Upload
peter-cook
View
220
Download
0
Tags:
Embed Size (px)
Citation preview
31st Annual Winter Update
Indiana Osteopathic Association
December 7, 2012
Indianapolis, IN
Outline History Epidemiology Transmission Natural History Testing Recommendations Diagnosis Clinical Manifestations Treatment Health Maintenance Hot Topics
Pre-exposure prophylaxis (PrEP)Post-exposure prophylaxis (PEP)
June 5, 1981: MMWR published 5 cases of PCP
in homosexual men from California
July 3, 1981: 26 additional cases
Dec 10, 1981: 3 NEJM papers describe cases
41 cases Kaposi’s Sarcoma (KS)
GRID = Gay-related Immune Deficiency
20 states with disease
AIDS = Acquired ImmunoDeficiency Syndrome
Hemophiliacs died
1292 of 3064 people died
James Mason isolated LAVRobert Gallo isolated HTLV-III
First test to identify HIV antibodies developed
July 1981
1982
June1982
July1982
Dec1982
1983
April1984
March1985
1985
Rock Hudson died of AIDS
50% of hemophiliacs infected
Surgeon General’s first report on AIDS
FDA approved first drug (AZT)
Ryan White died
FDA approved second drug (ddI)
1985
1986
1986
March1987
April1990
1991
1986 Drug trials begin (ACTG)
1988 45,000/83,000 patients had died
Ryan White CARE Act passed
AZT reduces MTCT
2 drugs are better than 1
HAART in use (3+ drugs)
DHHS guidelines recommend initiation of ART for CD4 <500
New hope for HIV prevention (PrEP)
1990
1994
1994
1996
2009
2010+
1995 First HIV viral load testing
2006 First one pill once daily regimen approved
8
0
5
10
15
20
25
30
35
40
1995 1996 1997 1998 1999 2000 2001
Dea
ths
per
100
per
son
-yea
rs
0
25
50
75
100 Percen
tage o
f patien
t-days o
n A
RT
DEATHS
USE OF ART
Mortality vs. ART utilization
Courtesy: AETC
AIDS Mortality Rates: 1995-2001
Adult HIV Prevalence, 2010
Courtesy: UNAIDS
Courtesy: UNAIDS
Courtesy: UNAIDS
Changes in HIV Incidence, 2001-2010
Epidemiology – Worldwide 34 million living with HIV / AIDS
~2/3 in Sub-Saharan Africa, mostly heterosexual60% unaware of being infected7,000 new infections each day (2.5 million/yr)
○ 900 of these are children < 15 yo○ 47% in women○ 39% in young people (15-24)○ African Americans 8x rate of HIV cases compared
to whites1.7 million died in 2011
Only 25% are receiving treatment !!
www.unaids.org
Epidemiology – U.S. 1,180,000 HIV+ (1 in 200)
20% undiagnosed488,000 living w/ AIDS21,000 die each yr
50,000 newly infected each yr61% MSM1 of every 5 homosexual urban males HIV+1 of every 22 African Americans will be
infected
Incidence in Washington D.C. is 3%!
Epidemiology – U.S.
Only 1 of 5 have undetectable virus -> (close to) non-contagious.
Over 800,000 have detectable virus -> CONTAGIOUS!
