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HIV Care 2012:New Trends, New Drugs, New Approaches
Chris Farnitano, MDNoon ConferenceJanuary 12, 2012
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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
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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.
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.
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.
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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
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With current approach, HIV incidence in US is not dropping
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Rate of new HIV diagnoses in women essentially unchanged
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The drop in rate of AIDS Cases and deaths is slowing
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Women are being diagnosed with AIDS at a high rate
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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
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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 phenytoinLong term boyfriend is HIV negativeFamily history of early CADSmoker
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Case Study: D.T.
Should you recommend antiviral therapy?
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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
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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
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Rationale of early treatment:
Treatment is better:– More options– Better efficacy– Less resistance– Better tolerability– Less long term toxicity
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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
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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.
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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
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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
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Trends in Phenotypic resistance to ARVs
Samples submitted for phenotypic resistance testing (N=68587) with any resistance detected:
Drug Class 2003 2010Protease Inhibitor 49% 26%Non-Nuke 70 60Nuke 76 67
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Trends in Phenotypic resistance to ARVs
Samples submitted for phenotypic resistance testing (N=68587) with any resistance detected:
Drug Class 2003 2010Single class 31% 54%2 class resistance 40 363 class resistance 29 11
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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
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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)
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Better, less toxic drugs: raltegravir
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Raltegravir Pros and Cons
Pros: Cons:Well tolerated Less long term dataVery potent Twice a day dosingNo lipid effects Low genetic barrier to
resistanceFew drug interactions
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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
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HIV tropism assay
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Better, less toxic drugs: etravirine
Intelence (etravirine) non-nucleoside reverse transcriptase inhibitor– 2 tablets (100 mg each) twice a day with food– Effective against 1st 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.)
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Options for One Pill, Once a day TherapyAtripla* (efavirenz/emtricitabine/tenofovir)Complera (rilpivirine/emtricitabine/tenofovir)Quad Pill (elvitegravir + cobicistat +
emtricitabine + tenofovir)
*indicates preferred regimen for initial therapy, DHHS guidelines
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Complera
Complera (rilpivirine/emtricitabine/tenofovir):Take with solid food, avoid PPIsLess rash, less CNS side effects, less discontinuations
vs. AtriplaHighly 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
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New drugs on the near horizon:
Cobicistat:Inhibitor of C--- that boosts levels of protease inhibitors, other drugsBoosting 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%)
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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 phenytoinLong term boyfriend is HIV negativeFamily history of early CADSmoker
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Case Study: D.T.
What to do now?
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Case Study: D.T.
Start on tenofovir/lamivudine (Truvada) one pill a day, raltegravir (Issentress) 1 pill BID
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It’s an infection, stupid, so treat it!
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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
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Case continued: CXR
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Case continued: Labs
HIV Ab PositiveT Cells 23HIV viral load >100,000Started on PCP treatment (high dose
TMP>SMZ), doxycycline, steroids
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What to do about antivirals?
1. Wait until PCP is fully treated?2. Start within 2 weeks of initiation of PCP
treatment3. Wait until patient is discharged and
established good HIV outpatient care before starting antivirals
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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
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What to do about antivirals?
ACTG A5164: RCT282 patients with PCP or Crypto
meningitis or bacterial infection70% with T Cells <50RCT to start ARVs ASAP (mean 12 d.) vs.
after OI treatment (mean 45 d.)
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What to do about antivirals?
ACTG A5164: ResultsImmediate 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)
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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 meningitisOther CNS infections
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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