Background: The improvements in HIV infection therapy and the large availability of
antiretroviral drugs have led to an increased survival among HIV infected people, and simultaneously
to a raised morbidity and mortality due to not-AIDS-related events in this group compared to
the general population. An increased systemic inflammation and a persistent immune activation
play a pivotal role in determining high rates of non-AIDS comorbidities. In the last years, many natural
or synthetic immunomodulatory molecules acting by different mechanisms have been conceived.
Pidotimod is a synthetic dipeptide molecule showing immunomodulatory properties. The
aim of this pilot study was to evaluate the effects of Pidotimod supplementation on residual inflammation
in HIV infected population.
Methods: Forty HIV positive individuals under cART were enrolled: 30 were treated with Pidotimod
supplementation (study group) and 10 served as control group (without Pidotimod supplementation).
For all participants, Cystatin C, PCR, ESR, microalbuminuria, TNF-α, INF-γ, IL-4, IL-10,
IL1β, IL-18 and IL-2 were measured at enrolment (T0), 4 weeks after of Pidotimod supplementation
(T1), and 4 weeks after completing supplementation (T2).
Results: In HIV positive participants treated with Pidotimod, the evaluation of cytokine levels
showed that IL-10, IFN gamma, and IL-4 were significantly higher at enrolment compared to the
control group. The increase under Pidotimod treatment persisted after supplementation suspension,
while the pro-inflammatory cytokines levels were reduced. Salivary IgA also increased during 4
weeks of supplementation and persisted at 4 weeks after completing supplementation. On the other
hand, the Cystatin C and microalbuminuria levels decreased over time, at a greater extent the Cystatin
C serum levels.
Conclusion: The study findings showed that the HIV population receiving Pidotimod achieved a rebalancing
of pro-inflammatory and anti-inflammatory cytokines as well as a significant reduction
in cystatin C levels. The treatment further allowed for an increase in salivary IgA levels at all the
analyzed times, as a secondary event to a remodulation of the immunological status obtained with
pidotimod. This approach could represent a new way to design new intervention strategies aimed at
improving the persistent immune activation status in the virologically suppressed HIV population.