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

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

None

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.   
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.

Antiretroviral therapy (ART) has dramatically improved the clinical outcome for HIV-infected patients. This clinical benefit is strongly correlated with CD4+ recovery (Baker et al. J Acquir Immune Defic Syndr 2008). Although the majority of the studies are focused on the CD4+ count increase as the main prognostic sign of immunological recovery after initiation of ART, some studies have described the potential usefulness of CD4+/CD8+ ratio and the CD4+ percentage (%CD4+) for estimating the immune recovery (Foglia et al. New Microbiologica 2014). So, Torti et al (Torti et al. Clin Microbiol Infect 2012) observed that the lack of increase in any of these immune indicators (CD4+/CD8+ ratio or CD4+ percentage) count appear to be deleterious for the achievement of excellent immune recovery in long-term HAART-treated patients. For this reason, the absolute CD4+ count could not be a surrogate marker of immune competent, even in patients with a high absolute CD4+ count. Recently, Foglia et al (Foglia et al. New Microbiologica 2014) described that %CD4+ <29% or CD4+/CD8+ ratio <1 display signs of immune deterioration notwithstanding CD4+ count =500/µl. However, patients with CD4+=500/µl, a CD4+/CD8+=1 and a %CD4+=29% displayed features of healthy subjects. These findings are in line with other articles of Serrano-Villar et al. (Serrano-Villar et al. J Infect 2013 & Serrano-Villar et al. HIV Med 2014) regarding the impact of CD4+/CD8+ ratio on immune activation and aging. This year, in a retrospective analysis of the cohort ICONA (Mussini et al. CROI 2014 #753), the authors observed that the normalization of CD4/CD8 ratio was uncommon following ART initiation and that the CD4/CD8 ratio normalization was associated with younger age, higher CD4/CD8 ratio at baseline, higher CD4+ cell count at baseline, and more recent ART initiation. There were no references to the use of integrase inhibitors. These authors also observed that a higher CD4/CD8 ratio on ART was associated with a lower risk of serious non-AIDS-related events or death.

For these reasons, although in the SINGLE study (Walmsley et al. NEJM 2013), the adjusted mean change from baseline at week 48 in the CD4+ T-cell count was greater with dolutegravir and abacavir-lamivudine than with efavirenz-tenofovir DF-emtricitabine (267/µl vs. 208/µl; P<0.001), it would be of interest to evaluate the likelihood of attaining CD4/CD8 ratio >=1 and %CD4+ >=29% after initiating ART and their relationship with subsequent clinical outcomes. No doubt it could strengthen the role of dolutegravir in the quality of immune recovery.

[{ "PostingID": 1388, "Title": "VIIV-ING114467", "Description": "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

Medicine: dolutegravir, Condition: Infection, Human Immunodeficiency Virus I, Phase: 3, Clinical Study ID: ING114467, Sponsor: ViiV" }]