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HIV IIIPrevention of HIV infection
Allison Liddell, MD
Monday, January 24th, 2005
HIV Curriculum
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HIV I-Diagnosis and HAART
HIV II-Complications of HIV/AIDS
HIV III-Prevention of HIV infection
HIV history
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Date of first published
case?
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June 5, 1981
MMWR
five cases of PCP among
previously healthy young
men in
What city?
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Los Angeles. All of the men
were described as
"homosexuals"; two had
died.
Who wrote it?
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Where?
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Local clinicians and the
Epidemic Intelligence
Service (EIS) Officer
stationed at the Los
Angeles County
Department of Public
Health
editorial note stated that
the histories suggested a
"cellular-immune
dysfunction related to a
common exposure" and a
"disease acquired
through sexual contact."
HIV history
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CDC's investigation drug unit, the sole
distributor of pentamidine, the therapy for PCP,
began to receive requests for the drug from
physicians also to treat young men
June 1981, CDC developed an investigative
team
Within 18 months, epidemiologists conducted
studies and prepared MMWR reports that
identified all of the major risks factors for
acquired immnodeficiency syndrome (AIDS).
HIV Prevention
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CDC initiative: Advancing HIV Prevention: New
Strategies for a Changing Epidemic
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reducing barriers to early diagnosis
increasing access to quality medical care, treatment
ongoing prevention services
emphasizes the use of proven public health approaches
to
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appropriate routine screening
identification of new cases
partner counseling and referral
increased availability of sustained treatment
prevention services for the infected
Barrier Methods. Do they work?
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must be used correctly
and consistently
Latex condoms are highly
effective in preventing
transmission of HIV. Well
documented.
reduce the risk of other
STDs
associated with a lower
rate of cervical cancer, an
HPV-associated disease.
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condoms lubricated with
spermicides are no more
effective
epidemiologic studies of STDs,
other than HIV, are
characterized by
methodological limitations
inconclusiveness of
epidemiologic data about
condom effectiveness for
other STDs indicates that more
research is needed--not that
latex condoms do not work
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Epidemiologic studies that are conducted in
real-life settings, where one partner is infected
with HIV and the other partner is not,
demonstrate conclusively that the consistent use
of latex condoms provides a high degree of
protection.
Vertical Transmission
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91% of all AIDS cases reported among U.S.
children
February 1994 PACTG Protocol 076
documented that ZDV chemoprophylaxis could
reduce perinatal HIV-1 transmission by nearly
70%
transmission rates can be reduced to less than
2% (Cooper 2002) compared with approximately 25%
when no interventions are given (Connor 1994).
Results of ACTG 076
30
66% reduction in risk
for transmission (P =
<0.001)
20
22.6
%
10
Placeb
o
Efficacy observed in all
subgroups
7.6
% Group
ZDV
Vertical Transmission
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perinatally acquired AIDS cases declined 90% in the US during
1992-2000 (912 cases to 90 cases) CDC unpublished data
Lifetime treatment cost for perinatally infected infants $51.8$68.5 million
 assumes 280-370 perinatal infections per year
 lifetime cost of $185,000 per infant (Mrus 2004).
90% of mothers were voluntarily tested for HIV before birth for
1999-2001.
79% of HIV-infected women and infants received antiretroviral
therapy prenatally
77% at labor/delivery
92% neonatally
8% of the HIV-infected pregnant women identified had not
received prenatal care (CDC 2004).
Another study concluded that approximately 14% of HIVinfected pregnant women do not receive any prenatal care
HIV in pregnancy
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pregnancy is not a
reason to defer standard
therapy
unique considerations
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need to alter dosage as a
result of physiologic
changes associated with
pregnancy
potential for adverse shortor long-term effects on the
fetus and newborn
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conflicting data on asso.
