AIDS at 25 Epidemilgy and Clinical Management Bld transfusin injectin drug use Sexual Intercurse hetersexual male t male Perinatal intrapartum breast feeding HIV Transmissin A glbal view f HIV infectin 38.6 millin peple [33.4-46. millin] living with HIV, 25 Fig 2.4 HIV prevalence trends amng pregnant wmen in majr cities in Cambdia, Myanmar and Thailand, 199 24 Increase in reprted HIV cases in the Russian Federatin and Ukraine, 1987 25 % HIV prevalenc e 5. 4. 3. 2. 1. Reprted HIV cases in the Russian Federatin 4 35 3 25 2 Russian Federatin Newly reprted cases Cumulative (previus years) Ukraine Reprted HIV cases in Ukraine 12 15 9 75 6. 199 1992 1994 1996 1998 2 22 24 1991 1993 1995 1997 1999 21 23 15 1 Newly reprted cases Cumulative (previus years) 45 3 Phnm Penh Mandalay and Yangn Bangkk 5 15 1987 1989 1991 1993 1995 1997 1999 21 23 25 Surces: Cambdia Natinal Center fr HIV/AIDS, Dermatlgy and STDs (Phnm Penh); Myanmar Ministry f Health (Mandalay and Yangn); Thailand Ministry f Public Health (Bangkk), 25. Fig 2.1 Surces: Russian Federal AIDS Centre; Ukranian AIDS Centre and Ministry f Health f Ukraine Fig 2.12 1
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 TB ntificatin rate in 2 African cuntries* versus HIV prevalence in sub-saharan Africa, 199 24 2 18 16 14 TB ntificatin 12 rate per 1,1 ppulatin 8 6 4 2 199199119921993199419951996199719981999221222324 TB ntificatin rate HIV prevalence 8 7 6 5 4 3 2 1 % Adult HIV prevalence (15-49) 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 Surce: United Natins Ppulatin Divisin (24). Wrld Ppulatin Prspects: The 24 Revisin, database. Fig 4.1 Surces: Wrld Health Organizatin (26), Glbal TB database; UNAIDS (26) Fig 4.5 Peple in sub-saharan Africa n antiretrviral treatment as percentage f thse in need, 22 25 25 25 22 23 24 Surce: WHO/UNAIDS (25). Prgress n glbal access t HIV antiretrviral therapy: An update n 3 by 5. Fig 7.2 2
HIV Prevalence and Mrtality in NYC Plasma HIV-1 RNA Level After Acute HIV-1 Infectin Predicts Disease Curse 1 6 Patients with AIDS 5 years after infectin HIV-1 RNA in Plasma (cpies/ml) 1 5 1 4 1 3 Detectin threshld 62% 49% 26% 8%.5 1. 1.5 2. Years After Infectin Reprinted with permissin f rm H. Science. 1996;272:1124-1125. Prbability f AIDS ver 3 years Prbability f AIDS within 3 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 3
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. AIDS Restrictin Genes Early indicatrs f HIV Infectin S. O Brien, G. Nelsn. Nature Genetics 24;36:565 4
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 may ccur (eg( eg: : tuberculsis) Chrnic suppressin needed after acute treatment. Immune recnstitutin with anti-retrviral therapy may reverse OI susceptibility Pneumcystis pneumnia in AIDS Cmmnest life threatening cmplicatin f AIDS in U.S. Subacute illness (fever, cugh, dyspnea). Diffuse interstitial infiltrate n x-ray. x 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. 5
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) OI Guidelines Nvember, 21 Cmparisn f Indicatins t Discntinue Primary and Secndary Prphylaxis Immune Recnstitutin with HIV Therapy Fcal MAC adenitis Agent PCP Tx. MAC Recmmendatin 1 CD 4 > 2 X 3 mnths 2 CD 4 > 2 X 3 mnths 1 CD 4 > 2 X 3 mnths 2 CD 4 > 2 X 6 mnths + initial Rx + asymptmatic 1 CD 4 > 1 X 3 mnths 2 CD 4 > 1 X 6 mnths + 12 m Rx + asymptmatic Inflammatry flare f CMV retinitis Wrsening f previusly stable hepatitis Develpment f cavitary TB MAC IRIS simulating TB r Lung cancer CNS crypt IRIS 12/28 3/13 6