ASHM Report Back

Clinical posts from members and guests of the Australasian Society for HIV, Viral Hepatitis and Sexual Health Medicine (ASHM) from various international medical and scientific conferences on HIV, AIDS, viral hepatitis, and sexual health.

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I have a couple more blogs planned from the excellent Hepatitis session on Friday that I should get done on the flight home depending on sedation titration but I wanted to take the opportunity before I leave BCN to thank ASHM for the sponsorship. It has been a great meeting of great educational value that will not doubt translate to better patient care.I hope you also found my blogs of educational value
Special thanks to Levinia Crooks and also to Samantha Williamson for the logistics.

Lastly, it is a long way to fly but sharing the cabin with the Stenmark twins certainly helped:

b2ap3_thumbnail_Twins.jpg

#22hourstarebear

Dr matt

Tagged in: EACS2015

This lecture on recreational drug use by Marta Boffito from London was a nice summary of some of the trends they are seeing in the UK and how this may affect treatment.

 

Marta started by highlighting a paper from 2014 - the ASTRA study which identified significant polydrug use (of recreational drugs) amongst MSM in the UK and its association with condomless sex. Whilst this may be a risk for HIV transmissions, the potential interactions with antiretrovirals in people living with HIV should also be considered. The Liverpool website neatly summarises some of these interactions here.

 

 

Of particular concern is the use of GHB or GBL (collectively known as ‘G’) as a party drug. This synthetic version of an endogenous hormone is rapidly absorbed and has a relatively short half life, leading to people sometimes taking multiple doses to maintain their ‘high’. The main concern with it is the fact that it has a narrow therapeutic range, and doses up to 3ml can cause death. In addition, ethanol interferes with the metabolism, as do ARVs such as PIs and cobicistat. Whilst crystal meth seems to be getting much attention at the moment (and something I see in my clinical practice in central Sydney frequently), the use of ‘G’ is of significant concern, particularly in patients with these potential drug-drug interactions. When reviewing or commencing PIs or pharmaco-enhancers such as cobicistat, it is crucial to take a full drug history and warn patients about potential interactions, even if they do not freely admit to using such drugs. 

 

Tagged in: EACS2015

 

STRIIVING

 

This is the eagerly anticipated large switch study for dolutegravir (DTG ) needed to round off the drug’s development and clinical applicability. The efficacy data was first presented at ICAAC in September with some focus here on secondary endpoints such as safety and satisfaction.

 

551 patients taking stable PI, INSTI and NNRTI based regimens were randomised to switch to ABC/3TC/DTG (n=277) or not (n=274). Switching to Triumeq was non-inferior to continuing ART, 85% vs 88%, difference -3.4% (CI95: -9.1%, 2.3%). No patients had protocol defined virologic failure and therefore no patients were evaluated for treatment-emergent resistance in either arm.  In conclusion this large, robust open label switch study had great results in terms of safety, satisfaction and efficacy.

 

On Thursday ( from Antiretroviral Therapy Session 1 ) I posted some very interesting pilot studies looking at DTG monotherapy in maintenance or novel bicombos in naïve patients such as 3TC/DTG. These are studies which are beginning to answer some of the burning questions that we have have about the genetic barrier of DTG.

 

STRIIVING is not one of those studies

 

The background to this is SWITCHMRK. In this study patients on stable PI based regimens who were randomised to switch to TDF/FTC/RAL exhibited virological failure if they had fostered NRTI mutations in the past.  Ever since this study switch studies have excluded patients at baseline who have had prior NRTI virological failure/resistance including the SPIRIT study (switch to TDF/FTC/RPV) and STRATEGY PI (switch toTDF/FTC/EVG/c). This study is no exception.

 

Therefore this study highlights an important point for clinicians considering switching patients it ABC/3TC/DTG. If the patient is on a stable PI based regimen one has to revise how they arrived there.  In essence this robust switch study does not yet answer the question “Can I put my first line failures on ABC/3TC/DTG?” It may be possible in the future as we discern more about DTG genetic barrier.

