1. HIV Care 2012: New Trends, New Drugs, New Approaches Chris Farnitano, MD Noon Conference January 12, 2012

2. Learning Objectives  Be familiar with recent advances in anti-HIV medications  Know the new threshold for initiating HIV treatment according to the current DHHS guidelines  Be able to discuss the reasons for these more aggressive treatment guidelines  Be familiar with current recommendations for routine HIV testing  Know when to initiate anti-HIV therapy in patients newly diagnosed with opportunistic infections

3. Routine HIV testing, Where are we?  The U.S. Preventive Services Task Force (USPSTF) strongly recommends that clinicians screen for human immunodeficiency virus (HIV) all adolescents and adults at increased risk for HIV infection. Grade: A Recommendation.A Recommendation  The USPSTF makes no recommendation for or against routinely screening for HIV adolescents and adults who are not at increased risk for HIV infection. Grade: C Recommendation.C Recommendation  Above is a reversal from a recommendation in 2006 in favor of testing low risk adolescents and adults  The USPSTF recommends that clinicians screen all pregnant women for HIV. Grade: A Recommendation.A Recommendation

4. Routine HIV testing  June 19, 2011: Institute of Medicine recommends annual screening for all US sexually active women: –A monogamous woman cannot always know that her partner is being monogamous, may underestimate her level of risk –Power issues often leave women not in control of the use of barrier contraceptives

5. With current approach, HIV incidence in US is not dropping

6. Rate of new HIV diagnoses in women essentially unchanged

7. The drop in rate of AIDS Cases and deaths is slowing

8. Women are being diagnosed with AIDS at a high rate

9. Worldwide impact on Women  Globally, the leading cause of death and disease among women of reproductive age (between the ages of 15 and 44) is HIV/AIDS –WHO, November 9, 2009

10. Case Study: D.T.  Ms. D. T. is a 31 y.o. woman just diagnosed HIV+ with T cells=650, viral load of 35,000, baseline genotype reveals K103N mutation (non-nuke resistance)  PMH: seizure disorder, on phenytoin  Long term boyfriend is HIV negative  Family history of early CAD  Smoker

11. Case Study: D.T.  Should you recommend antiviral therapy?

12. Case Study: D.T.  Issues: –T Cells over 500 –Transmitted non-nuke resistance –Prevention of transmission to partner –Drug interactions with protease inhibitors, efavirenz and phenytoin

13. Current DHHS Guidelines on when to start therapy:  “For patients with CD4 counts >500 cells, Panel members are evenly divided: 50% favor starting ART at this stage of HIV disease; 50% view initiating therapy at this stage as optional.” –Updated January 10, 2011  Much anticipation that this recommendation will change to more strongly recommend treatment

14. Rationale of early treatment:  Treatment is better: –More options –Better efficacy –Less resistance –Better tolerability –Less long term toxicity

15. Case Study: D.T.  Issues: –T Cells over 500 –Transmitted non-nuke resistance –Prevention of transmission to partner –Drug interactions with protease inhibitors, efavirenz and phenytoin

16. Science Names HIV Treatment as Prevention Breakthrough of 2011:  The journal Science has chosen the HPTN 052 clinical trial, an international HIV prevention trial, as the 2011 Breakthrough of the Year.  The HPTN 052 clinical trial found that heterosexual people with HIV taking antiretrovirals are 96 percent less likely to transmit the virus to their sexual partners.

17. Rationale of early treatment:  Uncontrolled viremia is bad: –Increased risk of CVD –Increased risk of malignancy –Decreased cognitive function –Accelerated aging –More end organ damage

18. Case Study: D.T.  Issues: –T Cells over 500 –Transmitted non-nuke resistance –Prevention of transmission to partner –Drug interactions with protease inhibitors, efavirenz and phenytoin

19. Trends in Phenotypic resistance to ARVs  Samples submitted for phenotypic resistance testing (N=68587) with any resistance detected:  Drug Class20032010  Protease Inhibitor49%26%  Non-Nuke7060  Nuke7667

20. Trends in Phenotypic resistance to ARVs  Samples submitted for phenotypic resistance testing (N=68587) with any resistance detected:  Drug Class20032010  Single class31%54%  2 class resistance4036  3 class resistance2911

21. Case Study: D.T.  Issues: –T Cells over 500 –Transmitted non-nuke resistance –Prevention of transmission to partner –Drug interactions with protease inhibitors, efavirenz and phenytoin

22. Better, less toxic drugs: raltegravir  Isentress (raltegravir) integrase inhibitor –1 tablet (400 mg) twice a day with or without food –SE: uncommon: nausea, dizziness –Avoid dosing with metal ions (calcium, ant- acids)

