COVID-19 pneumonia in an HIV-positive woman on antiretroviral therapy and undetectable viral load in Porto Alegre, Brazil

brazjinfectdis2020;24(5):455–457

w w w . e l s e v i e r . c o m / l o c a t e / b j i d

The

Brazilian

Journal

of

INFECTIOUS

DISEASES

Case

report

COVID-19

pneumonia

in

an

HIV-positive

woman

on

antiretroviral

therapy

and

undetectable

viral

load

in

Porto

Alegre,

Brazil

Murillo

Machado

Cipolat

_,

_Eduardo

_Sprinz

a_{HospitaldeClínicasdePortoAlegre,InfectiousDiseasesService,PortoAlegre,RS,Brazil} b_{UniversidadeFederaldeRioGrandedoSul,FaculdadedeMedicina,PortoAlegre,RS,Brazil}

a

r

t

i

c

l

e

i

n

f

o

Articlehistory:

Received6June2020 Accepted24July2020

Availableonline26August2020

Keywords: SARS-CoV-2 COVID-19 HIV AIDS

a

b

s

t

r

a

c

t

COVID-19pandemichasbeenaproblemworldwide.Itisimportanttoidentifypeopleat riskofprogressingtoseverecomplicationsandtoinvestigateifsomeexistingantivirals couldhaveanyactionagainstSARS-CoV-2.Inthiscontext,HIV-infectedindividualsand antiretroviraldrugsmightbeincluded,respectively.Hereinwepresentthecaseofa 63-year-oldHIV-infectedwomanwithundetectableviralload,ondolutegravir,tenofovirand lamivudine,whowashospitalizedduetoCOVID-19pneumonia.Inspiteofhavingsome clinicalmarkersofseverityonadmission,thepatientimprovedandwasdischargedafter aweek.Toourknowledge,thisisthefirstreportofsevereSARS-CoV-2infectioninan HIV-infectedindividualinBrazil.

©2020SociedadeBrasileiradeInfectologia.PublishedbyElsevierEspa ˜na,S.L.U.Thisis anopenaccessarticleundertheCCBY-NC-NDlicense(http://creativecommons.org/ licenses/by-nc-nd/4.0/).

Introduction

COVID-19,causedbythesevereacuterespiratorysyndrome coronavirustype-2 (SARS-CoV-2),has beendeclared a pan-demic in March 2020, following the first case reported in Wuhan,ChinainDecember2019.Somepatients,suchasthose sufferingfromcardiovasculardisease,diabetesmellitusand obesity,weresoonidentifiedatgreaterriskforworseclinical outcomes.Nevertheless,thereisstillalottobediscovered regardingthis disease.Inthis context,notonlythe riskof COVID-19complicationsamongpeoplelivingwithHIV(PLWH)

∗ _{Correspondingauthor.}

E-mailaddress:esprinz@hcpa.edu.br(E.Sprinz).

remainsuncertain,butalsothepotentialprotectivebenefits ofantiretroviral(ARV)drugs.

Despiteofmorethan12millioncasesofCOVID-19 world-wide as early July, reports of HIV/Sars-CoV-2 co-infection are stilluncommon,1 _{withthe firstknowncaseintheUSA}

only being reported on May 22, 2020,2 _{People living with}

HIVaccountedforonly1%of16,749patientswithCOVID-19 hospitalizedinthe UnitedKingdom,onalargeprospective observational cohort study,with HIV havingno impact on survival.3 _{Thereafter,the prognosisofPLWHafterthe}

diag-nosisofCOVID-19hasalsobeenasubjectofdebate.4_While

someresearchersbelievethatHIVimmunosuppressioncould resultingreatersusceptibilitytoSARS-CoV-2infection,5

oth-ers believethat thesepatients would beata lower riskof complications,sinceimpairmentincellularimmunitymight beassociatedwithlessinflammation,6_{reducingtheincidence} https://doi.org/10.1016/j.bjid.2020.07.009

1413-8670/©2020SociedadeBrasileiradeInfectologia.PublishedbyElsevierEspa ˜na,S.L.U.ThisisanopenaccessarticleundertheCC BY-NC-NDlicense(http://creativecommons.org/licenses/by-nc-nd/4.0/).

