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1、2024/9/20周智Acquired Immune Deficiency syndrome(AIDS)2024/9/20周智Definition bbAIDS is a fatal chronic infectious disease caused by the Human Immunodeficiency Virus(HIV), transmitted mainly through sexual contacts and body fluids, characterized pathologically by selective depletion of helper T(CD4+) ly
2、mphocytes and impairment of cell-mediated immunity, and clinically by severe opportunistic infections and malignancies. 2024/9/20周智bb Classification: HIV-1 and HIV-2, belong to family Retroviridae, subfamily Lentivirus, and were discovered in 1983 and 1985, respectively. . Etiology2024/9/20周智2024/9/
3、20周智2024/9/20周智吸附吸附脱衣壳脱衣壳逆转录逆转录环化环化前病毒前病毒,整合整合转录转录, 翻译翻译核心颗粒装配核心颗粒装配出芽出芽HIV动态感染过程动态感染过程2024/9/20周智The replication cycle of HIV 2024/9/20周智HIV genomeHIV genomeNine genes, 3 structure genes , 3 regulatory genes Nine genes, 3 structure genes , 3 regulatory genes and 3 unknown function genes .and 3 unkn
4、own function genes .bb(l) (l) GAG GAG (group (group antigen) antigen) gene gene encodes encodes main main core protein p24;core protein p24;bb(2) (2) pol pol (polymerase) (polymerase) gene gene encodes encodes reverse reverse transcriptase;transcriptase;bb(3) (3) ENV ENV gene gene encodes encodes su
5、rface surface proteins proteins gp gp 120 120 and gp 41and gp 41. .2024/9/20周智Tropism:bbHigh affinity of the viral gp 120 envelope protein for the CD4 molecule (receptor), which is normally on the surface of helper T lymphocytes, 10%-20% of blood monocytes and macrophages, 5% of B cells, neuroglia,
6、neurons of central nervous system, Langerhans cells in skin and colorectal epithelial cells are also know to express small amounts of CD4 on their surfaces.2024/9/20周智Initial ReportsbbJune 5, 1981: 5 cases of PCP in gay men from UCLA (MMWR)bbJuly 3, 1981: 26 additional casesbbDec 10, 1981: 3 NEJM pa
7、pers describe casesGottlieb MS NEJM 2001;344:1788-912024/9/20周智Other Early Developments 1bb1982: 1982: Term “AIDS” coinedTerm “AIDS” coined First cases in women reportedFirst cases in women reported First transfusion and vertically transmitted cases reportedFirst transfusion and vertically transmitt
8、ed cases reported1983:1983: Isolation of a retrovirus from a patient with AIDS Isolation of a retrovirus from a patient with AIDS by Montagniers groupby Montagniers groupbb1984: 1984: Detection of HTLV-III in pts with and at risk for AIDS (Gallo)Detection of HTLV-III in pts with and at risk for AIDS
9、 (Gallo)Sepkowitz K NEJM 2001;344:1764-722024/9/20周智Source : National AIDS case surveillance data, CDCMonths after OI diagnosis0.20.40.60.81.001981-1987Proportion surviving1030405060200Other Early Developments 2bb1985:1985: FDA approves first FDA approves first commercial HIV commercial HIV antibody
10、 testantibody testbb1986: 1986: NIH establishes the NIH establishes the AIDS Clinical Trials AIDS Clinical Trials GroupGroupbb1987:1987: AZT = first AZT = first antiretroviral approved antiretroviral approved by FDAby FDA2024/9/20周智EpidemiologyEpidemiologybbFirst case repoted in mid-1981 from USAFir
11、st case repoted in mid-1981 from USA；bb8080，000000，000 Infected person all over the 000 Infected person all over the wordword；bbOver 24, 800, 000 AIDS patients diedOver 24, 800, 000 AIDS patients died；bbNewly Increased 50,000,000 per year, 16000 Newly Increased 50,000,000 per year, 16000 patients ev
12、ery day,11 cases every minute.patients every day,11 cases every minute.bbAfrica AmericaAsiaEuropeAfrica AmericaAsiaEurope；bbAt least 1,000,000 infected person in China.At least 1,000,000 infected person in China.2024/9/20周智Estimated number of people newly infected with HIV globally, 19902007 2024/9/
13、20周智HIV epidemic in China bbSince the first case was reported in mid-1981 from U.S.A., over 150 nations in the world reported AIDS. AIDS was first reported in Beijing, China, in 1985. Since then the HIV epidemic has become more visible in China. The cases reported are increasing every year and have
14、spread throughout the country. 2024/9/20周智Four phases of the HIV epidemic in ChinabbFirst phase (1985First phase (1985 1988) was marked by a small 1988) was marked by a small number of AIDS cases in coastal cities.number of AIDS cases in coastal cities. bSecond phase (1989 1993) identification of HI
15、V infection in 146 drug users in southwestern Yunnan Province. bbThird Third phase phase (1994(1994 2000) 2000) HIV HIV infection infection had had been been reported reported in in all all 31 31 provinces, provinces, regions, regions, and and municipalities. municipalities. HIV HIV infection infect
16、ion had had been been reported reported in in all all 31 provinces, regions, and municipalities. 31 provinces, regions, and municipalities. bbFourth Fourth phase phase (2001(2001 ) ) the the silence silence surrounding surrounding HIV HIV in in China was beginning to end. China was beginning to end.
