GUIDELINES Gayle G Sherman, ME BCh, DCH (SA), DTM&H, MMed (Haem) Department of Molecular Medicine and HamullOfggy.Johannesburg Hospiuzl. Nazional Health Labararory Service and University of cbe Wi",,,,umand, ]oiuznmJlnng INFANT HN DIAGNOSTIC GUIDELINES TO FACILITATE ADOPTION !>errings: Guidelines for a Public Health Approach. Geneva: WHO, 2002- 5. Harries AD, Nyangu1u os. Hargreaves NJ, Kaluwa 0, Salaniponi FM. Pr~enting antiretroviral anarchy in sub-Saharan Africa Lancet 2001; 358: 410-414. 6. lrli GC, Vitoria MA. Fighting against AIDS: Tn/:' Brazilian ~jence. AIDS 2002; 16: 2373~238J. 7. Farmtt P, ~nd(e F, Mukherjee 15, ~r aL Community-based approach~ to HIV uea!metlt in (~urct·poor settings.. Lona:r200l; 358: 404-409. a Soulle A. Kenyan C. Skordis J, Wood R. Rationing HAART Part I: An ~Iotation of the rosts of a limited public sector antiretroviral ueatmem programm~ in South Africa. SAf, MN)2002; 92: 811-817. 9. BredeU COnsetlSUS Statement on the Irrperative to Expand Acttss to AntireuoviraJ Medicin~ fur Adults and O1ildren with HfV{A1DS in South Africa. NovefflOO- 2001. National Tret1tmenr Congress Resourct Docum~nr Numb~r 12. Cape Town: Treatment Action Campaign. 10. Report on the global HIVIAlDS epidemic. Joint United Nations Programme on HN!AlDS (UNA/oSj. Geneva: UNAIDS, July 2002. 11. Egger M, May M, Chene G, et al. Prognosis of HIV-1-infe<:ted patients starting highly active antiretroviral tIlerapy: a collaborative analysis of prospective studies. Lancer 2002; 360: 119-129. 12. Southern African HIV Clinicians Society. Clinical Guidelines: Antiretroviral Therapy in Adults. June 2002 vtrsion. Sourhern African Journal of HN Medicine 2002; July (Issue 8): 22~29. The qualitative HIV polymerase chain reaction (PCR) test is highly specific for HIV infection, but sensitivity varies with the age of the infant' The PeR identifies approximately 50% of infected infants at or just after birth and> 95% at 3 - 6 months of age" More recent evidence suggests that HIV PCR tests performed at ~ 1 month of age have a sensitivity of ~ 95% and specificity of > 99<\'0.' The Roche Amplicor Kit (Roche Molecular Systems, Somerville, NJ) ------------- THE SOUTHERN AFRICAN JOURNAL OF HIV MEDICINE 1. Morcroft Po, \/tlla 5, Benfield n.. eta/' Changing mortality across Europe in patients infected with HN-1. Lancet 1998; 352: 1725- 1730. Moore Ro, Chaisson RE. Natural history of HIV infection in the era of combination antiretroviral therapy. AIDS 1999; 13: 1933-1942 3. Palella FJ, DeJaney KM, Moorman AC, er 01. Declining morbidity and mortality among patients with advanced human immunodeficiency virus in~tion. N EnglJ MM 1998; 338: 853-860. 4 World Health Organisation. Scaling Up Anrirecrovirol Therapy in R~Itt-Lim;red subsequent or second-line regimen would be PI-based. REFERENCES Any interested treaters who would like to participate should e-mail the managing editor of the Southern African Journal of HIV Medicine at Igbekker@cormack.uctac.za, expressing the number of patients likely to be treated at their site in the next year. South Africa is currently estimated to have 300 000 HIV/AIDS orphans, and the figure is likely to increase to 2 million by 2015.' Facilitating adoption of children affected by HIV provides a highly effective strategy for addressing the HIV/AIDS orphan crisis, albeit on a very small scale. The legal and ethical issues surrounding HIV testing of abandoned children for the purposes of adoption are not addressed here. These guidelines were contributed to and are endorsed by: Or Ashraf H Coovadia Department of FlJediorrics, Coronation Hospital, and University of the Witwatersrand Or Mark F Cotton FlJediatric Infectious Disease Unit Tygerberg Children's Hospito( University ofSte/lenbosch Or Glenda E Gray Perinatal HIV Research Unit Chris Hani-Barogwanath Hospital and University of the Witwatersrand Professor Gregory 0 Hussey School of Child and Adolescent Health, University of Cape Town Or Leon J levi n Puediatn·cian in pfNate practice Or Tammy M Merers Department of FlJediatrics, Chris Hani-Baragwanath Hospital and University of the Witwatersrand Professor Lynn Morris AiDS Unit National Institute for Communicable Diseases and University of the Witwatersrand Or Adrian J Puren National Institute for Communicable Diseases and University of the Witwatersrand Or Wendy 5 Stevens Department of Molecular Medicine and Haematology. National Health Laborotory Service and University of the Witwatersrond Or Lynne M Webber Department ofMedical Virology, University of Pretoria MAY 2003 HIV DIAGNOSTIC PROTOCOL FOR ADOPTlON PURPOSES 6 weeks of age HIV EUSA to assess HIV exposure at birth [omit if the HIV EUSA of the mother is eonfirmed positive) Oualitative HIV PCR if the HIV EUSA of the infant (or the mother) is reactive 3 months of age Qualitative HIV PCR to eonfirm result of PCR at 6 weeks of age Notes 1. Clinical examination to assess for stigmata of HlV infection should be performed at 6 weeks and 3 months of age.. The 6-week clinical examination, when stigmata of HIV infection may be less evident, is likely to be less helpful than the 3-rnonth o:amination. 