25^th HIV Drug Resistance Workshop

This is the second time I have attended this meeting. It was very different from last year. Considerable attention was paid to transmitted resistance in the context of PrEP. While this does occur, it does not appear to be persistent.

There were also a number of papers looking at the practical implications of resistance in treatment. A number of presenters reported that resistance may not render a regimen defective. There was discussion about the utility of testing and while resistance testing remains too costly for use in many settings, it was also suggested that many clinicians in developed settings perform resistance testing, but don’t use it in regimen selection. There was some suggestion that resistance testing is becoming less important in the context of newer therapies. One take home message was that the longer people are on treatment, the greater the likelihood to resistance.

Preserving 2^nd and subsequent line therapy was seen as the major reasons for not switching, even in the absence of resistance testing, particularly in low and middle income settings.

Sequencing virus for epidemiological purposes is becoming increasingly important. A number of papers looked at clusters. It was suggested that some virus may be becoming more durable. With 30 clusters in one sample accounting for 1500 infections, while 1300 infections were seen as singleton transmissions. In this study the resistant virus was seen to be as fit as wild type virus. At a practical level what this means a new population is getting infected with lower sexual activity and with a lower testing frequency. There was also an interesting paper looking at clusters among injectors. The abstracts can all be found on line at https://www.informedhorizons.com/resistance2015/pdf/RW2015_Book.pdf

The new EACS guidelines give recommendation for treatment of asymptomatic primary HIV infection (PHI) even when CD4 count is >350. There is strong recommendation to treat if severe or prolonged symptoms, neurological disease, Age>50yrs and if CD4 <350. A French study (ANRS PRIMO cohort) showed rapid viral suppression in 327 patients treated within 1 month of diagnosis of primary infection (91.4% were symptomatic). Median CD4 count was 450. There were 2 cases of remission when treatment was interrupted in the ANRS OPTIPRIM study. The EACS guideline has recommended a regime including PI/r if resistance testing results are not available. Evidence is mostly derived from symptomatic patients and evidence on long term clinical benefits is lacking. The rapid suppression of viral load by Integrate inhibitors was discussed but has not been included in the guideline.  

Findings of the Phase 11a Proof of Concept Study for Second generation maturation inhibitor 176 was presented today. The mechanism of action of this drug is it stops the last step of protease cleavage during maturation. In vitro it showed better results than the first generation maturation inhibitors. 10 day monotherapy showed potent antiviral activity for both subtype B and C and it was generally well tolerated. There were no serious adverse events or discontinuations due to adverse events. A phase 11b global study is underway and looks promising. However in vitro resistance data is still being analysed.

A population pharmacokinetic model for a long acting injectable nanosuspension of Rilpivirine for IM injection was presented. The model was used to describe the absorption and disposition of RPV after IMI. The simulations were used to select different dosing regimens for further clinical evaluation. A cohort study showed that 73% of people wanted to use a long acting formulation. Long acting formulations are Cabotegravir 800mg 3 monthly and Rilpivirine 1200mg monthly. Phase 2 trials are underway. However with long acting formulations the risk is that if they miss a dose they can have prolonged periods of low drug levels posing a risk for resistance. They are more likely to be given to people who are less adherent in the first place. However it could be useful in adolescents who may find it harder to take a daily pill.

pneumocystis jiroveci revisited.

This afternoon session was of some clinical importance for those of us that look after patients whose CD4 count has never fully recovered despite many years of viral load below detection limits.

This Swiss cohort study produced elegant data with a combination of CD4 count and viral load as risk predictors of recurrent pneumocystis pneumonia.( H. Furrer)

This is consistent with the theme apparent in a lot of the presentations at this conference, of the ongoing problems associated with immune dysregulation from persistent viraemia.

In summary, patients with a CD4 count of 100 and persistent viral loads below detection limits have less risk of pneumocystis pneumonia than patients with a viral load of 400 and persistent moderate level viraemia. When I get hold of the elegant graphs I will try to post them.

I attended a few sessions of this course which runs on the first day. I hadn't read about the details beforehand, but it is very much in the style of an intensive workshop or refresher targeted towards specialist trainees or general or non-HIV physicians. I would certainly recommend attendance for these groups. Reference was also frequently made to the EACS Guidelines.

Both the toxicity session and the sexually transmitted infections session for instance comprised of a 15 minute clinical vignette of a moderate or higher complexity, followed by a 20-30 minute review on the topic. Particularly the toxicity session was ambitious and discussed about 20 items with traditional drug toxicity and all the metabolic complications.