Document Type: Review Article
Dept of Pathology, Imam Hospital Complex, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
Thrombosis Homeostasis Research Center, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
It is estimated that the number of HIV infected children globally has increased from 1.6 million in 2001 to 3.3 million in 2012. The number of children below 15 years of age living with HIV has increased worldwide. Published data from recent studies confirmed dramatic survival benefit for infants started anti-retroviral therapy (ART) as early as possible after diagnosis of HI. Early confirmation of HIV diagnosis is required in order to identify infants who need immediate ART. WHO has designed recommendations to improve programs for both early diagnoses of HIV infection and considering ART whenever indicated? It is strongly recommended that HIV virologocal assays for diagnosis of HIV have sensitivity of at least 95% and ideally greater than 98% and specificity of 98% or more under standardized and validated conditions. Timing of virological testing is also important. Infants infected at or around delivery may take short time to have detectable virus. Therefore, sensitivity of virological tests is lower at birth. In utero HIV infection, HIV DNA or RNA can be detected within 48 h of birth and in infants with peripartum acquisition it needs one to two weeks. Finally it is emphasized that all laboratories performing HIV tests should follow available services provided by WHO or CDC for quality assurance programs. Both clinicians and staffs providing laboratory services need regular communications, well-defined SOPs and nationally validated algorithms for optimal use of laboratory tests. Every country should use assays that have been validated by national reference laboratory.
- WHO; UNAIDS. Guidance on provider-initiated HIV testing and counselling in health facilities. Geneva: WHO; 2007. [09 December 2010]. http://whqlibdoc.who.int/publications/2007/9789241595568_eng.pdf.
- Morss SS. Factors in the emergence of infectious diseases. Emerg Infect Dis [serial online] 1995 Jan-Mar [cited 1996 Jun 5]; 1(1):[24 screens]. Available from: URL: http://www.cdc.gov/ncidod/EID/eid.htm
- De Cock KM, Fowler MG, Mercier E, de Vincenzi I, Saba J, Hoff E,et al. Prevention of mother-to-child HIV transmission in resource-poor countries:translating research into policy and practice. JAMA 2000 1; 283(9):1175-82.
- Sherman GG, Stevens G, Stevens WS. Affordable diagnosis of human immunodeficiency virus infection in infants by p24 antigen detection. Pediatr Infect Dis J 2004; 23(2):173-6.
- Cassol S, Gill MJ, Pilon R, Cormier M, Voigt RF, Willoughby B, et al. Quantification of human immunodeficiency virus type 1 RNA from dried plasma spots collected on filter paper. J Clin Microbiol 1997; 35(11):2795-801.
- Bertagnolio S, Soto-Ramirez L, Pilon R, Rodriguez R, Viveros M, Fuentes L, et al. HIV-1 drug resistance surveillance using dried whole blood spots. Antivir Ther 2007; 12(1):107-13.
- Brambilla D, Jennings C, Aldrovandi G, Bremer J, Comeau AM, Cassol SA, et al. Multicenter evaluation of use of dried blood and plasma spot specimens in quantitative assays for human immunodeficiency virus RNA: measurement, precision,and RNA stability. J Clin Microbiol 2003;41(5):1888-93.
- Isaakidis P, Raguenaud ME, Te V, Tray CS, Akao K, Kumar V, et al. High survival and treatment success sustained after two and three years of first-line ART for children in Cambodia. J Int AIDS Soc 2010 21;13:11.
- Janssens B, Raleigh B, Soeung S, Akao K, Te V, Gupta J, et al. Effectiveness of highly active antiretroviral therapy in HIV-positive children: evaluation at 12 months in a routine program in Cambodia. Pediatrics 2007; 120(5):e1134-40.
- Violari A, Cotton MF, Gibb DM, Babiker AG, Steyn J, Madhi SA, et al. Early antiretroviral therapy and mortality among HIV-infected infants. N Engl J Med 2008 20; 359(21):2233-44.
- Chiappini E, Galli L, Tovo PA, Gabiano C, Gattinara GC, Guarino A, et al. Virologic, immunologic, and clinical benefits from early combined antiretroviral therapy in infants with perinatal HIV-1 infection. AIDS, 2006, 20(2):207–215.
