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Background Viral blips (50–1000 copies/mL) are a common and often transient occurrence in people with HIV (PWH) on suppressive antiretroviral therapy (ART). With the widespread adoption of Two-Drug Regimens (2DR) and modern integrase inhibitor-based triple therapies, characterizing the temporal dynamics of these virological events is essential. We aimed to evaluate the timing of the first viral blip across different ART regimens to better understand their specific virological profiles.Material and Methods Retrospective study of 286 virologically suppressed PWH with 378 documented blips identified from 9,157 viral load measurements (2020–2025, Infectious Diseases Unit, AOU Policlinico Paolo Giaccone, Palermo). The timing of the first viral blip was calculated as the number of days from the initiation of the current ART regimen. The median time to the first blip (67.5 days) was used as a cut-off to categorize events as ‘Early’ (≤67.5 days) or ‘Late’ (>67.5 days). Associations between blip timing, therapeutic regimens (2DR, DTG/3TC, BIC-based), and baseline clinical characteristics were assessed using Pearson’s Chi-square and Fisher’s exact tests.Results The cohort (median age 54 years, 78% male) was treated primarily with 2DRs (43.7%, including DTG/3TC at 24.5%) and BIC-based regimens (38.8%). Baseline clinical severity included a CD4 nadir <100 cells/µL in 24.5% of patients and prior virologic failure in 15%. The overall median time to the 1st viral blip was 67.5 days. Bivariate analysis indicated that the first blip tended to occur earlier in patients receiving 2DRs (62.4% early vs 37.6% late, p < 0.001), including the DTG/3TC subgroup (61.4% early, p = 0.017). Conversely, blips during BIC-based regimens were more frequently observed later in the treatment course (36.9% early, p < 0.001). To evaluate potential confounders, baseline severe immunosuppression (CD4 nadir <100) and regimen complexity (multi-pill burden) were analyzed. Neither factor showed a significant impact on early blips globally (p = 0.099 and p = 0.246, respectively). When analyzing only the 2DR subgroup (n=125), neither CD4 nadir <100 (p = 0.519) nor pill burden (p = 0.325) significantly influenced blip timing.Conclusions Different ART regimens may exhibit distinct virological kinetics. In our cohort, the first viral blip occurred earlier after initiation of 2DRs (such as DTG/3TC) compared to BIC-based triple therapies, independent of baseline immune status or pill burden. These findings highlight different temporal distributions of low-level viremia rather than differences in long-term clinical efficacy. This study is limited by its retrospective design and the lack of adherence data and unmeasured pharmacological interactions, which could influence transient viral fluctuations. Further prospective investigations with adherence monitoring are required to fully interpret the virological dynamics underlying these early blip events.Abstract OC14 Table 1Baseline characteristics of the study cohort (n=286)Abstract OC14 Table 2Timing of first viral blip by ART regimen and clinical variables