HIV Update

H pdate

reatment and ecti e ana ement

he pipeline or H includes methods or prophyla is, such as potential accinations ith these added pre enti e measures, payers may prioritize strate ic mana ement o the o erall H space

Luke Merkel, Pharm.D., MBA Director of Pharmacy Services Avera Health n the S , an estimated million people are li in ith human immunodeficiency irus (H ), ith appro imately , ne H in ections occurrin annually, per data 1 n , there ere , deaths amon those dia nosed ith H in the S 1

Current Treatment Landscape

Per uidelines rom the S epartment o Health and Human Ser ices (HHS), current recommended H treatment is antiretro iral therapy ( R ), hich patients should be in as soon a ter dia nosis as possible to slow progression.2 here are se en classes o R nucleoside re erse transcriptase inhibitors ( R s), non-nucleoside re erse transcriptase inhibitors ( R s), protease inhibitors (P s), usion inhibitors, CCR anta onists, post-attachment inhibitors, and inte rase strand trans er inhibitors ( S s) PrEP

Pre-e posure prophyla is (Pr P) is an H -pre ention strate y recommended by the S Centers or isease Control and Prevention. here are currently t o -appro ed H Pr P therapies or daily use emtricitabine and teno o ir disopro il umarate ( R or Pr P®) and emtricitabine and teno o ir ala enamide ( SCO or Pr P®) dherence to Pr P medication as prescribed can reduce the ris o contractin H ia se ual contact and ia dru injection by and , respecti ely

here are three phases to appropriate care usin Pr P screenin , Pr P initiation, and ollo -up he initial screenin should include an H ris assessment, Pr P education, and an initial clinical e aluation that includes assessment o indications or Pr P, a brie medical history, and appropriate lab or Pr P initiation should occur ithin se en days o the screenin and include a re ie o Pr P basics and a prescription o Pr P or days or less ollo -up should be consistent and occur e ery three months, ith an H blood test a symptom re ie concurrent prescription o Pr P and assessment and counselin

or H ris beha ior, adherence, and pre nancy intent estin or se ually transmitted in ections and idney unction should be done e ery si months or ollo -up

Genotypic Drug-Resistance Testing

ru -resistance testin helps determine i an H patient has a orm o the irus that has mutated and does not respond to R Specifically, enotypic dru -resistance testin e amines the enotype o a patient s H to analyze or the presence o specific enetic mutations that are no n to cause resistance to R

Guideline Updates

n pril, HHS updated its uidelines or pediatric H treatment pdates included discussion o and uidance or the use o telehealth and telemedicine in pediatric H care an e pansion o pre erred re imen desi nation o dolute ra ir ( C ) plus t o R s to be recommended or anyone a e ee s or older, pro ided they ei h at least the addition o bicte ra ir, as part o bicte ra ir/emtricitabine/teno o ir ala enamide ( K R ®), in patients at least years old and ei hin at least and a distinction that R bac bone o abaca ir ( ia en) alon side either emtricitabine ( R ) or lami udine ( pi ir) is classified as pre erred or children at least month old, despite appro al or the dru s speci yin an a e o at least years old

HHS uidelines or the treatment o H in adults and adolescents ere most recently updated in and adjusted recommendations or first-line re imens he update added dolute ra ir/ lami udine ( O O) to the list o recommended initial re imens alon side bicte ra ir/emtricitabine/teno o ir ala enamide ( K R ®) or a treatment option in acutely or recently in ected people or hom enotypic dru -resistance testin had not yet been completed

Adherence and Single-Tablet Regimen vs. MultipleTablet Regimen

dherence is critical or patients to maintain iral suppression less e ecti e iral suppression is associated ith poor treatment adherence , he adherence thresholds ary bet een di erent classes o R Ho e er, impro ed outcomes, includin iral suppression and, in some cases, reduced ris o resistance mutations, are associated ith hi her adherence le els

he introduction o sin le-tablet re imen (S R) options has increased adherence or H patients and resulted in decreased

HIV UPDATE | Continued

Table 1. HIV Pipeline15

Drug Manufacturer Route of Administration Mechanism of Action Indication Status

abaca ir sul ate ( R ) ii Healthcare oral inte rase inhibitor nucleoside analogue reverse H - in ection phase three

cabote ra ir ( SK ) ii Healthcare la oSmithKline intramuscular S prophyla is phase three

islatravir ( K- )

lenacapa ir ( S- )

leronlimab (PRO ) erc oral

ilead Sciences oral S

Cyto yn S nucleoside re erse transcriptase translocation prophyla is H - in ection

H - in ection

entry inhibitor H - in ection phase three

phase three

phase three

cenicri iroc ( R )