23. Better, less toxic drugs: raltegravir

24. Raltegravir Pros and Cons  Pros:Cons:  Well toleratedLess long term data  Very potentTwice a day dosing  No lipid effectsLow genetic barrier to resistance  Few drug interactions

25. Better, less toxic drugs: maraviroc  Selzentry (maraviroc) CCR5 co-receptor blocker –need CCR5 tropism assay to see if will respond –80% of treatment experienced patients with Tcells<100 have CXCR4 virus –SE: uncommon: cough 5-10%, dizziness, fever, rare liver toxicity

26. HIV tropism assay

27. Better, less toxic drugs: etravirine  Intelence (etravirine) non-nucleoside reverse transcriptase inhibitor –2 tablets (100 mg each) twice a day with food –Effective against 1 st gen NNRTI resistant virus (K103N, Y181C) –SE: 10-18% of men and 34% women get transient rash –Contraindicated with atazanavir, fosamprenavir, tipranavir (levels markedly incr or dec.)

28. Options for One Pill, Once a day Therapy  Atripla* (efavirenz/emtricitabine/tenofovir)  Complera (rilpivirine/emtricitabine/tenofovir)  Quad Pill (elvitegravir + cobicistat + emtricitabine + tenofovir) *indicates preferred regimen for initial therapy, DHHS guidelines

29. Complera Complera (rilpivirine/emtricitabine/tenofovir): Take with solid food, avoid PPIs Less rash, less CNS side effects, less discontinuations vs. Atripla Highly potent: After 48 weeks, 84.3% fully suppressed vs. 82.3% with Atripla May be less likely to fully suppress HIV in patients with baseline viral load >100,000 vs. Atripla Higher rates of drug resistance if regimen fails vs. Atripla

30. New drugs on the near horizon: Cobicistat: Inhibitor of C--- that boosts levels of protease inhibitors, other drugs Boosting efficacy similar to ritonavir, better tolerated? BMS and Gilead planning co-formulation with atazanavir and cobicistat Quad pill: elvitegravir (integrase inhibitor) + cobicistat + emtricitabine + tenofovir -preliminary studies show better viral suppression (88%) vs. Atripla (84%)

31. Case Study: D.T.  Ms. D. T. is a 31 y.o. woman just diagnosed HIV+ with T cells=650, viral load of 35,000, baseline genotype reveals K103N mutation (non-nuke resistance)  PMH: seizure disorder, on phenytoin  Long term boyfriend is HIV negative  Family history of early CAD  Smoker

32. Case Study: D.T.  What to do now?

33. Case Study: D.T.  Start on tenofovir/lamivudine (Truvada) one pill a day, raltegravir (Issentress) 1 pill BID

34. It’s an infection, stupid, so treat it!

35. When to start antivirals in patients with active opportunistic infections?  Case:  26 yo MSM, not in primary care, presents with 3 weeks of SOB, cough, low grade fevers.  Temp 38.0, HR 120, BP 118/76, O2 sat 88% on RA  Lung exam: fine crackles throughout

36. Case continued: CXR

37. Case continued: Labs  HIV Ab Positive  T Cells 23  HIV viral load >100,000  Started on PCP treatment (high dose TMP>SMZ), doxycycline, steroids

38. What to do about antivirals?  1. Wait until PCP is fully treated?  2. Start within 2 weeks of initiation of PCP treatment  3. Wait until patient is discharged and established good HIV outpatient care before starting antivirals

39. What to do about antivirals?  Why wait? –Fear of immune reconstitution inflammatory syndrome (IRIS) –Overlapping toxicities –Drug-Drug interactions –Pill burden –Inadequate time for adherence counseling

40. What to do about antivirals?  ACTG A5164: RCT  282 patients with PCP or Crypto meningitis or bacterial infection  70% with T Cells <50  RCT to start ARVs ASAP (mean 12 d.) vs. after OI treatment (mean 45 d.)

41. What to do about antivirals?  ACTG A5164: Results  Immediate treatment group had trend to decreased rate of AIDS progression or death (14.2%) vs. deferred (24.1%)  No differences in IRIS (10 immediate vs. 13 deferred)

42. Summary of all studies: delayed vs. immediate treatment withARTs in patients with OIs  Good evidence to start ART shortly after starting therapy for acute OIs (and accept some risk of IRIS): –PCP –TB  Treat OI first and delay ART 2 weeks to reduce risk of lethal IRIS:  Crypo or TB meningitis  Other CNS infections

43. Learning Objectives  Be familiar with recent advances in anti-HIV medications  Know the new threshold for initiating HIV treatment according to the current DHHS guidelines  Be able to discuss the reasons for these more aggressive treatment guidelines  Be familiar with current recommendations for routine HIV testing  Know when to initiate anti-HIV therapy in patients newly diagnosed with opportunistic infections