456

Fig.1–ChestX-raywithperipheralopacitiesininferior lobesofbothlungs.

ofcytokinestormwhichhasbeenassociatedwithmoresevere casesofCOVID-19.

Thereisalsosomecontroversyaboutthepotential advan-tagesagainstSARS-CoV-2frombeingonARVs.7_Thereissome

invitroevidencethatthesedrugscouldhaveanimpactagainst thisvirus.8,9 _{Hereinwepresent thecaseofanHIV-infected}

womanonantiretroviraltherapywhowashospitalizedatour centerwithCOVID-19pneumonia.

Case

report

A63-year-oldwomanwasadmittedtoCOVID-19Unitat Hos-pitaldeClinicasdePortoAlegre(HCPA),onsouthernBrazil, onMay,2020.ThepatienthadbeendiagnosedwithHIV infec-tionin2005,andwasontenofovir (TDF),lamivudine(3TC), anddolutegravir(DTG)sinceNovember2019(beforeshewas onatazanavir/ritonavir,switchedforDTG).Herviralloadhad beenundetectableforalongtimeandherCD4+cellcountwas 426cells/mm3_{(CD4/CD8ratio1.25).Systemicarterial}

hyper-tension(SAH),wellcontrolledwithhydrochlorothiazideand losartan,wastheothercomorbidityshehad.

Atpresentation,shecomplainedoffever(39◦C),myalgia, inappetence,nausea,abdominalpain,diarrhea,hyposmiaand hypogeusia, inaddition tocough and dyspnea fora week. Upon admission, white blood cells (WBC) count was 9250 cells/mm3_{(76%neutrophils,and16%lymphocytes).Shehad}

elevatedC-reactiveprotein(65.5mg/L),totalcreatinekinase (307U/L)andlactatedehydrogenase(316U/L).Serum creati-ninewas0.84mg/dLandshehadnoabnormalitiesinclotting tests,includingaD-Dimerlevelof0.42ug/mL(withour ref-erencevaluebeingupto0.5ug/mL).Firstarterialbloodgas analysis(ABG)wasperformedwiththepatienton supplemen-taloxygenthroughanasalcannula,butshedidnotpresent hypoxemia,witha107mmHgpO2 and aperipheraloxygen

saturation (SpO2)of98.5%.Chest X-rayexhibitopacities in

middlethirdsofbothlungs(Fig.1).Sars-CoV-2wasdetected byRT-PCRinnasopharyngealsecretionswab.

The patient was treatedwith supportivemeasures that included oxygen via nasal cannula and received antibiotic therapywithamoxicillin/clavulanateforatotalofsevendays. Aftergivingconsent,shewasrandomizedtooneofthearms ofarandomizedclinicaltrial(Coalition-1trial10_)andreceived

hydroxychloroquine400mgbidplusazithromycin500mgper oralaccordingtotrialprotocol,withnosideeffectsrelatedto any ofthesetherapiesduringthis period.Eventhoughshe presentedsome severitymarkers onadmission, shehad a favorable clinical evolution, with no needfor treatmentin ICUorrequiringmoreinvasiveformsofoxygentherapy,being dischargedingoodclinicalconditionssevendaysafter hospi-talization.

Conclusion

Toourknowledge,thisisthefirstreportedcaseofCOVID-19 diseaseinanHIV-infectedindividualinBrazilandremainsthe onlyonethatwehadtheopportunitytocare.Thisfindingis ofspecialinterest,asPortoAlegre,thecapitalofthe southern-moststateofBrazil(RioGrandedoSul),isoneofthecitieswith highestHIVincidenceinBrazil.11_{Thisreporthasthepurpose}

toillustratetheseveralpeculiaritiesofSARS-CoV-2infection worldwide.Althoughthepatientpresentedaseverecourseof COVID-19,theARVsshewastakingdidnotprotectherfrom acquiringtheinfection.