- Guyatt GH, Oxman AD, Vist GE, Kunz R, Falck-Ytter Y, Alonso-Coello P,et al. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ 2008 26; 336(7650):924-6.
- Reynolds SJ, Ndongala LM, Luo CC, Mwandagalirwa K, Losoma AJ, Mwamba KJ, et al. Evaluation of a rapid test for the detection of antibodies to human immunodeficiency virus type 1 and 2 in the setting of multiple transmitted viral subtypes. Int J STD AIDS 2002; 13(3):171-3.
- Prendergast A, Mphatswe W, Tudor-Williams G, Rakgotho M, Pillay V, Thobakgale C, et al. Early virological suppression with three-class antiretroviral therapy in HIV-infected African infants. AIDS 2008, 22(11):1333–1343.
- Lambert JS, Harris DR, Stiehm ER, Moye J Jr, Fowler MG, Meyer WA ,et al. Performance characteristics of HIV-1 culture and HIV-1 DNA and RNA amplification assays for early diagnosis of perinatal HIV-1 infection. J Acquir Immune Defic Syndr 2003 15;34(5):512-9.
- Kline MW, Lewis DE, Hollinger FB, Reuben JM, Hanson LC, Kozinetz CA,et al. A comparative study of human immunodeficiency virus culture, polymerase chain reaction and anti-human immunodeficiency virus immunoglobulin A antibody detection in the diagnosis during early infancy of vertically acquired human immunodeficiency virus infection. Pediatr Infect Dis J 1994; 13(2):90-4.
- Kovacs A, Xu J, Rasheed S, Li XL, Kogan T, Lee M, Liu C, et al. Comparison of a rapid nonisotopic polymerase chain reaction assay with four commonly used methods for the early diagnosis of human immunodeficiency virus type 1 infection in neonates and children. Pediatr Infect Dis J 1995; 14(11):948-54.
- Prasitwattanaseree S1, Lallemant M, Costagliola D, Jourdain G, Mary JY.Influence of mother and infant zidovudine treatment duration on the age at which HIV infection can be detected by polymerase chain reaction in infants. Antivir Ther 2004; 9(2):179-85.
- Ribas SG, Ondoa P, Schüpbach J, van der Groen G, Fransen K.et al. Performance of a quantitative human immunodeficiency virus type 1 p24 antigen assay on various HIV-1 subtypes for the follow-up of human immunodeficiency type 1 seropositive individuals. J Virol Methods 2003; 113(1):29-34.
- Luo W, Yang H, Rathbun K, Pau CP, Ou CY.et al. Detection of human immunodeficiency virus type 1 DNA in dried blood spots by a duplex real-time PCR assay. J Clin Microbiol 2005; 43(4):1851-7.
- Lakshmi V, Sudha T, Bhanurekha M, Dandona L.et al. Evaluation of the Murex HIV Ag/Ab Combination assay when used with dried blood spots. Clin Microbiol Infect 2007; 13(11):1134-6.
- Ou CY, Yang H, Balinandi S, Sawadogo S, Shanmugam V, Tih PM,et al. Identification of HIV-1 infected infants and young children using real-time RT PCR and dried blood spots from Uganda and Cameroon. J Virol Methods 2007; 144(1-2):109-14.
- Sutcliffe CG, van Dijk JH, Bolton C, Persaud D, Moss WJ.et al. Effectiveness of antiretroviral therapy among HIV-infected children in sub-Saharan Africa. Lancet Infect Dis 2008; 8(8):477-89.
- Gulia J, Kumwenda N, Li Q, Taha TE.HIV seroreversion time in HIV-1-uninfected children born to HIV-1-infected mothers in Malawi. J Acquir Immune Defic Syndr 2007 v 1; 46(3):332-7.
- Beck IA, Drennan KD, Melvin AJ, Mohan KM, Herz AM, Alarcón J,et al. Simple, sensitive, and specific detection of human immunodeficiency virus type 1 subtype B DNA in dried blood samples for diagnosis in infants in the field. J Clin Microbiol 2001; 39(1):29-33.
