Research Article: HIV-1 coreceptor tropism: A syllogistic connection with The Veterans Aging Cohort Study Index and the CD4/CD8 ratio

Date Published: February 28, 2019

Publisher: Public Library of Science

Author(s): Armando Leone, Nicolò de Gennaro, Claudia Fabrizio, Luigia Scudeller, Luciana Lepore, Antonella Lagioia, Grazia Punzi, Annalisa Saracino, Gioacchino Angarano, Laura Monno, Jianming Tang.


The association between X4 virus and an increased risk of non-AIDS-events has been reported. Morbidity/mortality due to non-AIDS events, which are properly predicted by the CD4/CD8 ratio and VACS index, have become particularly remarkable in HIV-infected patients receiving effective combined antiretroviral therapy (cART).

We verified the validity of the syllogism: as HIV-tropism (CRT) contributes to the onset of non-AIDS events which are successfully predicted by the CD4/CD8 ratio and VACS index, then CRT correlates with these two variables. The CD4/CD8 ratio and VACS index at baseline and overtime were analyzed according to CRT tested before the first successful cART regimen in newly-diagnosed patients.

Patients with R5 variants had a significantly lower baseline VACS percentage risk [mean (95%CI):18.2%(16.1–20.3) vs 24.3%(18.2–22.5), p = 0.002] and higher baseline CD4/CD8 ratio [mean (95%CI):0.43 (0.38–0.47) vs 0.28 (0.19–0.36), p = 0.002] than non-R5 patients. After an initial drop, VACS increased again in R5 and non-R5 patients and the two trend curves almost overlapped. The CD4/CD8 ratio had an increasing trend in both R5 and non-R5 patients; however, even though non-R5 patients had a greater gain of CD4+, they maintained a lower CD4/CD8 ratio at any time point.

Our study confirms an association between pre-therapy CRT, CD4/CD8 ratio and VACS. A successful cART regimen positively affects the CD4/CD8 ratio; however, the disadvantage conferred by a non-R5 CRT is maintained overtime. The restoration of VACS in all patients could be directly due to variables included in the VACS calculation and to factors that adversely influence these variables.

Partial Text

Combination antiretroviral therapy (cART) has transformed HIV infection from an incurable disease into a long term chronic condition; however, although the evolution of HIV infection to full-blown AIDS is now preventable, non-AIDS events are increasingly contributing to morbidity and mortality in HIV-infected patients on cART [1–3]. As in the general population, multiple factors facilitate the occurrence of morbid events either in naive and treated HIV-infected patients even with high CD4 cell counts (≥350 cells/mm3); nevertheless, the higher incidence of these events in HIV-infected patients compared to their HIV-negative counterparts suggests the existence of additional and specific factors.

Patients were eligible for the study if they: (i) were newly diagnosed HIV-positive patients, (ii) naïve to previous antiretroviral therapy; (iii) initiated their first successful cART; (iiii) had co-receptor tropism coincident with HIV diagnosis and, in any case, before starting cART. Eligibility criteria also included the availability of demographic, laboratory and clinical data.

While fewer and fewer AIDS-related manifestations are being registered among HIV positive subjects, the proportion of non-AIDS events is increasing, so that there is still an excess morbidity/mortality risk for HIV infected persons compared with the general population. Admittedly, the pathogenesis of non-AIDS events is multifactorial and includes, among other factors, the immune activation that characterizes the HIV infection [22]. Although CRT on HIV provirus does not seem to influence the persistent immune activation and inflammation in HIV-infected patients [23], to our knowledge, only limited data are available that directly correlate pre-therapy CRT of replicating HIV with the onset of non-AIDS events during treatment.




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