HIV in Laura Waters Consultant Physician CNWL, Mortimer Market Centre, London

Transcription

1 HIV in 2016 Laura Waters Consultant Physician CNWL, Mortimer Market Centre, London

2 Content HIV epidemiology HIV testing Antiretroviral therapy Benefits of early treatment & when to start What to start Important issues Drug-drug interactions Vaccination

3 HIV TODAY: EPIDEMIOLOGY

4 Diagnosed HIV in the EU/EEA & WHO European Region* ,000 diagnoses in 2014 highest since reporting started in 1980s *excluding Russia European Centre for Disease Prevention and Control, WHO Regional Office for Europe. HIV/AIDS surveillance in Europe Stockholm: ECDC;

5 PHE: New HIV Diagnoses HIV New Diagnoses, Treatment and Care in the UK: 2015 report 85,600 Accessed 18/02/2016

6 PHE: New HIV Diagnoses HIV New Diagnoses, Treatment and Care in the UK: 2015 report >80% MSM infections NHSE from undiagnosed 3,360 2,490

7 Estimated number PLWH UK 2014: diagnosed and undiagnosed Overall: 18% % undiagnosed has declined Men who have sex with men: 14% Black more African than heterosexuals: the numbers 12-15% Other heterosexuals: 29-31%

8 HIV TODAY: DIAGNOSIS

9 Implications of undiagnosed HIV Undiagnosed HIV Individual Late presentation Illness Death Society Transmission Costs of advanced disease Prevention Prevention efforts must include testing

10 Late diagnosis in the UK by risk group CD4 <350 within 3 months of diagnosis 28% >50% >50%

11 Issues associated with late presentation Legacy effect? Transmission AIDS events Late presentation Health costs Mortality

12 The solution? Testing!

13 The solution? Testing! UPDATES ONGOING NOW!

14 British Guidelines Everyone attending particular services: GU, ANC & TOP clinics Drug dependency programmes TB, hepatitis B/C & lymphoma services If local prevalence >2 per 1000, test: All men and women registering in primary care All general medical admissions All with a risk: From a high prevalence country MSM History of IDU Diagnosed with an STI All individuals with indicator diseases AIDS & non-aids Unlinked anonymous testing of glandular fever screens from SE London showed 1% HIV+ [1] 1 Hsu et al HIV Medicine 2013

15 AIDS-defining & indicator conditions

16 HIDES-2: conditions where lower limit of 95% confidence interval >0.1 Hepatitis B and C Mononucleosis Lymphadenopathy Leucopenia, thrombocytopenia Pneumonia Neuropathy Seborrhoeic dermatitis Cervical dysplasia/cancer Lymphoma

17 AIDS-defining & indicator conditions TB 14.3% tested in London HIV

18 NICE TB guidelines Offer HIV testing before treating latent TB in line with NICE HIV testing guidelines Substance misus and prison services managing TB should test for HIV No blanket recommendation to test for HIV!

19 HIV TREATMENT

20 What are the benefits of ART? Individual Population Life expectancy Morbidity Risk to partners Health care costs Productivity Transmission

21 UK CHIC: life expectancy Expected age at death * Men Expected age at death * Women 85 Male UK life expectancy 78 years 85 Female UK life expectancy 82 years Years since ART Viral load 400 copies/ml CD4 350 CD CD4 <200 Viral load >400 copies/ml CD4 350 CD CD4 <200 * Expected age at death for a person aged 35 years with different durations of antiretroviral therapy according to current CD4 count and viral load suppression May M et al. AIDS 2014;28: Years since ART

22 START study results (95% confidence interval [CI], 0.30 to 0.62; P<0.001) n=2,359 n=2, Lundgren D, et al. IAS Vancouver, CAN. Oral # MOSY03; 2. Lundgren D, et al. NEJM 2015 Published Epub ahead of print July 20, 2015 DOI: /NEJMoa

23 Treatment as prevention: serodifferent couples HPTN % reduced transmissions initially 93% reduction in final analysis: 8 transmissions in ART arm 4 virological failures 4 prior to suppression PARTNER > 58,000 CLSA in 340 MSM & 548 heterosexual serodifferent couples where HIV+ partner on suppressive ART = ZERO transmissions 1. Cohen MS et al. N Engl J Med. 2011; 2.Cohen MS et al. IAS 2015 MOAC0106LB; 3. Eshleman SH et al. IAS 2015 MOAC0106LB; 4. Rodger A et al. CROI O153LB.