 

The answer to this question will likely come from a second line study recruiting now where NNRTI failures are randomised to receive either ABC/3TC/DTG or DTG/LPV/r viewable here on the clinicaltrials.gov site:

 

https://clinicaltrials.gov/ct2/show/NCT02227238?term=dolutegravir+second+line&rank=1

 

This study is called DAWNING.

Tagged in: EACS2015

I am quite of fan of the EACS guidelines particularly for co-morbidities and on  Friday they had a session detailing what's new in version 8.0 October 2015

 
1. ART
presented by Jose Gatell
 
The Europeans are now on page with everyone else with treatment recommended for all persons with established HIV infection regardless of CD4 count, the exception being elite controllers. This brings all 4 sets of guidelines into agreeance: DHHS, IAS and WHO (see table below)
 
b2ap3_thumbnail_Initiation-of-ART.jpg
The next slide is the greatly revised table of what to start with. Key features are:
 
13 regimens downsized to 6 (the DHHS guidelines have just 5, choosing to omit TDF/FTC/RPV whereas the EACS retains)
 
Increasing number of INSTI based regimens
 
Rentention of one each of PI and NNRTI based regimens
 
b2ap3_thumbnail_Initial-Combination-Regimens.jpg
 
 
2. PrEP
also presented by Jose Gatel
 
A whole new chapter in the guidelines and the only set of guidelines internationally to recommend "on demand" PrEP based on IPERGAY. CDC guidelines continue to support daily PrEP.  Ongoing concerns about on demand PrEP include reduced efficacy in MSM who may not be having sex as often as the men in IPERGAY or who may not be as good as tailoring Intermittent PrEP usage to perceived risk of sexual events as the men in IPERGAY. You can't deny the overall efficacy however. Will intermittent PrEP's inclusion in guidelines influence your practice?
 
 
b2ap3_thumbnail_PrEP.jpg
 
 
3. HCV/HBV Co-infection
Presented by Jurgen Rockstroh
 
Highly revised guidelines on which HCV patients to treat with DAAs. See the photo below. This table is adapted from the EASL guidelines drawn up in May and includes a footnote on who should be given priority for treatment independent of liver fibrosis. I think it is very forward thinking as it includes those with debilitating fatigue, extra hepatic manifestations such as cryoglobulinaemia and those at risk of HCV transmission including high risk MSMs. It is interesting how we are beginning to apply TasP principles to HCV. Applying TasP principles to the co-infection epidemic in MSM is not unfounded because it is concentrated and networked but it is probably unfounded in monoinfection with only an estimated 40% people diagnosed in most countries. 
 
 
b2ap3_thumbnail_Mngt-Chronic-HVCHIV-Coinfection.jpg
 
Finally the table below is a useful clinical tool for monitoring acute HCV infection. Spontaneous clearance is indicated by viral decay in log at certain time points. It still  lists IFN/RBV as treatment for acute infection only because we have not yet consolidated the evidence base for this with DAAs. That is about to change however with 3 datasets of DAA treatment in acute HCV almost ready. 
 
 
b2ap3_thumbnail_Acute-HCV.jpg
 
 
 
 
 
 
Tagged in: EACS2015
Data from the BMS-955176 Phase IIa proof of concept study was presented.
 
Short 10 day monotherapy were conducted for HIV-1 subtype B and C in treatment naive or experienced subjects to demonstrate virologic suppression. 1.64 log was achieved at doses above 40mg for B and 1.35 log for C.
 
The study also concluded comparable virologic control over 28 days with standard of care TDF+FTC+ATV/R with a 2.23 log fall in viral load at Day 28.
 
Still too early to tell I think.
Tagged in: EACS2015
Results were presented from the 0109 study funded by Gilead. Results from the study have been presented at multiple recent meetings.
 These results compared patients on standard of care Truvada plus boosted atazanavir to those subsequently switched to TAF/E/C/F (elvitegravir/cobicistat/FTC).
 
Follow up to 48 weeks supported at least non-inferior (perhaps superior) virologic control.
 