2. At 6 weeks of age, blood should be taken for both HIV EUSA and PeR tests and the PeR analysed only if the HIV EUSA test result is reactive. 3. Postnatal transmission of HIV infection is likely to be evident by 6 weeks after termination of breast-feeding; nevertheless it is recommended that the final qualitative HIV PeR test be performed 3 months after breast-feeding has ceased. Interpretation Two concordant qualitative HlV PeR results in an appropriate clinical context confirm the HIV status of the child. Discrepant PeR results require further investigation. ------------- THE SOUTHERN MRICAN JOURNAL OF HI MfOICINf REFERENCES All abandoned neonates estimated to be,.; 72 hours of age should be given post-exposure prophylaxis. If logistics are in place for obtaining HN test results quickly, only HIV- exposed neonates should be treated. It is theoretically possible for an HN-exposed child to have a non-reactive HIV ELlSA if the mother seroconverted late in pregnancy or, less plausibly, if she was terminally ill towards the end of the pregnancy. Both situations are associated with a high viral load and increased propensity for vertical transmission of HIV. The suggested diagnostic guidelines would not detect neonates exposed to HIV under these circumstances unless they presented with clinical stigmata. Despite the high prevalence of HIV in South Africa, it is expected to be rare for an HN-exposed child to have a non-reactive HIV ELlSA test, so qualitative HIV PCR testing of every child being investigated for adoption is not warranted. 1. Johtl5Ofl L. Dooington R The impact of AIDS on orphanhood in South Africa: A quanoratiV(' analysis.. Centre fut Actuarial R~rch: Monograph No. 4. 2001. ISBN 0799220892. www.commerce.uct.ac.za/care/Monographs/Monographs/monoO4.pdf (accessed 22 May 2ooJ}. 2. Working Group on Antirecroviral Therapy: Narional Pediatric HIV Resource Cent{'/". Antiretroviral therapy and medical management of the human immunodeficiency virus-infected child. Pediatr InfeceDisJ 1993; 12: 513-522 J. (enters for Disease Control. 1995 R~sed Guiddines for Prophylaxis Against Pneumocystis rorinii Pneumonia for Children Infecred With or ~narally &posed To Human Immunodeficiency Virus. MMWR Morbid Motrol Wily R~ 1995; 44(RR-4I: 1-11. 4. &njamin OK, Mill{'/" We, Fiscus SA. eeoL Rational resting of the HN-exposed inf.int Peaiorric:s 2001; 10S{TI: eJ. 5. American Acaaemy of fled.attics. Eva1Udtion ana mttIicaJ treatmer.r of the HN- exposed infant. Pediatnes 1997; 99{6): 909-917. Adoptive parents need to be aware of the fact that despite comprehensive general medical examinations and testing, there is no guarantee of a completely healthy child. In the context of HIV testing, this applies to the possibility of a negative HIV ELlSA in an HIV-exposed child, as well as the recommendation to do the final HIV PCR test at 3 months instead of the exceptionally expensive and extreme recommendation of an HIV EUSA at 24 months of age."" Performing additional HN tests is unlikely to yield different results from those achieved using the diagnostic guidelines suggested above. Current HIV diagnostic guidelines for perinatally exposed infants recommend that HIV infection be confirmed by 2 positive HIV PCR tests performed on different samples. Negative HN infection status is established if 2 HIV PCR tests, the first at ~ 1 month of age and the second at ~ 4 months, are negative in a non-breast-fed infant. To determine definitively that the child is not infected, seroreversion should be demonstrated by 2 negative HIV enzyme-linked immunosorbent assay (EUSA) tests, the final one performed at 24 months of age.'-S version 1.5, which has shown excellent sensitivity and specificity in the South African setting, is the recommended qualitative (DNA) PCR test There are no published HIV diagnostic guidelines for facilitating adoption. Such guidelines require a balance between making an accurate diagnosis of the child's HIV infection status and doing so as early in life as possible, factoring in practicalities and cost considerations. The second PCR test is done to confirm the first PCR result and to guard against technical or sample mix-up errors. This could be achieved by re-testing as soon as possible after the first PCR test result is known," but performing the second PCR at an older age increases the sensitivity of the test by detecting the < 5% of infants who will test positive for the first time after 1 month of age. The recommended HN diagnostic protocol for adoption purposes is explained in the box above The possibility that antiretroviral therapy used in prevention of mother-to-child transmission (PMTCn programmes may affect the timing of the PCR testing in infancy has not been substantiated.' Local data on clinical stigmata of HIV at 6 weeks and 3 months of age and the sensitivity and specificity of qualitative HIV PCR as well as the influence of nevirapine for PMTCT on the timing of PCR testing are expected shortly. These diagnostic guidelines are likely to evolve as new data and technical improvements in testing become available.' MAY ~003