24 PARTNER caveats Confidence intervals 1 Upper limit of 95% CI: 0.3% overall, 1% for anal sex in MSM where HIV+ partner insertive/top Higher estimated risk if +VL: 2.23% overall, 2.7% in MSM Author conclusion: We can fairly safely say that the chance of transmission from a virally suppressed HIV+ person during heterosexual sex is negligible, however, we need to collect more data on gay men before saying this with the same degree of certainty Accompanying editorial 2 Was the PARTNER population representative? 1. Rodger A et al. JAMA Jul 12;316(2): doi: /jama Daar E, Corado K. JAMA Jul 12;316(2)

25 When to start IAS-USA 1 DHHS 2 WHO 3 EACS 4 BHIVA 5 ART is recommended for treatment of HIV infection and prevention of transmission of HIV regardless of CD4 cell count (AIa-BIII) ART recommended for all regardless of pretreatment CD4. Strength of recommendation A1 (strong recommendation based on RCT) for all Start ART in all regardless of WHO clinical stage or CD4. Prioritise severe/advance clinical disease (WHO stage 3 or 4) and adults with CD4 350 ART should always be recommended irrespective of the CD4 count. Strong recommendation if CDC B or C (including TB) or CD4 <350 All people living with HIV should start ART 1. Günthard et al, JAMA, 2014; /05/2016; /05/2016; /05/2016; /05/2016.

26 When to start IAS-USA 1 DHHS 2 WHO 3 EACS 4 BHIVA 5 ART is recommended for treatment of HIV infection and prevention of transmission of HIV regardless of CD4 cell count (AIa-BIII) ART recommended for all regardless of pretreatment CD4. Strength of recommendation A1 (strong recommendation based on RCT) for all Start ART in all regardless of WHO clinical stage or CD4. Prioritise severe/advance clinical disease (WHO stage 3 or 4) and adults with CD4 350 ART should always be recommended irrespective of the CD4 count. Strong recommendation if CDC B or C (including TB) or CD4 <350 All people living with HIV should start ART NOT COMMISSIONED BY NHSE CURRENTLY 1. Günthard et al, JAMA, 2014; /05/2016; /05/2016; /05/2016; /05/2016.

27 %

28 UK: cascade of care % 100% 100% 80% 83% 75% 70% 60% 83% 90% 95% 40% 20% 0% HIV+ Diagnosed On ART Suppressed Adapted from: Delpech V at al. Abstract O2; BHIVA conference April

29 BHIVA guidelines 2016 NRTI Backbone Third Agent PREFERRED Tenofovir-AF/emtricitabine Tenofovir-DF/emtricitabine Atazanavir + RTV Darunavir + RTV Dolutegravir Elvitegravir/COBI d Raltegravir Rilpivirine c,* ALTERNATIVE Abacavir/lamivudine a,b,* Efavirenz a ABC is contraindicated if an individual is HLA B*5701 positive b Use recommended only if baseline viral load is <100,000 c/ml except when initiated with DTG then ABC/3TC can be used at any baseline viral load c Use recommended only if baseline viral load is <100,000 c/ml d EVG/COBI/FTC/TDF and EVG/COBI/FTC/TAF should not be initiated in individuals with CrCl <70 ml/min (TDF) and <30 ml/min (TAF), respectively * The viral load advice for 3TC/ABC & RPV applies only to initiating these agents in individuals with a detectable viral load. When these agents are used as a switch option in the context of viral load suppression the baseline viral load can be disregarded Adapted from BHIVA Guidelines for the Treatment of HIV-1 Positive Adults with Antiretroviral Therapy 2016 Interim Update. Accessed July 30,

30 Modern ART The basic recipe unchanged since the mid-1990s: TWO NRTI + ONE DRUG FROM A DIFFERENT CLASS Highly efficacious >90% suppression at year 1 in modern trials Failure rate about 1% a year in real-life Usually once daily Several single tablet regimens For how much longer? Increasing cost-based switches Much safer & better tolerated than older drugs