AmongthedrugsusedtotreatHIV,lopinavir/ritonavirwas thefirsttoassessedagainstSARS-CoV-2.Inspiteofthestudies in 2003duringSARSepidemicshowinga decreasein mor-tality, intubationrates and unfavorable outcomes on SARS with the use of lopinavir/ritonavir,12 _{a recent clinical trial}

showed no benefitofthis medication forthe treatmentof severecasesofCOVID-19.13 _{Othercombinationsofprotease}

inhibitorsareundertesting,withatazanavir/ritonavir show-inggreatestinhibitorypotentialinvitroagainstSARS-CoV-2.8

Aclinicaltrialofdarunavir/cobicistatfortreatmentof COVID-19iscurrentlyonprogressinChina.14OtherARVshavealso shownsomeactivityinvitroandinanimalmodels.DTG,an integraseinhibitor,haddemonstratedactivityagainst SARS-CoV-2.8,9,15,16 _{Likewise, TDF, a nucleotide analogue reverse}

transcriptaseinhibitor widelyusedinthetreatment ofHIV andHepatitisBinfections,hasemergedasanewinvestigative agentagainstCOVID-19.Itisfromthesameclassas remde-sivir, a novelnucleotide analoguethat hasactivity against SARS-CoV-2invitro17_{andhasbeenrecommendedfor}

hospi-talizedpatientswithsevereCOVID-19inmanyguidelines.18

However,noARVhasdemonstratedclinicalimpactsofar. One ofthe first publishedcase series, comprising of33 patientshospitalizedforCOVID-19followedupatHIVcenters in Germany,suggestedthat althoughSARS-CoV-2 infection couldoccurduringtreatmentwithARVs,thesepatientsdid notappeartobeatriskforworseclinicaloutcomesamong thosewithsymptomaticCOVID-19.19_{ArecentlargeSpanish}

cohort study of77,590HIV-infectedpeople onARVs identi-fiedsimilarriskfactorsforhospitalization,admissiontoICU, anddeathwhencomparedtothegeneralpopulation.20

How-ever, HIV-infectedpatients onTDF/FTChad alower riskof COVID-19 and related hospitalization than those receiving othertherapies.Whetherthedifferenceobservedisduetothe

brazj infect dis.2020;24(5):455–457

457

profilefeaturesofpatientsusingthisARTorthedirect antivi-raleffectofthedrugisstillamatterofdebate.20_Currently,

onetrialcombiningtenofovir-alafenamide/emtricitabineand lopinavir/ritonavir to treat COVID-19 patients and another with tenofovir/emtricitabine as pre-exposure prophylaxis againstCOVID-19inhealthcareworkersareonprogress.21_In

ourpatient,theseARVsdidnotpreventSARS-CoV-2infection. Still,a lotis stilltocomeregardingthis coronavirus infec-tionandthe clinicalcourseinHIV-infectedindividualsand thepossibleimpactofARVs.

r

e

f

e

r

e

n

c

e

s

1. BlancoJL,AmbrosioniJ,GarciaF,etal.COVID-19inpatients withHIV:clinicalcaseseries.LancetHIV.2020;7:e314–6,

http://dx.doi.org/10.1016/S2352-3018(20)30111-9.

2. PatelRH,PellaPM.COVID-19inapatientwithHIVinfection.J MedVirol.2020,http://dx.doi.org/10.1002/jmv.26049.Online aheadofprint.May22;10.1002/jmv.26049.

3. DochertyAB,HarrisonEM,GreenCA,etal.Featuresof16,749 hospitalizedUKpatientswithCOVID-19usingtheISARIC WHOclinicalcharacterizationprotocol.BMJ.2020,

http://dx.doi.org/10.1136/bmj.m1985.May22;369:m1985. 4. RidgwayJP,FarleyB,BenoitJL,etal.ACaseSeriesofFive

PeopleLivingwithHIVHospitalizedwithCOVID-19in Chicago,Illinois.AIDSPatientCareandSTDs.

2020;34(8):331–5,http://dx.doi.org/10.1089/apc.2020.0103. Epub2020May29.

5. WorldHealthOrganization.Q&AonCOVID-19,HIVand antiretrovirals;2020.Availableat:www.who.int/news-room/ q-a-detail/q-a-on-covid-19-hiv-and-antiretrovirals.[Accessed 9July2020].

