Joseph Cofrancesco Jr, MD, MPH, FACP

Transcription

1 Friday Case Series Joseph Cofrancesco Jr, MD, MPH, FACP Associate Professor of Medicine Director and Johns Hopkins Institute for Excellence in Education Professor of Medicine Join us on Facebook Follow us on Twitter Connect with us on LinkedIn

2 Objectives Introduce topics that will presented in more detail during each lecture Discuss cases and appreciate different approaches There may be more than one approach/answer to a question Not all options are valid Work with the panel to explore different solutions Have fun

3 Disclosures None

4 Panel Allison Agwu Jean Anderson Ashwin Balagopal Raphael Landovitz

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7 1: Gabriel and Lucas (Or: So Doc )

8 Case 1 Lucas is 42 year old gay male, HIV negative Husband Gabriel (also your patient) is HIV+ VL < 20 for 5 years Never failed a regimen; changed for better meds Lucas describes himself as a total bottom They are completely monogamous

9 So Doc should Lucas go on PrEP?

10 Audience: Do you recommend PreP? 1. Yes 2. No

11 So Doc should Lucas go on PrEP?

12 US Public Heath Service: Clinical Practice Guideline, 2014 Daily oral PrEP with the fixed-dose combination of tenofovir disoproxil fumarate (TDF) 300 mg and emtricitabine (FTC) 200 mg has been shown to be safe and effective in reducing the risk of sexual HIV acquisition in adults; therefore, PrEP is recommended as one prevention option for sexually-active adult MSM (men who have sex with men) at substantial risk of HIV acquisition (IA)1 PrEP is recommended as one prevention option for adult heterosexually active men and women who are at substantial risk of HIV acquisition. (IA) PrEP is recommended as one prevention option for adult injection drug users (IDU) at substantial risk of HIV acquisition. (IA) PrEP should be discussed with heterosexually-active women and men whose partners are known to have HIV infection (i.e., HIV-discordant couples) as one of several options to protect the uninfected partner during conception and pregnancy so that an informed decision can be made in awareness of what is known and unknown about benefits and risks of PrEP for mother and fetus (IIB)

13 So Doc Do we even need to use condoms?

14 Audience: Pair up and discuss 1. Yes 2. No

15 Audience: Do they even need to use condoms? 1. Yes 2. No

16 HPTN 052: Transmission Through Sex Multinational randomized control trial 1763 HIV-serodiscordant couples 97% heterosexual CD4+ count cells/mm 3 at enrollment Randomized immediate ART vs. delayed ART (CD4+ <250 or AIDS) All received HIV-related care and counseling 39 total infections 28 linked transmissions 27 in delayed ART arm 1 in immediate ART arm 96% reduction in RR of HIV transmission with early HIV treatment 0.3 transmission events per 100 pt-yrs HPTN = HIV Prevention Trials Network. Cohen M. Prevention of HIV-1 Infection with Early Antiretroviral Therapy, NEJM 2011

17 The Opposites Attract Study In process, Sero-discordant gay couples 135 couples Australia, 52 Bangkok, 47 Rio Couple together 39% couples together < 1 year 33% 1-5 years 28%> 5 years 43% monogamous 85% on ART and undetectable Grulich A et al. HIV transmission in male serodiscordant couples in Australia, Thailand and Brazil Conference on Retroviruses and Opportunistic Infections (CROI), Seattle, USA, abstract 1019LB, 2015.

18 The Opposites Attract Study 5905 occasions of sex, the HIV negative partner: Top 60% Bottom 40% NO (linked) transmissions thus far seen Grulich A et al. HIV transmission in male serodiscordant couples in Australia, Thailand and Brazil Conference on Retroviruses and Opportunistic Infections (CROI), Seattle, USA, abstract 1019LB, 2015.

19 PARTNER Study Thus far, no transmissions in a couple when partner had undetectable viral load 16,400 occasions of sex in the gay men 28,000 in the heterosexuals Despite high levels of STIs 2008 Swiss Statement declared that people with an undetectable viral load did not transmit HIV, but made an exception of people with an STI Rodger A et al. HIV transmission risk through condomless sex if HIV+ partner on suppressive ART: PARTNER study. 21st Conference on Retroviruses and Opportunistic Infections, Boston, abstract 153LB, 2014.

20 So Doc Do we even need to use condoms?

21 Lucas and Gabriel They have one child, Lucas was the biological father. Now, they want to have another, this time with Gabriel s sperm. They have a friend Molly who agrees to be the surrogate.