In relation to drug toxicity:
- The TAF arm had a change in creatinine of 0.00 compared to 0.03 mg/dL in the control arm from baseline.
- All measures of urinary protein were superior in the TAF arm.
- All lipids were increased in the TAF arm but investigators argued it was not clinically significant in light of a preserved total/HDL ratio.
- Improvement in BMD already at Week 24 and by Week 48, about 2% improvement, which in some cases was sufficient to move osteopenic patients to normal range.
 
Overall, I think TAF is very promising.
Tagged in: EACS2015

There was a lot of really good information today, not just from this stream but several others and I will be adding more over the next 2 days. But for now, here is GARDEL at 96 weeks

GARDEL 96 weeks

The 96 week data of this argentinian study was presented to show durability of the novel nucleoside sparing bicombo of 3TC/LPV/r.

The 48 week data was presented at this same meeting in Brussels 2013 by Pedro Cahn

426 naïve patients were randomised to receive a 3 drug regimen of 2NRTI/LPV/r or the novel 2 drug regimen of 3TC/LPV/r.

Virological efficacy of the nuc sparing arm was equivalent to the 3 drug arm at 96 weeks, 90% vs 84% (CI95: -2.3% to 14.1%). Equivalence in the high viral load stratum >100K which we saw at 48 weeks was also maintained here.

It needs to be said however that AZT/3TC accounted for 54% of the NRTI backbones in the 3 drug arm. One could therefore expect AZT toxicity discontinuations leading to underperformance of the 3 drug arm bringing about equivalence with 3TC/LPV/r in this ITT analysis. This makes the overall study findings questionable.  The analysis of protocol defined virological failures (PDVF) and resistance is however reassuring. For 3TC/LPV/r vs 2NRTI/LPV/r, PDVFs were 7 vs 6% with 4 vs 3 cases of M184V but no other NRTI RAMs or primary PI RAMs.

The other downside of course is that LPV/r is not really standard of care considering other options and so this is not a regimen most clinicans would consider. Hence the pilot that I fed back on yesterday looking at 3TC/DTG instead which Pedro Cahn will now take into Phase 3 following success of the pilot.

The road to nuc sparing has been a rocky one with futility of the likes of RAL/ATV, MRC/ATV/r and MRC/DRV/r.

This study poses the question: “is the only good nuc sparing regimen the one with the nuc in it lol?!”. Not even. At least we still have RAL/DRV/r, although even this falls down in sicker patients (CD4<200 and VL>500K).

We do however eagerly watch the development of newer generation NNRTI/INSTI nuc sparing bicombos: CBV/RPV and DTG/RPV in LATTE and SWORD respectively.

 

 

 

 

Normal.dotm 0 0 1 272 1552 TSPC 12 3 1905 12.0 0 false 18 pt 18 pt 0 0 false false false

 

Tagged in: EACS2015

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.  

Tagged in: EACS2015

I’m going to present two studies looking at HIV-1 RNA in the genital tract in the context of integrase inhibitors. The background of this issue relates to the fact that the male genital tract forms a separate reservoir of HIV.

 

The first study presented looked elvitegravir levels in seminal plasma in HIV-1 infected patients. This was a small study of just 10 patients who had already suppressed plasma viral loads at baseline with a median time on ARVs of 50 months. Patients were switched to elvitegravir/cobicistat/emtricitabine/tenofovir (EVG/COBI/FTC/TDF) single tablet regimen and paired blood plasma and seminal plasma samples were examined. All patients had undetectable blood and semen viral loads (<40 copies/ml) 4 weeks later. Some might argue the 4 week follow-up assessment may have missed a transient viral rebound in the seminal plasma. It could also have been too soon to identify viral rebound in this group, especially considering the extensive prior time on treatment (median 50 months). 

 

The second study from the same group examined the rates of HIV-1 RNA decay in seminal (SP) and blood plasma (BP) in naive patients commencing dolugravir (on ABC/3TC backbone). 15 patients were recruited to this open-label, single-arm study. Rate of HIV-1 RNA decay was initially higher in the BP compared with SP. Due to the lower baseline seminal HIV-1 RNA, viral suppression was achieved sooner in SP, although both groups were quite rapid. By the end of week 24, all but one patient had achieved an undetectable VL (<40 copies/ml) in the seminal fluid despite the groups median DTG concentrations being just 7.8% of total concentrations in the blood plasma.

