CD4/CD8 Ratio Outcome According to the Class of the Third Active Drug in Antiretroviral Therapy Regimens: Results From the Quebec Human Immunodeficiency Virus Cohort Study

Abstract Background The impact of different therapeutic classes of drugs in antiretroviral therapy (ART) regimens on the CD4/CD8 ratio is not well documented in people treated for HIV. The objective of this study was to analyze the long-term effect of exposure to integrase strand transfer inhibitor (INSTI) on CD4/CD8 ratio compared with nonnucleoside reverse transcriptase inhibitor (NNRTI) or protease inhibitor (PI) among ART-treated persons with HIV (PWH). Methods Data from the Quebec HIV Cohort collected from 31 August 2017 were used. Our analysis included all patients in the cohort who received a first or subsequent ART regimen composed of 2 nucleoside reverse transcriptase inhibitors (NRTIs) and a third active drug of a different class (NNRTI, PI, or INSTI) for at least 16 weeks. Marginal structural Cox models were constructed to estimate the effect of different therapeutic classes on the CD4/CD8 ratio outcome. Results Among the 3907 eligible patients, 972 (24.9%), 1996 (51.1%), and 939 (24.0%) were exposed to an ART regimen whose third active agent was an NNRTI, PI, or INSTI, respectively. The total follow-up time was 13 640.24 person-years. The weighted hazard ratio for the association between the third active class and CD4/CD8 ratio ≥1 was .56 (95% confidence interval [CI]: .48–.65) for patients exposed to NNRTI + 2 NRTIs and .41 (95% CI: .35–.47) for those exposed to PI + 2 NRTIs, compared with those exposed INSTI + 2 NRTIs. Conclusions For people treated for HIV, INSTI-based ART appears to be associated with a higher CD4/CD8 ratio than NNRTI and PI-based ART. Among antiretroviral therapy–treated persons with HIV, integrase strand transfer inhibitors seems more effective than nucleoside reverse transcriptase inhibitors and protease inhibitors for normalizing the CD4/CD8 ratio, a potential marker of reduced immune activation.