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. 2022 Oct 26;14(11):2350.
doi: 10.3390/v14112350.

Sustained Virologic Suppression Reduces HIV-1 DNA Proviral Levels and HIV Antibodies in Perinatally HIV-Infected Children Followed from Birth

Trevon Fuller  1   2 , Tara Kerin  3 , Ruth Cortado  3 , Maria de Lourdes Benamor Teixeira  2   4 , Maria Isabel Fragoso da Silveira Gouvêa  2   4 , Christianne Moreira  2 , Maria Leticia Santos Cruz  2 , José Henrique Pilotto  5   6 , Ivete Gomes  5 , Breno Santos  7 , Tauí Rocha  7 , Priya R Soni  8 , Esau Joao  2 , Myung Shin-Sim  3 , Yvonne Bryson  3 , Karin Nielsen-Saines  3
Affiliations

Sustained Virologic Suppression Reduces HIV-1 DNA Proviral Levels and HIV Antibodies in Perinatally HIV-Infected Children Followed from Birth

Trevon Fuller et al. Viruses. .

Abstract

The extent to which perinatally HIV-infected children, following cART initiation, develop a low proviral reservoir burden over time, as measured by HIV DNA droplet-digital polymerase chain reaction (ddPCR) and the effect on HIV antibody is not well characterized. We measured proviral HIV DNA and plasma RNA virus load (VL) in 37 perinatally HIV-infected children at 6 months of age who initiated stable cART. At 6-11 years of age, HIV proviral DNA, HIV VL (RNA), and HIV antibody by Western Blot (WB) were assessed. CART was initiated before 6 months of age in 13 children and after 6 months in 24. At school age, the HIV DNA levels did not differ by the timing of cART, and the HIV DNA levels were lower in children with negative/indeterminate WB (p = 0.0256). Children with undetectable HIV RNA VL > 50% of the time since cART initiation had lower median DNA VL than children with undetectable VL < 50% of the time (p = 0.07). Long-term viral suppression in perinatally HIV-infected children is associated with a decrease in HIV antibodies and reduced HIV reservoirs.

Keywords: HIV DNA droplet digital PCR; early HIV treatment; perinatal HIV infection; viral load kinetics; viral reservoir burden.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1
Flowchart of children living with HIV enrolled in the present study.
Figure 2
Figure 2
Kaplan–Meier survival curves indicating the effect of cART initiation on time to virologic suppression of HIV RNA (N = 37). In total 13 infants initiated cART at up to 6 months of life, and 24 after 6 months. There were 4 children who never achieved undetectable VL after starting cART.
Figure 3
Figure 3
Virologic and immunologic endpoints by time of treatment initiation. (A) HIV RNA VL at 6 months of age (N = 33); (B) HIV DNA ddPCR at 6 months of age (N = 32); (C) HIV RNA VL at 6–11 years of age (N = 37); (D) HIV DNA ddPCR at 6–11 years of age (N = 35).
Figure 4
Figure 4
HIV RNA viral load kinetics according to response to therapy status. (A) Complete responders (N = 15) children with an undetectable VL at study entry with HIV RNA viral loads undetectable more than 75% of the time since cART initiation in early childhood. The dashed red line depicts the child’s age at cART initiation. (B) Partial Responders (N = 8), children with an undetectable VL at study entry with undetectable HIV RNA VL between 50–75% of the time since cART initiation in early childhood. (C) Non-responders (N = 14), children with detectable HIV RNA VL at study entry and/or HIV RNA VL detectable up to 50% of the time since cART initiation in early childhood.
Figure 5
Figure 5
Viral reservoirs during childhood (6–11 years of age) measured by HIV DNA ddPCR. (A) HIV DNA ddPCR according to HIV-1 Western blot results; (B) HIV DNA ddPCR results according to response to cART; One child classified as a responder based on HIV RNA did not have ddPCR available, and 1 classified by HIV RNA as a non-responder did not have ddPCR.
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