Individuals unaware of their HIV+, particularly those recently infected, are major contributors to the ongoing epidemic
Epidemiology – Indiana Persons living with HIV/AIDS in Indiana
as of June, 30, 2012Total = 10,420
○ 80% Male (8,388)○ 20% Female (2,032)
Race/Ethnicity of HIV patients53% White (5,541) 0.1% infected36% Black (3,764) 0.6% infected7% Hispanic (780) 0.2% infected
Spotlight on HIV/STD/Viral Hepatitis, Indiana Semi-Annual Report, June 2012: http://www.in.gov/isdh/files/At_A_Glance-Dec.pdfIndiana IN Depth Profile. http://www.stats.indiana.edu/c2010/dp1/FactfinderINandUS.pdf
HIV Transmission/Acquisition Found in blood, semen, or vaginal fluid of an
infected person
HIV is transmitted/acquired by:Having sex (anal, vaginal, or oral) with someone
infected with HIVSharing needles, syringes with someone who has
HIVExposure (in the case of infants) to HIV before or
during birth, or through breast feeding
Probability of HIV Transmission
INFECTION ROUTE RISK OF INFECTIONSexual IntercourseMale-to-male transmission 1 in 10 - 1 in 1,600Male-to-female transmission 1 in 200 - 1 in
2,000Female-to-male transmission 1 in 700 - 1 in
3,000
Transmission from mother to infantWithout AZT 1 in 4With AZT Less than 1 in 10With HAART 1-2 in 100
OtherTransfusion of infected blood 95 in 100Needle stick 1 in 250Needle sharing 1 in 150
Royce, et al
Natural History
Acute Infection (days to weeks) Partial Control of HIV (weeks to months) Asymptomatic HIV Infection (1-10+
years) Symptomatic HIV Infection & AIDS
(years)
1200
1100
1000
900
800
700
600
500
400
300
200
100
0
10E7
10E6
10E5
10E4
10E3
Weeks Years0 3 6 9 1 2 3 4 5 6 7 8 9 10 1112
CD
4 T
Cel
ls/m
m3
Vire
mia
(co
pies
/mL
plas
ma)
Primaryinfection
Possible acute HIV syndromeWide dissemination of virusSeeding of lymphoid organs
Clinical latency
Death
Opportunisticdiseases
Constitutionalsymptoms
Natural History of HIV Infection
CD4 Lymphocyte Count
Reflects immune status Normal CD4 count: 500 - 1,500 cells/mm3 CD4 count decreases as HIV disease
progresses CD4 counts differ daily Overall trend of CD4 counts over time
most important
CD4 < 200 = AIDS (or opportunistic infection)
HIV Viral Load
Number of HIV RNA copies per mL of blood
“High” viral load: 5,000 to >1,000,000 copies High reproduction rateDisease will progress faster
“Low” viral load: 200 to 500 copies Low reproduction rateRisk of disease progression is low
“Undetectable” viral loads: <50 or <400Below the threshold needed for detection
2006 CDC HIV Testing Recommendations
CDC Testing Guidelines, 2006 Offer routine testing in all health care
settings to:13- to 64-year-olds
Anyone with Tuberculosis (TB)
All patient seeking treatment for STDs
All pregnant females
Any health care worker exposed to blood or body fluids
Anyone who requests testing
CDC Testing Guidelines, 2006
Who should be tested at least annually?IVDA and their sex partnersPersons who exchange sex for money or
drugsSex partners of HIV-infected personsPersons with multiple sex partners
Why emphasize early diagnosis? Individuals unaware of their HIV+,
particularly those recently infected, are major contributors to the ongoing epidemic
Earlier treatment: Lowers mortality
○ “Delayed Therapy” group (<500) had 94% higher mortality!* Decreases risk of transmission by 96%** May improve immune system by (partially) restoring CD4
count more towards normal May lower long-term complications associated w/
inflammation (though biomarkers of inflammation may never return to normal )
*Kitahata et al **Cohen et al
Diagnosis Screening: ELISA antibody (or other rapid
tests) Now recommended to be part of routine medical care
(yearly if high risk) Time to + : ~ 3 wks Newer assays may detect infection as early as 10 - 14
days; still, very early infection will not be detectable
Confirmation: Western Blot Time to + : ~4-5 weeks Any two: p24, gp41, gp120/160 -> positive One + band, or other + bands -> “indeterminate”
○ Either wait and repeat, or obtain quantitative assay for HIV by PCR = “viral load”
Some causes of False-Negative HIV Antibody Tests Acute HIV Infection
Advanced HIV Infection
Antiretroviral Therapy
Some causes of False-Positive HIV Antibody Tests Liver Disease Autoimmune Disorders CKD/ESRD Congenital bleeding disorders Recent Infection with dengue, malaria,
hepatitis B, leprosy Immunizations
Diagnosing Acute HIV: Window Period
Window Period = Time between infection and detectable HIV antibodiesWindow Period = Time between infection and detectable HIV antibodies
Courtesy: AETC
Diagnosing Acute HIV: Acute HIV
Acute HIV = patients may present with acute retroviral syndrome/illnessAcute HIV = patients may present with acute retroviral syndrome/illness
Acute HIV
Laboratory Diagnosis of Acute HIV
Acute HIV
• Positive HIV-1 RNA Assay• Negative HIV Antibody Test
• Positive HIV-1 RNA Assay• Negative HIV Antibody Test
Course of HIV Infection Chronic and progressive infection
Acute Retroviral Syndrome (Acute Infection)Flu-like symptoms Period of active viral replicationHIV Ab levels may be below the limit of detection
(negative ELISA), however the patient is HIGHLY CONTAGIOUS!
