HIV UpdateHIV Update

HistoryHistory

HIV was originally described in HIV was originally described in 19811981

Cluster of cases of Cluster of cases of Pneumocystis Pneumocystis cariniicarinii pneumonia (PCP) and pneumonia (PCP) and Kaposi's sarcoma (KS) in Kaposi's sarcoma (KS) in previously healthy males previously healthy males – Previously very unusual infections in Previously very unusual infections in

the U.S.the U.S.

PCP and KSPCP and KS

HistoryHistory

The virus was first identified in 1983The virus was first identified in 1983– Luc Montagnier and Robert GalloLuc Montagnier and Robert Gallo

The first blood test (ELISA) was The first blood test (ELISA) was developed in 1985developed in 1985– Screening of blood supply initiatedScreening of blood supply initiated

First HIV-1 InfectionsFirst HIV-1 Infections

Central AfricaCentral Africa– First human case in 1959First human case in 1959

US:US:– Haitian connection (UNESCO program to Congo in the Haitian connection (UNESCO program to Congo in the

1960s)1960s)– Airline steward helped disseminate HIV in the US and Airline steward helped disseminate HIV in the US and

EuropeEurope Worobey’s StudyWorobey’s Study

– Studied genetic relatedness of strains and hypothesized Studied genetic relatedness of strains and hypothesized that first infection occurred in ~1908that first infection occurred in ~1908

– Although HIV may have existed for decades, epidemic Although HIV may have existed for decades, epidemic began in the 1950s/1960s began in the 1950s/1960s

Urbanization, prostitution, needle use, war, and travel/tourismUrbanization, prostitution, needle use, war, and travel/tourism

HIV = ZoonosisHIV = Zoonosis-Cross-species infections

• Sooty Mangabey: HIV-2 • Chimpanzee: HIV-1

-Transmission via exposure to blood, including for chimps (cuts, ingestion)-Benign infection in Chimpanzees

• 98% homology with HIV (?? which genes protective)

-Did chimps die off millions of years ago from SIV?

Did NOT originate from: contaminated vaccines, biologic engineering/ weaponry; cats (feline leukemia virus), etc.

.10

SIVSTM

SIVSM

HIV-1 group OHIV-1 group O

HIV-1 group NHIV-1 group N

CPZANT

CPZGB

G A

A/EA/G

HF

CJD

B

HIV-1 group MHIV-1 group M

A

BHIV-2HIV-2

100

100

100

100

100

100

100

100

100

100

100

100

99

99

96

94

9277

76

Relationships Among Primate LentivirusesRelationships Among Primate Lentiviruses

HIV-1 SubtypesHIV-1 Subtypes

HIV VirusHIV Virus

Replication: 10 Billions copies/dayReplication: 10 Billions copies/day

HIV ReplicationHIV Replication

A global view of HIV infection33 million people [30–36 million] living with HIV, 2007

Total: 33 million (30 – 36 million)

Western & Central Europe

730 000730 000[580 000 – 1.0 million][580 000 – 1.0 million]

Middle East & North Africa

380 000380 000[280 000 – 510 000][280 000 – 510 000]Sub-Saharan Africa

22.0 million22.0 million[20.5 – 23.6 million][20.5 – 23.6 million]

Eastern Europe & Central Asia

1.5 million 1.5 million [1.1 – 1.9 million][1.1 – 1.9 million]

South & South-East Asia

4.2 million4.2 million[3.5 – 5.3 million][3.5 – 5.3 million]Oceania

74 00074 000[66 000 – 93 000][66 000 – 93 000]

North America1.2 million

[760 000 – 2.0 million]

Latin America1.7 million1.7 million

[1.5 – 2.1 million][1.5 – 2.1 million]

East Asia740 000740 000

[480 000 – 1.1 million][480 000 – 1.1 million]Caribbean230 000

[210 000 – 270 000]

