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Virology Treatment CenterVirology Treatment CenterAIDS Consultation ServiceAIDS Consultation Service
Maine Medical CenterMaine Medical Center
Consultation Team
Robert P. Smith, M.D., Medical DirectorSandra Putnam, RN, MSN, Psych/MH NP, FNP, Coordinator
Diane Harris, LCSW, Social WorkerPamela Perkins, RD, NutritionistCindy Boyak, M.D., Psychiatrist
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HIV in 2009HIV in 200933rdrd Decade in the Epidemic Decade in the Epidemic
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World PandemicWorld Pandemic >33 million people living with HIV or AIDS, 67% >33 million people living with HIV or AIDS, 67%
in sub-Saharan Africain sub-Saharan Africa Approximately 2 million deaths in 2007 Approximately 2 million deaths in 2007
(5500/day), 72% in sub-Saharan Africa(5500/day), 72% in sub-Saharan Africa 7400 new infections every day (95% in 7400 new infections every day (95% in
developing countries)developing countries) Fifty percent of adults living with HIV are women Fifty percent of adults living with HIV are women HIV is a disease of young people, 45 % of new HIV is a disease of young people, 45 % of new
infections in ages 15 to 24infections in ages 15 to 24 11-12 million orphans under age 18 in sub-11-12 million orphans under age 18 in sub-
Saharan AfricaSaharan Africa
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U.S. demographicsU.S. demographics
1.1 million people living with HIV1.1 million people living with HIV 53,600 new infections each year 53,600 new infections each year
(incidence rate stable)(incidence rate stable) 73% new infections in men; 27% in women73% new infections in men; 27% in women 45% of new infections in African 45% of new infections in African
Americans; 35% in whitesAmericans; 35% in whites 34% in ages < 30 years34% in ages < 30 years 562,793 deaths from AIDS562,793 deaths from AIDS Death rate dropped 70% post 1996Death rate dropped 70% post 1996
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MaineMaine 1163 cases since 19821163 cases since 1982
71 deaths in 199371 deaths in 1993 10-16 deaths/yr in 2002-200810-16 deaths/yr in 2002-2008
1200-1500 living with HIV; one third don’t 1200-1500 living with HIV; one third don’t know statusknow status
Approx 600 under care and treatment now: Approx 600 under care and treatment now: 86% male; 13% female86% male; 13% female
MSM – 61.2% of cases over-all; 64% of new MSM – 61.2% of cases over-all; 64% of new cases 2008cases 2008
IDU – 12.3%IDU – 12.3% Heterosexual – 9.3%Heterosexual – 9.3% Growing number of STD’s and new HIV cases, Growing number of STD’s and new HIV cases,
esp. in MSM pop. bet. ages of 25-40.esp. in MSM pop. bet. ages of 25-40.
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Maine STD Prevalence:Maine STD Prevalence:Danger signsDanger signs
GonorrheaGonorrhea YTD 2008: 78YTD 2008: 78 AVG. YTD totals, 2004-2008: 72 AVG. YTD totals, 2004-2008: 72
ChlamydiaChlamydia YTD 2008: 1428YTD 2008: 1428 AVG. YTD totals, 2004-2008: 1251AVG. YTD totals, 2004-2008: 1251
SyphilisSyphilis YTD 2008: 9YTD 2008: 9 Avg. YTD totals 2001-2008: 6Avg. YTD totals 2001-2008: 6
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Milestones of HIV Milestones of HIV TreatmentTreatment
1981 – first cases of AIDS reported1981 – first cases of AIDS reported 1985 – HIV antibody test1985 – HIV antibody test 1987 – AZT approved (11987 – AZT approved (1stst antiviral) antiviral) 1987-early 1990’s: more antiviral (NRTI) 1987-early 1990’s: more antiviral (NRTI)
agents (ie., DDI, D4T, 3TC); OI treatments agents (ie., DDI, D4T, 3TC); OI treatments improvedimproved
1996 – Vancouver Conference – PI’s in 1996 – Vancouver Conference – PI’s in combo: use of 3 drugs to treat HIV combo: use of 3 drugs to treat HIV becomes standard of care: virus is becomes standard of care: virus is controlledcontrolled
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Milestones continuedMilestones continued
1996-2008 - Continuing drug 1996-2008 - Continuing drug research: 6 classes of drugs now research: 6 classes of drugs now approved; 23 individual agentsapproved; 23 individual agents
Vaccine trials still not successful, Vaccine trials still not successful, but some hope with newest trial but some hope with newest trial from Thailand (use of 2 early from Thailand (use of 2 early vaccines together gave 30% vaccines together gave 30% immunity over 3 years)immunity over 3 years)
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Where and How Did HIV Where and How Did HIV Arise?Arise?
