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

BACKGROUND

Human immunodeficiency virus (HIV-1) infection leads to reduced telomere 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.

METHODS

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.

RESULTS

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).

CONCLUSIONS

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.

CLINICAL TRIALS REGISTRATION: PACTR202009897660297.