Therapeutic application of zinc in human immunodeficiency virus against opportunistic infections

The relevance of zinc in resistance to infections by virus, fungi and bacte ria is recognized because of its pivotal role in the efficiency of the enti re immune system, in particular in conferring biological activity to a thym ic hormone called thymulin, which has differentiation properties on T-cell lines, In infection with human immunodeficiency virus (HIV), the zinc-bound form of thymulin (active thymulin, ZnFTS) is strongly reduced in stage IV of the disease (Centers for Disease Control and Prevention classification) with concomitant decrements in CD4(+) cell count and zincemia values. The z inc-unbound form of thymulin (inactive thymulin, FTS) is, in contrast, very high. The in vitro addition of zinc to plasma samples induces a recovery o f the thymulin active form, suggesting low zinc bioavailability as the caus e of impaired thymic functions with consequent CD4(+) depletion, An analysi s of risk factors for the incidence of recidivism opportunistic infections shows CD4+ depletion and zinc deficiency to have significant scores. Supple mentation with zinc for 1 mo (45 mg Zn2+/d) associated with zidovudine (AZT ) therapy in stage IV induces recovery of active zinc-bound thymulin, of zi ncemia, of CD4(+) cells with concomitant reduction (50%) of recidivism oppo rtunistic infections compared with the AZT-treated group. Complete disappea rance of recidivism by Candida aesophagea or Pneumocystis carinii is observ ed after supplementation with zinc. The relative risk factors (CD4(+) deple tion and zinc-deficiency) have lower scores in the HIV-positive zinc-treate d group, confirming, as such, the relevance of zinc in opportunistic infect ions that involve extracellular matrix. Such an assumption is indirectly co nfirmed with new HAART, where no opportunistic infections occur. Indeed, HI V RNA is inversely correlated with both CD4(+) and zincemia values (r = -0. 73, P < 0.01) in HAART-treated subjects, Lower scores for the same relative factors for the appearance of opportunistic infections are present in HAAR T-treated subjects compared with those treated with AZT. These findings, on the one hand, show the poor efficacy of AZT therapy compared with HAART th erapy for the progression of HIV, but on the other hand, they suggest that the lack of occurrence of opportunistic infections by HAART may also result from major zinc bioavailability. This further supports the key role played by zinc against opportunistic infections in HIV with a possible independen t effect by either HIV or the pathogens involved.