Molecular epidemiology:Molecular epidemiology: HIV-1….SIVcpzHIV-1….SIVcpz HIV-2….SIVsmHIV-2….SIVsm
Emergence of HIV-1 in humans:Emergence of HIV-1 in humans: Time frame (1914-1941)Time frame (1914-1941) Where: Central AfricaWhere: Central Africa How?? Bushmeat trade (likely)How?? Bushmeat trade (likely)
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HIV/AIDS:HIV/AIDS:What is the Difference?What is the Difference?
HIV: A viral infection causing gradual HIV: A viral infection causing gradual depletion of T4 lymphocytes (a key depletion of T4 lymphocytes (a key WBC) by using them for replication and WBC) by using them for replication and in the process killing themin the process killing them
AIDS: A diagnosis given when T4 count AIDS: A diagnosis given when T4 count reaches 200 (normal is 1000), defined reaches 200 (normal is 1000), defined by CDC as point where Opportunistic by CDC as point where Opportunistic Infections are likely to occurInfections are likely to occur
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How Does HIV Harm the How Does HIV Harm the Human Immune System?Human Immune System?
The Virus…….The Virus…….
It is a Pretty ‘SMART’ Virus: well It is a Pretty ‘SMART’ Virus: well packaged to replicate!packaged to replicate!
RNA genetic material: needs cell DNA RNA genetic material: needs cell DNA to replicateto replicate
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The Irony……The Irony……
Our immune system tries to Our immune system tries to ‘remember’ HIV infection by ‘remember’ HIV infection by scooping up pro-viral DNAscooping up pro-viral DNA
BUT: These long-lived memory T-BUT: These long-lived memory T-cells that hold pro-viral DNA live for cells that hold pro-viral DNA live for 40-60 yrs.40-60 yrs.
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Viral DynamicsViral Dynamics
Avg. total HIV viron production per day:Avg. total HIV viron production per day:
10 billion RNA strands10 billion RNA strands
Avg. life span of infected T cell: 2.2 daysAvg. life span of infected T cell: 2.2 days
Min. duration of HIV life cycle: 1.2 daysMin. duration of HIV life cycle: 1.2 days
Avg. HIV generation time: 2 daysAvg. HIV generation time: 2 days
Memory T cells can live for 40- 60 yearsMemory T cells can live for 40- 60 years
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Summary of Viral Summary of Viral DamageDamage
HIV uses T4 Lymphocyte to make more HIV uses T4 Lymphocyte to make more of itselfof itself
HIV virus carries with it the enzymes it HIV virus carries with it the enzymes it needs to replicateneeds to replicate
The meds we use to slow the virus either The meds we use to slow the virus either block its entry into the T4 cell or block block its entry into the T4 cell or block the use of the enzymes it needs to break the use of the enzymes it needs to break itself down, insert itself into the T4 DNA, itself down, insert itself into the T4 DNA, or reassemble itself to bud out new or reassemble itself to bud out new vironsvirons
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As of today, we have nothing that As of today, we have nothing that can kill HIV or completely rid the can kill HIV or completely rid the body of it’s presencebody of it’s presence
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Summary continuedSummary continued
In going through this replication In going through this replication process, the virus damages the T4 process, the virus damages the T4 lymphocyte and it dies.lymphocyte and it dies.
The virus has amino acids on its The virus has amino acids on its surface which can mutate rapidly to surface which can mutate rapidly to provide resistance to drugs.provide resistance to drugs.
