Significance of ART vs. CD4 ratio

Importance of ART vs CD4 /CD8 ratio in HIV patients.

With the implementation of TARV, most HIV patients achieve CD4 cell recovery and viral suppression. However, immune dysfunction persists and both mortality and the risk of comorbidities remain high. The CD4/CD8 ratio is postulated as a potential marker of immune status and risk of complications.

HIV infection, due to highly effective antiretroviral therapy (TAR), it has now become a chronic disease that can be controlled. (1). With the available treatment, the complications of the disease are mainly determined to be conditions not associated with acquired immunodeficiency syndrome (AIDS). (1,2). Therefore, it is necessary to provide continuous clinical follow-up to the patient, in order to know if the patient is adequately controlled and if it is possible to prevent any type of complication.

ART has been shown to help restore CD4+ LT counts in a significant proportion of patients. However, most of them persist with elevated CD8+ T-lymphocyte (CD8+ LT) counts, so if CD8+ LT counts are not taken into account in calculating the index, we may be left without knowing the true status of the CD8+ T-lymphocyte (CD8+ LT). (3). The balance between immune reconstitution and inflammation/immune activation may be compromised during the patient’s trend toward normalization of the CD4:CD8 ratio.

A low CD4:CD8 ratio has been associated with aging and acts as a predictor of mortality in the general population. ( 4 – 5 ). This index may represent combined effects of inflammation and immunological changes that some have called inflammaging ( 3 ). Patients with CD4+ LT recovery who remain at a low value (less than 1) have increased immune activation, immune senescence phenotypes, and a higher risk of non-AIDS morbidity and mortality ( 3 ) .

Davy-Méndez et al. (6) in 2018 reported that, CD4 count and CD4:CD8 ratio remain elevated in those patients with acute infection, compared to patients with chronic infection, who have baseline CD4s less than 200 cells/mm3 and CD4:CD8 ratios <Although the time of HIV diagnosis was not taken into account in our study, in part the findings reported by these authors could explain the reason for finding a higher rate of HIV infection in our study than in our study. < 1 in patients with a lower CD4 count, with the baseline CD4+ LT count and the length of time the patient has been infected being the really important factors for this analysis. Thus, in the study mentioned above, (6) the possible relationship between the time of initiation of therapy and the time to normalization of the index is presented; a finding that could also explain this outcome. n the other hand, in chronic patients the rate of CD4:CD8 ratio recovery was lower, partially due to persistently elevated CD8 counts.

In 2014, Serrano-Villar et al. (7) wanted to examine which CD4:CD8 abnormality was associated with early or delayed TAR initiation (6 months vs. 2 years). At the time of diagnosis, the mean index was significantly lower in individuals newly diagnosed with HIV compared to the uninfected group. Subsequently, the late ART initiation group had a decrease of 274 cells/mm3 in CD4+ LTs, mean CD8+ LTs increased by 125 cells/mm3 and, the CD4:CD8 ratio decreased from 0.76 to 0.38 during this period. Therefore, the time from diagnosis to initiation of TAR could also explain the findings of the present investigation.

En el año 2012, Torti et al. (8) publicaron un artículo en el cual también mencionan que la recuperación exitosa de los LT CD4+ y del índice CD4:CD8 depende del tiempo de inicio de la TAR después de la infección por VIH y estado inmunológico basal del paciente (9).

To the aforementioned, the factor of adherence can be added, since poor drug intake and lack of continuity in treatment could explain why patients with a low index have decreased CD4+ LT levels and are more prone to present a viral failure.

These findings are useful as a first step in understanding the factors that may be associated with the persistence of a low CD4:CD8 ratio in HIV-infected patients, despite receiving antiretroviral therapy. Although the results were not conclusive in describing significant differences in variables such as the number of regimens, differences were evidenced in these variables as well as in viral control and the proportion of patients with adequate virological suppression.

There are potential limitations to explain these results, including the type of study, which does not clearly identify a time sequence that provides an approximation of the risk of not improving the index according to the variables evaluated, as well as some factors not assessed, such as patient adherence, which should be taken into account when adjusting the results, since almost all patients were receiving antiretroviral treatment.

The results of these studies are useful to emphasize the importance of obtaining the CD4:CD8 ratio in all HIV-infected patients, as well as the need to maintain an adequate follow-up of these patients, insisting on continuous surveillance, adequate virological suppression with treatment and proactively intervening in situations that may alter it, so that this population does not increase the risk of presenting complications associated or not with AIDS.

Our cytometry technology will enable this appropriate patient follow-up and Annar Health Technologies provides you with state-of-the-art technology and comprehensive results to achieve the best patient treatment outcomes. For more information, please contact patricia.fandino@annardx.com o yohana.martinez@annardx.com.

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