Adults and children estimated to be living with HIV, 2007

Over 7,400 new HIV infections a day in 2007

• More than 96% are in low and middle income countries

• About 1,000 are in children under 15 years of age

• About 6,300 are in adults aged 15 years and older of whom:

— almost 50% are among women— about 45% are among young people (15-24)

25 years of AIDS25 years of AIDS

9 In 1991-1993, HIV prevalence in young pregnant women in Uganda and in young men in Thailand begins to decrease, the first major downturns in the epidemic in developing countries

10 Highly Active Antiretroviral Treatment launched

11 Scientists develop the first treatment regimen to reduce mother-to-child transmission of HIV

12 UNAIDS is created13 Brazil becomes the first developing

country to provide antiretroviral therapy through its public health system

14 The UN General Assembly Special Session on HIV/AIDS. Global Fund to fight AIDS, Tuberculosis and Malaria launched

15 WHO and UNAIDS launch the "3 x 5" initiative with the goal of reaching 3 million people in developing world with ART by 2005

16 Global Coalition on Women and AIDS launched

40

30

20

10

0

50

35

25

15

5

45

Mill

ion

1980 1985 1990 1995 2000 2005

1 2 3 45 6

8

9

11

12

13

14

1516

7

10

1 First cases of unusual immune deficiency are identified among gay men in USA, and a new deadly disease noticed

2 Acquired Immune Deficiency Syndrome (AIDS) is defined for the first time

3 The Human Immune Deficiency Virus (HIV) is identified as the cause of AIDS

4 In Africa, a heterosexual AIDS epidemic is revealed

5 The first HIV antibody test becomes available6 Global Network of People living with HIV/AIDS (GNP+) (then International Steering Committee of People Living with HIV/AIDS) founded

7 The World Health Organisation launches the Global Programme on AIDS

8 The first therapy for AIDS – zidovudine, or AZT -- is approved for use in the USA

People People living living with with HIVHIV

Children Children orphaned orphaned by AIDS in by AIDS in sub-sub-Saharan Saharan AfricaAfrica

1.1

Reason for Falling Reason for Falling Death RatesDeath Rates Impact of HAARTImpact of HAART

– Highly Active Anti-Retroviral TherapyHighly Active Anti-Retroviral Therapy Defined as three or more ARV drugsDefined as three or more ARV drugs

– Protease inhibitors were approved for use in 1995Protease inhibitors were approved for use in 1995 Earlier recognition & treatmentEarlier recognition & treatment

– Identifying HIV patients so they could be treatedIdentifying HIV patients so they could be treated Still an issue: approximately 250,000 undiagnosed Still an issue: approximately 250,000 undiagnosed

cases in the U.S.!cases in the U.S.! Response: CDC recommends testing for all persons Response: CDC recommends testing for all persons

(regardless of risk factors) from ages 13 to 64 years(regardless of risk factors) from ages 13 to 64 years– Annual testing for high-risk personsAnnual testing for high-risk persons

OI prophylaxis, multi-discplinary HIV care, OI prophylaxis, multi-discplinary HIV care, etc.etc.

Current IssuesCurrent Issues

Continued new infections despite Continued new infections despite knowledge of preventionknowledge of prevention

Lack of safe sex practicesLack of safe sex practices– High rate of STIs (e.g., syphilis)High rate of STIs (e.g., syphilis)

False sense of security after HAART False sense of security after HAART availabilityavailability

Lack of ART availability for the entire Lack of ART availability for the entire worldworld

Long term health effects of chronic HIV Long term health effects of chronic HIV infection as well as long term ART useinfection as well as long term ART use

How HIV is transmittedHow HIV is transmitted

Unprotected SexUnprotected Sex– Anal>vaginal>oralAnal>vaginal>oral– Risk is Risk is most most associated with Viral Loadassociated with Viral Load

Increased risk with bleeding or tearing of tissuesIncreased risk with bleeding or tearing of tissues Higher risk in the receptive partnerHigher risk in the receptive partner Concurrent STIConcurrent STI Lack of circumcisionLack of circumcision

