Anti-HIV type 1 Glycoprotein 120, Glycoprotein 160 polyclonal antibody

Objectives Raltegravir (RAL) that can form chelates with multivalent metal cations shows lateral interactions with multivalent metal cation and polycationic polymer. We investigated the interactions of RAL with multivalent metal cation preparations, Al(OH)(3)and LaCO3, and polycationic polymer preparations, bixalomer (Bxl) and sevelamer (Svl). Methods Immediately before the oral administration of 40 mg/kg RAL, the rats were administered orally with the vehicle, Al(OH)(3), LaCO3, Bxl, or Svl, and the time course of RAL serum concentration was followed. Thein vitrobinding affinity of RAL with multivalent metal cation and polycationic polymer was also evaluated using isothermal titration calorimetry (ITC). Results When Al(OH)(3), LaCO3, Bxl, or Svl was concomitantly administered with RAL, the maximum concentration and area under the curve were significantly lower than those when RAL was administered alone. ITC showed the interaction of RAL with Al(OH)(3)as an enthalpy-driven reaction and its interactions with LaCO(3)and Bxl as entropy-enthalpy mixed reactions. Conclusions The interaction of RAL with Al(OH)(3), LaCO(3,)Bxl, or Svl can inhibit RAL absorption into the gastrointestinal tract, and thus, the multivalent metal cation and polycationic polymer are the modifying factors that can affect RAL pharmacokinetics.

Successful suppression of viral replication by combined antiretroviral therapy (cART) in HIV-1 infected individuals is paradoxically also accompanied by an increased prevalence of HIV-associated neurocognitive disorders (HAND) in these individuals. HAND is characterized by a state of chronic oxidative stress and inflammation. Microglia are extremely sensitive to a plethora of stimuli, including viral proteins and cART. The current study aimed to assess the effects of cART-mediated oxidative stress on the induction of inflammatory responses in microglia. In the present study, we chose a combination of three commonly used antiretroviral drugs-tenofovir disoproxil fumarate, emtricitabine, and dolutegravir. We demonstrated that exposure of microglia to the chosen cART cocktail induced generation of reactive oxygen species, subsequently leading to lysosomal dysfunction and dysregulated autophagy, ultimately resulting in the activation of microglia. Intriguingly, the potent antioxidant, N-acetylcysteine, reversed the damaging effects of cART. Thesein vitrofindings were further corroboratedin vivowherein cART-treated HIV transgenic (Tg) rats demonstrated increased microglial activation, exaggerated lysosome impairment, and dysregulated autophagy in the prefrontal cortices compared with HIV Tg rats not exposed to cART. Similar toin vitrofindings, the treatment of HIV Tg rats with N-acetylcysteine also mitigated the deleterious effects of cART. Taken together, our findings suggest that oxidative stress-mediated lysosomal dysfunction plays a critical role in the pathogenesis of HAND in drug-treated HIV-infected individuals and that antioxidant-mediated mitigation of oxidative stress could thus be considered as an adjunctive therapeutic strategy for ameliorating/dampening some of the neurological complications of HAND.