Thanyawee Puthanakit1,2, Jintanat Ananworanich3,4,5, Siriwat Akapirat6, Supanit Pattanachaiwit7, Sasiwimol Ubolyam2, Vatcharain Assawadarachai6, Panadda Sawangsinth5, Thidarat Jupimai1, Suvaporn Anugulruengkitt1, Monta Tawan1, Pope Kosalaraksa8, Thitiporn Borkird9, Piyarat Suntarattiwong10, Suparat Kanjanavanit11, Mark S de Souza5. 1. Center of Excellence for Pediatric Infectious Diseases and Vaccines, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand. 2. HIV-NAT, The Thai Red Cross AIDS Research Centre, Bangkok, Thailand. 3. The Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD. 4. United States Military HIV Research Program, Bethesda, MD. 5. SEARCH, Thailand The Thai Red Cross AIDS Research Centre, Bangkok, Thailand. 6. Department of Retrovirology, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand. 7. Thai Red Cross AIDS Research Centre, Bangkok, Thailand. 8. Srinagarind Hospital, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand. 9. Hat Yai Hospital, Songkhla, Thailand. 10. Queen Sirikit National Institute of Child Health, Bangkok, Thailand; and. 11. Nakornping Hospital, Chiang Mai, Thailand.
Abstract
BACKGROUND: Previous studies have shown low frequencies of seroreactivity to HIV diagnostic assays for infected infants treated with antiretroviral therapy (ART) early in infection. METHODS: Fifty-eight HIV-infected infants treated with ART at a median age of 1.9 months (range: 0.2-5.4) for up to 4 years of life were assessed for seroreactivity to 4 routinely used HIV clinical immunoassays (IA): Second-generation (2ndG) IA and 2 rapid diagnostic tests (RDT), based on third-generation principles, measuring antibody only and a fourth-generation (4thG) antigen/antibody IA. HIV Western blot assay was also performed to assess HIV-specific antibodies. RESULTS: The 2ndG IA demonstrated the highest frequency of seroreactivity in children (69%) followed by the 4thG IA (40%) and the RDT (26%) after one year of ART. Infants initiating ART during ages 3-6 months (N = 15) showed a greater frequency (range: 53%-93%) and breadth (median and range: 3 [1-4]) of reactivity across the assays compared with those treated within 3 months (N = 43):16%-61% and breadth (1 [0-4]). The 4thG IA showed significantly reduced reactivity relative to the 2ndG IA at one (P = 0.016) and 3 (P = 0.004) years of ART. Western blot profiles following 3 years of ART showed the highest frequency of reactivity to HIV Gag p24 (76%) and lowest reactivity to Env gp120 and gp41, with only 24% of children confirmed positive by the assay. CONCLUSIONS: These results suggest that the use of 4thG IA and RDT test combination algorithms with limited HIV antigen breadth may not be adequate for diagnosis of HIV-infected children following early treatment.
BACKGROUND: Previous studies have shown low frequencies of seroreactivity to HIV diagnostic assays for infected infants treated with antiretroviral therapy (ART) early in infection. METHODS: Fifty-eight HIV-infected infants treated with ART at a median age of 1.9 months (range: 0.2-5.4) for up to 4 years of life were assessed for seroreactivity to 4 routinely used HIV clinical immunoassays (IA): Second-generation (2ndG) IA and 2 rapid diagnostic tests (RDT), based on third-generation principles, measuring antibody only and a fourth-generation (4thG) antigen/antibody IA. HIV Western blot assay was also performed to assess HIV-specific antibodies. RESULTS: The 2ndG IA demonstrated the highest frequency of seroreactivity in children (69%) followed by the 4thG IA (40%) and the RDT (26%) after one year of ART. Infants initiating ART during ages 3-6 months (N = 15) showed a greater frequency (range: 53%-93%) and breadth (median and range: 3 [1-4]) of reactivity across the assays compared with those treated within 3 months (N = 43):16%-61% and breadth (1 [0-4]). The 4thG IA showed significantly reduced reactivity relative to the 2ndG IA at one (P = 0.016) and 3 (P = 0.004) years of ART. Western blot profiles following 3 years of ART showed the highest frequency of reactivity to HIV Gag p24 (76%) and lowest reactivity to Env gp120 and gp41, with only 24% of children confirmed positive by the assay. CONCLUSIONS: These results suggest that the use of 4thG IA and RDT test combination algorithms with limited HIV antigen breadth may not be adequate for diagnosis of HIV-infected children following early treatment.
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