Sharing needles or IV drug useSharing needles or IV drug use Infected mother to her babyInfected mother to her baby

– While baby is developing in the wombWhile baby is developing in the womb– During the birthing processDuring the birthing process– From breastfeeding (30-40% risk in 6 months)From breastfeeding (30-40% risk in 6 months)

Blood transfusion (1:1 Million)Blood transfusion (1:1 Million)

How HIV is How HIV is notnot transmittedtransmitted CoughingCoughing SneezingSneezing Shaking handsShaking hands Casual kissCasual kiss Toilet seatsToilet seats Bites from mosquitoes or fleasBites from mosquitoes or fleas

TransmissionTransmission

The risk for transmission is The risk for transmission is highest during the first year after highest during the first year after being infectedbeing infected– Viral load is highest during early Viral load is highest during early

infection (and in the late stages)infection (and in the late stages)– Unfortunately, most people do not Unfortunately, most people do not

know they are infected during this know they are infected during this timetime

DiagnosisDiagnosis

HIV ELISAHIV ELISA– Usually positive within 3-4 weeks, rarely test Usually positive within 3-4 weeks, rarely test

can become positive up to 6 months after can become positive up to 6 months after infectioninfection

Confirmatory Western Blot testConfirmatory Western Blot test– Indeterminate test due to advanced HIV, HIV-2, Indeterminate test due to advanced HIV, HIV-2,

autoimmune disease, pregnancyautoimmune disease, pregnancy– Overall, between the two tests it is very Overall, between the two tests it is very

accurateaccurate Polymerase Chain Reaction (PCR)Polymerase Chain Reaction (PCR)

– Positive earlier than ELISAPositive earlier than ELISA– Used to test people when we suspect Used to test people when we suspect

“Seroconverting Illness”“Seroconverting Illness”

Stages of HIV InfectionStages of HIV Infection

Viral transmission Viral transmission Primary HIV infection (acute HIV infection or Primary HIV infection (acute HIV infection or

acute seroconversion syndrome) acute seroconversion syndrome) – Occurs in approximately 60% of casesOccurs in approximately 60% of cases

Seroconversion Seroconversion – ELISA becomes positive due to antibody productionELISA becomes positive due to antibody production

Clinical latent period Clinical latent period – Typically 8-10 years in durationTypically 8-10 years in duration

AIDS AIDS End-Stage/DeathEnd-Stage/Death

Seroconverting Seroconverting SymptomsSymptoms FeverFever 87%87% RashRash 68%68% PharyngitisPharyngitis 48%48% MyalgiasMyalgias 42%42% HeadacheHeadache 39%39% DiarrheaDiarrhea 32%32% Abdominal PainAbdominal Pain 32%32% ArthralgiasArthralgias 29%29% Nausea/VomitingNausea/Vomiting 29%29%

Seroconverting RashSeroconverting Rash

Natural History of HIVNatural History of HIV

Genetics and Disease Genetics and Disease ProgressionProgression Science; 313:462-6Science; 313:462-6

T h e P a th o g e n e s is o f H IV -1 In fe c t io n :C o m p a r tm e n ts

C o lo n , D u o d e n u m a n dR e c tu m C h ro m a ffin C e lls

L y m p h o c y te s in B lo o d ,S e m e n a n d V a g in a l F lu id

S k in L a n g e rh a n s ’ C e lls

B o n e M a rro w

B ra in M a c ro p h a g e sa n d G lia l C e lls

L y m p h N o d e s

T h y m u s G la n d

L u n g A lv e o la rM a c ro p h a g e s

AIDSAIDS

Defined by CD4 count below 200 (<14%) Defined by CD4 count below 200 (<14%) or an AIDS-defining condition*or an AIDS-defining condition*– P. carinii/jiroveciP. carinii/jiroveci pneumonia pneumonia – Esophageal candidiasis Esophageal candidiasis – Wasting Wasting – Kaposi's sarcoma Kaposi's sarcoma – Disseminated Disseminated M. aviumM. avium infection (MAC) infection (MAC) – Tuberculosis Tuberculosis – Cytomegalovirus disease Cytomegalovirus disease – HIV-associated dementia HIV-associated dementia – And so forth (a total of 26 conditions)And so forth (a total of 26 conditions)

