AIDS at 3 Epidemilgy and Clinical Management Bld transfusin injectin drug use Sexual Intercurse hetersexual male t male Perinatal intrapartum breast feeding HIV Transmissin Adults and children estimated t be living with HIV, 27 Western & Eastern Eurpe Central Eurpe & Central Asia Nrth America 73 1.5 millin [58 1. millin] [1.1 1.9 millin] 1.2 millin East Asia [76 2. millin] 74 Middle East & Nrth [48 1.1 millin] Caribbean Africa 23 38 Suth & Suth-East [21 27 ] [28 51 ] Asia Sub-Saharan Africa 4.2 millin Latin America 22. millin [3.5 Oceania 5.3 millin] 1.7 millin [2.5 23.6 millin] [1.5 2.1 millin] 74 [66 93 ] Ttal: 33 millin (3 36 millin) July 28 e 4 Increase in reprted HIV cases in the Russian Federatin and Ukraine, 1987 25 Reprted HIV cases in the Russian Federatin 4 35 3 25 2 15 1 5 Russian Federatin Newly reprted cases Cumulative (previus years) Ukraine Newly reprted cases Cumulative (previus years) 1987 1989 1991 1993 1995 1997 1999 21 23 25 Reprted HIV cases in Ukraine 12 15 9 75 6 45 3 15 Impact f AIDS n life expectancy in five African cuntries, 197 21 7 65 6 55 Life 5 expectancy 45 at birth (years) 4 35 3 25 2 197 1975 198 1985 199 1995 2 25 1975 198 1985 199 1995 2 25 21 Btswana Suth Africa Swaziland Zambia Zimbabwe 6/6 e Surces: Russian Federal AIDS Centre; Ukranian AIDS Centre and Ministry f Health f Ukraine 26 Reprt n the Fig 2.12 6/6 e Surce: United Natins Ppulatin Divisin (24). Wrld Ppulatin Prspects: The 24 Revisin, database. 26 Reprt n the Fig 4.1
CS2146-A CS2146-A TB ntificatin rate in 2 African cuntries* versus HIV prevalence in sub-saharan Africa, 199 24 Peple in sub-saharan Africa n antiretrviral treatment as percentage f thse in need, 22 25 25 2 8 18 7 16 6 14 12 5 TB ntificatin % Adult HIV rate per 1,1 4 prevalence ppulatin 8 (15-49) 3 6 2 4 2 1 25 19919911992 19931994 19951996 1997 19981999 221 2223 24 TB ntificatin rate HIV prevalence 22 23 24 Cnsistently reprting each year: Algeria, Angla, Btswana, Camern, Cmrs, Cng, Côte d'ivire, Demcratic Republic f Cng, Ghana, Guinea, Kenya, Malawi, Mauritius, Mzambique, Nigeria, Senegal, Suth Africa, Uganda, United Republic f Tanzania, Zimbabwe 6/6 e Surces: Wrld Health Organizatin (26), Glbal TB database; UNAIDS (26) 26 Reprt n the Fig 4.5 6/6 e Surce: WHO/UNAIDS (25). Prgress n glbal access t HIV antiretrviral therapy: An update n 3 by 5. 26 Reprt n the Fig 7.2
HIV Prevalence and Mrtality in NYC Plasma HIV-1 RNA Level After Acute HIV-1 Infectin Predicts Disease Curse Plasma (cpies/ml) 1 6 1 5 1 4 Patients with AIDS 5 years after infectin 62% 49% 26% HIV-1 RNA in 1 3 Detectin threshld 8%.5 1. 1.5 2. Years After Infectin Reprinted with permissin frm H. Science. 1996;272:1124-1125. Prbability f AIDS ver 3 years within 3 Prbability f AIDS w years 1% 8% 6% 4% 2% 32.6% 32.6% 42.9% 9.5% 64.4% 85.5% 16.1% 16.1% 4.1% 4.1% 8.1% 8.1% 8.1% 2.% 2.% 3.7% 3.2% 2.% %.% > 11K 41-11K 14-41K 3-14K < 3K HIV-1 RNA cncentratin (cpies/ml) < 2 21-35 351-5 51-75 > 75 CD4 cunt
