Pattern and Frequency of Seroreactivity to Routinely Used Serologic Tests in Early-Treated Infants With HIV

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.

Influence of Combination Antiretroviral Therapy on HIV-1 Serological Responses and Their Implications: A Systematic Review and Meta-Analysis

“…Our searches returned a total of 2,321 records from 28 studies ( 4 , 14 – 29 , 31 – 40 , 75 ). The median sample size is 41 (interquartile range (IQR): 16–101).…”

“…Eleven studies (N = 565) were conducted in the United States, 5 (N = 376) in Thailand, 3 (N = 369) in South Africa, 2 (N = 75) in Italy, and one each in Zimbabwe (N = 129), Mali (N = 97), China (N = 73), Canada (N = 69), France (N = 44), Spain (N = 14), and the United Kingdom (N = 10). There were 20 surveys with a median sample size of 29 (IQR: 13–107) to evaluate the serostatus in cART-treated vertically infected children of ≥16 months old ( 4 , 14 – 29 , 31 – 33 ), while the frequency of seronegativity in the cART-treated adult population was reported in 8 investigations with a median sample size of 80 (IQR: 36–101) ( 34 – 40 , 75 ).…”

“…Among the 20 selected studies that focus on cART-treated children ( Table 1 ), the frequency of seronegativity was reported in 11 studies in which early-treated children were included with a median age of 2.2 months (IQR: 1.7–2.7, N = 583) when cART started ( 4 , 14 – 16 , 20 – 22 , 26 , 29 , 32 , 33 ) and in 4 studies that deferred-treated children were included with a median age of 55.7 months (IQR: 37.4–86.4, N = 587) ( 18 , 23 – 25 ). In addition, 5 studies included both early-treated and deferred-treated children and separately reported the frequency of seronegativity in the two groups ( 17 , 19 , 27 , 28 , 31 ).…”

The contemporary immunoassays for HIV diagnosis: a concise overview

“…The structure of HIV along with the p24 antigen is represented in Figure 3 . Several studies have examined the properties of p24 antigen and its association with other biomarkers during HIV infection [ 65 ]. With the advanced research in virology, the next-generation technologies for intended resources limited setting could use the p24 antigen as the most effective virological target.…”