*1993 CDC Surveillance Case Definition*1993 CDC Surveillance Case Definition

HIV Care in the HIV Care in the MilitaryMilitary

HIV positive persons may remain on AD statusHIV positive persons may remain on AD status– Cannot serve overseas (policy being reconsidered)Cannot serve overseas (policy being reconsidered)

Must attend 2-week “Initial” evaluation upon diagnosis at Must attend 2-week “Initial” evaluation upon diagnosis at one of the 3 Navy HIV Clinicsone of the 3 Navy HIV Clinics

6-month and annual evaluations thereafter:6-month and annual evaluations thereafter:– History and PhysicalHistory and Physical– Laboratory evaluations including CD4 counts and viral loadLaboratory evaluations including CD4 counts and viral load

Initial genotypeInitial genotype Annual syphilis test and PPD and basic lab testsAnnual syphilis test and PPD and basic lab tests

– Initiate ARVs when appropriateInitiate ARVs when appropriate– VaccinesVaccines– Treat any complications / other medical conditionsTreat any complications / other medical conditions– Social and mental health supportSocial and mental health support– Education about HIVEducation about HIV– Preventive Med sessions/safe sexPreventive Med sessions/safe sex

Medical Board if diagnosed with AIDSMedical Board if diagnosed with AIDS

CD4 Count and Risk for CD4 Count and Risk for Opportunistic DiseasesOpportunistic Diseases

CD4 is the best measure for immune CD4 is the best measure for immune competence and stage of diseasecompetence and stage of disease

Basis for treatment initiationBasis for treatment initiation Closely related to risk for an opportunistic Closely related to risk for an opportunistic

condition:condition:– <200<200

PCPPCP– <100<100

ToxoplasmosisToxoplasmosis Cryptococcal meningitis/disseminated diseaseCryptococcal meningitis/disseminated disease Candidal esophagitisCandidal esophagitis

– <50<50 MACMAC CNS lymphomaCNS lymphoma

Viral LoadViral Load

Viral load describes the rate of HIV progression

Higher VLs are usually associated with faster declines in the CD4 count

Not a primary reason to begin HAART

History of History of AntiretroviralsAntiretrovirals

11stst Drug: AZT, zidovudine Drug: AZT, zidovudine March 1987March 198722ndnd NRTI: DDI, didanosine NRTI: DDI, didanosine October 1991October 1991Protease Inhibitors (Saquinavir)Protease Inhibitors (Saquinavir) December December

19951995Non-nucleosides (Nevirapine)Non-nucleosides (Nevirapine) June 1996June 199644thth class: Fusion inhibitors class: Fusion inhibitors March 2003March 200355thth class: CCR5 inhibitors class: CCR5 inhibitors August 2007August 200766thth class: Integrase inhibitors class: Integrase inhibitors October October

20072007

NNRTI

’’8787 ’’9191 ’’9292 ’’9494 ’’9595 ’’9696 ’’9797 ’’9898 ’’9999 ‘‘0000’’8888 ’’8989 ’’9090

NRTINRTI

PIPI

Since ’95, 26 new products were introduced

Approval of Approval of AntiretroviralsAntiretrovirals

RetrovirRetrovir

NorvirNorvir

InviraseInvirase

CrixivanCrixivan

FortovaseFortovaseKaletraKaletraViraceptViracept

ZiagenZiagen

CombivirCombivir

VidexVidex

HividHivid

ZeritZerit

EpivirEpivir

TrizivirTrizivir

Rescriptor

SustivaViramune

’’0101

VireadViread

EmtrivaEmtriva

FuzeonFuzeon

ReyatazReyataz

‘‘0202 ’’03 03 ’’9393

AgeneraseAgeneraseLexivaLexiva

’’0404 ’’0505 ’’0606

Entry inhEntry inh

AtriplaAtripla

TruvadaTruvadaEpzicomEpzicom

AptivusAptivusPrezistaPrezista

CCR5 Inh

‘07

Selzentry

Integrase Inh

Raltegravir

Pros and Cons of Early Pros and Cons of Early TherapyTherapyBENEFITSBENEFITS Control of viral Control of viral

replication easier to replication easier to achieve and maintainachieve and maintain

