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Proposal 1028

Title of the Proposed Research

Impact of dolutegravir on CD4+/CD8+ ratio and CD4+ percentage in HIV-infected naive patients.

Lead Researcher

José Ramón Blanco, MD, PhD

Affiliation

Hospital San Pedro
Center for Biomedical Research of La Rioja (CIBIR)
Logroño , SPAIN

Funding Source

None

Potential Conflicts of Interest

Lead Researcher: I have participated in advisory boards, received honoraria for speaking engagements at scientific conferences and received grants from Abbott, Abbie, Bristol-Myers Squibb, Boehringer-Ingelheim, Gilead Sciences, GlaxoSmithKline, MSD, Janssen, and ViiV Healthcare.

Researcher 1: I have participated in advisory boards, received honoraria for speaking engagements at scientific conferences and received grants from Abbott, Abbie, Boehringer Ingelheim, Bristol-Myers Squibb, Boehringer-Ingelheim, Gilead Sciences, MSD, Janssen, and Roche.

Data Sharing Agreement Date

1 October 2014

Lay Summary

The immune system is composed of a variety of different cell types and proteins. One of these types of cells are lymphocytes (included among the white blood cell). There are two main types of T-lymphocytes (CD4 and CD8). Because the CD4 count is so variable, some researchers look at the CD4/CD8 ratio and the CD4 percentage. Healthy persons generally have a CD4/CD8 ratio greater than 1 and a CD4 percentage greater than 29%.

HIV-1 infection has a negative impact in the immunological status. Since CD4 cells are the main targets of HIV, the CD4 count falls after the infection while the CD8 count increases causing a decrease in the CD4/CD8 ratio. There is a direct correlation between the CD4 count and the risk of morbidity and mortality.

The goal of antiretroviral therapy is to inhibit viral replication so that the patient can improve its immune response trying to revert it to 'normal'. However, achieving an apparent normal or even highCD4 count may not translate into a fully restored health. To realize its importance, HIV-infected patients on stable antiretroviral therapy with durable viral control that had a high CD4 count but a low CD4/CD8 ratio or a low CD4 percentage have a higher morbi-mortality risk. Meanwhile, those patients with a high CD4 count and a higher CD4/CD8 ratio and a higher CD4 percentage have a lower morbi-mortality risk, similar to the healthy people.

At present, not all the antiretroviral treatments have the same immunological recovery efficacy. Even, the normalization of CD4/CD8 ratio and CD4 percentage is uncommon following antiretroviral. These parameters have not been evaluated in a newer class of HIV therapy, the integrase inhibitors. So, in the SINGLE study, those patients who initiated their first treatment with dolutegravir, an integrase inhibitor, plus abacavir/lamivudine achieved a significantly higher CD4 increase than those treated with efavirenz/tenofovir/emtricitabine. Undoubtedly, if dolutegravir were able to achieve, as demonstrated, not only a higher CD4 restoration but also a greater CD4/CD8 ratio and CD4 percentage, it could strengthen the role of dolutegravir in the quality of immune recovery.

Study Data Provided

Study ING114467: A Randomized Double-Blind Study of the Safety and Efficacy of GSK1349572 Plus Abacavir/Lamivudine Fixed-Dose Combination Therapy Administered Once Daily Compared to Atripla over 96 Weeks in HIV-1 Infected Antiretroviral Therapy Naive Adult Subjects

Statistical Analysis Plan

This will be added after the research is published.

Publication Citation