Impact of delaying antiretroviral treatment during primary HIV infection on telomere length. Journal of Infectious Diseases
Telomere length (TL) shortens during aging, HIV seroconversion, and untreated chronic HIV infection. In this work, Raffenberg et al. aimed to evaluate any independent association of the time of antiretroviral therapy (ART) start with TL in participants with documented primary HIV infection (PHI) in the Zurich Primary HIV Infection Study (ZPHI), and to estimate the impact of early ART start relative to other factors with known TL association such as age.
The authors measured TL in peripheral blood mononuclear cells by quantitative polymerase chain reaction in participants of the Zurich PHI Study with samples available for ≥6 years. They obtained univariable/multivariable estimates from mixed-effects models and evaluated the association of delaying ART start or interrupting ART with baseline and longitudinal TL.
In 105 participants with PHI (median age 36 years, 9% women), median ART delay was 25, 42, and 60 days, respectively, in the first (shortest), second, and third (longest) ART delay tertile. First ART delay tertile was associated with longer baseline TL (P for trend = .034), and longer TL over 6 years, but only with continuous ART (P < .001), not if ART was interrupted ≥12 months (P = .408). In multivariable analysis, participants in the second and third ART delay tertile had 17.6% (5.4%–29.7%; P = .004) and 21.5% (9.4%–33.5%; P < .001) shorter TL, after adjustment for age, with limited effect modification by clinical variables.
In conclusion, this longitudinal study of TL in patients with PHI in Switzerland has 4 major findings: First , this is the first study to document that an ART delay in PHI of just a matter of weeks is independently associated with shorter TL. Second, the ART delay effect on TL (approximately 17%–22% shorter TL) in the multivariable model was approximately twice as large compared to the effect of being 10 years older (8.2% shorter TL) and therefore appears clinically relevant. Third , the favorable effect on TL of early continuous ART in PHI was sustained for >6 years. Fourth , the favorable effect on TL of early ART was offset by subsequent ART interruption. These results point to the potential for clinical intervention that PHI needs to be diagnosed expeditiously and that ART, when started immediately during PHI, might preserve TL and as a result prevent or dampen effects on biological aging and associated diseases.