Delay or prevention of Delay or prevention of immune system immune system compromisecompromise

Lower risk of Lower risk of resistance with resistance with complete viral complete viral suppressionsuppression

Decreased risk of HIV Decreased risk of HIV transmissiontransmission

RISKSRISKS Drug-related reduction Drug-related reduction

in quality of lifein quality of life Greater cumulative Greater cumulative

drug-related adverse drug-related adverse eventsevents

Earlier development of Earlier development of drug resistance, if viral drug resistance, if viral suppression is sub suppression is sub optimaloptimal

Limitation of future Limitation of future antiretroviral antiretroviral treatment optionstreatment options

DHHS/USPHS DHHS/USPHS GuidelinesGuidelinesPlasma HIV

Clinical Category CD4 RNA RecommendationSymptomaticSymptomatic

(AIDS, severe symptoms)(AIDS, severe symptoms) AnyAny Any Any TreatTreat

Asymptomatic >200/mm3 & Any Treat 350/mm3

Asymptomatic >350

Asymptomatic >350

Asymptomatic <200/mm3 Any Treat (14%)

Defer (follow closely) ≥100,000

Defer therapy <100,000

Recommended RegimensRecommended Regimens

NON-NON-NUCLEOSIDE NUCLEOSIDE REVERSE REVERSE TRANSCRIPTASETRANSCRIPTASE INHIBITOR INHIBITOR “NON-NUKE”“NON-NUKE”

BOOSTED BOOSTED PROTEASE PROTEASE INHIBITOR INHIBITOR “PI”“PI”

TWO NUCLEOTIDE/NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS “NUKES”

+OR

Nucleoside Reverse Nucleoside Reverse Transcriptase Inhibitors Transcriptase Inhibitors (NRTIs)(NRTIs)

Generic Name

Abbreviation Trade Name Co-Formulation*

Abacavir ABC Ziagen® Trizivir® Epzicom®

ABC+3TC+ZDVABC+3TC

Didanosine ddI Videx®

Emtricitabine FTC Emtriva™ Truvada™ FTC+TDF

Lamivudine 3TC Epivir® Combivir® Epizicom® Trizivir®

3TC+ZDVABC+3TCABC+3TC+ZDV

Stavudine d4T Zerit®

Tenofovir TDF Viread® Truvada™ FTC+TDF

Zalcitabine ddC Hivid®

Zidovudine AZT, ZDV Retrovir® Combivir®

Trizivir®

3TC+ZDVABC+3TC+ZDV

Non-Nucleoside Non-Nucleoside Reverse Transcriptase Reverse Transcriptase Inhibitors (NNRTIs)Inhibitors (NNRTIs)Generic Name Abbreviation Trade Name

Efavirenz EFV Sustiva®

Nevirapine NVP Viramune®

Etravirine TMC125 Intelence®

Protease Inhibitors (PIs)Protease Inhibitors (PIs)Generic NameGeneric Name AbbreviationAbbreviation Trade NameTrade Name

AmprenavirAmprenavir APVAPV AgeneraseAgenerase®®

AtazanavirAtazanavir ATVATV ReyatazReyataz™™

FosamprenavirFosamprenavir F-APVF-APV LexivaLexiva™™

IndinavirIndinavir IDVIDV CrixivanCrixivan®®

Lopinavir +Lopinavir + ritonavir ritonavir LPV/rLPV/r KaletraKaletra®®

NelfinavirNelfinavir NFVNFV ViraceptViracept®®

DarunavirDarunavir TMC114TMC114 PrezistaPrezista®®

RitonavirRitonavir RTVRTV NorvirNorvir®®

Saquinavir hard gel Saquinavir hard gel capsulecapsule SQV-hgcSQV-hgc InviraseInvirase®®

