Judith A. Aberg, MD, FIDSA, FACPChief, Infectious DiseasesMount Sinai Health SystemGeorge Baehr Professor of MedicineIcahn School of Medicine at Mount Sinai

Meet the Professor: Antiretroviral Therapy

Learning Objectives

• DescribethefactorswhichshouldbeconsideredinselectingantiretroviraltherapyfornewlydiagnosedpersonswithHIV

• IdentifythechallengesinselectingantiretroviraltherapyforpersonswithHIVwhoaretreatmentexperienced

Mr. INSTI

• HIV dx 1992. Not in care. Never had an UD HIV RNA• 3/99: AZT/3TC/EFV: stopped 1/01• 8/07-11/07: TDF/FTC/EFV (Resistance testing: none)• 5/08-12/10: TDF/FTC/ATVr• Multiple hospitalizations with cryptosporidiosis• June 2011 CD4 49 and started TDF/FTC/EFV/RAL• Developed intolerable nightmares: TDF/FTC/ETR/RAL• March 2012: TDF/FTC/DRVr• S. pneumonia Bacteremia, VATS

Mr. INSTI

• May 2014: TDF/FTC/EVGc; dMAC 5/14• Sept 2014: EVG resistant- ABC/3TC/TDF/ATVr• March 2015: PCP • HIV VL range 18,723 to 978,915• Switched to FDC ABC/3TC/DTG + TDF

Genotype Sep 2014

Genotype Sep 2014

Genotype May 2015

Mr. INSTI

• March 2017: 154,573 with CD4 11/3%• Admitted with neutropenic fever• T41MO rectal CA, s/p XRT and chemo

• OPEN FOR DISCUSSION

Summary

• Management of Treatment experienced patients requires thorough review of prior regimens and resistance testing if available

• Barriers to Adherence should be addressed• Dolutegravir should be prescribed twice daily if

underlying INSTI resistance

Mrs CI

• 48 yo BF referred for complex HIV management

• DX HIV 1990s. • 2003: AZT/3TC/EFV GI intolerance• Switched TDF/FTC/ATVr: developed SJS• Declined ART until 2009: AZT/3TC/NVPTook ART for one year but family moved in and she could only “sneak doses when nobody looked”

What to do?

• Went to FP who restarted AZT/3TC/NVP Spring 2015 but no virologic response so told her to stop all and sent to HIV expert. Referral restarted TDF/FTC to maintain low replication capacity

• Previous resistance tests : R: all NRTIs and NNRTIs• Trophile DM• CD4: 9/2% and HIV-1 RNA 124,732• Atovaquone, FCZ and AZ for OI prophylaxis

Genotype

AI438047/205888

• Started TDF/FTC/DTG BID/BMS 663068 January 2016• Week 8: HIV VL less than 40 copies/mL

• Remains undetectable one year later with CD4 266/22%

Clinicaltrials.gov: NCT02362503Agent bought by Glaxo-Smith-Kline

Summary

• Options may be limited by hypersensitivity reactions in addition to resistance

• Risk of hypersensitivity reactions: Not all drugs in a class cross-react

• Consideration for clinical trials

Ms. IC

• 52 yo F, Ivory Coast on vacation in US• HIV dx 14 years ago• ON TDF/3TC/EFV, CD4 and VL unknown• Presents with productive cough x 6 weeks, weight loss,

diarrhea• Bibasilar consolidations, >RLL, right hilar LN• Fevers during hospitalization• PMH: 2006 pt states she was blind for 6 months for

unknown cause. Pt prayed and sight restored. Ophthoexam 2017: HIV retinopathy

Ms. IC

§ Labs return§ CD4 17 (2%)§ HIV VL 301,577§ Serum CRAG -1:512§ CSF (opening pressure normal)

