Role of resistance testing in the current treatment environment - CDC HIV Drug Resistance Workshop

This workshop is being run adjacent CROI to facilitate participation. John Mellors stressed the ongoing importance of resistance testing and subsequent drug selection so as not to render treatment scale up futile. The focus of the meeting has also shifted to being largely focused on resistance as it impacts middle and low income settings. But there were considerable references back to high income countries, particularly in relation to resistance development in the context of PrEP.

The opening presentation from Shannon Hader reviewed the current position of resistance testing in the global environment of scale-up of ART and meeting the 90:90:90 testing, treatment and viral suppression targets. NOW was seen as the time where, through a shifting focus toward quality improvement and funding high impact programs, these targets might be realised by 2030. The contracting funding climate was what was seen as driving this need to get more bang from prevention and treatment buck.

Reducing cost from not unnecessarily changing to 2nd line therapy was seen as something resistance testing could inform. Likewise making sure that individuals starting PrEP are in fact HIV negative was seen as essential and something which could be determined by earlier use of viral load.

Neil Parkin questioned the constant need for gold standard, when such aims might mean that no change is achieved. This notion was revisited throughout both days. Neil was specifically looking at the efficacy of dry blood spot viral load and resistance testing. It was recognized the DBS uses a very small sample size, thus hindering detection at lower concentrations (largely because whole blood, unlike plasma, introduces other confounding material into the sample). But this was pitched against the collection and transport benefits of DBS sample collection. In some places conventional samples cannot be collected, transported or analysed due to cost and complexity.

Suzanne Crowe provided an overview of current point of care test development for CD4 and viral load. Suzanne defined PoCT not as the technology, but the extent to which a technology could be used easily and reliably in close proximity to the patient. Like a number of other speakers, Suzanne identified the need for training. And operator proficiency as one of the largest sources of performance variation between any of the tests. The ongoing need for CD4 in the context of viral load was discussed and CD4 was seen as having a continuing place if not a rosy future.

The later discussions focused on the clinical impact transmitted resistance and the role resistance might play in the roll-out of PrEP. Interesting here was the level of discussion about clinical and preventative applications. This was great to see as previously I have witnessed a big disconnect between the science and its implementation. Dan Kuritzke questioned whether transmitted AZT resistance really meant anything in the context of AZT-free treatment regimens. Likewise there was speculation about what was driving the identification of resistant virus among 13-19 yr old MSM in large scale surveillance studies from USA. This was thought to probably be behavioural and possibly associated with amphetamines and frequency of sex and sex partners.

Clearly resistance remains very important in guiding clinical choices and in mapping transmissions. Just how these two functions can dovetail was also topical. Is it ethical to link clusters and transmissions to programs to get people on treatment? And if you have information about where infections are occurring is it ethical to not use that information? Not having HIV transmission as a crime was seen as enabling this information to be used for clinical and scientific purposes, rather than punishment. Tulio de Oliveira identified this as a facilitator of clinical and surveillance programs in South Africa.

Many of the speakers from this workshop are also presenting at CROI so no doubt much more on this topic.