g Protease inhibitor (PI)-based antiretroviral therapy (ART) can effectively suppress HIV-2 plasma load and increase CD4 counts; however, not all PIs are equally active against HIV-2, and few data exist to support second-line therapy decisions. To identify therapeutic options for HIV-2 patients failing ART, we evaluated the frequency of PI resistance-associated amino acid changes in HIV-2 sequences from a cohort of 43 Senegalese individuals receiving unboosted indinavir (n ‫؍‬ 18 subjects)-, lopinavir/ritonavir (n ‫؍‬ 4)-, or indinavir and then lopinavir/ritonavir (n ‫؍‬ 21)-containing ART. Common protease substitutions included V10I, V47A, I54M, V71I, I82F, I84V, L90M, and L99F, and most patients harbored viruses containing multiple changes. Based on genotypic data, we constructed a panel of 15 site-directed mutants of HIV-2 ROD9 containing single-or multiple-treatment-associated amino acid changes in the protease-encoding region of pol. We then quantified the susceptibilities of the mutants to the HIV-2 "active" PIs saquinavir, lopinavir, and darunavir using a single-cycle assay. Relative to wild-type HIV-2, the V47A mutant was resistant to lopinavir (6.3-fold increase in the mean 50% effective concentration [EC 50 ]), the I54M variant was resistant to darunavir and lopinavir (6.2-and 2.7-fold increases, respectively), and the L90M mutant was resistant to saquinavir (3.6-fold increase). In addition, the triple mutant that included I54M plus I84V plus L90M was resistant to all three PIs (31-, 10-, and 3.8-fold increases in the mean EC 50 for darunavir, saquinavir, and lopinavir, respectively). Taken together, our data demonstrate that PI-treated HIV-2 patients frequently harbor viruses that exhibit complex patterns of PI cross-resistance. These findings suggest that sequential PI-based regimens for HIV-2 treatment may be ineffective.

Telemetric HRV, particularly RMSDD and HF, can be used to provide a sensitive, valid and reliable assessment of autonomic control of heart rate.

Across the globe there is significant variation between and within indigenous populations in terms of world view, culture, and socio-political forces. However, many indigenous groups do share a striking commonality: greater rates of non-communicable diseases and shorter life expectancies than non-indigenous compatriots. Notably, this health gap persists for 'developed' countries, including Australia, Canada, New Zealand and the United States. The question of who is responsible for equalizing the gap is complicated. Using Australia as an exemplar context, this commentary will present arguments 'for' and 'against' the governments of developed nations being held liable for closing the indigenous health gap. We will discuss the history and nature of the health gap, actions needed to 'close the gap', and which party has the necessary resources to do so.