HIV/AIDS HIV/AIDS M3 lectureM3 lecture

Angela Remington, MD MSAngela Remington, MD MS

Fellow Infectious DiseasesFellow Infectious Diseases

Updated 2005 Updated 2005

IntroductionIntroduction

AIDS first recognized 1981AIDS first recognized 1981 HIV RNA retrovirus discovered 1983HIV RNA retrovirus discovered 1983 22ndnd leading cause of disease burden leading cause of disease burden

worldwideworldwide Leading cause of death in AfricaLeading cause of death in Africa Approx 1 million people currently Approx 1 million people currently

diagnosed in Americadiagnosed in America

Transmission of HIVTransmission of HIV

Blood, semen, breast milk, salivaBlood, semen, breast milk, saliva Sexual, parenteral, verticalSexual, parenteral, vertical Risk of contracting infection Risk of contracting infection

dependent ondependent on– Viral loadViral load– Integrity of the exposed siteIntegrity of the exposed site– Type of body fluidType of body fluid– Volume of body fluidVolume of body fluid

Transmission of HIVTransmission of HIV

Risk after a single exposureRisk after a single exposure– >90% blood or blood products>90% blood or blood products– 14% vertical14% vertical– 0.5-1% injection drug use0.5-1% injection drug use– 0.2-0.5% genital mucous membrane0.2-0.5% genital mucous membrane– <0.1% non-genital mucous membrane<0.1% non-genital mucous membrane

MTCT of HIVMTCT of HIV

Developing countries 40%Developing countries 40% On Zidovudine alone 7%On Zidovudine alone 7% Zidovudine with C-section 2%Zidovudine with C-section 2% HAART <1% if viral load <50 copiesHAART <1% if viral load <50 copies 80% of those infected vertically are 80% of those infected vertically are

infected close to the time of deliveryinfected close to the time of delivery

TransmissionTransmission

Risk of transmission is now Risk of transmission is now 1/10,000,000 with each unit of blood1/10,000,000 with each unit of blood

100 confirmed cases from healthcare 100 confirmed cases from healthcare exposureexposure

Risk with needle stick 0.32%Risk with needle stick 0.32% Risk with mucous membrane Risk with mucous membrane

exposure 0.03%exposure 0.03%

globalglobal

Estimated 42 million people living Estimated 42 million people living with HIV/AIDS in 2002with HIV/AIDS in 2002

5 million new infections per year5 million new infections per year 3 million deaths per year3 million deaths per year Parts of Africa 25-40% of adults are Parts of Africa 25-40% of adults are

infectedinfected 85% heterosexual transmission 85% heterosexual transmission

worldwideworldwide

The VirusThe Virus Glycoproteins (gp 120, gp41)Glycoproteins (gp 120, gp41) 2 copies of ssRNA, viral enzymes2 copies of ssRNA, viral enzymes Attachment with gp 120 to CD4 receptorAttachment with gp 120 to CD4 receptor Fusion mediated by gp 41Fusion mediated by gp 41 Inside cell RNA transcribed to DNA by RTInside cell RNA transcribed to DNA by RT DNA incorporated into cell genomeDNA incorporated into cell genome DNA is copied and translated to viral DNA is copied and translated to viral

enzymes, proteasesenzymes, proteases New infectious virus buds from host cell to New infectious virus buds from host cell to

repeat processrepeat process

ImmunologyImmunology

Gradual reduction in number of Gradual reduction in number of circulating CD4 cells inversely circulating CD4 cells inversely correlated with the viral loadcorrelated with the viral load

Any depletion in numbers of CD4 cells Any depletion in numbers of CD4 cells renders the body susceptible to renders the body susceptible to opportunistic infectionsopportunistic infections

Lymphatic tissue (spleen, lymph Lymphatic tissue (spleen, lymph nodes, tonsils/adenoids) main nodes, tonsils/adenoids) main reservoir of HIVreservoir of HIV

Primary InfectionPrimary Infection

70-80% symptomatic, 3-12 weeks 70-80% symptomatic, 3-12 weeks after exposureafter exposure

