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HIV DISEASE

Introduction HIV disease - disease is infectious disease caused by HIV(human immunodeficiency virus), a human retrovirus  AIDS (Acquired ImmunoDeficiency Syndrome)is Late stage of infection ith HIV  Acquired immunodeficiency syndrome (AIDS) as first recognised as a c!inica! entity in "#$" hen the first c!uster of cases of Pneumocystis carinii %neumonia and &a%osi's sarcoma ith evidence of deficiency of ce!!-mediated immunity (()I) ere re%orted in homose*ua! men+ Modes of transmission A+ Se*ua! - 4n%rotected se* ith infected %artner+ 5+ 6arentera! "+ In7ection 8 intravenous drug users (ID4s) 1+ 9ransfusion of infected b!ood and b!ood %roducts :+ 9rans%!antation of an organ donated by an infected %erson 3+ 4se of contaminated, unsteri!e hos%ita! equi%ment ;+ Infected need!e-stic. in7uries in hea!th-care or.ers (H(<s) (+ Vertica! "+ In utero - from infected mother to foetus 1+ During !abour - during foeta! %assage through vagina :+ After birth - infected breast mi!.

HIV structure  HIV is an ,-A virus be!onging to a grou% of human retroviruses hich are a subfami!y of !entiviruses+  ,-A viruses hose ha!!mar. is the reverse transcri%tion of its genomic ,-A to D-A by the en/yme reverse transcri%tase  0ach mature virion is s%herica! and has a !i%id membrane !ined by a matri* %rotein that is studded ith g!yco%rotein (g%)"12 and g%3" s%i.es surrounding

and s!o er %rogression to AIDS Life cycle of HIV  9he virus infects the (D3 ce!! in a com%!icated sequence of events beginning ith engagement of the vira! g%"12 and the (D3 ce!! rece%tor+  9his %ermits interaction ith one of t o chemo.3 or ((.HIV-" most common) and HIV-1+ HIV-" can be subdivided into grou% ).ine co-rece%tors ((>(. s!o er (D3 dec!ine.-A genome and vira! en/ymes+ 9here are t o ty%es of HIV virus.. a D-A co%y is transcribed from the .) hich is fo!!o ed by membrane fusion and ce!!u!ar entry invo!ving g%3"  After %enetrating the ce!! and uncoating.(rare.   a cone-sha%ed %rotein core+ 9his core houses t o co%ies of the sing!e-stranded .-A genome by the reverse transcri%tase (. !o er rates of vertica! transmission.9) en/yme that is carried by the infecting virion+  9his D-A is trans%orted into the nuc!eus and integrated random!y ithin the host ce!! genome via integrase en/yme+ . grou% = and grou% . high!y divergent) ty%es+ HIV-1 differs from HIV-" in that %atients have !o er vira! !oads.

(D3 or Langerhans ce!!s. HIV is trans%orted to the !ym%h nodes via dendritic.-A co%ies hich are %rocessed and e*%orted from the nuc!eus. the ?%o!@ (%o!ymerase) encoding for three im%ortant en/ymes. of HIV disease is a %rofound immunodeficiency+  9his resu!ts from a %rogressive deficiency of the subset of 9 !ym%hocytes ((D3A 9 ce!!s). vira! m. any de%!etion in numbers renders the body susce%tib!e to o%%ortunistic infections and oncogenic virus-re!ated tumours+ . and the ?gag@ for vira! %roteins+ Pathophysiology and immunopathogenesis  After mucosa! e*%osure. ?env@ encoding for enve!o% %rotein. monocytes. or bone marro Bderived dendritic ce!!s+  A sma!! %ercentage of 9 ce!!s enter a !atent %hase and re%resent the main reservoir of HIV+  <ithin these ce!!s there is ongoing !o -!eve! re%!ication even hen %!asma !eve!s of HIV are be!o the !eve! of detection as a resu!t of antiretrovira! treatment+  (D3 ce!!s are %ivota! in orchestrating the immune res%onse. incor%orating the host ce!! membrane as their o n !i%id bi!ayer coat.    this D-A co%y is used as a tem%!ate to transcribe ne .-A then being trans!ated into vira! %e%tide chains+ 9he %recursor %o!y%roteins are then c!eaved by the vira! %rotease en/yme to form ne vira! structura! %roteins and vira! en/ymes such as the reverse transcri%tase and %rotease+ 9hese then migrate to the ce!! surface and are assemb!ed using the host ce!!u!ar a%%aratus to %roduce infectious vira! %artic!es+ 9hese bud from the ce!! surface. here infection becomes estab!ished+  9here are t o ty%es of 9 ce!!s a) (D3 he!%er 9 ce!!s. %robab!y 9 !ym%hocytes. the virus infects (D3A ce!!s. referred to as he!%er or inducer 9 ce!!s+  After initia! transmission. and ce!! !ysis occurs+ 9he virus contains three structura! genes. name!y.these ce!!s are essentia! for both the ce!!-mediated and antibody-mediated branches of the immune system8 b) (D$ cytoto*ic 9 !ym%hocytes 9hey secrete mo!ecu!es that destroy the ce!! to hich they have bound+  Ha!!mar.