17、 2024/9/20周智EpidemiologyEpidemiology Sources of infectionSources of infectionbbpatientpatientbbNon-symptom carriersNon-symptom carriersHIV exists in Blood Blood saliva salivasemen tearsemen tearVaginal discharges milkVaginal discharges milk HIV in Body FluidsHIV in Body FluidsSemen11,000Vaginal Flui
18、d7,000Blood18,000Amniotic Fluid4,000Saliva1Average number of HIV particles in 1 ml of these body fluidsRoutes of Transmission of HIVRoutes of Transmission of HIVSexual Contact:Sexual Contact:Male-to-maleMale-to-maleMale-to-female or vice versaMale-to-female or vice versaFemale-to-femaleFemale-to-fem
19、aleBlood Exposure:Blood Exposure: Injecting drug use/needle sharingInjecting drug use/needle sharing Occupational exposureOccupational exposure Transfusion of blood productsTransfusion of blood productsPerinatal:Perinatal: Transmission from mom to babyTransmission from mom to babyBreastfeedingBreast
20、feeding2024/9/20周智2024/9/20周智EpidemiologyEpidemiology High risk groups bbMale homosexuals, sexual provision including prostitution, i.v.drug addicts and hemophiliacs repeated use serum products. 2024/9/20周智PathogenesisPathogenesisbbCD4+T lymphocyte and other CD4+ cells CD4+T lymphocyte and other CD4
21、+ cells are largely damaged by HIV in direct and are largely damaged by HIV in direct and indirect way, and lead to dysfunction and indirect way, and lead to dysfunction and deficiency in cell-mediated immune deficiency in cell-mediated immune response .response .2024/9/20周智Clinical manifestationCli
22、nical manifestation Incubation period2-10 yearsbAcute HIV infection bAsymptomatic HIV infection bPersistent generalized lymphadenopathy b(PGL) b AIDS 2024/9/20周智Stage 1 - PrimarybbShort, flu-like illness - occurs one to six weeks after infectionbb no symptoms at allbb Infected person can infect othe
23、r people2024/9/20周智Stage 2 - AsymptomaticbbLasts for an average of ten years bbThis stage is free from symptomsbbThere may be swollen glandsbbThe level of HIV in the blood drops to very low levels bbHIV antibodies are detectable in the blood2024/9/20周智Stage 3 - SymptomaticbbThe symptoms are mildbbTh
24、e immune system deteriorates bbemergence of opportunistic infections and cancers2024/9/20周智Stage 4 - HIV AIDSbbThe immune system weakensbbThe illnesses become more severe leading to an AIDS diagnosis2024/9/20周智Clinical manifestation Clinical manifestation AIDSAIDSconstitutional symptoms: Fever, mala
25、ise, anorexia, diarrhea, loss of body weight etc. also known as AIDS related complex (ARC). Central nervous system symptoms: Headache, epilepsy, progressive dementia, paraplegia etc etc 2024/9/20周智bSevere opportunistic infections: Pneumocystic Carinii Pneumonia (PCP), Cryptococcal meningitis, pulmon
26、ary tuberculosis, Candidiasis, cryptosporidiosis, Histoplasmosis, etc2024/9/20周智bbOpportunistic malignancies: Kaposi sarcoma, non-Hodgkin lymphoma etc.bbOther disorders associated with severe immune suppression: Chronic lymphoid interstitial pneumonia etc. 2024/9/20周智Figure 9-222024/9/20周智Clinical M
27、anifestationsClinical ManifestationsbbWasting syndromeWasting syndromebbKaposis sarcomaKaposis sarcoma2024/9/20周智Kaposis sarcoma in a patient with AIDS 2024/9/20周智Clinical ManifestationClinical ManifestationbbHerpes zosterHerpes zosterbbMamillaMamilla2024/9/20周智bbCryptozoiteCryptozoitebsporotrichosi
28、s2024/9/20周智Clinical manifestation in various systems 1 11. Respiratory system1. Respiratory system1. Respiratory system1. Respiratory systembbPneumocystic Carinii Pneumonia (PCP),Pneumocystis jiroveci(耶氏肺耶氏肺孢子子菌菌)bbLung tuberculosisLung tuberculosisLung tuberculosisLung tuberculosisbbCytomegaloviru
29、s Cytomegalovirus Cytomegalovirus Cytomegalovirus infection infection infection infectionbbFungal pneumoniaFungal pneumoniaFungal pneumoniaFungal pneumoniabbKaposi sarcomaKaposi sarcoma2024/9/20周智Clinical manifestation in various systems 222. Didestive system2. Didestive systembbOral cavity and esop