TipranavirTipranavir TPVTPV AptivusAptivus®®

Saquinavir soft gel Saquinavir soft gel capsulecapsule SQV-sgcSQV-sgc FortovaseFortovase®®

Recommended Recommended RegimensRegimens

Two nucleosides:Two nucleosides:– Tenofovir (TDF) & emtricitabine (FTC) Tenofovir (TDF) & emtricitabine (FTC)

[[TruvadaTruvada]]– Zidovudine (AZT) & lamuvidine (3TC) Zidovudine (AZT) & lamuvidine (3TC)

[[EpzicomEpzicom]] PI or NNRTI:PI or NNRTI:

– Lopinavir/ritonavirLopinavir/ritonavir– Atazanavir/ritonavirAtazanavir/ritonavir– Fosamprenavir/ritonavirFosamprenavir/ritonavir– EfavirenzEfavirenz

Nevirapine (only use if CD4<250 in women or Nevirapine (only use if CD4<250 in women or <400 in men)<400 in men)

4 drugs are not better than 3! 4 drugs are not better than 3!

AtriplaAtripla™™

*First 1 pill a day *First 1 pill a day for the complete for the complete treatment of HIVtreatment of HIV

*July 2006*July 2006*Consists of *Consists of

tenofovir, FTC, tenofovir, FTC, and sustivaand sustiva

*$13,800/year*$13,800/year

Medications to Medications to AvoidAvoid in Combinationin Combination AZT & D4T (antagonism)AZT & D4T (antagonism) D4T & DDI (toxicity)D4T & DDI (toxicity) Tenofovir & DDI (Poor CD4 response)Tenofovir & DDI (Poor CD4 response) Tenofovir & abacavir (genetic Tenofovir & abacavir (genetic

fragility)fragility) 3TC & FTC (same mechanism)3TC & FTC (same mechanism) Triple nucleoside regimens Triple nucleoside regimens

(inferiority)(inferiority)

Drug Resistance Drug Resistance TestingTestingIf HIV viral load becomes “detectable” If HIV viral load becomes “detectable” or the patient fails to suppress viral or the patient fails to suppress viral load, obtain resistance testing to guide load, obtain resistance testing to guide therapytherapy– Genotype and/or phenotype testingGenotype and/or phenotype testing

Other indications for genotypic testing:Other indications for genotypic testing:– New “initial” patientsNew “initial” patients

Rising rate of primary resistance (10%)Rising rate of primary resistance (10%)

Mu

tate

d P

osi

tio

n in

th

e H

IV P

rote

ase

Gen

e

Stanford HIV Drug Resistance Database. Available at: http://hivdb.stanford.edu. Accessed July 24, 2006.

High-level resistanceIntermediate resistanceLow-level resistanceContributes to resistanceNo resistanceHypersusceptibilityx

x

x x x x x x

30N48VM

50V50L

82ATFS84VAC

46IL47A

53L54VTAS

24I32I

73CSTA

88S

10IVFR20MRIT

36IV63P

71VTI77I

NFV SQV IDV RTV FPV LPV ATV

54ML23I

76V

88D

47V

Mutations Associated Mutations Associated With With PI ResistancePI Resistance

90M

Adverse Events Adverse Events Associated With Associated With Antiretroviral Antiretroviral TherapiesTherapies

Serious or Potentially Life-Threatening

Events

Events With Potential Long-term

Complications

Events That May Compromise

Quality of Life

• Hepatic events• Lactic acidosis• Hepatic steatosis• Pancreatitis• Stevens-Johnson

syndrome/toxic epidermal necrosis

• Hypersensitivity reaction• Bleeding episodes• Bone marrow suppression• Nephrolithiasis• Nephrotoxicity• Skin rash

