Unsuppressed Viremia and Lower CD4 Count Associated With Faster Telomere Attrition in African Children With Perinatal Human Immunodeficiency Virus on Long-term Antiretroviral Therapy.

<h4>Background</h4>Human immunodeficiency virus (HIV-1) infection leads to reduced telomere(definition) length (TL), a biomarker of immune aging. We investigated relationships between HIV viral load (VL) and CD4 count with TL and its rate of attrition in children with HIV from Zambia and Zimbabwe.<h4>Methods</h4>Buffy coat was obtained at baseline and 48 weeks from children aged 11-19 years with perinatally acquired HIV taking combination antiretroviral therapy (cART) for >6 months recruited into the VITALITY trial. Relative TL was measured using monochrome multiplex quantitative polymerase chain reaction, standardizing units for analysis. Cross-sectional analyses used multivariable linear regression adjusting for age, sex, and study site; longitudinal analysis additionally adjusted for baseline TL.<h4>Results</h4>Among participants at baseline (N = 842; mean ± SD age, 15.5 ± 2.6 years; 53.2% female), 678 (80.5%) had HIV VL <60 copies/mL, 66 (7.8%) had 60-1000 copies/mL, and 98 (11.6%) had >1000 copies/mL. The mean CD4 count was 584 ± 243 cells/μL. Compared to participants with VL <60 copies/mL, those with VL >1000 copies/mL had shorter TL (β = -.239 [95% confidence interval {CI}, -.451 to -.026]; P = .028), whereas those with 60-1000 copies/mL did not (P = .836). Lower CD4 cell count was associated with shorter TL (β = -.038 [95% CI, -.009 to -.066] per 100 CD4 cells/μL; P = .009). In longitudinal analysis (n = 783) after mean 336 ± 6 days, those with HIV VL >1000 copies/mL at both timepoints had an accelerated telomere attrition rate (β = -.276 [95% CI, -.546 to -.005]; P = .046) compared with participants with VL <1000 copies/mL. Lower baseline CD4 count was associated with faster telomere attrition rate (β = -.033 [95% CI, -.008 to -.057]; P = .009).<h4>Conclusions</h4>HIV VL >1000 copies/mL among children with HIV on cART in Africa is associated with a degradation of immune age within 1 year, which may increase risk of comorbidities later in life.<h4>Clinical trials registration</h4>PACTR202009897660297.