30、hagitisOral cavity and esophagitisbOral cavity hairy leukoplakiabbInfectious diarrheaInfectious diarrheabbCrissum, rectum Crissum, rectum herpesvirus infectionbbHepatic lesionHepatic lesion2024/9/20周智Various oral lesions in HIV-infected individuals. A. Thrush 2024/9/20周智Barium swallow of a patient w
31、ith Candida esophagitis. 2024/9/20周智Clinical manifestation in various systems33 3.Nervous systembbopportunistic infectionsopportunistic infections Cryptococcal meningitis,Cryptococcal meningitis,Etc.Etc.bbOpportunistic maliganencyOpportunistic maliganency primary lymphoma primary lymphomabbHIV direc
32、k infection dementia dementia syndromesyndrome2024/9/20周智Central nervous system toxoplasmosis Central nervous system lymphoma 2024/9/20周智Clinical manifestation in various systems 444.Skin mucous membranebbKaposis sarcomaKaposis sarcomabbMonilia infectionMonilia infectionbherpes pudendalis, cauliflow
33、er excrescence2024/9/20周智Clinical manifestation in various systems 555.Ocular regionbRetinitis (CMV)bb Toxoplasmosis of brain choroiditisbbKaposis sarcomaKaposis sarcoma2024/9/20周智Laboratory Examination1Laboratory Examination11. Routine examinations: Anemia, leucocytopenia, proteinuria.2.Immunologic
34、al examinations: T lymphocytopenia, especially CD4+ T lymphocytes(healthy T cell levels range from 500 to 1500), decrease in CD4CD8 ratio,less than 1(normal 1.75-2.1). 2024/9/20周智Laboratory Examination2Laboratory Examination2b3. Serological findings: Positive anti-HIV by ELISA and Western blot（ anti
35、-gp24, anti-gp120 and anti-gp41, anti-gp64 and anti-gp31）.b4. Plasma HIV RNA Assays: RT-PCR, branched DNA (bDNA)bIsolation Virus2024/9/20周智2024/9/20周智Diagnosis1Diagnosis1Criteria Criteria for for adult adult AIDS AIDS patients.patients.Confirmed patients.Confirmed patients HIV infection HIV infectio
36、n Epidemiolgy,Anti-HIV(+), Epidemiolgy,Anti-HIV(+), WB(+). WB(+).2024/9/20周智 AIDS patients AIDS patientsbbEpidemiology and clinical manifestation.bbAnti-HIV(+),CD4 number 0.2 X109/L or 0.2-0.5X109/L，bbVarious pathogens leading to opportunistic infections or opportunistic malignancies .2024/9/20周智Dia
37、gnosis2Diagnosis22.Suspected patients Epidemiology and clinical manifestation, but anti-HIV(-)HIV(-)； Children from HIV(+) parentsChildren from HIV(+) parents； Body Body weight weight loss loss more more than than 1010，chronic chronic cough cough or or diarrhea diarrhea lasted lasted more more than
38、than one one monthmonth， fever fever more more than than one one monthmonth， generalized generalized lymphadenopathy.lymphadenopathy. 2024/9/20周智Epidemiology, no clear cilinical manifestations, CD4+ lymphocytes0.2 109/L,(5)opportunistic infections and opportunistic malignancies, needing to follow an
39、ti- HIV。 2024/9/20周智Differential diagnosisbb1. Idiopathic CD4+ lymphocytopenia.bb2. Secondary CD4+ lymphocytopenia after cancer therapy or resulting from autoimmune diseases. 2024/9/20周智TreatmentTreatmentb1. Antiretroviral therapy When used in combinations, these medications are termed Highly Active
40、 Antiretroviral Therapy (HAART). HAART combines three or more anti-HIV medications in a daily regimen, sometimes referred to as a cocktail. 2024/9/20周智bb(1) (1) Nucleoside Nucleoside reverse reverse transcriptase transcriptase inhibitors inhibitors (NRT1): (NRT1): Zidovudine Zidovudine (AZT, (AZT, Z
41、DV), ZDV), Didanosine Didanosine (ddI), (ddI), Zalctabine Zalctabine (ddC), (ddC), Lamivudine(3TC), Lamivudine(3TC), Stavudine (d4T) and AbacavirStavudine (d4T) and Abacavirbb(2) (2) Non-nucleoside Non-nucleoside reverse reverse transcriptase transcriptase inhibitors inhibitors (NNRTI): (NNRTI): Del