between HAART and
preterm delivery
to prevent perinatal
transmission, ZDV
chemoprophylaxis should
be incorporated into the
antiretroviral regimen
AZT alone may be considered for
prophylaxis of perinatal
transmission in pregnant women
with HIV RNA <1,000 copies/mL
Current Antiretroviral
Medications
PI
NRTI
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Abacavir
Didanosine
Emtricitabine
Lamivudine
Stavudine
Zidovudine
Zalcitabine
Tenofovir
ABC
DDI
FTC
3TC
D4T
ZDV
DDC
TDF
NNRTI
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Delavirdine
Efavirenz
Nevirapine
DLV
EFV
NVP
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Amprenavir
Atazanavir
Fosamprenavir
Indinavir
Lopinavir
Nelfinavir
Ritonavir
Saquinavir
 soft gel
 hard gel
APV
ATV
FPV
IDV
LPV
NFV
RTV
SQV
SGC
HGC
Fusion Inhibitor
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Enfuvirtide
T-20
HAART in pregnancy
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Nevirapine
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Increases in hepatic
transaminase levels (ALT and
AST) associated with rash or
systemic symptoms may be
observed during the first 18
weeks
risk increases with CD4+ cell
count
nevirapine-associated liver
failure or hepatic mortality
0.04-0.40%
severe rash has 5.5 to 7.3
times more common in women
(overall 2%)
Woman >250 12 fold RR
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not reported for single doses
given to mother and child for
prevention of perinatal HIV
infection
deaths due to hepatic failure
have been reported in HIVinfected pregnant women
frequent monitoring of clinical
symptoms and LFTs
use with caution in pregnant
antiretroviral-naïve women with
higher CD4
label now recommends against
starting nevirapine treatment in
women with CD4>250
cells/mm3 unless benefits
clearly outweigh risks (1/19/05)
HAART in pregnancy
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Protease inhibitors
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Hyperglycemia
Nelfinavir preferred
Newer ones no data
NRTI’s
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Efavirenz
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Significant malformations
(anencephaly,
anophthalmia, cleft palate)
in 3/20 (15%) infants born
to monkeys receiving
efavirenz during first
trimester
3 case reports of neural
tube defects in humans
w/first trimester exposure
Lots of data
mitochondrial dysfunction
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affinity for mitochondrial
gamma DNA polymerase
highest for
ddC>ddI>stavudine
>ZDV>3TC>abacavir
>tenofovir
generally has resolved
with discontinuation
possible genetic factor
Tenofovir
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Insufficient data
Prenatal screening
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In 2003, CDC recommended that HIV testing be
included in the standard battery of prenatal tests
and procedures, with notification to pregnant
women that the test would be performed and
could be declined (CDC 2003b).
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similar to recommendations by the Institute of
Medicine (IOM 1999)
American College of Obstetricians and Gynecologists
(AAP, ACOG 1999).
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American Academy of Pediatrics (AAP, ACOG 1999).
Key Strategies
Universal, routine HIV screening of all pregnant women
Universal, routine retesting in the third trimester if:
1.
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2.
HIV seroprevalence (>0.5%) or
high risk
1.
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6.
3.
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history of sexually transmitted diseases (STDs)
sex for money or drugs
multiple sex partners during pregnancy
illicit drugs
sex partner(s) known to be HIV+ or at high risk,
signs and symptoms of seroconversion) Universal, routine rapid HIV
testing among untested women on arrival
rapid HIV testing of newborns whose mothers were not previously
screened for HIV
Appropriate treatment for pregnant women determined to be HIVinfected and prophylaxis for their infants.
Prevention of transmission
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3-part regimen
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oral ZDV initiated at 14-34 weeks' gestation
intravenous ZDV during labor
oral ZDV to infant for 6 weeks after delivery
No breastfeeding if safe alternatives available
HIV prevention in the workplace
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Key is good policies
and procedures and
education, education,
education
NIOSH
Transmission of Infection to
HCW’s
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Airborne/Droplet
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Feces
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Tuberculosis
Influenza, RSV
pertussis
SARS
Hep A
Contact
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Scabies
Varicella
RSV
GAS
Blood and body
fluids
Hep B
Hep C
HIV
Question
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Assuming a nonimmune HCW and no treatment, which virus is
most likely to result in transmission after a percutaneous
exposure?
 Hep A
 Hep B
 Hep C
 HIV
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Hep B (2-40%) > Hep C (3-10%) > HIV (0.1-0.5%)
But, HCW’s should be protected against B
We can prevent and treat HIV
We can treat C
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Bloodborne pathogen exposure
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Nurses most common
Physicians, others
underreport
Risk factors
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Hollow-bore device
Visible blood
Depth of injury
Patient factors
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Prevention
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Safety devices
Training
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procedures
no recapping
proper disposal
Recommendations and Reports
January 21, 2005 / 54(RR02);1-20
Antiretroviral Postexposure Prophylaxis After Sexual,
Injection-Drug Use, or Other Nonoccupational Exposure to
HIV in the United States
Recommendations from the U.S. Department of Health and Human Services.htm
Link to Recommendations
Nonoccupational Exposures
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Voluntary sex
Sharing needles
Accidental injury
Blood transfusion
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Sexual assault
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MMWR January 21, 2005 / 54(RR02);1-20
13% of adult women report
having been raped (60%
before age 18)
5% more than once
5% of reported rapes in ER
involved men assaulting men
National Crime Victimization
Survey 1999
 In >12yo, 11.6 % men
only 3 documented cases of
HIV infection resulting from
rape
Transmission via sexual assault
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Study of men incarcerated in
Rhode Island
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1% of convicted rapists were
HIV infected (3% of all prisoners
and 0.3% of the general males)
multiple characteristics increase
risk for HIV transmission. Study
of 1,076 cases:
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20% multiple assailants
39% strangers
83% of females were vaginally
penetrated
17% sodomized.
