The clinical significance of viral blips as an indicator of drug resistance and subsequent virologic failure continues to be debated in the HIV literature. The two critical components associated with the failing of a patient’s antiretroviral regimen are the genetic barrier to resistance and “forgiveness” of the components of the regimen. This study looked at the frequency of virologic blips and virologic outcomes in patients with HIV on first-line ART who were part of clinical trials GS-1489 and 1490. The ART regimens in these trials included bictegravir (BIC)/emtricitabine (FTC)/tenofovir alafenamide (TAF), dolutegravir (DTG)/abacavir (ABC)/lamivudine (3TC), and DTG + F/TAF. Subjects with at least one HIV RNA value on-treatment were included in the analysis. A “viral blip” was an HIV-RNA value ≥ 50 c/mL followed by a viral load of <50 c/mL. This was after confirmed suppression with two consecutive viral loads of < 50 c/mL. There was a total of 1,240 participants with viral suppression of whom 143 (11.5%) had at least one blip through 144 weeks of therapy. There were similar blip frequencies between the three treatment arms. A total of 186 viral blips events occurred with 110 having a single viral blip and 33 having multiple blips. The proportion of participants with blips less than or greater than 200 c/mL was similar between the study treatment arms. Of the combined viral blips, 47% were low-level (50-199 c/mL) and 53% were > 200 c/mL.  Low-level blips were observed with high adherence (>95%) and many of these could be due to assay variation. High-level viral blips ≥200 c/mL were observed more commonly with cumulative adherence of ≤ 95%. Ninety-seven percent of subjects with blips <200 c/mL were undetectable at week 144 as were 91% with viral blips > 200 c/mL.

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