Gaining the Upper Hand

Thanks to recent advances in antiretroviral (ARV) therapy, the life expectancy of HIV patients is now almost equal to that of the general population – at least in more developed nations. But, as life expectancy continues to increase, long term HIV-associated complications, such as HIV-associated neurocognitive disorder (HAND), represent a growing health concern (1). The pathology of HAND is underscored by an accumulation of HIV particles in the central nervous system; over time, the disorder prevents sufferers from carrying out basic tasks and eventually results in death. But which ARV drugs are likely to be most effective?

Thanks to recent advances in antiretroviral (ARV) therapy, the life expectancy of HIV patients is now almost equal to that of the general population – at least in more developed nations. But, as life expectancy continues to increase, long term HIV-associated complications, such as HIV-associated neurocognitive disorder (HAND), represent a growing health concern (1). The pathology of HAND is underscored by an accumulation of HIV particles in the central nervous system; over time, the disorder prevents sufferers from carrying out basic tasks and eventually results in death. But which ARV drugs are likely to be most effective?

Sooraj Baijanth and colleagues at the University of KwaZulu-Natal in Durban, South Africa, used LC-MS/MS and matrix-assisted laser desorption/ionization MS imaging (MALDI-MSI) to study the spatial distribution of two ARV drugs, elvitegravir and tenofovir, in rat brains (2). The researchers found that elvitegravir demonstrated around 20 times higher blood-brain barrier penetration than tenofovir, reaching a maximum concentration of 976 ng/g. 

According to Baijanth, the approach developed by the researchers provides higher spatial resolution than other modalities and should allow them to map numerous analytes in tissue sections. Such capability will prove useful as they complete an evaluation of all FDA-approved ARV drugs before assigning them to a “brain penetration index.” The team hopes that the index will eventually help clinicians select the most appropriate treatment regimen for patients presenting with HAND symptoms.

Progress that cannot come soon enough, Baijanth remarks, reflecting on the “constraints and dangers associated with exposure to radioactivity” associated with PET imaging - the technique historically associated with tissue imaging studies. Baijanth is confident that improvements in the speed, accuracy and resolution of MALDI-MSI will continue as MS-based imaging becomes increasingly popular: “Such advances are sure to enhance the ability of researchers to conduct imaging experiments in situ, and will subsequently encourage translation into the clinic.”