Genital in 53%
sperm or semen was detected
in 48%
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40% of assaulted women (70% of
nulliparas) had vaginal
lacerations, compared with 5%
after consensual sex
sexual assault survivors often
decline nPEP
many who do take it do not
complete the 28-day course.
In Vancouver
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71/258 assault survivors accepted
the 5-day starter pack of nPEP
29 returned for additional doses
8 completed 4 weeks.
Those with the highest risk for HIV
exposure more likely to begin and
complete nPEP.
Nonoccupational Exposure (nPEP)
•Known HIV +
•<72 hours after nonoccupational exposure to blood, genital secretions,
or other potentially infectious body fluids of a person
•substantial risk for transmission
•28-day course of (HAART)
•initiated ASAP after exposure.
•consider nPEP for serious risk for transmission, even if >72 hours if
benefit>risk
•Frequent, voluntary exposure-no HAART
•Unknown HIV status
•substantial risk for transmission if the source were HIV infected
•no recommendations are made for the use of nPEP
•evaluate risks and benefits of nPEP on a case-by-case basis.
•no substantial risk for HIV transmission or who seek care >72 hours-no
HAART
•Risk-reduction counseling and indicated intervention services should be
provided to reduce the risk for recurrent exposures.
MMWR January 21, 2005 / 54(RR02);1-20
Concerns about nPEP
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increases in risk behavior-not supported
by data
Toxicity
Selection of resistance
Cost effectiveness
MMWR January 21, 2005 / 54(RR02);1-20
Toxicity
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PEP registry
 492 health-care workers.
 76% reported certain
symptoms (i.e., nausea
[57%] and fatigue or
malaise [38%]).
 8% had laboratory
abnormalities.
 All resolved promptly at the
end of antiretroviral
treatment.
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Six (1.3%) reported severe
adverse events.
Four stopped PEP because
of side effects.
Of 68 workers who stopped
taking PEP despite exposure
to a source person known to
be HIV-positive, 29 (43%)
stopped because of side
effects.
MMWR January 21, 2005 / 54(RR02);1-20
Toxicity
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U.S. nPEP surveillance
registry, among.
 107 exposures.
 initial regimen stopped or
modified in 22%; 50% due
to side effects.
 serious side effects have
been reported (e.g.,
nephrolithiasis and
hepatitis).
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Nevirapine 1997--2000.
 22 severe ADRs for PEP or
nPEP reported to FDA.
 12 severe hepatotoxicity
(one transplant), 14 severe
skin reactions, 4 both.
 risk of nevirapinecontaining regimen for
occupational PEP
outweighs benefits.
 nevirapine should not be
used for nPEP.
MMWR January 21, 2005 / 54(RR02);1-20
Selection of Resistance
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“probably rare”
PEP failures have been documented after at least one
sexual and 21 occupational exposures
 3/4 AZT only
 Only 4 3+ drugs
 1 had 3TC mutation, but source unknown
Consider resistance testing if patient does seroconvert
MMWR January 21, 2005 / 54(RR02);1-20
Cost effectiveness
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US study
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cost-effective only with known
HIV+ source or after
unprotected receptive anal
intercourse with a
homosexual or bisexual man
of unknown serostatus.
(already doing nPEP)
 >50% did not fit criteria (e.g.,
for exposure to intact skin).
 use of nonindicated nPEP
doubled the cost per HIV
infection prevented ($530,000
vs. $230,000)
French study
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nPEP cost-saving for
unprotected receptive anal
intercourse with known HIV +
partner and for receptive anal
intercourse with a
homosexual or bisexual
partner of unknown
serostatus
not cost-effective for penilevaginal sex, insertive anal
intercourse, or other exposures
considered.
British Columbia study
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Even if nPEP is cost-effective
for highest risk exposures,
behavioral interventions more
cost-effective.
Emphasizes the importance of
providing risk-avoidance and
risk-reduction counseling to
reduce the occurrence of future
HIV exposures.
MMWR January 21, 2005 / 54(RR02);1-20
Barriers to nPEP
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Failure to report
Cost to patient
Harder to test source
Evaluation of Exposure
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Blood is key source
Infected saliva very low
risk
Rapidly test and interview
source (?viral load,
HAART, prior resistance)
If experts not immediately
available, do not delay
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Facilitate adherence
Frank, nonjudgemental
counseling about risk
behaviors
Treatment for other blood
borne or sexually
transmitted infections
Emergency contraception
Referral for psychiatric
services
Question
35yo WM found HIV+ on insurance exam. Only
symptom is occasional night sweats. Thrush
on exam. CD4 260. Viral load 1550.
Management?
Begin treatment with a 3-drug regimen and start
PCP prophylaxis.
