Unsuppressed viraemia and lower CD4 count associated with faster telomere attrition in African children with perinatal HIV on long-term antiretroviral therapy

Background:
HIV leads to reduced telomere length (TL), a biomarker of immune ageing. We investigated relationships between HIV viral load (VL) and CD4 count with TL and its rate of attrition in children with HIV (CWH) 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 [Trial registration no: PACTR202009897660297]. Relative TL was measured using monochrome multiplex qPCR, standardising 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 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[95%CI]=-0.239[-0.451, -0.026], P=0.028) whereas those with 60-1000 copies/mL did not (P=0.836). Lower CD4 cell count was associated with shorter TL (β[95%CI]=-0.038[-0.009, -0.066] per 100 CD4 cells/μL, P=0.009). In longitudinal analysis (N=783) after 336±6 days, those with HIV VL>1000 copies/mL at both timepoints had an accelerated telomere attrition rate (β[95%CI]=-0.276[-0.546, -0.005], P=0.046) compared with participants with VL<1000 copies/mL. Lower baseline CD4 count was associated with faster telomere attrition rate (β[95%CI]=-0.033[-0.008, -0.057], P=0.009).

Conclusions:
HIV VL>1000 copies/mL among CWH on cART in Africa is associated with a degradation of immune age within one year, which may increase risk of co-morbidities later in life.