22 Audience: What do you recommend? 1. Molly uses PreP only around the time of possible insemination 2. Molly starts full HAART for the entire time 3. Molly needs no medications, the risk is essentially zero 4. Gabriel find a place that does sperm washing 5. Molly should refuse to be the surrogate unless Lucas is the donor

23 What do you recommend? 1. Molly uses PreP only around the time of possible insemination 2. Molly starts full HAART for the entire time 3. Molly needs no medications, the risk is essentially zero 4. Gabriel find a place that does sperm washing 5. Molly should refuse to be the surrogate unless Lucas is the donor

24 Questions/Discussion

25 2: Pedro (Or: So Doc )

26 Pedro Pedro is 16 y.o bisexual male He is in a monogamous relationship with a 16 y.o. female She is on OCP Both live with their mothers Pedro is very serious about school and focus his energies on going to college

27 So doc About once a year, during spring break, I go to Florida and allow myself to play (usually men) He notes he sometimes uses condoms He asks: Should I just use condoms? Do I need PrEP? How should I take it?

28 Audience: What do you recommend? 1. Start TDF/3TC a week before a trip, take through trip, and take for a week afterward. 2. Always ask their new partner(s) if they are HIV negative, if so don t worry. 3. Condoms alone, reinforce proper condom use 4. Recommend year-round TDF/3TC 5. Tell him it s wrong to play

29 What do you recommend? 1. Start TDF/3TC a week before a trip, take through trip, and take for a week afterward. 2. Always ask their new partner(s) if they are HIV negative, if so don t worry. 3. Condoms alone, reinforce proper condom use 4. Recommend year-round TDF/3TC 5. Tell him it s wrong to play

30 Condom Effectiveness for HIV Prevention by Consistency of Use Among Men Who Have Sex With Men in the United States 2 prospective cohort studies EXPLORE VAX004 Based on self-report Efficacy: 70% effectiveness consistent use (v. never) No protection sometimes use (v. never) Smith DK et al JAIDS 2015

31 iprex: PrEP MSM & Transgender Women N = 2499 randomized: TDF/FTC v placebo Counselling Results: Sexual practice similar in both groups 44% HIV acquisition/136 wks 42% /144 wks 9% of seroconverters had detectable drug levels vs. 51% of nonseroconverters Among subjects with detectable drug levels, relative reduction 92% (95% CI, 40 to 99; P<0.001). AEs of PrEP mild, time limited [2] No evidence of resistance in seroconverters Grant RM, et al. N Engl J Med. 2010;363:

32 On Demand PreP (ANRS Ipergay Trial) Methods Double blinded, randomized, placebo controlled Approx 200 each arm Median 9.3 months How taken 2 tabs 2-24 hr before sex 1 tab 24 hr later 1 tab 48 hr later October 23, 2014, DSMB recommended discontinuation of the placebo arm Molina JM et al. NEJM 2015

33 On Demand PrEP Results 14 infections 6.6 per 100 PY (Placebo) 2, 0.94 per 100 PY (TDF/FTC) NO resistance 86% Relative Reduction (40-99%, p=0.002) Participants took median 15 pills/month Higher rate of GI and renal AE Molina JM et al. NEJM 2015

34 On Demand PrEP Molina JM et al. NEJM 2015

35 Is HIV all he has to worry about? Specifically, he worries about the risk of getting Hepatitis C

36 HIV-1 Infection With Multiclass Resistance Despite Preexposure Prophylaxis (PrEP) 43 year old MSM Consistently taking TDF/FTC Pharmacy dispensing records demonstrated consistent prescription refills. Dried Blood Samples revealed TVF-DP of 2,297 fmol/punch indicating consistent dose-taking in the preceding 1-2 months, thus overlapping with the seroconversion time. Standard and deep sequencing of virus from day 7: CCR5-tropic clade B HIV-1 Multiple mutations, conferring resistance to NRTIs (41L, 67G, 69D, 70R, 184V, 215E) NNRTIs (181C) INSTIs (51Y, 92Q), suggesting transmitted rather than acquired resistance Phenotypic drug resistance testing INSTI: reduced response to all integrase inhibitors Phylogenetic analysis revealed a very narrow range of sequence diversity, consistent with infection from a single source. Knox DC et al. HIV-1 Infection with Multiclass Resistance despite Pre-exposure Prophylaxis (PrEP). Conference on Retroviruses and Opportunistic Infections, Boston, abstract 169aLB, 2016

37 Questions/Discussion

38 3: Quick Case

39 Which ART? 33 y.o. female HIV + 3 years Well controlled on TDF/3TC/EFV (first regimen) Continues with CNS side effects Married 7 months ago and ready to get pregnant Her HIV provider asks 2 questions He wants to change her ART anyway; what do you recommend

