Opportunities and Threats to ART success and related CROI abstracts

Opportunities and Threats to ART success (session 36) and related CROI abstracts

Greetings from Atlanta, home to CDC, CNN and Coca Cola of which I have ingested output from all three during this visit.

For those interested in the obstacles to ART implementation and its therapeutic success including new antiretroviral drugs and formulations, there was a terrific symposium held yesterday that addressed these issues.

Jennifer Kates from Kaiser Family Foundation outlined issues arising from Obama’s Affordable Care Act (ACA) as they pertain to HIV care and treatment access. Like Australia, the US Federal- State divisions and discords can be disconcerting. In the US states have the choice of accepting the expansion of the public health fund Medicaid or not. For those states that accept it, people living with HIV will have greater access and financial support for their HIV care. Currently 68% of people living with HIV in the USA live in states that will support Medicaid’s expansion but this leaves the potential for disparate levels of care for people living in the remaining states who decline Medicaid expansion. A good talk for those who seek to better understand the ACA.

Sharon Lewin from Alfred/Burnet/Monash gave an outstanding talk on the impact of the residual inflammation experienced by virologically suppressed HIV positive people on ART.  Sharon addressed the impact of residual inflammation upon risk for mortality and non-AIDS diseases. She addressed the drivers of this inflammation and the current (largely theoretical) therapeutic approaches we could take to decrease inflammation. A must-watch talk on CROI’s webcast.

Raph Hamers from Academic Med Ctr of the University of Amsterdam gave a very good talk on ARV drug resistance. He discussed in detail transmitted drug resistance, which is a key issue for populations living in eastern and southern Africa where transmitted NNRTI resistance predominates. Also he addressed the recently published observation that K65R resistance appears to occur more rapidly in clade C infected patients whose first-line therapy included tenofovir. K65R is also selected in patients who have been treated previously with stavudine (d4t). He highlighted the importance of switch studies from first to second line therapy.

Of note ASHM President-elect Mark Boyd and his colleagues’ SECOND-LINE study’s 48-week results were presented as a late breaker poster (180LB).  The study results support switching to a boosted lopinavir + raltegravir, NRTI-sparing regimen for individuals failing their first-line NNRTI with 2N(t)RTIs regimens. This approach was non-inferior to switching to boosted lopinavir +2-3N(t)RTI regimens and was associated with a significantly higher CD4 cell recovery.

Joe Eron from the University of North Carolina gave Trip Gulick’s talk on new ARVs, which was, thankfully optimistic. There are a number of new ARV formulations in the pipeline including atazanavir/cobicistat, darunavir/cobicistat which precludes use of ritonavir as a boosting agent. Rilpivirine is also being studied in a nanoparticle form and as a long-acting intramuscular injection. Efavirenz and atazanavir are also being considered for nanoparticle formulation. Antiretroviral agents can be formulated as solid or liquid suspension nanoparticles. Theoretically nanoparticles could afford better bioavailability and higher tissue concentrations as they are taken up and then released into tissues by mononuclear phagocytes. Abstract 513 reported on successful in vitro studies of Efavirenz formulated as solid drug nanoparticles.   

The talk provided an excellent table of all the up and coming drugs- check out this talk via the CROI webcast site to view the table.

Importantly Joe Eron mentioned the new tenofovir pro-drug tenofovir alafenamide (TAF). TAF is notable because its plasma levels are 90% lower than those of tenofovir but it has a 5-fold increase in intracellular TFV diphosphate compared to tenofovir, which affords it the potential for lower toxicity. Indeed significantly lower bone and renal toxicity was observed in the TAF arm of a phase 2 randomised, double blind trial presented as a late breaker oral presentation (abstract 99LB). Here elvitegravir/ cobicistat/ emtricitabine/tenofovir was compared to elvitegravir/cobicistat/emtricitabine/ tenofovir alafenamide. The two regimens had comparable efficacy at week 24 and the findings support scaling up to a phase 3 study. All points bulletin to bones and kidneys: watch this space!