§ O WBC§ 12 RBC§ Glucose 50§ Protein 24§ CSF CRAG Negative

Genotype March 2017NRTI Drug Class

VIDEX, (didanosine, ddI) Resistance VIREAD, (tenofovir, TDF) Resistance* ZERIT, (stavudine, d4T) Possible Resistance ZIAGEN, (abacavir, ABC) Resistance* EMTRIVA, (emtricitabine, FTC) Resistance RETROVIR, (zidovudine, ZDV) None EPIVIR, (lamivudine, 3TC) Resistance

NRTI drug resistance mutations identified: K65R, Y115F, M184V

NNRTI Drug Class

SUSTIVA, (efavirenz, EFV) Resistance*** VIRAMUNE, (nevirapine, NVP) Resistance*** INTELENCE, (etravirine, ETR) Possible Resistance*** EDURANT, (rilpivirine, RPV) Possible Resistance***

NNRTI drug resistance mutations identified: K103N, Y188C, M230L

Genotype March 2017PI+ Drug Class

VIRACEPT, (nelfinavir, NFV) None APTIVUS, (tipranavir, TPV) None CRIXIVAN, (indinavir, IDV) None KALETRA, (lopinavir + ritonavir, LPV) None REYATAZ, (atazanavir, ATV) None PREZISTA, (darunavir, DRV) None LEXIVA, (fosamprenavir, FPV) None FORTOVASE / INVIRASE, (saquinavir, SQV) None

PI+ drug resistance mutations identified: None

Choice of ART

• Pt plans to return to Ivory Coast• Need to consider options available there• CSF culture grew Cryptococcus : High dose Fluconazole

• currently 70% of people living with HIV in Côte d’Ivoire know their HIV status, 44% of people who knew their status were accessing antiretroviral treatment and 36% of people accessing treatment had suppressed viral loads.

http://www.unaids.org/en/regionscountries/countries/ctedivoire

Summary

• Provision of Care may vary by country• Optimal management of Cryptococcal infection• Resources for ART• Audience Suggestions for ART include:

Mr. VT

27 yo M Vertical Transmission HIVOn ARVs since birthTDF/ddI/EFV as long as he can rememberSwitched to TDF/FTC/EFVJune 2011: CD4 257; HIV VL 13,000GT K103NSwitch to TDF/FTC/ATVrJanuary 2012: CD4 303 (27%); HIV VL 40February 2014: HIV VL 128; Switch to TDF/FTC/DRVrAugust 2014: CD4 627/36%Dec 2016: CD4 222/22%; HIV VL 4946

Genotype VT

Remember to consider previous GT

Discussion/Summary

• Why is he failing TDF/FTC/DRVr?• Off and on meds for past year• Working• Girlfriend

• Data for TDF/FTC/INSTI in setting of M184V• INSTI plus NNRTI?

Mr. No-Nukes

50 yo Male dx 1990 Started ART 1997, CD4 nadir 250Reports taking AZT/3TC; AZT/3TC/ABC; NVP-developed rash ; ETR stopped 2008; LPVr 2004-2015Reports history of resistance to all NRTIsCurrent regimen: MVC (2005?), RAL (2008) and DRVr (2015)Participates in condomless sex and uses crystal methDiagnosed with heart failure January 2017CD4 810/39%; HIV VL 3100Trophile: R5

No-Nukes GT Jan 2017VIDEX, (didanosine, ddI) None VIREAD, (tenofovir, TDF) None ZERIT, (stavudine, d4T) None ZIAGEN, (abacavir, ABC) None EMTRIVA, (emtricitabine, FTC) None RETROVIR, (zidovudine, ZDV) None EPIVIR, (lamivudine, 3TC) None

NRTI drug resistance mutations identified: M41L

NNRTI Drug Class

SUSTIVA, (efavirenz, EFV) None VIRAMUNE, (nevirapine, NVP) None INTELENCE, (etravirine, ETR) None EDURANT, (rilpivirine, RPV) None

