Similar CD4/CD8 Ratio Recovery After Initiation of Dolutegravir Plus Lamivudine Versus Dolutegravir or Bictegravir-Based Three-Drug Regimens in Naive Adults With HIV

Abstract

BackgroundThe initiation of antiretroviral treatment based on a 2-drug regimen (2DR) with dolutegravir plus lamivudine has demonstrated non-inferior efficacy than dolutegravir-based three-drug regimens (3DR). We aimed to assess whether the treatment initiation with this 2DR has a different impact on the CD4/CD8 ratio recovery than INSTI-based 3DR.MethodsWe emulated a target trial using observational data from the Spanish HIV Research Network cohort (CoRIS). The outcomes of interest were the normalization of the CD4/CD8 ratio at 48 weeks using three different cutoffs: 0.5, 1.0, and 1.5. We matched each participant who started 2DR with up to four participants who received 3DR. Subsequently, we fitted generalized estimating equation (GEE) models and used the Kaplan–Meier method for survival curves.ResultsWe included 485, 805, and 924 participants for cutoffs of 0.5, 1.0, and 1.5, respectively. At 48 weeks, 45% of participants achieved a CD4/CD8 ratio >0.5, 15% achieved a ratio >1.0, and 6% achieved a ratio >1.5. GEE models yielded a similar risk of reaching a CD4/CD8 ratio >0.5 (OR 1.00, 95% CI 0.67 - 1.50), CD4/CD8 >1.0 (OR 1.03, 95% CI 0.68 - 1.58), and CD4/CD8 >1.5 (OR 0.86, 95% CI 0.48 - 1.54) between both treatment strategies. There were no differences between 2DR and 3DR in the incidence ratio of CD4/CD8 ratio normalization at 0.5, 1.0 and 1.5 cut-offs.ConclusionsIn this large cohort study in people with HIV, ART initiation with dolutegravir plus lamivudine vs. dolutegravir or bictegravir-based triple antiretroviral therapy showed no difference in the rates of CD4/CD8 normalization at 48 weeks.

Response to Commentary: Long-term Changes of Inflammatory Biomarkers in Individuals on Suppressive Three-Drug or Two-Drug Antiretroviral Regimens

“…As we learned from the experiences using dolutegravir in monotherapy (12,13), even under this inferior regimen, a readily measurable virological event such as a viral rebound can be slow to occur. Llibre et al ( 1) noted that we have recently reported a similar rate of CD4/CD8 ratio recovery after 48 weeks of dolutegravir plus lamivudine versus dolutegravir or bictegravir-based 3DR in naïve PLWH (14). These results are reassuring, but we could only evaluate differences after 48 weeks of ART, and as we previously showed, the CD4/CD8 ratio correlates poorly with inflammatory biomarkers (15).…”

Commentary: Long-Term Changes of Inflammatory Biomarkers in Individuals on Suppressive Three-Drug or Two-Drug Antiretroviral Regimens

“…Once HIV suppression has been achieved and maintained, it is highly unlikely that different dolutegravir-or bictegravir-based antiretroviral regimens could be associated with significantly different levels of inflammation or immune activation unless they include drugs with intrinsic toxicity. Actually, a similar CD4/CD8 ratio recovery has been reported after initiation of a 2DR (dolutegravir plus lamivudine) versus dolutegravir-or bictegravir-based 3DR in naive PLWH (6).…”

Reporting of Observational Studies Explicitly Aiming to Emulate Randomized Trials

“…We retrieved 3133 unique records, of which 200 were included in the review (Figure 1). All reasons for excluding records after full-text review are given in eAppendix 6 in Supplement 1.…”

“…Seventy studies (35%) reported in the title that the study aimed to emulate a target trial; 180 (90%) did so in the Methods section. Twenty studies (10%) reported the study was prospectively registered, 16 of these 20 (80%)…”

“…Most studies (187 [94%]) reported the set of variables that authors had decided to adjust for (eg, because they were potential confounders) in analyses, and 77 (39%) reported how these variables were selected. One hundred and thirty-one studies (66%)…”