Question
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25yo WM in ER for fever/cough x 2weeks.
HIV+ in prison for 4+ years, now on parole.
Decreased BS in right mid lung, sat 98%
RA, RML infiltrate on CXR. You admit.
Plan?
Airborne isolation, rx for CAP and collect
sputa
Question
30 yo WM HIV+, no meds, 1 week HA, fever,
anorexia, N/V. Thin, lethargic. Neck supple,
neuro exam nonfocal. WBC 2.5, plts 150K
LP OP 39cm, WBC 25, pro 65, glu 50.
India ink +, crypto ag titer >1:8192. Plan?
Begin antifungal therapy (Ampho + 5FC) and
repeat the LP daily (normal opening pressure
10-20 cm)
Controversial whether to start HAART
Question
36yo WM HIV+ 10 years, no HAART in 5 yrs, to ER
w/new onset seizures. 2 weeks memory loss, odd
behavior. Confused, disoriented. MRI single ringenhancing lesion left cerebral hemisphere arising
in basal ganglia, with significant mass effect and
midline shift.
Admit, steroids, CD4=17, toxo IgM neg, IgG+,
CMV IgM neg, IgG+. Next step?
Start empiric pyrimethamine/sulfa (or clinda). No LP.
Question
25yo BF HIV+ for 2 years, now in 8th week of
pregnancy. Asympto, CD4>700, viral loads
<1000. NO HAART ever. Plan?
AZT only starting beginning of second trimester,
then routine perinatal AZT.
Question
38 yo LAM with chronic HIV admit w/pneumonia.
Migrant worker from Mexico. Bilateral
interstitial infiltrates, no HAART, no history of
OIs. Hypoxic, intubated. Worsens on PCP rx,
bronch shows long larvae. Dx?
Strongyloides stercoralis
Question
29yo AIDS and TB. 3 TB drugs and
abacavir/lamivudine/efavirenz started. Improves,
then at week 4 comes in with huge fluctuant
cervical nodes, fever, palpable spleen, pleural
effusion. Aspirate of node no organisms. Next
step?
a)
b)
c)
d)
e)
Add ethambutol
Substitute tenofovir for abacavir
Lymph node biopsy
Thoracentesis
Treat symptomatically, consider steroids
Question
47yo WM w/chronic HIV on PI regimen for 2 years.
Presents with increasing abdominal girth. Undetectable,
good CD4 recovery. Feels well. 10 lb weight loss, exam
has large dorsocervical fat pad, extremity wasting and
protruding abdomen with hepatomegaly and striae.
Diagnosis?
HIV-associated lipodystrophy
Question
34 yo WF new HIV. Fatigue, mild anorexia, but weight
stable. CD4 230, viral load 99,000.
abacavir/3TC/efavirenz started. One week later, rash,
nausea, nonproductive cough and fever to 38.9.
Symptoms wax and wane, feels best first thing in the
morning and early evening. Plan?
Substitute another drug for abacavir and watch
closely
Question
Employee needlestick from IDU’r with multiple sex
partners, but no bad behavior in a year. Never
tested. Plan?
1.
2.
3.
4.
5.
Begin 3 drug HAART immediately and continue for 2 months
Wait on results of testing
Begin 3 drugs then stop if negative
Obtain viral load testing on source and employee now and in 6
weeks
Obtain baseline testing of both source and employee, now and
again in 6 weeks and 6 months.
Question
24 yo sexually active WF requests HIV test. EIA +,
Western blot + in 1 band (p24). Viral load is 324.
Interpretation?
Indeterminate. Single band nondiagnostic and very
low viral load could be false +. Repeat in 6
weeks, 3 months and 6 months (and counsel)
Question
37yo WM HIV+, on HAART 3 years since
presenting with CMV retinitis. CD4 gone from 12
to 480 over 18 months. He has been
undetectable for a year. He is on Bactrim,
azithromycin and valganciclovir. What can you
stop?
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All 3 prophylactic drugs.
Question
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What virus presents as a rash in kids, arthritis in
adults? How does it present in HIV patients?
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Parvovirus B19
Severe anemia
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Name that HIV drug…
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Causes bone marrow
suppression?
Pancreatitis?
Absolutely contraindicated in
pregnancy?
Severe flu-like hypersensitivity
reaction, fatal on rechallenge?
diabetes
Rash and hepatitis?
Peripheral neuropathy?
Nightmares?
Nephrolithiasis?
Lactic acidosis?
Lipodystrophy?
Ingrown toenails?
Worst diarrhea?
hyperlipidemia
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Zidovudine
Didanosine, stavudine
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Efavirenz
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Abacavir
PIs
Nevirapine
Didanosine, stavudine
Efavirenz
Indinavir
Stavudine, didanosine, etc.
PIs and RTIs
indinavir
Nelfinavir
PIs
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