• Cardiovascular events• Hyperlipidemia• Insulin resistance/diabetes

mellitus• Osteonecrosis

• Central nervous system events

• Fat maldistribution• Gastrointestinal

intolerance• Peripheral neuropathy

Fat Distribution Fat Distribution ChangesChangesLipohypertrophyLipohypertrophy

Fat Distribution Fat Distribution ChangesChangesLipohypertrophyLipohypertrophy

Fat Distribution Fat Distribution ChangesChangesLipoatrophy of the Lipoatrophy of the faceface

HIV TreatmentHIV Treatment

New therapiesNew therapies

– Novel locations in the life cycle of HIV to inhibit the virus’ Novel locations in the life cycle of HIV to inhibit the virus’ replication (e.g., maturation inhibitors).replication (e.g., maturation inhibitors).

– Penetration into HIV reservoirs: brain, genital area/secretionsPenetration into HIV reservoirs: brain, genital area/secretions

– Possible inducing latently infected cells into the the active cell Possible inducing latently infected cells into the the active cell population (Valproic acid)population (Valproic acid)

VaccinesVaccines

– No supporting data for good efficacy to date for prevention or No supporting data for good efficacy to date for prevention or for the treatment of HIVfor the treatment of HIV

– HIV has many clades and subtypes to cover; in addition, each HIV has many clades and subtypes to cover; in addition, each person has many quasispeciesperson has many quasispecies

Opportunistic Infections – Opportunistic Infections – ProphylaxisProphylaxis

CD4 count <200: Risk for CD4 count <200: Risk for Pneumocystis cariniiPneumocystis carinii pneumonia pneumonia (PCP) (PCP)

– Septra 1 tablet dailySeptra 1 tablet daily

– Also reduces risk for toxoplasmosis, diarrhea, respiratory Also reduces risk for toxoplasmosis, diarrhea, respiratory infections, MRSA, Listeria, Nocardia, etc.infections, MRSA, Listeria, Nocardia, etc.

CD4 count <50: Risk for CD4 count <50: Risk for Mycobacterium aviumMycobacterium avium infections infections

– Azithromycin 5 tablets weeklyAzithromycin 5 tablets weekly

Positive TB skin test: Positive TB skin test:

– INH for 9 monthsINH for 9 months

Prevention of infections slows HIV progression and Prevention of infections slows HIV progression and morbidity/mortality from opportunistic infections!morbidity/mortality from opportunistic infections!

Life ExpectancyLife Expectancy

Life expectancy at age 20 years increased Life expectancy at age 20 years increased from 36 years to 49.4 years (1996 to 2005)from 36 years to 49.4 years (1996 to 2005)– Women had higher life expectancies Women had higher life expectancies – Patients with transmission via injecting drug use Patients with transmission via injecting drug use

had lower life expectancies had lower life expectancies – Life expectancy was lower in patients with lower Life expectancy was lower in patients with lower

baseline CD4 cell counts than in those with higher baseline CD4 cell counts than in those with higher baseline counts (32 years for CD4 cell counts baseline counts (32 years for CD4 cell counts below 100 cells per mL vs. 50 years for counts of below 100 cells per mL vs. 50 years for counts of >>200 cells per mL)200 cells per mL)11

1: Lancet. 2008 Jul 26;372(9635):293-9

Medical Conditions Medical Conditions among HIV Patientsamong HIV Patients

Leading causes of death:Leading causes of death:– Heart DiseaseHeart Disease– Liver/cirrhosisLiver/cirrhosis– CancersCancers– Renal dysfunctionRenal dysfunction

Role of chronic HIV/inflammation vs. ARV side Role of chronic HIV/inflammation vs. ARV side effectseffects