Fever, rash, cervical Fever, rash, cervical lymphadenopathy, aseptic meningitis, lymphadenopathy, aseptic meningitis, encephalitis, myelitis, polyneuritisencephalitis, myelitis, polyneuritis

Surge in viral RNA copies to >1 millionSurge in viral RNA copies to >1 million Fall in CD4 count to 300-400 Fall in CD4 count to 300-400 Recovery in 7-14 daysRecovery in 7-14 days

SeroconversionSeroconversion

3-12 weeks, median 8 weeks3-12 weeks, median 8 weeks Level of viral load post Level of viral load post

seroconversion correlates with risk of seroconversion correlates with risk of progression of diseaseprogression of disease

Differential for this syndrome: EBV, Differential for this syndrome: EBV, CMV, Strep pharyngitis, CMV, Strep pharyngitis, toxoplasmosis, secondary syphilistoxoplasmosis, secondary syphilis

Asymptomatic phaseAsymptomatic phase

Remain well with no evidence of HIV Remain well with no evidence of HIV disease except for generalized disease except for generalized lymphadenopathylymphadenopathy

Fall of CD4 count by about 50-150 Fall of CD4 count by about 50-150 cells per yearcells per year

Symptomatic phaseSymptomatic phase

Mild impairment of immune systemMild impairment of immune system Chronic weight lossChronic weight loss FeverFever DiarrheaDiarrhea Mild candida infectionsMild candida infections Recurrent herpes infectionsRecurrent herpes infections Pelvic inflammatory diseasePelvic inflammatory disease Bacillary angiomatosisBacillary angiomatosis Cervical dysplasiaCervical dysplasia

AIDSAIDS

CD4 <200CD4 <200– Pneumocystis pneumoniaPneumocystis pneumonia– Esophageal CandidiasisEsophageal Candidiasis– Mucocutaneous herpes simplexMucocutaneous herpes simplex– Miliary/extrapulmonary TBMiliary/extrapulmonary TB– CryptosporidiumCryptosporidium– HIV-associated wastingHIV-associated wasting– MicrosporidiumMicrosporidium– Peripheral neuropathyPeripheral neuropathy

AIDSAIDS

CD <100CD <100– Cerebral toxoplasmosisCerebral toxoplasmosis– Non-Hodgkin’s lymphomaNon-Hodgkin’s lymphoma– Cryptococcal meningitisCryptococcal meningitis– HIV-associated dementiaHIV-associated dementia– Primary CNS LymphomaPrimary CNS Lymphoma– Progressive multifocal Progressive multifocal

leukoencephalopathyleukoencephalopathy

AIDSAIDS

CD4<50CD4<50– CMV retinitis, gastroenteritisCMV retinitis, gastroenteritis– Disseminated Mycobacterium avium Disseminated Mycobacterium avium

complexcomplex

DiagnosisDiagnosis

Antibody test, ELISAAntibody test, ELISA Western blot Western blot HIV RNA viral loadHIV RNA viral load

Skin and Oral diseaseSkin and Oral disease Seborrheic dermatitisSeborrheic dermatitis XerodermaXeroderma Itchy folliculitisItchy folliculitis ScabiesScabies TineaTinea Herpes zosterHerpes zoster PapillomavirusPapillomavirus Oral and vaginal candidiasisOral and vaginal candidiasis Oral hairy leukoplakiaOral hairy leukoplakia Aphthous ulcersAphthous ulcers Herpes simplexHerpes simplex GingivitisGingivitis Kaposi’s sarcomaKaposi’s sarcoma Molluscum contagiosumMolluscum contagiosum Bacillary angiomatosisBacillary angiomatosis

GI diseaseGI disease

Esophageal candidiasisEsophageal candidiasis Large bowel disease (bloody diarrhea)Large bowel disease (bloody diarrhea)

