Medical Microbiology

454 8 VirusesasHumanPathogen

Epidemiologyandprevention.HIVistransmittedbyblood,bloodproducts,

andsexualintercourse.Theviruscanalsobetransmittedfrommotherto

child inintrauterine infection, perinatal transmission, or themother’s

milk.Infectionviasalivaorinsectbitehasnotbeenconfirmed.Accordingly,

threerulesofbehaviorarenowpropagatedtopreventthespreadofHIV:usea

good-qualitycondomforeachactofsexualintercourse.Fori.v.drugcon-

sumptionuseonlysterilesyringesandneedles;nevershareorpassonthese

injectionutensils.CouplesoneofwhomisHIV-positiveshouldavoidanun-

plannedpregnancy.

Intensiveeffortsarebeingmadetodevelopavaccine(activeimmuniza-

tion)andseveralvaccineswillsoonbereadyforfieldtrials.Thetypesunder

considerationincludesplitvaccines(p.403),genome-freeparticles,attenu-

atedviruses,nakedDNA,andinactivatedvirions.Itisnotpracticabletocover

thisfieldofresearchindetailhereduetothefast-moving,andthenecessarily

tenuous,natureoftheongoingwork.

Therapy.Therecommendedtherapeuticprocedureisalsosubjecttorapid

changes,wherebythecommongoalistoreducethenumberofvirusesas

faraspossible(< 50 RNAcopiesperml)andassoonaspossible.Doingso

candelaytheoccurrenceofclinicalsymptoms,eliminateexistingsymptoms

andsloworstopthedevelopmentofresistanceintheHIviruses.

Ingeneral,therapyisconsideredinreactiontotheinitialretroviralsyn-

drome.Therapyisrecommendedinthefirst,asymptomaticstageatCD4+cell

countsbelow 3 50,andifthecountishigherthan 350 onlyiftheviralloadis

raised(considertherapyat 500 0,therapyrecommendedat> 30000 RNA

copies/ml).PregnancyinanHIV-positivewomanisafurthertherapeutic

indication.

ThreeclassesofsubstancesareavailableforHIVtherapy(seealsop. 40 4f.):

— Nucleosidic(ornucleotidic)reversetranscriptaseinhibitors(NRTI)(for

example:azidothymidine,AZT;lamivudine,3TC;didanosine,ddI,etc.).

Thesearenucleosideanalogsthatbindtotheactivecenteroftheenzyme

areintegratedintheDNAstrands,resultingin“chaintermination.”

— Nonnucleosidicreversetranscriptaseinhibitors(NNRTI)(forexample:

efavirenz,EFV;nevirapine,NVP,etc.).Thisclassofsubstancesalsoinhibits

theproductionofviralcDNAbyreversetranscriptase,butdoesnot

preventviralproductionbyinfectedcells.

— Proteaseinhibitors(PI)(forexample:indinavir,IDV;ritonavir,RTV;sa-

quinavir,SQV,etc.):PIsinhibitviralproteaseandthusviralmaturation.

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Kayser, Medical Microbiology © 2005 Thieme