 

What is the significance of this? Clearly these are very small studies, however they demonstrate promising findings in terms of efficacy in the male genital tract with these two new INSTI agents. In the day and age of treatment as prevention, viral suppression in this reservoir may be an important consideration. Further information around HIV transmission in MSM on ART should be gained from the Opposites Attract study which also has a semen analysis sub-study.

Tagged in: EACS2015

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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.

 

 

Tagged in: EACS2015

Two sub-studies, which formed part of START trial, were presented this morning.

 

The first study looked at lung-function decline in the immediate versus deferred arms of the START trial. The authors acknowledge the emergence of COPD as a co-morbidity in HIV, with prior studies showing mixed results on the the effects of ART on COPD risk.

 

This sub-study involved approximately 1000 patients divided between immediate and deferred treatment arms. The median follow-up time was relatively short - just 2 years. No difference of FEV1 slope was detected between the study arms, in both smokers and non-smokers.

 

This study suggests immediate vs deferred ART has no impact on lung function decline in HIV with CD4 >500. Further longitudinal data continues to be collected on this study population.

 

The second START sub-study presented looked at the effects of immediate versus deferred ART on bone density (abstract not available at time of writing this post). 424 naive patients with CD4 counts over 500 were enrolled (206 in the immediate group, 218 in the deferred arm).

 

Bone mineral density (BMD) was assessed by DEXA at the hip and lumbar spine at baseline and annually. The median age was young, 32 years old, with 26% female patients. Osteoporosis and low BMD were lower than in other cohorts (3.3% and 38%, respectively).

 

Over the course of the follow-up, 37% of patients in the deferred arm ended up on treatment. In the immediate treatment arm, 79% were on tenofovir containing regimens. Controlling for variables, significantly greater BMD loss was seen at both the hip and spine in those randomised to immediate ART. This effect was most pronounced in the first year, after which point it stabilised. No difference in the development of osteoporosis was seen between groups (or fractures - as presented in the results from the full START study population).

 

Both of these studies were extremely well presented, as one would expect from such a large multi-centre, multi-national trial. The presenter of the lung function sub-study acknowledges that they do not anticipate significant differences between the two study arms at the 3 year mark.

 

Clearly smoking status remains the most significant risk factor for lung function decline in HIV-infected individuals, and our focus should remain on supporting smoking cessation in this group. As for the bone sub-study, with the advent of TAF, I suspect the relevance of this study and associated concerns, certainly in Australia, will be further diminished.

Tagged in: EACS2015

Whilst we should try to adhere to the guidelines re PJP prophylaxis for sustained CD4 counts over 200 prior to cessation, there is enough reason to not panick if a patient is having difficulty being adherent , and

1. Their CD4 count is above 100, or

2. Their CD4 count is above 75 and the viral load is <400

and

3. They do not have underlying lung disease or another cause of immunodeficiency.

This particularly useful to have in mind for those patients with difficulty with adherence and a Bactrim allergy! It might be easier to prioritise another medication as opposed to upset rapport by trying to administer pentamidine or atovaquone which are less efficacious.

Tagged in: EACS2015

Matthew Shields has already done an excellent summary of the three most interesting presentations in "Antiviral therapy 1".

I will try to add a few points without doubling too much over the content.

Follow up of all small cohorts were to 24 weeks only.

The first presentation was on dolutegravir 50mg bd monotherapy in virologically suppressed treatment experienced individuals with healthy CD4 counts (many on atypical regimens including PI monotherapy) in a 33 patient "spur of the moment" pilot study. The authors explained 1 failure through extenuating psychosocial circumstances.

The second presentation from France was on dolutegravir 50mg once daily monotherapy in an older (mean 47, duration ART 17 years) virologically suppressed treatment experienced individuals (1/3 mono, 1/3 dual, 1/3 triple therapy). Three treatment failures were linked to resistance mutations in integrase but those identified were not classically for dolutegravir.