– C. diffC. diff– CMVCMV

Small bowel disease (watery diarrhea)Small bowel disease (watery diarrhea)– CryptosporidiumCryptosporidium– MicrosporidiumMicrosporidium– GiardiaGiardia– MACMAC– CMVCMV

Pulmonary DiseasePulmonary Disease

Pneumocystis pneumoniaPneumocystis pneumonia Bacterial pneumoniaBacterial pneumonia NocardiaNocardia

Pneumocystis pneumoniaPneumocystis pneumonia

Most common AIDS presenting illnessMost common AIDS presenting illness Reactivation of infection (original airborne Reactivation of infection (original airborne

transmission, asymptomatic, early age)transmission, asymptomatic, early age) Inversely correlated with CD4 countInversely correlated with CD4 count 40% of patients with CD4 <100 and not 40% of patients with CD4 <100 and not

prophalaxed will have pneumonia prophalaxed will have pneumonia annuallyannually

Prophalaxis started at CD4 <200, Prophalaxis started at CD4 <200, trimethoprim/sulfa, dapsone, atovaquone, trimethoprim/sulfa, dapsone, atovaquone, pentamidinepentamidine

Pneumocystis pneumoniaPneumocystis pneumonia

2-3 week history of SOB and dry 2-3 week history of SOB and dry coughcough

HypoxemiaHypoxemia Perihilar ground glass appearance on Perihilar ground glass appearance on

CXRCXR Silver stain of organism in sputumSilver stain of organism in sputum High dose trimethaprim/sulfa, steroid High dose trimethaprim/sulfa, steroid

if hypoxicif hypoxic

Nervous system diseaseNervous system disease

ToxoToxo CryptoCrypto PMLPML CMV retinitisCMV retinitis DementiaDementia Peripheral neuropathyPeripheral neuropathy

ManagementManagement

Treatment recommended when Treatment recommended when symptomatic or CD4 count below 200symptomatic or CD4 count below 200

Earlier if high viral load, rapidly Earlier if high viral load, rapidly falling CD4 count, hepatitis C co-falling CD4 count, hepatitis C co-infectioninfection

antiretroviralsantiretrovirals

Nucleoside reverse transcriptase Nucleoside reverse transcriptase inhibitorsinhibitors

Non-nucleoside reverse transcriptase Non-nucleoside reverse transcriptase inhibitorsinhibitors

Protease inhibitorsProtease inhibitors Fusion inhibitorsFusion inhibitors R5/X4 inhibitorsR5/X4 inhibitors

NRTIsNRTIs

ddCddC ddIddI 3TC3TC ZDVZDV d4Td4T AbacavirAbacavir FTCFTC

NNRTIsNNRTIs

NevirapineNevirapine EfavirenzEfavirenz DelavirdineDelavirdine

PIsPIs

IndinavirIndinavir SaquinavirSaquinavir RitonavirRitonavir NelfinavirNelfinavir Lopinavir/ritonavirLopinavir/ritonavir AmprenavirAmprenavir FosamprenavirFosamprenavir TipranavirTipranavir AtazanavirAtazanavir

OthersOthers

T-20T-20 TenofovirTenofovir R5/X4 under developmentR5/X4 under development

Side effectsSide effects NRTIs: mitochondrial dysfunctionNRTIs: mitochondrial dysfunction ddC, ddI, d4T: neuropathyddC, ddI, d4T: neuropathy d4T, ddI: hepatic steatosis, lactic acidosisd4T, ddI: hepatic steatosis, lactic acidosis ddI: pancreatitisddI: pancreatitis ZDV: anemiaZDV: anemia d4T: fat atrophyd4T: fat atrophy Abacavir: hypersensitivity reactionAbacavir: hypersensitivity reaction Tenofovir: renal failureTenofovir: renal failure NNRTIs: rash, liver toxicityNNRTIs: rash, liver toxicity PIs: fat redistribution, insulin resistance, PIs: fat redistribution, insulin resistance,

hyperlipidemiahyperlipidemia Indiavir: renal stonesIndiavir: renal stones Nelfinavir: diarrheaNelfinavir: diarrhea