– Suicide/trauma/accidentsSuicide/trauma/accidents Similar problems as the general Similar problems as the general

populationpopulation

PreventionPrevention

For every 1 person on HAART, For every 1 person on HAART,

there are 5 other new infectionsthere are 5 other new infections Prevention is a MUST!Prevention is a MUST! The idea of combining treatment The idea of combining treatment

and prevention strategies realizedand prevention strategies realized

Prevention StrategiesPrevention Strategies

– ABCsABCs AbstinenceAbstinence Be faithfulBe faithful CondomsCondoms

– Early HIV testingEarly HIV testing– Voluntary counseling and testing Voluntary counseling and testing

(VCT)(VCT)– EducationEducation

For both young and oldFor both young and old

– Partner NotificationPartner Notification

Prevention StrategiesPrevention Strategies

– Male CircumcisionMale Circumcision Among men (heterosexual in Africa); still a Among men (heterosexual in Africa); still a

question for women or MSMquestion for women or MSM 60% reduction in HIV acquisition60% reduction in HIV acquisition

Prevention StrategiesPrevention Strategies

– HAART for patients with HIV HAART for patients with HIV Reduces HIV VL and transmissionReduces HIV VL and transmission

– MicrobicidesMicrobicides– Vaccine (future)Vaccine (future)– Universal precautions (PPE)Universal precautions (PPE)– Screening blood supply/organsScreening blood supply/organs– Needle exchange programsNeedle exchange programs– Sperm washing/IVFSperm washing/IVF– STD diagnosis and treatment (e.g. HSV2)STD diagnosis and treatment (e.g. HSV2)

Prevention Strategies - Prevention Strategies - MothersMothers

– MTCT- testing and treatment MTCT- testing and treatment – C-section C-section

Especially if VL >1000 copies/mlEspecially if VL >1000 copies/ml

– Formula vs. breast milkFormula vs. breast milk Avoid mixingAvoid mixing

Post-Exposure Post-Exposure Prophylaxis (PEP)Prophylaxis (PEP) Treatment of a person recently Treatment of a person recently

exposed to HIVexposed to HIV– Best results within first 48-72 hoursBest results within first 48-72 hours– Validated for needle-stick injuries among Validated for needle-stick injuries among

healthcare workershealthcare workers– Guidelines from CDC regarding sexual Guidelines from CDC regarding sexual

exposuresexposures– Typically involves 2-3 HIV drugs for 30 Typically involves 2-3 HIV drugs for 30

days and repeated HIV testing up to 6 days and repeated HIV testing up to 6 monthsmonths

Pre-Exposure Pre-Exposure Prophylaxis (PrEP)Prophylaxis (PrEP)

Not proven in humans to dateNot proven in humans to date Oral tenofovir protected infant macaques against Oral tenofovir protected infant macaques against

SIV infection by oral exposureSIV infection by oral exposure Tenofovir vaginal gelTenofovir vaginal gel

– Safety and tolerability in HIV-infected and HIV-Safety and tolerability in HIV-infected and HIV-uninfected womenuninfected women

Trials under way exploring oral tenofovir (plus FTC) Trials under way exploring oral tenofovir (plus FTC) as pre-exposure prophylaxis against sexual as pre-exposure prophylaxis against sexual transmissiontransmission– Trials among women in Africa and among MSM in the Trials among women in Africa and among MSM in the

developed world underwaydeveloped world underway

SummarySummary

HIV has established itself as the great HIV has established itself as the great pandemic of our timepandemic of our time

With advances in HIV care, HIV is now a With advances in HIV care, HIV is now a chronic disease treated with medicationschronic disease treated with medications– Similar to diabetes, heart disease, etc.Similar to diabetes, heart disease, etc.

““Cocktails” and large number of pills are Cocktails” and large number of pills are things of the past (for the most part)things of the past (for the most part)

Future directionsFuture directions– New medications with less side effects, better New medications with less side effects, better

penetration into reservoir sites, etc are neededpenetration into reservoir sites, etc are needed– A vaccine would be the best, but no effective A vaccine would be the best, but no effective

vaccine is in sight for the near futurevaccine is in sight for the near future

QuestionsQuestions

??