42、avirdine, Delavirdine, Nevirapine, Nevirapine, Efavirenz.Efavirenz.bb(3) (3) Protease Protease inhihitors inhihitors (PI): (PI): Saquinavir, Saquinavir, Ritonavir, Indinavir and Nelfinavir.Ritonavir, Indinavir and Nelfinavir.bb(4)(4) Fusion Inhibitors.2024/9/20周智bb Therapeutic principle: Combination
43、 Recommonded regimens: 2 NRTIs+ 1 PI and so on. Indications: patients with CD4+ lmyphocyte count 5,000-10,000copies/ml; patients with AIDS.bbSide effects and drug resistance.2024/9/20周智2. 2. 2. 2. Treatment of complications:Treatment of complications: (1) (1) PCP: PCP: Pentamidine Pentamidine 4 4 mk
44、g mkg im im or or iv iv forl4 forl4 days: days: sulfamethoxazole-trimethoprim sulfamethoxazole-trimethoprim (SMZ-(SMZ-TMP) #3 bid.TMP) #3 bid. (2) (2) Kaposi Kaposi sarcoma: sarcoma: AZT+ AZT+ interferon; interferon; bleomycin; vinblastine; adriamycin. bleomycin; vinblastine; adriamycin. (3) (3) Cry
45、ptosporidiosis Cryptosporidiosis and and histoplasmosis: histoplasmosis: Spiramycin.Spiramycin. (4) (4) Cytomegalovirus Cytomegalovirus (CMV) (CMV) infection: infection: Gancyclovir.Gancyclovir. (5) cryptococcal meningitis: Fluconazole. (5) cryptococcal meningitis: Fluconazole. 2024/9/20周智bb3. Suppo
46、rtive and symptomatic treatments: (1) Blood transfusion to treat anemia. (2) Immunomodulation: Recombinant IL-2(in experiment). HIV Occupational ExposurebReview facility policy and report the incidentbMedical follow-up is necessary to determine the exposure risk and course of treatmentbBaseline and
47、follow-up HIV testingbFour week course of medication initiated one to two hours after exposure bLiver function tests to monitor medication tolerancebExposure precautions practiced2024/9/20周智Prevention b1. Isolation of patients and concurrent disinfection.b2. Blocking routes of transmission:b(1) Educ
48、ation of the public.b(2) banning of drug addiction and prostitution. 2024/9/20周智bb(3) Strict screening of blood and blood products.bb(4) Popularize disposal syringes and needles.bb(5) Sterilization of medical instruments and facilities used by AIDS patients. 2024/9/20周智bb3. Protection of susceptible
49、s:bb(1) Restrict the marriage with HIV carriers.bb(2) Use of condoms and avoid sexual perversion.bb(3) Vaccination: still at experimental stage.2024/9/20周智Four ways to protect yourself?bAbstinencebMonogamous RelationshipbProtected SexbSterile needles2024/9/20周智AbstinencebbIt is the only 100 % effect
50、ive method of not acquiring HIV/AIDS. bbRefraining from sexual contact: oral, anal, or vaginal.bbRefraining from intravenous drug use2024/9/20周智Monogamous relationshipbbA mutually monogamous (only one sex partner) A mutually monogamous (only one sex partner) relationship with a person who is not inf
51、ected relationship with a person who is not infected with HIV with HIV bbHIV testing before intercourse is necessary to HIV testing before intercourse is necessary to prove your partner is not infectedprove your partner is not infected2024/9/20周智Protected SexbbUse condoms (female or male) every time
52、 you have sex (vaginal or anal)bbAlways use latex or polyurethane condom (not a natural skin condom)bbAlways use a latex barrier during oral sex2024/9/20周智When Using A CondomRemember To:bbMake sure the package is not expiredbbMake sure to check the package for damagesbbDo not open the package with y
53、our teeth for risk of tearingbbNever use the condom more than oncebbUse water-based rather than oil-based condoms2024/9/20周智Sterile NeedlesbbIf a needle/syringe or cooker is shared, it must be disinfected:Fill the syringe with undiluted bleach and wait Fill the syringe with undiluted bleach and wait at least 30 seconds.at least 30 seconds.thoroughly rinse with waterthoroughly rinse with waterDo this between each persons useDo this between each persons use2024/9/20周智Needle Exchange ProgrambbNon-profit Organization, which provides sterile needles in exchange for contaminated ones2024/9/20周智