- Berhan Z, Abebe F, Gedefaw M, Tesfa M, Assefa M, Tafere Y. Risk of HIV and associated factors among infants born to HIV positive women in Amhara region, Ethiopia: a facility based retrospective study. BMC Res Notes 2014 4;7(1):876.
- Divala O, Michelo C, Ngwira B. Morbidity and mortality in HIV-exposed under-five children in a rural Malawi setting: a cohort study. J Int AIDS Soc 2014 2; 17(4 Suppl 3):19696.
- Hatcher AM, Woollett N, Pallitto CC, Mokoatle K, Stöckl H, MacPhail C,et al. Bidirectional links between HIV and intimate partner violence in pregnancy: implications for prevention of mother-to-child transmission. J Int AIDS Soc 2014 3; 17:19233.
- Odeny TA, Newman M, Bukusi EA, McClelland RS, Cohen CR, Camlin CS. Developing content for a mHealth intervention to promote postpartum retention in prevention of mother-to-child HIV transmission programs and early infant diagnosis of HIV: a qualitative study. PLoS One2014 2; 9(9):e106383.
- Blumental S, Ferster A,Van den Wijngaert S, Lepage P. HIV transmission through breastfeeding: still possible in developed countries. Pediatrics 2014; 134(3):e875-9.
- Sohn AH, Thanh TC, Thinh le Q, Khanh TH, Thu HK, Giang le T, et al. Failure of human immunodeficiency virus enzyme immunoassay to rule out infection among polymerase chain reaction-negative vietnamese infants at 12 months of age. Pediatr Infect Dis J 2009; 28(4):273-6.
- Chantry CJ, Cooper ER, Pelton SI, Zorilla C, Hillyer GV, Diaz C. Seroreversion in human immunodeficiency virus-exposed but uninfected infants. Pediatr Infect Dis J 1995; 14(5):382-7.
- Rakusan TA, Parrott RH, Sever JL.Limitations in the laboratory diagnosis of vertically acquired HIV infection. J Acquir Immune Defic Syndr 1991; 4(2):116-21.
- Makuwa M, Souquière S, Niangui MT, Rouquet P, Apetrei C, Roques P, et al. Reliability of rapid diagnostic tests for HIV variant infection. J Virol Methods 2002 16; 103(2):183-90.
- Phillips S, Granade TC, Pau CP, Candal D, Hu DJ, Parekh BS.Diagnosis of human immunodeficiency virus type 1 infection with different subtypes using rapid tests. Clin Diagn Lab Immunol 2000; 7(4):698-9.
- Rouet F, Montcho C, Rouzioux C, Leroy V, Msellati P, Kottan JB,et al. Early diagnosis of paediatric HIV-1 infection among African breast-fed children using a quantitative plasma HIV RNA assay. AIDS 2001 28;15(14):1849-56.
- Souza IE, Azevedo ML, Succi RC, Machado DM, Diaz RS.RNA viral load test for early diagnosis of vertical transmission of HIV-1 infection. J Acquir Immune Defic Syndr 2000 1; 23(4):358-60.
- Alvarez-Muñoz MT, Zaragoza-Rodríguez S, Rojas-Montes O, Palacios-Saucedo G, Vázquez-Rosales G, Gómez-Delgado A, et al. High correlation of human immunodeficiency virus type-1 viral load measured in dried-blood spot samples and in plasma under different storage conditions. Arch Med Res 2005;36(4):382-6.
- Fischer A, Lejczak C, Lambert C, Servais J, Makombe N, Rusine J, et al. Simple DNA extraction method for dried blood spots and comparison of two PCR assays for diagnosis of vertical human immunodeficiency virus type 1 transmission in Rwanda. J Clin Microbiol 2004; 42(1):16-20.
- Nesheim S, Palumbo P, Sullivan K, Lee F, Vink P, Abrams E,et al. Quantitative RNA testing for diagnosis of HIV-infected infants. J Acquir Immune Defic Syndr 2003 1; 32(2):192-5.