Acute Retroviral Syndrome
80 - 90% with acute HIV infection report symptoms consistent with acute retroviral syndrome“Mononucleosis-like” syndrome
Onset of symptoms typically 2-4w after exposure
Median duration of symptoms is 2 weeks
Fever (96%), adenopathy (74%), pharyngitis (70%), rash (70%), myalgia (59%), night sweats (50%), thrombocytopenia (45%), leukopenia (45%), diarrhea, headache
May also present as “aseptic/viral meningitis”
Acute Retroviral Syndrome Most acutely infected patients seek
medical attention
This syndrome may be missed in up to 75% of presenting patients
HIV antibody levels usually negative Check HIV RNA PCR
Course of HIV Infection Asymptomatic Phase (6 months - >10 years)
Host immune response controls viral replicationCD4 cell count gradually declines
Symptomatic PhaseHost immune response begins to waneCD4 cell count < 500 cells
○ Bacterial pneumonia, thrush, vaginal candidiasis, shingles, oral leukoplakia
CD4 cell count < 200 cells○ Opportunistic infections
Pneumocystis jirovecii pneumonia, CMV retinitis, Candida esophagitis, Toxoplasma encephalitis, Histoplasmosis, Cryptococcal meningitis, MAC, lymphoma, etc
CD4 Count & Risk of Clinical Disease
Clinical Findings in HIV Infection General
Generalized LAD
Thrombocytopenia (ITP)
Elevated total protein
DermatologicSeborrheic dermatitis
Zoster (shingles)
Superficial fungal infections
Warts
Eosinophilic folliculitis
MucocutaneousOropharyngeal candidiasisOral or genital herpesGingivitis/peridontitisOral Hairy Leukoplakia
RespiratoryRecurrent sinusitis
Community acquired pneumonia
Tuberculosis
Images courtesy of: AIDS Images Library www.aidsimages.ch
Images courtesy of: AIDS Images Library www.aidsimages.ch
Other clues to possible HIV Unusual presentation of a common illness
Pneumococcal pneumonia w/ bacteremia in a young person
Salmonella, shigella, campylobacter bacteremia
Presentation of an unusual illnessMore advanced/severe dx than expectedUnusual age for illness
TB, especially w/ unusual presentation Other STDs
Other clues to possible HIV Common complaints
Persistent fatigue, recurrent fevers, chills/night sweats, persistent diarrhea, weight loss
Routine lab abnormalitiesLeukopenia (low WBC)Lymphopenia (low lymphocytes)Thrombocytopenia (low platelets)Mild transaminitisElevated protein
Goals of HIV Therapy Maximal and durable suppression of viral load
– reduces the risk of disease progression Restoration and/or preservation of
immunologic function Improvement in quality of life Reduction in HIV-related morbidity and
mortality Prevent vertical transmission of HIV
Over 90% of HAART Regimens PI Based100
80
60
40
20
0
35
30
25
20
15
10
5
0
1994 1995 1996 1997 1998 1999
HOPS: Mortality and Frequency HOPS: Mortality and Frequency of HAART Useof HAART Use
Dea
ths
per
100
pers
on-y
ears Deaths
Use of HAART
HA
AR
T, % patient-days
Palella. N Engl J Med 1998;338:853. Update: Palella. Personal Communicat ion, 1999.
When to Treat?* Symptomatic, or “AIDS-defining” illness CD4 at 500 or less Pregnancy HIV-associated nephropathy (to preserve kidney
function) Active hepatitis B co-infection (10% of U.S. HIV+) HIV RNA > 100,000 copies/mL High risk for secondary transmission Age > 50
*March 27, 2012 - NIH Guidelines for the use of Antiretroviral Agents in HIV-1 Infected Adults and Adolescents
When to Treat?*
When circumstances permit, offer to ALL individuals, regardless of CD4 count
*Thompson et al.
Predictors of Inadequate Adherence Regimen complexity & pill burden Poor clinician-patient relationship Active drug use or alcoholism Unstable housing Mental illness Lack of patient education Medication adverse effects Fear of medication adverse effects
Current Treatment Options 31 drugs currently
6 classes
Now 3 options for 1 pill once dailyAtripla ®Complera ®Stribild ®
Treatment
Benzodiazepines Antidepressants Anticonvulsants Rifampin OCPs
Statins Erectile dysfunction
agents Antifungals Acid reducers Nasal steroids
Common drug interactions with HAART to consider:
Health Maintenance
ImmunizationsInfluenza Annually (IM route)Pneumovax (entry into care and 5 years
later)Hepatitis A vaccine seriesHepatitis B vaccine seriesTdap/Td
Annual PPD/quantiferon
CDC. 2011 ACIP Guidelines
Health Maintenance
Immunizations to AVOID:Live vaccines to avoid:
○ Intranasal Influenza vaccine○ Smallpox○ OPV (no longer available in U.S.)○ BCG
May be ok if CD4 >200 and pt asymptomatic:○ MMR○ Varicella○ Zoster
CDC. 2011 ACIP Guidelines
Health MaintenancePatients trust their primary care providers. Your support of is
critical in keeping HIV patients healthy.
