Comparative effect of dolutegravir and raltegravir on CD4+/CD8+ ratio, CD4%, and multiple T-cell marker recovery. SPRING-2 study.

Comparative effect of dolutegravir and raltegravir on CD4+/CD8+ ratio, CD4%, and multiple T-cell marker recovery. SPRING-2 study.

R Blanco has carried out consulting work for Abbvie, Bristol-Myers Squibb, Gilead Sciences, Janssen, Merck, and ViiV Healthcare; has received compensation for lectures from Abbvie, Bristol-Myers Squibb, Gilead Sciences, Janssen, Merck, and ViiV Healthcare, as well as grants and payments for the development of educational presentations for Gilead Sciences and Bristol-Myers Squibb, and ViiV Healthcare.S Moreno has carried out consulting work for Abbvie, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead Sciences, Janssen, Merck, Roche and ViiV Healthcare; has received clinical grants and compensation for lectures from Abbvie, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead Sciences, Janssen, Merck, Roche and ViiV Healthcare.

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%. Healthy persons
generally have a CD4/CD8 ratio >1 and a CD4% >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 (ART) 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 high CD4 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% have a higher morbi-mortality risk. Meanwhile, those patients with a high CD4
count and a higher CD4/CD8 ratio and a higher CD4% 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% is uncommon following
ART. Indeed, immunological recovery could be dependent on the drug class used.
INSTIs are an effective and well-tolerated class of antiretroviral drugs that currently are
included in all the HIV treatment guidelines. Recently it has been showed that
raltegravir (RAL), the first available INSTIs, showed a faster CD4/CD8 ratio
normalization than efavirenz [1], a finding with potential clinical implications. Whether
other INSTIs have a similar impact for this outcome remains to be explored. So, in the
SPRING-2 study, patients who initiated their first treatment with the INSTIs-containing
regimen dolutegrair (DTG) or RAL showed a similar CD4+ recovery after 48 [2] and 96
[3] weeks of treatment.
Undoubtedly, if DTG were able to achieve a higher immunological recovery (CD4/CD8
ratio, CD4 percentage,…) it could strengthen the role of DTG in the quality of immune
recovery.

[{ "PostingID": 1387, "Title": "VIIV-ING113086", "Description": "A randomized, double blind study of the safety and efficacy of GSK1349572 50mg once daily to raltegravir 400mg twice daily both administered with fixed-dose dual nucleoside reverse transcriptase inhibitor therapy over 96 weeks in HIV-1 infected antiretroviral therapy naive adult subjects" }]

Blanco JR, Alejos B, Moreno S. Immune recovery markers in a double blind clinical trial comparing dolutegravir and raltegravir based regimens as initial therapy (SPRING-2). PLoS One. 2020 Jan 16;15(1):e0226724.
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0226724