Plasma HIV-1 RNA and CD4+ T-cell counts are determinants of virological non-suppression outcomes with initial integrase inhibitor-based regimens: A prospective RESPOND cohort study. Clinical Infectious Diseases
Álvarez et al. for the RESPOND (International Cohort Consortium of Infectious Diseases) Study Group aimed to examine baseline factors associated with virological nonsuppression outcomes (blips, low-level viremia [LLV], residual viremia [RV], and virological failure [VF]) in treatment-naive persons with HIV (PWH) who started a 3-drug antiretroviral therapy (ART) regimen in the integrase strand transfer inhibitor (INSTI) era in 2014–2020.
Viral suppression (VS) was defined as HIV-1 RNA levels <50 copies/mL; LLV, as the first of ≥ 2 consecutive plasma HIV-1 RNA measurements of 50–199 copies/mL, following VS; viral blip, as an isolated plasma HIV-1 RNA level of 50–199 copies/mL with previous and subsequent HIV-1 RNA levels <50 copies/mL, following VS; RV, as any detectable and quantifiable plasma HIV-1 RNA between 20 and 49 copies/mL, among participants with a HIV-1 RNA measurement with a limit of detection of 20 copies/mL, following VS; and VF, as the first of 2 consecutive plasma HIV-1 RNA measurements ≥50 copies/mL, with 1 measurement ≥200 copies/mL, following VS.
Of 4’310 eligible participants, 72% started INSTI-based regimens. At 48 and 96 weeks, 91.0% and 93.3% achieved virological suppression (VS), respectively. At 48 weeks, Kaplan-Meier estimates of rates were 9.6% for viral blips, 2.1% for LLV, 22.2% for RV, and 2.1% for VF. Baseline HIV-1 RNA levels >100 000 copies/mL and CD4+ T-cell counts ≤200/µL were negatively associated with VS at weeks 48 (adjusted odds ratio, 0.51 [95% confidence interval, .39–.68] and .40 [.27–.58], respectively) and 96 and with significantly higher rates of blips, LLV, and RV. CD4+ T-cell counts ≤200/µL were associated with higher risk of VF (adjusted hazard ratio, 3.12 [95% confidence interval, 2.02–4.83]). Results were consistent in those starting INSTIs versus other regimens and those starting dolutegravir versus other INSTIs.
In conclusion, baseline plasma HIV-1 RNA levels >100 000 copies/mL and CD4+ T-cell counts ≤350/µL were associated with lower rates of VS at 48 and 96 weeks, and higher rates of viral blips, RV, and LLV. CD4+ T-cell counts ≤200/µL were associated with a higher risk of VF. Importantly, the association between HIV-1 RNA levels or CD4+ T-cell count and these virological outcomes persisted in participants initiating INSTI-based and specifically dolutegravir-based regimens. These data suggest that baseline HIV-1 RNA levels and CD4+ T-cell counts are determinants associated with virological nonsuppression outcomes regardless of the antiretroviral regimen initiated and point to underlying mechanisms established before ART initiation, likely focused on the HIV reservoir size. Further research is warranted to explore the impact of bictegravir-emtricitabine-TAF, doravirine, and INSTI-based 2-drug regimens on long-term virological non[1]suppression outcomes.