Remune nited ioPharma

obira herapeutics a eda Pharmaceutical Company

Immune Response ioPharma oral

IM iral attachment bloc er

entry inhibitor

H accine H - in ection

H - in ection

prophyla is phase three

phase two

phase t o (CR / / )

pharmacy costs and hospitalizations hen compared to e istin multiple-tablet re imens ( R) , n an analysis o patients initiatin R , patients on S R ere more than t ice as li ely to be adherent hen compared to R patients Persistence as more common amon S R patients, as R patients ere more li ely to discontinue treatment

n a pilot H care-mana ement pro ram acilitated by a ellan ethod, edicaid patients prescribed at least one H medication, ith the e ception o Pr P, ere included in an outreach pro ram aimed to assess the impact o the pro ram on R adherence and the proportion o patients ho are irolo ically suppressed 11 Prior to the contact period, more than hal o the participatin patients had a proportion o days co ered (P C) o less than 11 O erall, patients on S R had hi her adherence than patients on R prior to contact, o S R patients had a P C o less than compared to o R patients Si months a ter enrollment in the pro ram, there as an increase in P C to about o erall, compared to pre-contact period 11 his data sho s an opportunity or patient en a ement in addressin patient adherence in the H patient population mpro ed adherence can lead to sustained iral suppression, better outcomes, and impro ed cost management.

Newly Approved Therapies

Cabotegravir and Rilpivirine (CABENUVA) and Cabotegravir (VOCABRIA)12

n anuary, the appro ed cabote ra ir e tended-release injectable suspension and rilpi irine e tended-release injectable suspension (C , ii Healthcare), co-pac ed or intramuscular use, or H - -in ected adults t is the first -appro ed injectable complete re imen indicated or H that is administered once monthly he t o-dru co-pac a ed products include cabote ra ir, an H - S , and rilpi irine, an H - R t is indicated as a complete re imen to replace current antiretro iral re imen in those ho are irolo ically suppressed on a stable antiretro iral re imen ith no treatment ailure and no no n or suspected resistance to either drug.

Focused measures to increase treatment adherence in HIV patients can lead to lower costs overall, including pharmacy and hospitalizations.

he also appro ed cabote ra ir m tablets ( OC R ) indicated to be ta en in combination ith oral rilpi irine or one month prior to starting treatment with the two-drug extendedrelease injectable to ensure the medications are ell tolerated be ore s itchin

o phase-three randomized, multicenter, acti e-controlled, parallel-arm, open-label, non-in eriority trials e aluated the e cacy o C n the R trial, H -in ected, R -na e subjects recei ed dolute ra ir S -containin re imen or ee s, and subjects ho ere irolo ically suppressed ere randomized to recei e either a cabote ra ir plus rilpi irine re imen or remain on the current R re imen

n ebruary, HHS determined C injections can be used to optimize treatment in patients ith H ho are currently on oral R ith documented iral suppression or at least three months and ho ha e no baseline resistance to either medication, prior irolo ic ailures, or acti e hepatitis irus are not pre nant or plannin to become pre nant and are not recei in medications ith si nificant interactions n patients ho may be dra n to monthly injection o er daily pills, C may become the pre erence Fostemsavir (Rukobia)14

n uly , the appro ed ostemsa ir (Ru obia, ii Healthcare), indicated or adults li in ith H ho ha e tried multiple H medications and hose in ection cannot be success ully treated ith other therapies due to resistance, intolerance, or sa ety considerations trial o hea ily treatment-e perienced adult participants ith hi h irus le els as conducted ith participants in the main trial arm and an additional participants recei in ostemsa ir in a di erent arm o the trial Participants in the main trial arm recei ed either ostemsa ir or a placebo t ice daily or ei ht days in addition to the pre iously ailin antiretro iral re imen On day , participants recei in ostemsa ir had a si nificantly reater decrease in irus le els compared to those recei in the placebo, and a ter day , all participants recei ed ostemsa ir alon ith other antiretro iral dru s i ty-three percent o participants achie ed iral suppression a ter ee s o ostemsa ir plus other antiretro iral dru s inally, a ter ee s, o participants continued to ha e iral suppression he most common side e ect as nausea ho e er, more se ere ad erse e ents included ele ations in li er enzymes amon participants also in ected ith hepatitis or C irus and chan es in the immune system

Payer Implications

Research sho s that ith the e pansion o edicaid under the ordable Care ct ( C ) came an increase in the identification o undia nosed H in ections and use o H -pre ention ser ices an estimated increase in H dia noses as associated ith edicaid e pansion, accordin to data rom the ni ersity o llinois. his shi t, alon ith accompanied appropriate treatment and use o pre enti e ser ices, as lin ed directly to the impro ed access to care throu h edicaid, as dia noses ere most common in populations li ely a ected by edicaid e pansion, includin lo -income indi iduals en a ed in injection dru use rom rural counties ith hi h uninsured rates prior to the C

Research shows that with the expansion of Medicaid under ACA came an increase in the identification o undiagnosed HIV infections and use of HIV-prevention services; an estimated 13.9% increase in HIV diagnoses was associated with Medicaid expansion.