The third study was DTG+3TC in 20 treatment naive individuals and marked as sponsored by ViiV, who will fund a clinical trial soon in the area. Patients had viral loads less than 100,000 copies/ml and CD4 above 200. All patients had viral loads <400 copies by Week 3 and <50 by Week 8.

My conclusions were:

1. Follow up to 24 weeks was a significant limitation to these pilot studies. Further work is needed.

2. Dolutegravir resistance is certainly possible.

3. First line two drug dolutegravir containing therapy may certainly be a possibility, either with lamivudine or otherwise, but data is currently insufficient to support this.

4. Dolutegravir monotherapy could be considered in treatment experienced patients who have burnt out other options but there isn't enough to recommend switching for simplicity of regimen.

5. Early virological suppression does not necessarily translate to treatment efficacy.

 

 

 
 
Tagged in: EACS2015
Antiviral Therapy Session 1

There was a theme to this stream with 3 presentations on simplified therapy built around dolutegravir (DTG)  either as DTG monotherapy in maintenance or novel bicombos for naïve patients.

The background to this is that, in addition to high DTG potency (-2.5 log in monotherapy studies), there is also evidence that DTG may have a genetic barrier similar to that of a boosted PI (PI/r) since no resistance associated mutations (RAMs) were seen in patients meeting protocol defined virological failure in its Phase 3 program: SINGLE, SPRING 2 and FLAMINGO.

If DTG proved to have a genetic barrier similar to a boosted PI, its clinical applicability would potentially involve simpler (?2 drug) regimens with reduced cost and toxicity for naïve patients. In addition there would also be scope for extension of DTG to our patients who have some compliance chaos and most importantly regimen simplification and reduced toxicity in our treatment experienced patients still dependent on boosted PIs.

These 3 studies put these aspirations for DTG to the test!

Pedro Cahn from Argentina presented the week 24 results of the PADDLE study, a single arm pilot study, where naïve patients (n=20) commenced 3TC/DTG as a novel nuc sparing bicombo. It was noted that although only patients with VL<100K were chosen for the study, 4 had VL >100K at baseline.

At 24 weeks 100% of patients were <50 copies

What is nice about this study is that it builds on the increasing proof of concept that 2 drugs is enough for durable viral suppression but pushes the bar in that it is not just as a maintenance but from outset.

The study is the sequel to Pedro’s other study GARDEL looking at 3TC/LPV/r which showed virological success at 48weeks, the 96 week data of which will be presented tomorrow.

Despite the success of GARDEL, LPV/r is not really standard of care making 3TC/DTG a much better option in terms of tolerability and toxicity.

In conclusion this was overall a promising result for a simple nontoxic bicombo although perhaps 24 weeks is too early to evaluate efficacy. We need to see durable viral suppression out to 96weeks in a larger study and this is recruiting now.

The next 2 studies were pilots looking at DTG monotherapy as maintenance, a very attractive option if the genetic barrier of DTG holds up!

The background to this off course are the PI/r monotherapy studies. This concept fell out of favour last year after the PILOT study taught us that although resistance can be avoided low grade viraemia was common and this is a both a headache for monitoring as well as potentially a concern in terms of chronic immune activation and potentiation of reservoirs in places such as brain.

Could it be that the increased potency of DTG over PI/r means that this low grade viraemia could be avoided?

Esteban Martinez and Christine Katlama both presented small pilot studies from their respective cities Barcelona and Paris

In both studies there was a high proportion of patients coming from stable PI/r monotherapy and so in that sense they were pre selected for virological success

In Esteban’s study (n=33), 55% of the patients were coming from stable PI/r mono therapy ( the rest from stable 2 and 3 drug regimens) and all maintained VL< 50 copies at 24 weeks except for one and DNA genotypic resistance testing revealed no integrase mutations at 4 and 24 weeks.