Therefore, adequate drug levels are Therefore, adequate drug levels are essential to keep replication from essential to keep replication from occurringoccurring
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PRIMARY HIVPRIMARY HIV
Usually within 2-4 weeks of getting the virus; lasts Usually within 2-4 weeks of getting the virus; lasts 2-4 weeks2-4 weeks
HIV Viral Load usually very high; at greatest risk HIV Viral Load usually very high; at greatest risk for transmissionfor transmission
Negative mono-spot and symptomaticNegative mono-spot and symptomatic
Indeterminant or negative HIV serology or recent Indeterminant or negative HIV serology or recent seroconversionseroconversion
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Acute HIV Acute HIV Syndrome/Primary HIV:Syndrome/Primary HIV:
A Flu-like illnessA Flu-like illness FeverFever Sore throatSore throat Swollen lymph nodesSwollen lymph nodes RashRash HeadacheHeadache Arthralgias/myalgiasArthralgias/myalgias Lethargy/malaiseLethargy/malaise Anorexia/weight lossAnorexia/weight loss Nausea/vomiting/diarrheaNausea/vomiting/diarrhea
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Diagnosis of HIV DiseaseDiagnosis of HIV Disease
Blood Test: (Gold Standard): ANTIBODY TESTBlood Test: (Gold Standard): ANTIBODY TEST --ELISAELISA for screening for screening -Western Blot-Western Blot for confirmation of (+) test for confirmation of (+) test -99% sensitive and 97% specificity-99% sensitive and 97% specificity
Rapid Tests: Saliva, blood, mucus membranesRapid Tests: Saliva, blood, mucus membranes ELISA ONLYELISA ONLY
-OraQuick HIV-1-OraQuick HIV-1 -OraSure Test -OraSure Test -Still needs Western Blot confirmation if (+)-Still needs Western Blot confirmation if (+) HIV RNA PCRHIV RNA PCR -Only used in acute viral syndrome; to test newborns born -Only used in acute viral syndrome; to test newborns born
to HIV + mothersto HIV + mothers
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Monitoring Monitoring Disease Disease
ProgressionProgression
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Essential LabsEssential Labs
HIV-1 RNA Viral loadHIV-1 RNA Viral load Ultrasensitive (<48 - >1 million Ultrasensitive (<48 - >1 million
copies/ml)copies/ml)
CD4/T4 Lymphocyte CountCD4/T4 Lymphocyte Count Normal=1000Normal=1000 AIDS dx. at 200AIDS dx. at 200
HIV RNA GenotypeHIV RNA Genotype
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Viral LoadViral Load
Highest in initial infectionHighest in initial infection
Patient’s ‘set point’ determines Patient’s ‘set point’ determines risks/rate of progression of infectionrisks/rate of progression of infection
Key to monitoring effectiveness of Key to monitoring effectiveness of antiviral therapiesantiviral therapies
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T4 Lymphocyte CountT4 Lymphocyte Count
Normal Count approx. 1000Normal Count approx. 1000
On average, with HIV lose approx. On average, with HIV lose approx. 50-100 cells a year (production vs. 50-100 cells a year (production vs. destruction)destruction)
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HIV Virus MutationHIV Virus Mutation
Occurs with every viral life cycleOccurs with every viral life cycle
Involves shifts in amino acid Involves shifts in amino acid condons on the viruscondons on the virus
Can be transmittedCan be transmitted Occur in the presence of drug if Occur in the presence of drug if
levels not adequatelevels not adequate
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Goals of Treatment: Viral Goals of Treatment: Viral SuppressionSuppression
Viral SuppressionViral Suppression
Preserve /improve immune function: Preserve /improve immune function: Increase in T4 cell Increase in T4 cell count/strengthen immune functioncount/strengthen immune function
Delay/abort disease progressionDelay/abort disease progression
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No Cure: Just Viral No Cure: Just Viral Suppression: Then Suppression: Then
Improved Immune FunctionImproved Immune Function All the drugs control viral replication: All the drugs control viral replication:
They DO NOT KILL HIV They DO NOT KILL HIV
By suppressing virus, allows immune system By suppressing virus, allows immune system to recover, make naïve T4 lymphocytesto recover, make naïve T4 lymphocytes
But ONLY if drugs taken exactly rightBut ONLY if drugs taken exactly right
EVERY DAY, EVERY DOSEEVERY DAY, EVERY DOSE
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Problems With Low T4 Problems With Low T4 Lymphocyte CountsLymphocyte Counts
<200 : AIDS Diagnosis<200 : AIDS Diagnosis Susceptibility to Opportunistic Susceptibility to Opportunistic
Infections:Infections: PCPPCP MAIMAI ToxoToxo ThrushThrush Skin rashesSkin rashes CancersCancers
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The Antiviral MedicationsThe Antiviral Medications
Where and How They WorkWhere and How They Work
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Classes of HIV Antiviral Classes of HIV Antiviral DrugsDrugs
Reverse Transcriptase Inhibitors: Reverse Transcriptase Inhibitors: RTIsRTIs
Nucleoside analogs/Nucleotide analogsNucleoside analogs/Nucleotide analogs
Non-nucleoside analogsNon-nucleoside analogs
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Antiviral Drugs cont’dAntiviral Drugs cont’d
Protease InhibitorsProtease Inhibitors
Fusion InhibitorsFusion Inhibitors
Entry InhibitorsEntry Inhibitors
Integrase InhibitorsIntegrase Inhibitors
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When Treatment Is When Treatment Is StartedStarted
CD4 Count ~350CD4 Count ~350 Viral load >50,000Viral load >50,000 SymptomaticSymptomatic
Post-occupational exposurePost-occupational exposure Post-sexual exposure ??Post-sexual exposure ?? Pre-sexual exposure ??Pre-sexual exposure ??
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What Meds to Take?What Meds to Take?