- Rouet F, Sakarovitch C, Msellati P, Elenga N, Montcho C, Viho I, et al.Pediatric viral human immunodeficiency virus type 1 RNA levels, timing of infection, and disease progression in African HIV-1-infected children. Pediatrics 2003;112(4):e289.
- Cachafeiro A, Sherman GG, Sohn AH, Beck-Sague C, Fiscus SA.Diagnosis of human immunodeficiency virus type 1 infection in infants by use of dried blood spots and an ultrasensitive p24 antigen assay. J Clin Microbiol 2009; 47(2):459-62.
- Report of the WHO Technical Reference Group, Paediatric HIV/ART Care Guideline GroupMeeting. Geneva, World Health Organization, 2008 (http://www.who.int/hiv/pub/paediatric/WHO_Paediatric_ART_guideline_rev_mreport_2008.pdf).
- Antiretroviral therapy of HIV infection in infants and children: towards universal access:recommendations for a public health approach Geneva, World Health Organization, 2007(http://whqlibdoc.who.int/publications/2007/9789241594691_eng.pdf).
- WHO case definitions of HIV for surveillance and revised clinical staging and immunological classification of HIV-related disease in adults and children. Geneva, World HealthOrganization, 200 (http://whqlibdoc.who.int/publications/2007/9789241595629_eng.pdf).
- Guidance on provider-initiated HIV testing and counselling in health facilities. Geneva, World Health Organization, 2007 (http://whqlibdoc.who.int/publications/2007/9789241595568_eng.pdf).
- Gleaves CA, Welle J, Campbell M, Elbeik T, Ng V, Taylor PE,et al. Multicenter evaluation of the Bayer VERSANT HIV-1 RNA 3.0 assay: analytical and clinical performance. J Clin Virol 2002;25(2):205-16.
- World Health Organization and Joint United Nations Programme on HIV/AIDS (UNAIDS). HIV assays: operational characteristics. Geneva, World Health Organization, 2009 (http://www.who.int/diagnostics_laboratory/evaluations/hiv/en/index.html accessed on 18 December 2009).
- Antiretroviral Therapy for HIV infection in infants and children: Toward universal access Recommendations for a public health approach, 2010 Revision .WHO.
- Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection National Institutes of Health, USA, August 16, 2010.
- Garrido C, Zahonero N, Corral A, Arredondo M, Soriano V, de Mendoza C.et al. Correlation between human immunodeficiency virus type 1 (HIV-1) RNA measurements obtained with dried blood spots and those obtained with plasma by use of Nuclisens EasyQ HIV-1 and Abbott Real Time HIV load tests. J Clin Microbiol 2009; 47(4):1031-6.
- Mwaba P, Cassol S, Nunn A, Pilon R, Chintu C, Janes M, et al. Whole blood versus plasma spots for measurement of HIV-1 viral load in HIV-infected African patients. Lancet 2003 20; 362(9401):2067-8.
- Braun J, Plantier JC, Hellot MF, Tuaillon E, Gueudin M, Damond F, et al. A new quantitative HIV load assay based on plasma virion reverse transcriptase activity for the different types, groups and subtypes. AIDS 2003 14; 17(3):331-6.
- Crowe S, Turnbull S, Oelrichs R, Dunne A.Monitoring of human immunodeficiency virus infection in resourceconstrained countries. Clin Infect Dis 2003 1; 37(Suppl 1):S25-35.
- Sutthent R, Gaudart N, Chokpaibulkit K, Tanliang N, Kanoksinsombath C, Chaisilwatana P.p24 Antigen detection assay modified with a booster step for diagnosis and monitoring of human immunodeficiency virus type 1 infection. J Clin Microbiol 2003; 41(3):1016-22.
- Maliwichi M, Rosenberg NE, Macfie R, Olson D, Hoffman I, van der Horst CM,et al. CD4 count outperforms World Health Organization clinical algorithm for point-of-care HIV diagnosis among hospitalised HIV-exposed Malawian infants. Trop Med Int Health 2014 Aug;19(8):978-87.
