56 Dean Street, Chelsea and Westminster Hospital, London Conversation 3: Chemsex: its compatibility with PrEP and ART and impact on treatment adherence Dr Nneka Nwokolo 56 Dean Street, Chelsea and Westminster Hospital, London

Conflict of Interest Dr Nwokolo has received speaker fees, honororaria and support for attendance at conferences from Gilead Sciences, Viiv, GSK, Janssen

What needs to be done to make PrEP as successful as possible? Increase awareness, particularly in non-MSM groups Correctly identify individuals who would benefit Ensure that at-risk individuals know where to get it Support people to take it properly (e.g. identify and manage factors that might affect adherence)

The sex and the drugs

Definition Chemsex or ‘party ‘n play’ - use of any combination of the following psychoactive drugs or “chems” to facilitate or enhance sexual activity Methamphetamine/MDMA Gamma-hydroxybutyrate (GHB)/gammabutyrolactone (GBL) Mephedrone Poppers Ketamine Benzodiazepines Erectile dysfunction agents

NOT the same as traditional recreational drug use Associated with Extended periods of sexual activity for many hours/several days in house parties or clubs Extreme sexual practices associated with significant mucosal trauma Multiple partners – >10 in 1 session Stuart D and Collins S, HIV Treatment Bulletin 2015.

Consequences Associated with harms consequent on loss of inhibition Disinhibition facilitates condomless, often traumatic, sexual activity with multiple partners Linked to increasing rates of sexually transmitted infections (STIs), acute hepatitis C and HIV infections in large cities around the world Injecting chems, “slamming” increasingly prevalent

Association between chems and HIV acquisition Behaviours linked to increased risk of HIV acquisition e.g. condomless sex; multiple partners; fisting/and use of sex toys; use of HIV postexposure prophylaxis; history of previous sexually transmitted infection Virtually no published data showing causal association Pakianathan et al: 5x higher HIV incidence in GBM disclosing chemsex Sewell et al Int J Drug Policy 2017; Esser &Rowley EACS 2016;

Chems and ART adherence Use of chems associated with reduced adherence esp. at weekends 30% HIV+ reported poor adherence to ART – 56 Dean Street CODE clinic Others have demonstrated similar experiences (Marquez et al AIDS Care 2009; Garin et al BMJ Open 2017) No data that reduced adherence causes treatment failure

Interactions between chems and antiretrovirals Do ARVs increase levels of chems? No DDI PK/dose-effect relationship data Risk of potentially toxic interactions can be only be surmised from case reports or cohort studies ARVs and Chems… the question is do we have to worry about increased exposure of Chems in patients taking ARVs? There are some case reports of fatalities due increased exposure of recreational substances (with MDMA, metamphetamine) Formal studies about DDIs are lacking and therefore we do not know what the dose-effect relationship of the interactions is

Interactions (2) Ritonavir and cobicistat inhibit activity of CYP2D6 and 3A4 Crystal meth, mephedrone, MDMA, ketamine, EDA, benzodiazepines, cocaine all metabolized by CYP Increased potential for overdose

Interactions (3) Most interactions between recreational drug and ARV interactions are potentially NOT toxic Efavirenz, etravirine and nevirapine can induce drug metabolism and decrease desired effect (e.g. EDA, BDZ) NRTIs, rilpivirine, raltegravir, dolutegravir, and maraviroc are characterized by a low potential for drug–drug interactions The extent of the interaction is also dependent from the route of administration, the doses and frequency of use,…..etc…

What needs to be done to make PrEP as successful as possible? Increase awareness, particularly in non-MSM groups Correctly identify individuals who would benefit Ensure that at-risk individuals know where to get it Support people to take it properly (e.g. identify and manage factors that might affect adherence)