You can:• Manage co-morbid conditions (Diabetes, Cardiovascular Health)• Provide routine preventative care – (PAPs, Immunizations, Colonoscopy,
etc..)• Encourage routine dental and vision care• Provide support messages about reducing tobacco use, EtOH use and/or
other drug use• Drive home the importance of proper diet, exercise and rest• Promote “Safer Sex” prevention practices• Support adherence (meds and follow-up with ID)• Provide emotional support, recommend counseling if needed• Referral to local AIDS service organizations: Damien Center, Concord
Center, Step-Up, etc
You are the Experts!
Pre-Exposure Prophylaxis (PrEP) In PrEP, an HIV uninfected individual
takes antiretroviral medication (oral or topical) ahead of ongoing HIV exposures. By having these medications in the bloodstream/tissues, HIV may be unable to establish infection.
Pre-Exposure Prophylaxis (PrEP)
Select, high-risk circumstancesOnce daily Truvada ®
(FTC/TDF)75+% effective among those w/
detectable drug levelsControversial ExpensiveSee Truvada.com
○ Includes a 17-point check list, agreement form, training guide, etc
Pre-Exposure Prophylaxis (PrEP) Vaginal gel (Tenofovir)
Initial study (CAPRISA 004) showed it to be >50% effective when used regularly*
Also showed decreased genital herpes transmission
Less effective in other studiesMore studies ongoingNot yet ready for “Prime Time”
*Karim et al.
Post-Exposure Prophylaxis (PEP) Needle stick
Determine status of both source and patient at baseline if possible for:○ HIV, HBV, HCV, RPR
If source is HIV positive, ideally treatment should be started within 2 hours (72 hours max)○ Treatment continued for 28 days○ Choice of regimen complex, based on many
factors (typically 3 drugs)○ Post Exposure Prophylaxis (PEP) hotline:
1-888-448-4911 (24 hours a day)
Post-Exposure Prophylaxis (PEP) Needle stick (cont’d)
Risk of transmission is 1 in 300 (0.3%)○ Highly correlated with viral load
Close monitoring of patient while on PEP○ Weekly visits
Rechecking labs up until 6-12 months post exposure○ 6 weeks, 3 months, 6 months, 12 months
Post-Exposure Prophylaxis (PEP) Sexual encounter
May be unable to determine source patient status
Risk of transmission dependent on sexual act (0.01-0.5%)
If felt to be a high risk situation, may decide to start PEP○ Check baseline status on patient○ Start PEP within 72 hours (3 drug regimen)○ Monitor closely (weekly appts)
Continued f/u for 6-12 months after exposure
Summary
20-25% of HIV infected individuals do not know they are infected
Test often, treat early Effective treatment can:
Reduce risk of transmission to near zero!Better long term survival
HIV is evolving into a chronic disease, PCPs play a prominent role in overall health
References http://www.aidsetc.org http://www.aidsinfo.nih.gov http://www.unaids.org Spotlight on HIV/STD/Viral Hepatitis, Indiana Semi-Annual Report, June 2012:
http://www.in.gov/isdh/files/At_A_Glance-Dec.pdf Indiana IN Depth Profile. http://www.stats.indiana.edu/c2010/dp1/FactfinderINandUS.pdf Royce, et al. NEJM 336:1072-1078, 1997 CDC. Revised guidelines for HIV counseling, testing, and referral. MMWR 2006;55[No. RR-14]:1-
17 CDC. General Recommendations on Immunization. Recommendations of the Advisory Committee
on Immunization Practices (ACIP). MMWR January 28, 2011;60 (RR02); 1-60 Thompson et al. Antiretroviral Treatment of Adult HIV Infection. JAMA 2012;308: 387-402 Kitahata M et al, NEJM 2009; 360:1815-26 Cohen et al. Medical Progress: Acute HIV Infection. NEJM 2011;364:1943-54 Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of
antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. March 27, 2012. Available at http://aidsinfo.nih.gov/Guidelines/HTML/1/adult-and-adolescent-arv-guidelines/0
Interim Guidance for Clinicians Considering the Use of Preexposure Prophylaxis for the Prevention of HIV Infection in Heterosexually Active Adults. MMWR. August 10, 2012 / 61(31);586-589
Q Abdool Karim et al. Science 2010;329:1168-1174 Grant R et al, N Engl J Med 2010;363:2587-99