NNRTI drug resistance mutations identified: None

No-Nukes GT Jan 2017VIRACEPT, (nelfinavir, NFV) None APTIVUS, (tipranavir, TPV) None CRIXIVAN, (indinavir, IDV) None KALETRA, (lopinavir + ritonavir, LPV) None REYATAZ, (atazanavir, ATV) None PREZISTA, (darunavir, DRV) None LEXIVA, (fosamprenavir, FPV) None FORTOVASE / INVIRASE, (saquinavir, SQV) None

PI+ drug resistance mutations identified: None

Discussion

• What to prescribe in absence of previous resistance testing

• Define Virologic Failure• When to Change vs Trial of Same ART to re-suppress

Mr. No-Nukes

Visit March 2017. No change in ART.CD4 549/32%HIV VL : 28 copies/mL

Mr. Traveler

36 yo MSM presents to walk-in clinic late Friday afternoon

• 10 day history headache: worse headache ever, Bitemporal, bright sun bothered eyes, now resolving

• Noted rash on chest 3 days ago, now extending to extremities including palms and soles

• Thinks he had fever, “hasn’t felt well”• Recently traveled to Greece/Turkey on Cruise. HA

started on day he came back.

History continued

• Immediately after the cruise, he went to VA eastern shore: “eat up by mosquitoes” ; was in brush looking at wild horses but cannot recall if he saw any ticks. Had some GI sx after eating oysters

• Has been “resting” on Fire Island and came in because “the rash is everywhere”

• Does engage in condomless sex as his HIV infected partner is on ART. Admits to sex with others during cruise

• As you are sending him to the ER for further evaluation, he tells you that his grandmother gave him amoxicillin about 5-6 days ago.

Rash

Differential Diagnosis ?

What Labs would you order?

Labs:

• CBC with diff and Chem profile NL• CSF: 1 WBC, 100% lymphs, glucose: 57,

Protein: 25. GS and CRAG negative• HIV rapid test negative• HIV-1 RNA PCR, tests for Lyme, syphilis, RMSF

sent

Which of the following would you do in addition to safer sex counseling?

1. Start antiretroviral therapy for acute HIV2. Prescribe Pre-exposure Prophylaxis3. Ceftriaxone 250 mg IM and Azithromycin 1 gram oral4. Benzathine penicillin G 2.4 million units IM5. PCN, CTX, AZ in doses above6. Reassurance. Rash is probably secondary to amoxicillin

Case Continues

■ Was given PCN, CTX and AZ in ER■ RPR 1:128, CSF VDRL negative■ HIV-1 RNA PCR undetectable; all other labs were

negative except Lyme

Returns to clinic 3 weeks later after his UK vacation

§ Pt asks about PrEP§ Main partner is infected and is on ART and undetectable§ Had a “few “ contacts while in London while intoxicated. Does

not recall if used condoms§ Had condomless sex yesterday

Which of the following would you do?1. Repeat rapid HIV ab test and HIV-1 RNA PCR

before prescribing PrEP2. Rapid HIV ab Test and if negative, prescribe

PrEP3. Tell him that he is not a candidate for PrEP if he

is not going to use condoms too4. Prescribe post exposure prophylaxis

Lab Results

■ Rapid HIV ab test negative■ HIV-1 RNA PCR 786,000 copies/mL

At this point, you order a genotypic resistance test and1. Hold ART until genotype results are

available2. Start ART with 2 NRTIs and a boosted

Protease inhibitor3. Start ART with 2 NRTIs and an integrase

inhibitor4. Not give ART as insufficient data to

recommend in setting of acute infection

Case Summary

■ Be aware of conditions that mimic acute HIV■ Low Threshold to test frequently in patients at risk■ Conversion of PEP to PrEP cautions

Final Summary

■ Document all history including all past ART■ Review all prior treatments and resistance

testing■ Hypersensitivity Reactions may or may not be

cross reactive within a class■ Still requires an expert: Not one regimen for all