virologic testing. Maternal IgG antibodies cross the placenta into the fetal circulation through pregnancy and are also secreted in breast milk. As infants may retain these maternal antibodies for up to 18 months after birth, conventional HIV antibody tests are of limited use in determining positive infection status. Instead it is necessary to directly identify HIV infection using a virologic method, typically polymerase chain reaction (PCR) testing to detect viral DNA or RNA. PCR testing is expensive and, in most developing countries, available only through specialty laboratories. Because PCR testing is more complex than other common HIV laboratory assays (e.g. CD4+ cell counting), it requires technicians with considerably more training and technical skill, involves longer sample preparation time, and can be considerably more costly than other diagnostic tests. Thus, most countries with large populations of HIV-infected children have extremely limited capacity to carry out PCR testing. Even where PCR is available, pediatric HIV diagnosis may remain difficult in breastfeeding populations because infants are at continued risk of infection until breastfeeding is completely stopped. A negative PCR test during breastfeeding does not guarantee that the infant will remain uninfected. The alternative - serial testing for HIV infection - would result in an exponential increase in cost. Indeed, a convincing argument can be made that rather than monitoring HIV-exposed breastfeeding children for HIV infection, it may be more appropriate to simply monitor for treatment eligibility, followed by a definitive antibody test at 15-18 months or a few months after breastfeeding has stopped. Those children who meet criteria for treatment could be commenced on ART; those who do not would continue to undergo periodic screening until they were weaned and old enough to have a final (definitive) antibody test. For HIV-exposed infants without access to HIV PCR testing - the vast majority in Africa - development of such an algorithm would have the obvious benefit of providing reliable evaluation for treatment eligibility in the first 18 months of life. Even in settings where HIV PCR testing is available - but may be limited - the introduction of such algorithms could reduce the volume of HIV PCR tests required at a programmatic level, and thus lead to substantial cost-savings. The overall goal of this protocol is to develop and evaluate a set of non-virologic diagnostic algorithms that can be used to monitor HIV-exposed children of unknown infection status for treatment eligibility during the first 12 weeks of life, with validation of our model among HIV-exposed children up to 12 months of age. We will evaluate the performance of different algorithms in two separate but common scenarios in Africa: (1) where infant PCR testing is not available, and (2) where infant PCR may be available, but poorly accessible due to cost and resource considerations. Although DNA PCR testing has become available in Zambia, only three sites currently provide this type of testing and capacity may be limited for country-wide screening. Our study was designed to determine HIV infection and antiretroviral therapy (ART) eligibility using more commonly used "non-virologic" tests, such as CD4, CD8, HIV antibody, total lymphocyte count, hemoglobin, and clinical staging. Previous studies have demonstrated that these indicators by themselves do not perform well in the absence of DNA PCR testing. In this exploratory study, we hypothesize that combinations of these tests - in formalized algorithms - can yield high performance and be used in rural settings where reliable DNA PCR services are not yet available or remain limited.
Study Type	Observational
Study Design	Time Perspective: Cross-Sectional
Target Follow-Up Duration	Not Provided
Biospecimen	Not Provided
Sampling Method	Probability Sample
Study Population	HIV-infected mothers and their exposed infants seek care in a primary care setting in Lusaka, Zambia
Condition	HIV Infections
Intervention	Not Provided
Study Groups/Cohorts	Not Provided
Publications *	Not Provided
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status	Completed
Actual Enrollment; (submitted: July 18, 2011)	1126
Original Estimated Enrollment; (submitted: October 14, 2010)	1054
Actual Study Completion Date	June 2011
Actual Primary Completion Date	June 2011 (Final data collection date for primary outcome measure)
Eligibility Criteria	Inclusion Criteria: mother with documented HIV infections; mother willing to give informed consent for participation; mother willing to allow child to participant in the study; infant equal or less than 60 weeks of age Exclusion Criteria: infants accompanied by someone other than the mother; infants already received antiretroviral therapy
Sex/Gender	Sexes Eligible for Study: All
Ages	up to 60 Weeks (Child)
Accepts Healthy Volunteers	No
Contacts	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries	Zambia
Removed Location Countries
Administrative Information
NCT Number	NCT01222130
Other Study ID Numbers	MQ-00-6-300-01206-0-00
Has Data Monitoring Committee	No
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Benjamin Chi, MD, MSc, University of North Carolina, Chapel Hill
Study Sponsor	University of North Carolina, Chapel Hill
Collaborators	Elizabeth Glaser Pediatric AIDS Foundation
Investigators	Not Provided
PRS Account	University of North Carolina, Chapel Hill
Verification Date	September 2014