Frequency f HIV Nn-Prgressrs San Francisc City Clinic Chrt 489 HIV+ Gay men with knwn sercnversin date. 13% develped AIDS by 5 years; 51% develped AIDS by 1 years. 89% had died, develped AIDS r had CD4<5 by 1 years. [Rutherfrd et al. BMJ. 199; 31:1183-8 ] Explaining the variability f HIV disease Viral Factrs Nef deletin Nn-clade B subtypes? Hst Factrs Chemkine c-receptrs Immune respnse Gender? Envirnmental Factrs Infectin, diet?, stress? HIV C-receptrs Effect f C-receptr Heterzygsity CD4 necessary but nt sufficient fr infectin. Beta chemkine receptrs act as HIV c-receptrs. CXCR4 (lymphcyte) CCR5 (macrphage) Hmzygus CCR5 deletin fund in <1%. MACS High risk chrt: N HIV+ amng thse hmzygus fr deletin. 3.6% f HIV Negative were hmzygus. Amng persistently HIV Neg: up t 33% were hmzygus fr CCR5 deletin. AIDS Restrictin Genes Early indicatrs f HIV Infectin S. O Brien, G. Nelsn. Nature Genetics 24;36:565
Key features f OIs in AIDS HIV causes prfund defect mstly restricted t T cell- based immunity (restricted range f pathgens) OIs usually reflect reactivatin f latent infectins. Reinfectin ect may ccur (eg: tuberculsis) s) Chrnic suppressin needed after acute treatment. Immune recnstitutin with anti-retrviral therapy may reverse OI susceptibility (but may als trigger an inflammatry respnse t active OIs) Pneumcystis pneumnia in AIDS Cmmnest life threatening cmplicatin f AIDS in U.S. Subacute illness (fever, cugh, dyspnea). Diffuse interstitial infiltrate n x-ray. Additin f crticsterids t antimicrbials cuts mrtality in severe disease 5%. Fully preventable with trimethprim-sulfa. CD4 cunt predicts risk f PCP CNS txplasmsis Prtzn parasite; cats shed cysts; farm animals incidental hsts; humans infected frm cysts, uncked meat. Cmmnest cause f fcal CNS disease in AIDS. Serum IgG antibdy reliable marker f past infectin. Reactivatin in AIDS assciated with CD4<1. Cryptcccal disease in AIDS Ubiquitus sil fungus. Initial assymptmatic pneumnia. Reactivatin in advanced HIV disease (CD4<1). Meningitis cmmnest presentatin but wide disseminatin frequent. CMV disease in AIDS Cmmn viral infectin (5% adult serprevalence). Reactivatin at CD4<5 Retinitis cmmnest. Other sites: Cln, CNS.
Disseminated Mycbacterium-avium avium cmplex (MAC) disease in AIDS Cmmn in envirnment (water). Lcal lung disease knwn prir t AIDS. Widespread visceral disseminatin in AIDS. Diagnsis by bld culture. Absence f inflammatin in tissue sites. Prphylaxis f Opprtunistic Infectins Pathgen Indicatin PCP Tx MAC TB CD4<2 CD4<1 and IgG+ CD4<5 +PPD (5mm) Regimen Trimethprim-sulfa Trimethprim-sulfa r Dapsne +Pyrimethamine Clarithr/Azithrmycin INH (9 mnths) Discntinuatin f Prphylactic r Suppressive Regimens Primary Prphylaxis Secndary Prphylaxis Pathgen CD4 Threshld CD4 Duratin r suppressin : Additinal criteria PCP 2 3 mnths Nne Tx 2 3 mnths CD4>2 fr 6 mnths Cmpleted initial Rx. MAC 1 3 mnths CD4>1 fr 6 mnths Cmpleted 12 m Rx. Cryptcccus NA NA CD4>2 fr 6 m. Cmpleted initial Rx. CMV NA NA CD4>1 fr 3-6 m. N active disease Immune Recnstitutin with HIV Therapy Fcal MAC adenitis Inflammatry flare f CMV retinitis Wrsening f previusly stable hepatitis Develpment f cavitary TB MAC IRIS simulating TB r Lung cancer HSV IRIS suppressed by thalidmide