of virus re%!ication ta.es %!ace ithin !ym%hoid tissue . during hich the infected individua! remains e!! ith no evidence of disease e*ce%t for the %ossib!e %resence of %ersistent genera!ised !ym%hadeno%athy(6HL)  At this stage the bu!.es %!ace !ater at :-"1 ee. ase%tic meningitis  9his coincides ith a surge in %!asma HIV-.s( indo %eriod) Asymptomatic stage  Asym%tomatic infection fo!!o s and !asts for a variab!e %eriod.-A !eve!s and a fa!! in the (D3 count+  Sym%tomatic recovery occurs after "-1 ee.Natural history 5ased on natura! history HIV disease has four stages Primary infection  6rimary infection is sym%tomatic in C2-$2D of cases and usua!!y occurs 1-E ee.s and %ara!!e!s the return of the (D3 count and fa!! in the vira! !oad+  Diagnosis of this stage is made by detecting HIV-.-A in the serum since a%%earance of s%ecific anti-HIV antibodies in serum (seroconversion) ta. 6haryngitis ith cervica! !ym%hadeno%athy )ya!giaGarthra!gia.s after e*%osure+  (!inica! features of this stage inc!ude Fever ith rash.

Her%es /oster. of brain Natural history of HIV . %rimary. any site (%u!monary or e*tra%u!monary) o P.-A !eve!s+ Symptomatic disease  9his stage occurs hen ce!!ur immunity dec!ines+  6atients may deve!o% various o%%ortunistic infections but not AIDS defining+  (ommon diseases that can occur in this stage are recurrent oro%haryngea! candidiasis. o (ytomega!ovirus disease o (andidiasis. tumours+  (ommon AIDS defining diseases are o Mycobacterium tuberculosis. carinii %neumonia o (ry%tococcosis. eight !oss etc Acquired immunodeficiency syndrome AIDS!  9his is !ast stage of HIV disease and characterised by %rofound !oss of immunity+  It is defined by the deve!o%ment of s%ecified o%%ortunistic infections. eso%hagea! o (ry%tos%oridiosis o &a%osi@s sarcoma o Lym%homa. (hronic diarrhea. 9his %eriod may !ast u%to $-"2 years+ . recurrent vagina! candidiasis.ate of disease %rogression is direct!y corre!ated ith %!asma HIV .

s after infection HIV 0LISA test may be negative because during this %eriod anti HIV antibodies are not yet formed+ 9his %eriod is ca!!ed %indo% period& b) <estern b!ot  )ost common!y used confirmatory test  Detects antibodies to HIV antigens of s%ecific mo!ecu!ar eights c) 6!asma %13 antigen !eve!s  Increase during the first fe ee.La"oratory diagnosis #! $o detect HIV infection a) 0n/yme immunoassay (0IA) (en/yme-!in.ed immunosorbent assay)  Standard screening test for HIV infection  9he test is high!y sensitive (I##+. for ()V disease and infection ith Mycobacterium avium intracellulare b) HIV . before the a%%earance of anti-HIV antibodies+  4sefu! test during indo %eriod (1) Monitoring HIV infection and response to therapy a) (D3A 9-ce!! count  Henera!!y acce%ted indicator of immuno!ogic com%etence+  Shou!d not be used for diagnosis of HIV disease  (!ose re!ationshi% bet een the (D3A count and c!inica! manifestations of AIDS  J 122GKL8 high ris.2GKL8 high ris.D)+  During first :-E ee.-A !eve! .s fo!!o ing infection. of infection ith Pneumocystis carinii  J .

