title: Loss of detectability and indeterminate results: Challenges facing HIV infant diagnosis in South Africa's expanding ART programme.
abstract: BACKGROUND
  Early infant diagnosis with rapid access to treatment has been found to reduce HIV-associated infant mortality and morbidity considerably. In line with international standards, current South African guidelines advocate routine HIV-1 polymerase chain reaction (PCR) testing at 6 weeks of age for all HIV-exposed infants and 'fast-track' entry into the HIV treatment programme for those who test positive. Importantly, testing occurs within the context of increasing efforts at prevention of mother-to-child transmission (PMTCT) by means of maternal and infant antiretroviral therapy (ART). In addition, infants already initiated on combination ART (cART) may be retested with PCR assays for 'confirmatory' purposes, including assessment prior to adoption. The potential for cART to compromise the sensitivity of HIV-1 PCR assays has been described, although there are limited and conflicting data regarding the effect of PMTCT regimens on HIV-1 PCR diagnostic sensitivity.
  
  
  METHODS
  We describe a case series of three infants with different ART exposures in whom HIV diagnosis, confirmation or the result of retesting for adoption purposes were uncertain.
  
  
  RESULTS
  These cases demonstrate that ART can be associated with a loss of detectability of HIV, leading to 'false-negative' HIV-1 PCR results in infants on cART. Furthermore, current PMTCT practices may lead to repeatedly indeterminate results with a subsequent delay in initiation of cART.
  
  
  CONCLUSIONS
  The sensitivity of HIV-1 PCR assays needs to be re-evaluated within the context of different ART exposures, and diagnostic algorithms should be reviewed accordingly.
authors.affiliation: Department of Medical Virology, Tshwane Academic Division, National Health Laboratory Service, and University of Pretoria, South Africa. ahmad.haerimazanderani@up.ac.za.
authors.forename: Ahmad F
authors.initials: AF
authors.lastname: Haeri Mazanderani
authors.forename: Nicolette Marie
authors.initials: NM
authors.lastname: Du Plessis
authors.forename: Winifred Nancy
authors.initials: WN
authors.lastname: Thomas
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Venter
authors.forename: Theunis
authors.initials: T
authors.lastname: Avenant
mesh_terms: D023241:Antiretroviral Therapy, Highly Active; D005188:False Negative Reactions; D005260:Female; D015658:HIV Infections / Q000175:diagnosis*; D015497:HIV-1; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical; D016133:Polymerase Chain Reaction; D012367:RNA, Viral / Q000032:analysis; D013019:South Africa
chemical_list: D012367:RNA, Viral