STANDARD of CARE:STANDARD of CARE:
3 antivirals at all times3 antivirals at all timesUse of at least 2 classesUse of at least 2 classes
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Problems With HIV Problems With HIV AntiviralsAntivirals
Drug/drug interactionsDrug/drug interactions (Cytochrome P- (Cytochrome P-
450 interactions)450 interactions)
Multiple drug Multiple drug side effects/toxicitiesside effects/toxicities: :
vary from person to personvary from person to person
Need for nearly Need for nearly perfect adherenceperfect adherence
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Monitoring Antiviral Monitoring Antiviral TherapyTherapy
- ADHERENCE - ADHERENCE
- CD4 and Viral Load - CD4 and Viral Load 3-4 wks after start therapy3-4 wks after start therapy Every 4-8 weeks until undetectableEvery 4-8 weeks until undetectable Every 3 months after stabilizationEvery 3 months after stabilization
- RESISTANCE TESTIING- RESISTANCE TESTIING
At diagnosisAt diagnosis
With viral reboundWith viral rebound
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Assessing ResistanceAssessing Resistance
GenotypeGenotypeEssential to target correct antiviralsEssential to target correct antivirals
PhenotypePhenotype
Used for difficult resistance Used for difficult resistance decisionsdecisions
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HIV Antiviral Side Effects:HIV Antiviral Side Effects:These are not unsafe These are not unsafe
medications!medications! Lactic AcidemiaLactic Acidemia Lipid abnormalitiesLipid abnormalities
Triglycerides/CholesterolTriglycerides/Cholesterol Glucose intolerance/Insulin Glucose intolerance/Insulin
ResistanceResistance Body fat composition abnormalitiesBody fat composition abnormalities
LipodystrophyLipodystrophy LipoatrophyLipoatrophy
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More Side Effects:More Side Effects:Neurologic ComplicationsNeurologic Complications
CNS opportunistic infectionsCNS opportunistic infections ToxoplasmosisToxoplasmosis Cryptococcal meningitisCryptococcal meningitis
Primary CNS lymphomaPrimary CNS lymphoma Progressive multifocal Progressive multifocal
leukoencephalopathy (PML)leukoencephalopathy (PML) Peripheral neuropathy (15-50%)Peripheral neuropathy (15-50%) Myelopathy (degeneration of nerves Myelopathy (degeneration of nerves
in spinal cord (22-55%)in spinal cord (22-55%)
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Other Complication:Other Complication:
Hepatitis C Co-infectionHepatitis C Co-infection Hepatitis B Co-infectionHepatitis B Co-infection TBTB CancersCancers GI disturbancesGI disturbances Cardiac IssuesCardiac Issues OsteoporosisOsteoporosis
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Why Do We Still See AIDS Why Do We Still See AIDS in the US a Decade Post in the US a Decade Post
HAART??HAART?? ““Late testers”: 40% present with AIDS Late testers”: 40% present with AIDS
Inability to adhere to antiviral Inability to adhere to antiviral regimens (for whatever reason: regimens (for whatever reason: denial, psychiatric disease, substance denial, psychiatric disease, substance abuse, chaotic lives, etc.)abuse, chaotic lives, etc.)
Development of multi-resistant HIVDevelopment of multi-resistant HIV
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New Testing GuidelinesNew Testing Guidelines
CDC New Testing Guidelines:CDC New Testing Guidelines: Routine testing adults ages 13-64Routine testing adults ages 13-64 Annual testing in those at riskAnnual testing in those at risk ““Opt out” provision: implied consent vs. Opt out” provision: implied consent vs.
written informed consentwritten informed consent
Rapid Diagnostic Tests: 4 approvedRapid Diagnostic Tests: 4 approved ““Point of care”Point of care” Home testingHome testing
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Continuing HIV Treatment Continuing HIV Treatment ChallengesChallenges
20092009 Must be continued indefinitelyMust be continued indefinitely Must be adhered to at a high levelMust be adhered to at a high level Requires 3 active agentsRequires 3 active agents Significant side effects may occurSignificant side effects may occur Drug interactions are commonDrug interactions are common Drug resistance is commonDrug resistance is common Co-infections (Hep B/C, TB) are common Co-infections (Hep B/C, TB) are common
and complicate treatmentand complicate treatment
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Biggest ChallengeBiggest Challenge
Belief that YOU are not at RiskBelief that YOU are not at Risk
Therefore, NOT GETTING TESTEDTherefore, NOT GETTING TESTED
GOAL: Everyone be “Safe”GOAL: Everyone be “Safe” GET TESTEDGET TESTED
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HIV Is Here To Stay…..HIV Is Here To Stay…..
PREVENTIONPREVENTION of Transmission
is the ONLY WAY !!!!