- Selik RM, Gebo KA, Borkowf CB, Whitmore SK, Espinoza L. CD4 T-lymphocyte percentages corresponding to CD4 T-lymphocyte count thresholds in a new staging system for HIV infection. J Acquir Immune Defic Syndr 2014 Aug 1;66(4):e92-4.
- Frizzera Dias C, Moreira-Silva SF, Reis MA, Ribeiro Patrício L, Biancardi Gavioli CF, Miranda AE. Late diagnosis and HIV infection in children attending a service of specialized care for pediatric AIDS in Brazil. Rev Soc Bras Med Trop 2014 Jan-Feb;47(1):93-6.
- Smit PW, Sollis KA, Fiscus S, Ford N, Vitoria M, Essajee S,et al. Systematic review of the use of dried blood spots for monitoring HIV viral load and for early infant diagnosis. PLoS One 2014 Mar 6;9(3):e86461.
- Gupta R, Praveen R, Sharma M. Can we prevent pediatric HIV? An experience at a tertiary care hospital. Med J Armed Forces India 2013 Jul;69(3):218-21.
- Corró G, Crudeli CM, Rocco CA, Marino SA, Sen L. High levels of anti-Nef antibodies may prevent AIDS disease progression in vertically HIV-1-infected infants. J Int AIDS Soc 2014 Feb 14;17:18790.
- Motswere-Chirwa C, Voetsch A, Lu L, Letsholathebe V, Lekone P, Machakaire E,et al. Follow-up of infants diagnosed with HIV - Early Infant Diagnosis Program, Francistown, Botswana, 2005-2012. MMWR Morb Mortal Wkly Rep 2014 Feb 21;63(7):158-60.
- Shiau S, Kuhn L, Strehlau R, Martens L, McIlleron H, Meredith S, et al. Sex differences in responses to antiretroviral treatment in South African HIV-infected children on ritonavir-boosted lopinavir- and nevirapine-based treatment. BMC Pediatr 2014 Feb 12; 14:39.
- Gebremedhin A, Gebremariam S, Haile F, Weldearegawi B, Decotelli C. Predictors of mortality among HIV infected children on anti-retroviral therapy in Mekelle Hospital, Northern Ethiopia: a retrospective cohort study. BMC Public Health 2013 Nov 6;13:1047.
- Shiau S, Kuhn L. Antiretroviral treatment in HIV-infected infants and young children: novel issues raised by the Mississippi baby. Expert Rev Anti Infect Ther 2014 Mar; 12(3):307-18.
- HIV Paediatric Prognostic Markers Collaborative Study. Predictive value of absolute CD4 cell count for disease progression in untreated HIV-1-infected children. AIDS 2006, 20(9):1289–1294.
- Joint United Nations Programme on HIV/AIDS (UNAIDS) and World Health Organization. AIDS epidemic update: December 2009. Geneva, Joint United Nations Programme on HIV/ AIDS (UNAIDS), 2009 (http://whqlibdoc.who.int/unaids/2009/9789291738328_eng.pdf).
- Patton JC, Sherman GG, Coovadia AH, Stevens WS, Meyers TM.Ultrasensitive human immunodeficiency virus type 1 p24 antigen assay modified for use on dried whole-blood spots as a reliable, affordable test for infant diagnosis. Clin Vaccine Immunol 2006; 13(1):152-5.
- Schüpbach J.Measurement of HIV-1 p24 antigen by signal-amplification-boosted ELISA of heat-denatured plasma is a simple and inexpensive alternative to tests for viral RNA. AIDS Rev 2002; 4(2):83-92.
- Zijenah LS, Tobaiwa O, Rusakaniko S, Nathoo KJ, Nhembe M, Matibe P, et al. Signal-boosted qualitative ultrasensitive p24 antigen assay for diagnosis of subtype C HIV-1 infection in infants under the age of 2 years. J Acquir Immune Defic Syndr 2005 1; 39(4):391-4.
- Poulsen AG, Aaby P, Gottschau A, Kvinesdal BB, Dias F, Mølbak K, et al. HIV-2 infection in Bissau, West Africa, 1987–1989: incidence, prevalences, and routes of transmission. J Acquir Immune Defic Syndr 1993; 6(8):941-8.