40 Which ART? What practices of advice do you give in terms of conception: PreP for husband? No condoms only during fertile periods Use turkey baster Just have sex when you want

41 Questions/Discussion

42 4: Isabelle

43 Isabel 42 y.o. female Longstanding HIV Lots of prior regimes Very well controlled Infected at age 14 (abused by cousin) Former IDU but none in 4 year Failed prior Hep C treatment Now ready to start the new Hep C treatment

44 Isabel PHM Polysubstance abuse, none in 4 years No alcohol Quite smoking 3 years ago Mild asthma, uses albuterol MDI PRN PGH G5P3 Had an IUD in place, but heard they were bad so had it removed several months ago She was advised to return because she had h/o abnormal PAP She is sexually active with one male partner and they sometimes use condoms

45 Isabel Date CD4 VL Meds 1988 HIV Positive 1988 AZT TC s 32 copies 67 N/D, 70 K/R, 184V s 20-80K k TDF 3TC EFV LPV/r As above + 219N s < PLANNED Treatment Interruption

46 HC Date CD4 VL Meds s 50K K ATV/r EFV/TDF/FTC Higher dose of ATV 600s < <50 DRV/r <50 ATV/r Diarrhea <20 She s ready to start new Hep C treatment

47 Hep C data Genotype 1a 2005 bridging fibrosis on liver biopsy 2012: mild inflammation, minimal steatosis, and portal fibrosis 2014 liver elastography reflecting score of 6.9 kpa (mild fibrosis) 2015 :repeat fibroscan 7.4 kpa; (unchanged) Extensively treated (IFN, RBV, PEG IFN) Non-responder

48 Ready for Hep C treatment She is on: ATV/r + TDF/FTC/EFV Cr mg/dl Plan for 12 weeks: sofosbuvir/ledipasvir (harvoni)

49 Stanford HIV DB Algorithm

50 Audience: What do you do with HIV regimen? 1. No change, add sofosbuvir/ledipasvir, watch closely 2. Change TDF to ABC 3. Stop ATV/r, use just TDF/3TC/EFV 4. Change TDF + 3TC + DTG 5. Change to ATV/r + RPV 6. Something else Currently Taking: ATV+r + TDF/FTC/EFV Genotype: 67, 70, 184, 219

51 What do you do with HIV regimen? 1. No change, add sofosbuvir/ledipasvir, watch closely 2. Change TDF/FTC to ABC/3TC 3. Change TAF/FTC/EGV/c 4. Stop ATV/r, just Atripla 5. Change to ATV/r + RPV Currently Taking: ATV+r + TDF/FTC/EFV Genotype: 67, 70, 184, 219

52 How would you treat the Hep C?

53 What happened Planned for ATV/r + EFV (hold TDF/FTC) Insurance/pharmacy etc. issues Continued all meds Cr rises to 1.4 mg/dl with trace glucose and protein in urine concerning for tenofovir renal injury.

54 And then Completes full course Hep C treatment Hep C VL undetectable by week 6 Cr now back to 1.2 mg/dl Urine bland

55 Audience: Now what? 1. We dodged a bullet - leave her on TDF/3TC/EFV + ATV/r 2. Change to ABC + 3TC + NVP + ATV/r 3. Change to ATV/r + ETV 4. Change to ATC/c + MVC 5. Something else Currently Taking: ATV+r + TDF/FTC/EFV Genotype: 67, 70, 184, 219

56 Now what? In the US, with TAF (Tenofovir Alafenamide) and the many TAF/FTC + 3 rd drug combinations, we would select one of these newer combinations. 1. We dodged a bullet - leave her on TDF/3TC/EFV + ATV/r 2. Change to ABC + 3TC + NVP + ATV/r 3. Change to ATV/r + ETV 4. Change to ATC/c + MVC 5. Something else 6. Currently Something Taking: else ATV+r + TDF/FTC/EFV Genotype: 67, 70, 184, 219

57 What about birth control? Options Drug-drug interactions Her comment about IUDs Permanent birth control

58 Questions/Discussion

59 5: Quick Case 2

60 Transitions You have been seeing a congenitally infected patient Now well controlled on regimen: TAF/FTC, DRV/c and RAL He s had a tough time when young, but now stable He is turning 21 and still resists leaving your adolescent practice. Do/How do you transition, and what advice do you give adult practitioners?

61 Questions/Discussion

62 Thanks to the Panel

63 THANK YOU!