measures the vira! !oad in the %eri%hera! b!ood as number of vira! co%iesGm! of b!ood+ '! $o diagnose opportunistic infections&  History and %hysica! e*amination  (>.  .F9..in test for !atent tubercu!osis  )ini-)enta! Status 0*amination for HIV 0nce%ha!o%athy (AIDS Dementia (om%!e*)  Sero!ogies for he%atitis A. 5.5S..outine chemistry and hemato!ogy B (5(. 6redicts hat i!! ha%%en to the (D3A 9 ce!! count in the near future and may itse!f be corre!ated ith immune dysfunction  9he quantitative 6(.FL6.a%id %!asma reagin test for sy%hi!is  Anti-Toxoplasma antibody titer  6urified %rotein derivative s. and ( . LF9. 4rina!ysis  6a% smear for cervica! cancer  .

9I@s A6I AN$I/E$/)VI/AL D/0(S -lass -uc!eoside reverse transcri%tase inhibitors (-.9I 1-..educe transmission Indications for the Initiation of Antiretro.iral $herapy in Patients %ith HIV Infection I+ Acute infection syndrome II+ (hronic infection A+ Sym%tomatic disease 5+ Asym%tomatic diseases "+ (D3A 9 ce!! count J:.9Is) • • • • E1ample Lamivudine Midovudine Stavudine Abacavir -ommon side effects Mitochondrial to1icities  6eri%hera! neuro%athy  !actic acidosis  6ancreatitis .e patient& 1-. before starting HAA.9I@s A --.2 GL shou!d be monitor (D3 counts once in :Emonths+ Principles of HIV therapy ") 9reatment is !ife !ong+ 1) 9reatment inc!udes combination of !east : drugs+ (High!y Active Antiretrovira! 9hera%y .educe the vira! !oad to an undetectab!e !eve! (J .9)+ :) 9reat o%%ortunistic infections first.MANA(EMEN$ )* HIV  )anagement of HIV invo!ves a) 9reatment of the HIVvirus and b) 6revention and treatment of o%%ortunistic infections+ A! $he aims of HIV treatment are to+  .HAA.9+ 3) (ounse!ing the %atient and hisGher fami!y and socia! su%%ort is im%ortant %art of management+ -ommon com"ination of drugs in treatment na.2 co%iesGm!) for as !ong as %ossib!e  Im%rove the (D3 count  Increase the quantity and im%rove the qua!ity of !ife ithout unacce%tab!e drugre!ated side-effects or !ifesty!e a!teration  .2GL 1+ 6regnancy III+ 6ost e*%osure %ro%hy!a*is L 6atients ith (D3 count more than :.

a!tegravir L site of action for all drugs is given in HIV part 1 notes.9+ Post3e1posure prophyla1is PEP!  Fo!!o ing need!e stic.ity reactions  .H(< must ash the area ith soa% and ater or antise%tic immedia!ty+  Assessment of nature of e*%osure and %atient shou!d be done to decide on need for 6ost-e*%osure %ro%hy!a*is+  .IN*E-$I)NS )rganism7infection Indication *irst3line : Pneumocystis (D3 J 122 ce!!sGmm (o-trimo*a/o!e : $o1oplasmosis (D3 J "22 ce!!sGmm (o-trimo*a/o!e : -ryptococcus (D3 J "22 ce!!sGmm Itracona/o!e $u"erculosis 6ositive tubercu!in s.ashGStevens-Nohnson syndrome  He%atitis Meta"olic side effects  Fat redistribution  Hy%er!i%idaemian  Hy%erg!ycaemia  Hastrointestina! into!erance Fusion inhibitors 0ntry inhibitors Integrase inhibitors 0nfuvirtide )araviroc . in7ury of hea!th care or.ise in vira! !oad hich as %revious!y undetectab!e vira! !oad+  Fa!! in (D3 count on HA.9Is) 6rotease inhibitors (6Is) • • • • • • Indinavir .iral drugs for patients on HAA/$ is required  .er(H(<) from HIV %atient . $reatment of patients on HAA/$ 2$/EA$MEN$3E4PE/IEN-ED2 PA$IEN$S! -hange of antiretro.itonavir -e!finavir Lo%inavir  AnaemiaGneutro%enia  0*tremity fat !oss Hypersensiti.in I-H test Pneumocystis Infections  Pneumocystis is an o%%ortunistic funga! %athogen that is an im%ortant cause of %neumonia+ .ecommended 606 is Lamivudine and Midovudine AG-indinavir for 1$ days+ 5! P/)PH6LA4IS )* )PP)/$0NIS$I..• 0mitricitabine -evira%ine 0faviren/ -on-nuc!eoside reverse transcri%tase inhibitors (--.

