2-3-10 Principles Therapy for HIV Disease 1.

Review the parts of the viral life cycle where we can interfere with drugs. Fusion inhibitors: block viral entry Nucleoside and Nucleoside RT Inhibitors: block reverse transcription Protease Inhibitors: block viral precursor assembly and viral protein processing after release. Integrase Inhibitor: block integrase acti ity !insertin" transcribed D#$ into the cell "eno%e& Coreceptor antagonists: block chemokine receptor that binds alon"side 'D( receptor 2. escribe the ti!e course of "I# infection. There are t)o )ays of ie)in" HIV infection: *+ld, paradi"%$ it )as belie ed that after ac-te infection. the disease regresses into a latent phase )here there/s little replication in ir-s -ntil 'D( co-nts beco%e lo) eno-"h. This concept does not e0plain the "rad-al loss of 'D( cells o er ti%e. *#e), paradi"%: after an initial b-rst of iral replication d-rin" ac-te infection. replication decreases and le els off1at different le els !so%e patients )ill le el off at hi"h le els. others %oderate or lo)er& d-e to "enetics. 2o%e patients )ill pro"ress to $ID23lo) 'D( co-nt d-rin" ac-te infection !tho-"h it/s rare&. )hile others )ill not pro"ress at all despite HIV infection for 104 years !kno)n as long term progressors )ho %aintain chronic i%%-ne control o er the HIV infection. keepin" lo) iral loads and nor%al 'D( co-nts&. 2pread of HIV3$ID2 is pri%arily a disease of de elopin" nations. Treat%ents are pri%arily a ailable only in )ealthy co-ntries. %. iscuss the appropriate ti!e to intervene and current controversies regarding when to treat. The c-rrently p-blished "-idelines for )hen to start $5T !antiretro iral therapy& fro% DHH2: 6 eryone )ith &I ' or 'D( co-nt 7 %(). $lso for pre"nancy. chronic Hep 8. and HIV nephropathy 'D( 390-900: 99: of panel reco%%ends tron"ly. )hile (9: of the panel reco%%ended it %oderately 'D( ; 900: half of the panel considers $5T optional. )hile 90: fa ors startin" in all. '$V6$T: patients initiatin" $5T sho-ld be )illin" to co%%it to lifelon" treat%ent and -nderstand the benefits3risks of therapy and the i%portance of adherence. Patients %ay choose to postpone therapy. or pro iders sho-ld defer therapy based on clinical or psychosocial factors. <or %ost patients without symptoms or a CD4<200. delay is reco%%ended. +f co-rse. yo- sho-ld keep follo)in" the patient to i%pro e ed-cation. psychiatric3dr-" ab-se co-%orbidities. and control of other %edical proble%s !diabetes. hypertension&. *. Review the ec 2))+ ""' reco!!endations for initial retroviral treat!ent There are fo-r options reco%%ended for initial therapy !note that all incl-de 2 n-cleoside 5T inhibitors !tenofovir,e!tricitabine&:

2 n-cleoside 5T inhibitors inhibitors. 2 n-cleoside 5T inhibitors inhibitors 2 n-cleoside 5T inhibitors inhibitor 2 n-cleoside 5T inhibitors inhibitor !t)ice daily&

!tenofo ir4e%tricitabine& pl-s ata-anavir.ritonavir protease !tenofo ir4e%tricitabine& pl-s darunavir.ritonavir protease !tenofo ir4e%tricitabine& pl-s /faviren- non-n-cleoside 5T !tenofo ir4e%tricitabine& pl-s Raltegravir inte"rase

(. escribe the co!!on to0icities of the !ost co!!only used drugs. Tenofovir: rare <anconi 2yndro%e !pro0i%al renal t-b-le dysf-nction leadin" to acidosis&. loss of bone %ineral density /!btricitabine: none &ta-anavir: increased indirect bili. P5 prolon"ation arunavir: rash /faviren- 1/F#2: '#2 effects !=iddiness. so%nolence. inso%nia. abnor%al i id drea%s. conf-sion. i%paired concentration. a%nesia. a"itation. depersonali=ation. hall-cination&. rash. hypersensiti ity. terato"enicity !>?2T "i e birth control for )o%en of repro a"e& Raltegravir: no co%%on3se ere to0icities@ headache. na-sea. diarrhea %ay occ-r. 3. /!phasi-e the critical i!portance of adherence. >onotherapy res-lts in resistance 100: of the ti%eA 6 en brief periods of non-adherence !i.e. one )eek& can hose the entire re"i%en and ca-se %-lti-dr-" resistance. Adding single drugs to ailing regimens is the recipe or !"#$ #$%&%'A(C$ and continue ailure)