Quantitative HIV antibody (Ab) levels may be useful for screening for viral suppression or residual, cell-associated HIV DNA levels in children receiving antiretroviral therapy (ART), according to a study recently published in Clinical Infectious Diseases.

HIV-related morbidity and mortality in children are drastically reduced through use of combination ART. Early ART initiation in children before age 3 to 6 months is particularly effective for long-term control of HIV replication, reducing HIV-related illnesses and mortality, and preserving immune functions. However, methods for quantifying plasma HIV RNA and peripheral blood mononuclear cell (PBMC)‑associated HIV DNA in children are logistically challenging and expensive, especially in settings with limited resources. Previous studies have suggested that children who achieve durable virologic suppression after early (age <3 months) ART have very low levels PBMC-associated HIV DNA, and the majority lack persistent HIV IgG antibodies; children who initiate treatment after age 3 to 6 months have higher levels of PBMC-associated HIV DNA and remain HIV Ab-positive. Therefore, this study measured serial plasma HIV-specific Ab levels in children who initiated ART before age 2 years, and evaluated their relationships to peripheral blood HIV DNA and RNA levels (ClinicalTrials.gov identifier: NCT00000872).

A total of 66 children aged 0 to 24 months were included and grouped by HIV infection status, age at ART initiation (age <3 months, early therapy; or age >3 months to 2 years, late therapy), and response to ART (responder or nonresponder). Investigators also included 20 children who did not have HIV, but who were born to mothers with HIV, as control participants. Plasma IgG Ab levels were serially measured using quantitative enzyme-linked immunosorbent assays and were directed against several markers: HIV envelope (gp160, gp41), gag (caspid, p24; matrix, p17), reverse transcriptase (p66/51), and integrase (p31).

Baseline anti-gp160, anti-RT, anti-p24, and anti-p17 levels were similar across all groups. In the control group, baseline anti-gp41 Ab levels were significantly higher than in both groups of participants who responded to ART (both early-treatment and late-treatment recipients), as well as children in the nonresponder group (P =.002). Baseline anti-p31 Ab levels were also significantly higher than in the late treatment-responder group (P =.008) and the nonresponder group (P =.04). The decline of HIV Ab rates in the early treatment-responder group were similar to those in the control group for all specificities except p17 (P =.01). Further, for all tested Ab specificities, Ab decline rates in the late treatment-responder group and the nonresponder group were significantly slower than in the control group. After age 1 year, p31 and p17 Ab levels were significantly associated with HIV RNA levels (P <.001); Ab levels to gp160 and gp41 were significantly associated with cell-associated HIV DNA levels (P <.001 for both).

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Overall, the study authors concluded that, “Since the measurement of quantitative HIV-1 Ab levels requires small blood volumes and is generally more rapid, less expensive, and less technically-intensive than the measurement of HIV-1 nucleic acids, the measurement of quantitative antibodies may also be useful for screening for virologic suppression and HIV-1 DNA persistence in early-treated children in limited-resource settings.”

Disclosure: K Luzuriaga has received compensation from Gilead for consulting, outside the submitted work.

Reference

McManus M, Henderson J, Gautam A, et al. Quantitative human immunodeficiency virus (HIV)-1 antibodies correlate with plasma HIV-1 RNA and cell-associated DNA levels in children on antiretroviral therapy [published online September 5, 2018]. Clin Infect Dis. doi: 10.1093/cid/ciy753