HAART AND suPAR IN HIV-1 INFECTION
The profound decline in blood and tissue VL after starting HAART accounts for the ensuing deactivation of the immune system evidenced by reductions in circulating/tissue levels of soluble and cellular immune activation markers [93,116,161-164].
Starting HAART immediately reduces circulating bulk-suPAR [109,116], suP AR(I), suP AR(II-III) and suPAR(I-III) [93] and CSF bulk-suPAR [109]. This reduction is in accordance with therapy-induced reductions in circulating suPAR in pulmonary tuberculosis [13], acute malaria [30], acute myeloid leukemia [71] and therapy-induced reductions in urine-suPAR in uro-sepsis [17]. The finding of unchanged suPAR levels in patients with low/normal suPAR levels pre-HAART [116] is comparable to the diminished therapyresponse observed in pulmonary tuberculosis [13] or acute myeloid leukemia [71] patients with low/normal pre-therapy suPAR levels.
The disparate suPAR change in HIV-1 infected patients with high vs. low circulating suPAR may be attributed to e.g., differences in HIV disease severity [11,12,14,93,109,116], comorbidity [116], dysmetabolism [123,157] and/or genetic polymorphism(s) - although there is no published evidence yet for associations between the suPAR level and polymorphism(s) in promoters of uPAR [15] or other genes.
It remains to be determined if the blood level of suPAR or changes in this post-HAART may be able to predict ensuing viral or immunologic non-response or failure and studies are ongoing to enlighten these issues.