HIV UPDATE | Continued

MRx PIPELINE

A VIEW INTO UPCOMING SPECIALTY & TRADITIONAL DRUGS

JANUARY 2021

Our latest quarterly report on anticipated specialty and traditional drugs in the pipeline

magellanrx.com/pipeline

he data su ests access to health insurance and proper care impro ed H testin rates and use o pre enti e care, leadin to hi her rates o indi iduals li in ith H ccess to care and proper mana ement or patients ith H are critical in impro in outcomes

ith se eral enerics enterin the mar et or on the horizon, there is potential or cost mana ement in this cate ory Combination therapies ha e created the opportunity or combinin se eral eneric therapies here brand-only therapies ere pre iously utilized Stron policy ill be ey in dri in eneric utilization in this space dditionally, by prioritizin the H population, payers can better mana e this space ocused measures to increase treatment adherence in H patients can lead to lo er costs o erall, includin pharmacy and hospitalizations 11 he pipeline or H includes methods or prophyla is, such as potential accinations ith these added pre enti e measures, payers may prioritize strate ic mana ement o the o erall H space, includin identi yin appropriate populations and ensurin access to prophylactic therapies Proper pre enti e care, coupled ith e ecti e mana ement o populations ith H , could lead to impro ed lon -term outcomes and cost mana ement

ith an e pandin pipeline, payers may strate ize to achie e cost sa in s by incenti izin and steerin patients to ard lo ercost eneric alternati es

References

1. S Statistics HIV.gov, ar , https // hi o /hi basics/o er ie /data-and-trends/statistics 2. H reatment O er ie HIV.gov, ar , https // hi o /hi -basics/stayin -in-hi -care/hi -treatment/hi -treatmentoverview. Pre-e posure Prophyla is (Pr P) Care System U.S. Centers for

Disease Control and Prevention, Sept , cdc o /hi / e ecti e-inter entions/pre ent/prep/inde html H ru Resistance estin Stanford Health Care, https // stan ordhealthcare or /medical-conditions/se ual-and-reproducti ehealth/hi -aids/treatments/hi -dru -resistance-testin html Hel and, yles hat s e in S H Clinical reatment uidelines TheBodyPro, pr , https // thebodypro com/article/ hats-ne -in-the-us-hi -clinical- uidelines Schaecher, Kenneth he mportance o reatment dherence in

H American Journal of Managed Care, Sept , https // ajmc com/ ie /a sep schaecher s Hines, ionne, et al reatment dherence and Persistence mon

H - Patients e ly Startin reatment Patient Preference and

Adherence, o , https // ncbi nlm nih o /pmc/articles/

P C / Cohen, Cal in, et al ssociation bet een daily antiretro iral pill burden and treatment adherence, hospitalization ris , and other healthcare utilisation and costs in a S edicaid population ith

H BMJ Open, , https //bmjopen bmj com/content/ / / e Sa , Paul, et al dherence to antiretro iral treatment and correlation ith ris o hospitalization amon commercially insured H patients in the nited States PloS One, , https //pubmed ncbi nlm nih o / / 10. an ness, acob, et al Comparison o adherence rates or antiretro iral, blood pressure, or mental health medications or

H -positi e patients at an academic medical center outpatient pharmacy Journal of Managed Care and Specialty Pharmacy, , https //pubmed ncbi nlm nih o / / 11. Kan ethe, nne, et al nalysis o a Pilot H Care ana ement

Pro ram Academy of Managed Care Pharmacy, , https // ma ellanr com/documents/ / /analysis-o -a-pilot-hi -caremana ement-pro ram pd / 12. ppro es Cabenu a and ocabria or the reatment o H - n ection U.S. Food and Drug Administration, an , da o /dru s/human-immunodeficiency- irus-hi / da-appro escabenu a-and- ocabria-treatment-hi - -in ection HHS dults and dolescents ntiretro iral uidelines Panel

Recommendation or the on - ctin njectable ntiretro iral

Re imen o Cabote ra ir and Rilpi irine Clinical Info, eb , https //clinicalin o hi o /en/ uidelines/adult-and-adolescent-ar / hhs-adults-and-adolescents-antiretro iral- uidelines-panel ppro es e H reatment or Patients ith imited reatment Options U.S. Food and Drug Administration, uly , https // da o /ne s-e ents/press-announcements/ daapproves-new-hiv-treatment-patients-limited-treatment-options. P nalytics elson, Hannah edicaid pansion Helped etect ndia nosed

H n ections Health Payer Intelligence, an , https // healthpayerintelli ence com/ne s/medicaid-e pansion-helpeddetect-undia nosed-hi -in ections