In Christine’s study (n=28), 32% were coming from stable PI/r monotherapy and 89% maintained VL<50 copies at 24 weeks

However there were 3 virological failures and all 3 were found to have INSTI RAMs as detailed below:

Patient1:  92Q and 74L (the latter being a polymorphism in 12% of patients)

Patient2: 138K, 140A and 148R

Patient3: 155H

Interestingly all 3 had had prior INSTI exposure but without known failure. This was clarified very competently with DNA genotypic resistance testing at baseline and therapeutic drug monitoring. None of the 3 patients had these RAMs at baseline verifying that they were treatment emergent and all 3 had DTG concentrations in the normal range.

I put these mutations into the Stanford Database and although all of them are signature for RAL and EVG none are signature for DTG. However 2 or more together were typically associated with a >10 fold loss of activity of DTG in vitro. (See the photo below)


b2ap3_thumbnail_HIVdb.jpg

Christine concluded by saying that the findings argued for clarification with a larger study with perhaps less treatment experienced patients, since the patients had been taking ART for a median of 17 years.

I actually think it is quite foreboding and would not be comfortable putting my patents in that study!

In conclusion it suggests the genetic barrier of DTG is not good enough for monotherapy

Tagged in: EACS2015

 

Things got off to an early start this morning at EACS, starting with 4 different ‘Meet the Expert’ sessions to chose from. I attended the session on vaccination in HIV.

This session provided a nice overview of recommended vaccinations and their rationale in HIV positive patients. This was a good reminder to me to ensure patients are appropriately vaccinated at baseline and to intermittently check antibody status where indicated. In a day and age where many patients seem to be commencing antiretroviral therapy so early in their care (and at increasingly higher CD4 counts), it is easy to forget that such individuals still carry an elevated risk of complications.

Four Cases

Four cases were used to demonstrate infections that were preventable through vaccination. The first case was about measles. The presenter highlighted the fact that in some European countries, up to 13% of patients with HIV have no detectable antibodies against measles (particularly in patients born after 1983).

Many patients are unsure of their vaccination history and it may therefore be important to check antibody status. Another important consideration relates to the measles vaccine being a live attenuated vaccine (along with Yellow fever and varicella). European guidelines recommend only using live attenuated vaccines in people well controlled on ART with CD4 counts >200 (14%), or off ARVs with higher CD4 counts (500, >20%).

The presenter suggested considering antibody titres where indicated. However, it is important to remember that antibody responses are used as a surrogate marker and may not reflect impaired cell-mediated immunity in HIV positive patients.

The second case was a reminder to ensure all patients with HIV have an annual influenza vaccine. They highlighted a study which showed no increase in immunogenicity through booster doses or increased antigen dose of influenza vaccine in HIV positive patients.

The second presenter discussed a case of a patient with pneumococcal pneumonia. Whilst the most vulnerable patients are those with low CD4 counts and those not on ART, strep pneumonia remains a problem even in the HAART era, with patients with HIV at greater risk of complications. I found this particularly interesting as I feel there is a lot of uncertainty around appropriate pneumococcal vaccine choice and timing in patients with HIV. 

In patients with HIV, conjugate vaccines (such as 13-PCV) have been shown to have greater immunogenicity (compared with polysaccharide vaccines such as 23-PPV) and it is for that reason they are recommended for initial vaccination where available in the EACS guidelines (and DHHS). EACS guidelines do not recommend booster doses at present. whereas the DHHS guidelines do. 23-PPV can be given 8 weeks after 13-PCV (or after CD4 increases over 200 on ART). In patients who has 23PPV initially, 13-PCV can be given after 1 year. The full DHHS guidelines can be found here: http://aidsinfo.nih.gov/guidelines

The final case discussed was around hepatitis B vaccination. Serological responses to standard dose vaccines are impaired in HIV-infected individuals (with lower response in low CD4 setting and off-ART). There are numerous schemes for non-responders which can be used - one study showed good response (86%) with re-vaccination with the standard schedule (especially if less than 3 months from the last dose of first schedule). Additionally, both double-dose schedules and intradermal vaccination showed improved response rates.

