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Amplifying and Quantifying HIV-1 RNA in HIV Infected Individuals with Viral Loads Below the Limit of Detection by Standard Clinical Assays
Published on: September 26, 2011
Quantitative HIV-1-specific antibodies as predictors of peripheral blood cell-associated HIV-1 DNA concentrations
Margaret McManus1, Brad Karalius2, Kunjal Patel2
1Program in Molecular Medicine.
Insights
HIV-1 antibody levels, specifically to gp41 and gp160, can predict low cell-associated HIV-1 DNA in children on antiretroviral therapy. This finding may help identify candidates for HIV remission protocols.
Area of Science:
- Pediatric Infectious Diseases
- Immunology
- Virology
Background:
- Perinatally HIV-infected (PHIV) children on antiretroviral therapy (ART) can achieve viral suppression.
- Monitoring cell-associated HIV-1 DNA is crucial for assessing viral persistence.
- Predictive markers for low viral DNA are needed to guide treatment strategies.
Purpose of the Study:
- To evaluate HIV-1 antibody levels as predictors of cell-associated HIV-1 DNA in PHIV children with long-term viral suppression on ART.
- To identify specific HIV-1 antibodies that correlate with low viral DNA levels.
Main Methods:
- Quantitative measurement of HIV-1 IgG antibodies to six HIV-1 proteins using ELISA.
- Measurement of cell-associated HIV-1 DNA levels by droplet digital PCR.
- Analysis of antibody levels and HIV-1 DNA in 61 PHIV children and 20 controls.
Main Results:
- Antibody levels to gp160 and gp41 were higher in children with longer viral suppression (1-5 years) compared to those with shorter suppression (<1 year).
- Receiver operator curve and ensemble learning approaches identified gp41 and gp160 antibodies as significant predictors of low HIV-1 DNA (<10 or <100 copies/million PBMC).
- C-statistics and AUC estimates indicated good predictive performance for these antibody levels.
Conclusions:
- Quantitative HIV-1 gp41 and gp160 antibody levels can serve as rapid, inexpensive screening tools.
- These antibody levels may help identify children with low PBMC HIV-1 DNA for inclusion in remission protocols.
Objective:
This study evaluated HIV-1 antibody levels as predictors of cell-associated HIV-1 DNA levels in perinatally infected (PHIV) children with long-term viral suppression on antiretroviral therapy (ART).
Design:
HIV-1 antibody and HIV-1 DNA levels were measured in blood specimens from 61 children and adolescents from the Pediatric HIV/AIDS Cohort Study: Adolescent Master Protocol. Twenty perinatally HIV-1-exposed, uninfected children studied through 2 years served as controls.
Methods:
HIV-1 IgG antibodies to six HIV-1 proteins were measured by quantitative ELISA; HIV-1 DNA levels were measured by droplet digital PCR.
Results:
Among 13 children with viral suppression at less than 1 year, antibodies to gp160 and gp41 were low but stable longitudinally; antibodies to p17, p24, and RT decreased, and antibodies to p31 were low or undetectable. Among 48 children with viral suppression between 1 and 5 years, antibody levels to all six HIV-1 proteins were higher than in children with earlier viral suppression and remained high over time. A receiver operator curve approach identified gp41 and gp160 as useful predictors of HIV-1 DNA less than 10 or less than 100 copies per million PBMC (cpm); C-statistics including all antibodies ranged from 0.75 to 0.77. An ensemble learning approach also identified gp41 and gp160 as important predictors of HIV-1 DNA less than 10 or less than 100 cpm; area under the curve estimates utilizing all HIV-1 antibodies ranged from 0.70 to 0.81.
Conclusion:
Quantitative HIV-1 gp41 and gp160 antibody levels may serve as rapid, inexpensive screening tools for low PBMC HIV-1 DNA levels in children with viral suppression on ART, facilitating inclusion into remission protocols.
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