Integrase inhibitors associated with higher increases in CD4:CD8 ratio than PI- or NNRTI-based ART

Simon Collins, HIV i-Base

A retrospective analysis of 3,907 participants starting or switching ART in an observational Canadian cohort study between 2006 – 2017 reported higher CD4:CD8 ratio responses compared to PI- or NNRTI-based ART.

The study included used dual NRTIs in all combinations with the third drug being an NNRTI, PI, or INSTI in 25%, 51% and 24% of participants, respectively. The INSTIs in the analysis were raltegravir (38%), elvitegravir (19%) and dolutegravir (43%).

The analysis adjusted for all standard demographic and HIV-related variables, including calendar year and previous treatment history in people switching ART.

After 13,640 person-years of follow-up, 1790/3907 participants had a CD4:CD8 ration >1.0 after a median of 4.4 years (IQR: 2.1 to 7.4). Overall, the median (IQR) follow-up was 5.8 years (3.1 to 8.4), 4.5 years (2.0 to 7.4) and 2.9 years (1.7 to 5.3) for NNRTI, PI and INSTI groups, respectively.

The adjusted hazard ratio (HR) for the achieving a CD4/CD8 ratio >1.0 compared to INSTI-based ART was 0.56 (95%CI: 0.48 to 0.65) for NNRTI- and 0.41 (95% CI: 0.35 to 0.47) for PI-based ART.

The results were similar using the CD4:CD8 ratio cut-offs of 0.3, 0.5, 0.8 and 1.2. Results were also similar when the analysis was restricted to either treatment-naive or treatment-experienced participants.

The NNRTI effect compared to PIs was driven by a decrease in CD8 count (p=0.025) as CD4 changes were similar for NNRTIs and PIs (p=0.702).

Overall, the positive difference associated with INSTI-based ART was driven by increases in CD4 count.

The results were published ahead-of-print in Clinical Infectious Diseases in February 2023.


Sangaré MN et al. CD4/CD8 ratio outcome according to the class of the third active drug in antiretroviral therapy (ART) regimens: results from the Quebec Human Immunodeficiency Virus (HIV) Cohort Study, Clinical Infectious Diseases, 2023;, ciad056, doi: 10.1093/cid/ciad056. (1 February 2023).

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