6. MascoloS,RomanelliA,CarleoMA,EspositoV.CouldHIV infectionaltertheclinicalcourseofSARS-CoV-2infection? Whenlessisbetter.JMedVirol.2020,

http://dx.doi.org/10.1002/jmv.25881.

7. Ballester-ArnalR,Gil-LlarioMD.TheVirusthatChanged Spain:ImpactofCOVID-19onPeoplewithHIV.AIDSBehav. 2020;24(8):2253–7,

http://dx.doi.org/10.1007/s10461-020-02877-3. 8. BeckBR,ShinB,ChoiY,ParkS,KangK.Predicting

commerciallyavailableantiviraldrugsthatmayactonthe novelcoronavirus(SARS-CoV-2)throughadrug-target interactiondeeplearningmodel.ComputStructBiotechnolJ. 2020;18:784–90,http://dx.doi.org/10.1016/j.csbj.2020.03.025, eCollection2020.

9. KhanRJ,JhaRK,AmeraGM,etal.TargetingSARS-CoV-2:a systematicdrugrepurposingapproachtoidentifypromising

inhibitorsagainst3C-likeproteinaseand2’-O-ribose methyltransferase.JBiomolStructDyn.2020:1–14,

http://dx.doi.org/10.1080/07391102.2020.1753577.Published online2020Apr20.

10.https://clinicaltrials.gov/ct2/show/NCT04322123?term= coalition&cond=Covid19&cntry=BR&draw=2&rank=3. 11.BoletimEpidemiológicoHIV/Aids2019,Departamentode

Doenc¸asdeCondic¸õesCrônicaseInfecc¸õesSexualmente Transmissíveis,daSecretariadeVigilânciaemSaúde,do MinistériodaSaúde(DCCI/SVS/MS):

www.aids.gov.br/pt-br/pub/2019/boletim-epidemiologico-de-hivaids-2019.

12.ChanKS,LaiST,ChuCM,etal.Treatmentofsevereacute respiratorysyndromewithlopinavir/ritonavir:amulticentre retrospectivematchedcohortstudy.HongKongMedJ. 2003;9:399–406.

13.CaoB,WangY,WenD,etal.ATrialofLopinavir-Ritonavirin AdultsHospitalizedwithSevereCovid-19.NEnglJMed. 2020;382(19):1787–99,

http://dx.doi.org/10.1056/NEJMoa2001282.Epub2020Mar18. 14.https://clinicaltrials.gov/ct2/show/NCT04252274.

15.ElfikyAA.Ribavirin,Remdesivir,Sofosbuvir,Galidesivir,and TenofoviragainstSARS-CoV-2RNAdependentRNA polymerase(RdRp):amoleculardockingstudy.LifeSci. 2020;253:117592,http://dx.doi.org/10.1016/j.lfs.2020.117592. 16.ParkSJ,YuKM,KimYI,etal.Antiviralefficaciesof

FDA-approveddrugsagainstSARS-CoV-2infectioninferrets. mBio.2020;11(3):e01114–20,

http://dx.doi.org/10.1128/mBio.01114-20.

17.ClososkiGC,SoldiRA,SilvaRM,etal.Tenofovirdisoproxil fumarate:newchemicaldevelopmentsandencouraging invitrobiologicalresultsforSARS-CoV-2.JBrazChemSoc. 2020;00:1–5,http://dx.doi.org/10.21577/0103-5053.20200106. 18.BeigelJH,TomashekKM,DoddLE,etal.Remdesivirforthe TreatmentofCovid-19-PreliminaryReport.NEnglJMed. 2020,http://dx.doi.org/10.1056/NEJMoa2007764.Onlineahead ofprint.NEJMoa2007764.

19.HärterG,SpinnerCD,RoiderJ,etal.COVID-19inpeopleliving withhumanimmunodeficiencyvirus:acaseseriesof33 patients.Infection.2020:1–6,

http://dx.doi.org/10.1007/s15010-020-01438-z.Onlineaheadof print.

20.DelAmoJ,PoloR,MorenoS,DíazA,etal.Incidenceand SeverityofCOVID-19inHIV-PositivePersonsReceiving AntiretroviralTherapy:ACohortStudy.AnnInternMed.2020,

http://dx.doi.org/10.7326/M20-3689.Onlineaheadofprint. M20-3689.