carinii in rats Symptoms 8 Signs  (hest discomfort and Dys%nea  Fever  -on%roductive cough  9achy%nea and 9achycardia  (yanosis Diagnosis ")S%utum  S%utum can be obtained by e*%ectoration or by Fibero%tic bronchosco%y ith bronchoa!veo!ar !avage (5AL)  Since most %atients have dry cough.are!y %neumothora* can be seen+ $reatment  9)6-S)> (. 32 mg qd for .g of S)>) qEB$h 6= for 1" days for HIV-infected %atients+  A!ternative regimens for mi!d to moderate disease  Clindamycin %!us %rimaquine  Pentamidine  For )oderate to severe infection defined as8 6a=1 of OC2 mmHg hen %atient is breathing room air and ABa gradient of P:. !iver.A diffuse bi!atera! interstitia! shado s simi!ar to that of A. mmHg ora! Prednisone (32 mg bid for . 1. to!uidine b!ue.B$2D of AIDS %atients not receiving %ro%hy!a*is =. e*%ectorated s%utum is minima! 5AL is %refferd method+  S%ecia! stains are used disgnosis pneumocystis  )ethenamine si!ver. 12 mg qd for "" days) shou!d be used+ -omplications  Disseminated infection -9he most common sites of invo!vement are the !ym%h nodes. mgG. days. ith a (D3A ce!! count of J "22GKL+  Species. mgG.) is most sensitive+ 1)Serum !eve!s of !actate dehydrogenase (LDH) usua!!y are e!evated+ :)A5H-arteria! b!ood gases sho ty%e I res%iratory fai!ure ith significant A-a gradient+ 3)(hest *-ray .DS+ . Pneumocystis infection occurs in C.Pneumocystis iroveci in !umans and P. days. s%!een.g of 9)6. and bone marro +  Pneumothorax Prophyla1is  6rimary %ro%hy!a*is is indicated for HIV-infected %atients ith (D3A ce!! counts of J 122GQL or a history of oro%haryngea! candidiasis+ Persistent generali9ed lymphadenopathy P(L!  6a!%ab!e adeno%athy morethna "cm . se!ective!y stain the a!! of Pneumocystis cysts+  <right-Hiemsa stains the nuc!ei of a!! deve!o%menta! stages+  D-A am%!ification by %o!ymerase chain reaction (6(.

ia • Hairy !eu.o%!a. %articu!ar!y in the mouth and on the tongue • Lesions are usua!!y %ain!ess+ b) Vu!vovagina! thrush • 6ruritus • Vagina! discharge • 6ain on intercourse • 6ain on urination c) 0so%hagea! candidiasis • Substerna! %ain • Sense of obstruction on s a!!o ing Diagnosis • )ost!y often c!inica! • <et smear -Demonstration of %seudohy%hae • 0so%hagea! candidiasis .4%%er HI sco%y Differencial diagnosis • Leu.ia $reatment .o%!a. )ore than P 1 e*trainguina! sites  %ersists for more than I : months  ithout e*%!anation other than HIV infection -andidiasis Definition • Funga! infections caused by "andida s%ecies -linical presentations a) )ucocutaneous infections =ra! thrush Vu!vovagina! thrush 0so%hagea! candidiasis b) Invasive infections (andidemia Symptoms and Signs  In HIV %atients mucocutaenous !esions are seen hen (D3 count is !ess than 122ce!!s Gm! a) =ra! thrush • Discrete and conf!uent adherent hite %!aques on the ora! and %haryngea! mucosa.

aginal candidiasis A/o!e cream or su%%ository (miconazole. times a day for CB"2 days) )/ Fluconazole tab!et ("22 mgGd for CB"2 days) 5! • • -! • • Vul. clotrimazole) Sing!e dose of ora! fluconazole (".o.A! )ropharyngeal candidiasis • • Clotrimazole troche (.2 mg) Esophageal candidiasis Fluconazole tab!et ("22B122 mgGd for "2 days) or Itraconazole so!ution (122 mgGd for "2 days) .