If you made it to the end of this blog, my take home points from this session were: 

  • don’t assume prior vaccination (particularly with primary vaccines), take a full vaccine history and check titres where indicated
  • use live attenuated vaccines with caution and as per guidelines
  • conjugate vaccines appear to have higher immunogenicity and are therefore preferred (e.g. pneumococcal vaccine)
  • double dose Hep B vaccinations in non-responders are easy to administer and show improved response rates 

 

Tagged in: EACS2015

Prostate cancer screening was discussed in the context of HIV at a presentation today by  L. Shepherd.

Her group showed some PSA difference perhaps in HIV positive men.

The study used conditional logistic regression models to investigate potential relationships between markers and prostate cancer. The suggestion from the study was that prostate cancer may occur at lower PSA levels in HIV positive men.

I found this suggestion remarkable given that the guidelines for the general population are so hotly debated. In this study there was no detail about how prostate cancer was defined.

It was not clear whether this was a true "screening" PSA process or whether these were symptomatic men.

 

This data will not change my view about PSA screening in all men positive or negative.

Tagged in: EACS2015

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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.

 

Tagged in: EACS2015

This morning's meet the experts session about drug interactions was very interesting. There are an enormous number of potential drug interactions but the significance of many of them is unknown.

New drugs are being added to the database every week.

We will be faced with a large number of patients on multiple medications and particularly with the co-infected some clinical dilemmas.

The key useful points and questions for clinical care in the primary care setting are:

1. Are the other drugs necessary?

For instance statins and low-level antihypertensives could be ceased for a 12 week treatment course.

2. Are there any alternatives with less or no predicted interactions?

If so switch

Can the DDI be managed?

If the answer is yes then dose.adjust and monitor for toxicity. There was some discussion about trying to monitor for efficacy which is a little more difficult but very important.

If the answer is no

- the risk needs to be explored and discussed with the patient to decide whether the risk is worth taking.

A very valuable clinical point was made that a large number of patients with HIV on therapy have other medications with known DDI's in the current regimen prior to starting hepatitis C treatment. These probably do not have to be approached fearfully as they have been already sorted out.

 

 

 

Tagged in: EACS2015

The Pre congress workshop was aimed at junior specialists and professionals in training and followed a theme of challenging case presentations followed by an overview of the topic by an expert. Women living with HIV seems to be a problem area in London mainly in black African backgrounds. The topic covered was contraception and take home messages were that women tend to go to their GP for contraceptive issues and tend not to disclose their HIV status and end up getting a contraceptive method which interacts with her ART.

There seems to be trend of prescribing Truimeq for women of childbearing age despite the fact that there is no data on teratogenicity of Dolutegravir, in case they have an unplanned pregnancy. Generally regimes are unchanged if they do fall pregnant mainly because by the time the pregnancy is discovered it is usually past 6 weeks. A study is currently underway in African pregnant women on Dolutegravir looking at teratogenicity and so far there have been no reports. 

Caesarean section rates seem to be still high in regional centres despite viral suppression to undetectable levels. This is party accounted for the number of women with a previous section but they are hoping it will go down in future. Considering the poor compliance of women coming back for contraception at 6 weeks post partum, intracaesarian IUD insertion had been effective both in the USA and Africa with expulsion and infection being rare and may be used for an occasional poorly compliant woman.

The session on 'Chem sex' was quite interesting as I learnt a lot of new jargon relating to sex and drugs. There is about a 15% rise in IVDU among MSM in UK in the last decade giving rise to the risk of spread of HIV, HBV, HCV, HDV, and of course STI's. Slamming is another word used for using psychoactive substances in a party or sex settings. A qualitative study done in Paris showed that men using these drugs were unaware of their HIV and HCV status rates being as high as 40-60%.

When considering the amount of MSM turning up at the clinic on Monday afternoon for PEP after a 'wild weekend', I think that chemsex would be a potential problem in Sydney and other major cities in Australia very soon. Repeated HCV infections are a major problem in this group.

For both contraception and chemsex, a most valuable site is the Liverpool drug interactions website.  www.hiv-druginteractions.org

STI session was quite interesting and increased rates of gonorrhoea, Chlamydia and syphilis were universal all across Europe in the last couple of years.

Funny fact - In the olden days gonorrhoea was treated by hitting the penis with a bible! :)

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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.

 

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