31 HIV TODAY: IMPORTANT ISSUES TO COMMUNICATE

32 Important issues Adherence still important Ensure cost-based switches don t have a negative impact Impact on routine laboratory tests Several drugs inhibit tubular secretion of creatinine Atazanavir causes unconjugated hyperbilirubinaemia Some drugs have an adverse impact on lipids Drug-drug interactions are manifold Decreased concentrations = reduced efficacy Increased concentrations = toxicity

33 Drug-drug interactions (DDI) Cytochrome P450 mediated Ritonavir and cobicistat are potent inhibitors of the 3A4 isoenzyme in the cytochrome P450 system (CYP3A4) Also interact with several other enzymes and transporters Main, but not only, source of drug-drug interactions (DDI) Absorption Acid-reducing agents Chelation Many others! P-glycoprotein, organic cation/anion transporters, MATE.

34 Examples: toxicity Steroids and Iatrogenic Cushing s: CYP 3A4 inhibitors markedly increase concentrations of some steroids eg. fluticasone, Triamcinolone Many are fine eg beclomethasone, methylprednisolone Protease inhibitors & simvastatin: Rhabdomyoloysis Anti-arrhythmics: Amiodarone & flecanide contra-indicated with PI Concentrations may be reduced by NNRTI

35 Examples: toxicity Midazolam Oral contra-indicated with boosters & efavirenz 3 Parenteral cautious dosing with close monitoring Diazepam Sedative effect may be prolonged by boosters Lorazepam glucoronidated so fine 1. Prezista SPC, June 2012; Norvir Prescribing Information, February 2012; Reyataz SPC, April Prezista Prescribing Information, Tibotec Inc, June Sustiva SPC, July 2011.

36 Examples: loss of ART efficacy Phenytoin Reduces concentrations of several antiretrovirals Acid-reducing agents & ART: PPI and atazanavir/ritonavir Commonly used PI Up to 20mg omeprazole or equivalent OK PPI and rilpivirine Commonly used NNRTI, high risk of resistance PPI contra-indicated

37 Prevalence of recreational drug use in the previous 3 months (n=2,248 MSM) Nitrites (Poppers) Cannabis Pro-erection drugs (Viagra etc) Cocaine Ketamine Ecstasy GHB/GBL Methamphetamine (Crystal meth) Mephedrone Amphetamine (Speed) Anabolic steroids LSD Codeine Crack cocaine Khat Heroin Morphine Opium % 20% 40%

38 Mephedrone, GHB, crystal meth High risk sex Potential for drug-drug interactions: All undergo hepatitic metabolism Near fatal GHB/ART interaction first published 1999 Overdose: Supportive treatment Benzodiazepines for GHB withdrawal and for mephedrone & crystal meth intoxication Avoid haloperidol No effective antidotes currently

39 Dear Doctor, RE: Mr X I saw this gentlemn with HIV..he is on Stribild. Please note there is a risk of drug interactoins (see footer). He needs anual flu vaccination and a pneumococcal vaccine. Your sincerely Dr L Waters Blurb about vaccinations and drug interactions in general I m sure noone actually bothers to read it so that s why I type important interactions in myself. I wonder if you ll read this? Will you??

40 What we do now GP and referral letter templates have the following at the top of the letter: Please note there is a significant risk of drug-drug interactions between HIV therapy and other drugs, e.g: Ritonavir/cobicistat is a potent inhibitor of CYP3A4; important interactions include simvastatin (risk of rhabdomyolysis) and several inhaled/intranasal/injected steroids such as fluticasone and triamcinolone (risk of iatrogenic Cushing s) Rilpivirine has significant interactions with acid-reducing agents; PPI are contra-indicated; H2A and antacids require careful dose spacing Atazanavir interacts with PPI and H2A please discuss with us

41 Resources

42 Patient information card

43 Vaccination advice: examples Influenza vaccine Annual in all PLWH Pneumococcal vaccine: PCV-13: single dose for all PLWH PPV-23: national programme for all >65 or a co-morbidity other than HIV The two should be given more than 3 months apart

44 MODERN MEDICINE.

45 The ideal

46 The reality

47 The reality

48 Our role as HIV clinicians

49 Our role as HIV clinicians?

50 UK: a cascade worth protecting 120% 100% 100% 80% 83% 75% 70% 60% 83% 90% 95% 40% 20% 0% HIV+ Diagnosed On ART Suppressed Adapted from: Delpech V at al. Abstract O2; BHIVA conference April

51 Thank