HIV III-
Prevention of HIV infection
Allison Liddell, MD
Monday, January 24th, 2005
HIV Curriculum
HIV I-Diagnosis and HAART
HIV II-Complications of HIV/AIDS
HIV III-Prevention of HIV infection
HIV history
Date of first published Who wrote it?
case? Local clinicians and the
June 5, 1981 Epidemic Intelligence
Service (EIS) Officer
Where? stationed at the Los
MMWR Angeles County
five cases of PCP among Department of Public
Health
previously healthy young
men in editorial note stated that
the histories suggested a
What city?
"cellular-immune
Los Angeles. All of the men
were described as dysfunction related to a
"homosexuals"; two had common exposure" and a
died. "disease acquired
through sexual contact."
HIV history
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
CDC initiative: Advancing HIV Prevention: New
Strategies for a Changing Epidemic
reducing barriers to early diagnosis
increasing access to quality medical care, treatment
ongoing prevention services
emphasizes the use of proven public health approaches
to
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?
must be used correctly condoms lubricated with
and consistently spermicides are no more
effective
Latex condoms are highly epidemiologic studies of STDs,
effective in preventing other than HIV, are
transmission of HIV. Well characterized by
documented. methodological limitations
reduce the risk of other inconclusiveness of
epidemiologic data about
STDs condom effectiveness for
associated with a lower other STDs indicates that more
rate of cervical cancer, an research is needed--not that
HPV-associated disease. latex condoms do not work
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
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 =
20
250
Woman >250 12 fold RR cells/mm3 unless benefits
clearly outweigh risks (1/19/05)
HAART in pregnancy
Protease inhibitors NRTI’s
Hyperglycemia Lots of data
Nelfinavir preferred mitochondrial dysfunction
Newer ones no data affinity for mitochondrial
gamma DNA polymerase
Efavirenz highest for
Significant malformations ddC>ddI>stavudine
(anencephaly, >ZDV>3TC>abacavir
anophthalmia, cleft palate) >tenofovir
in 3/20 (15%) infants born generally has resolved
to monkeys receiving with discontinuation
efavirenz during first possible genetic factor
trimester Tenofovir
3 case reports of neural Insufficient data
tube defects in humans
w/first trimester exposure
Prenatal screening
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).
similar to recommendations by the Institute of
Medicine (IOM 1999)
American College of Obstetricians and Gynecologists
(AAP, ACOG 1999).
American Academy of Pediatrics (AAP, ACOG 1999).
Key Strategies
1. Universal, routine HIV screening of all pregnant women
2. Universal, routine retesting in the third trimester if:
1. HIV seroprevalence (>0.5%) or
2. high risk
1. history of sexually transmitted diseases (STDs)
2. sex for money or drugs
3. multiple sex partners during pregnancy
4. illicit drugs
5. sex partner(s) known to be HIV+ or at high risk,
6. signs and symptoms of seroconversion) Universal, routine rapid HIV
testing among untested women on arrival
3. rapid HIV testing of newborns whose mothers were not previously
screened for HIV
4. Appropriate treatment for pregnant women determined to be HIV-
infected and prophylaxis for their infants.
Prevention of transmission
3-part regimen
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
Key is good policies
and procedures and
education, education,
education
NIOSH
Transmission of Infection to
HCW’s
Airborne/Droplet Blood and body
Tuberculosis fluids
Influenza, RSV
pertussis Hep B
SARS Hep C
Feces HIV
Hep A
Contact
Scabies
Varicella
RSV
GAS
Question
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
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
Bloodborne pathogen exposure
Nurses most common
Physicians, others
underreport
Risk factors Prevention
Hollow-bore device Safety devices
Visible blood Training
Depth of injury procedures
Patient factors 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
Voluntary sex Sexual assault
13% of adult women report
Sharing needles having been raped (60%
before age 18)
Accidental injury 5% more than once
Blood transfusion 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
MMWR January 21, 2005 / 54(RR02);1-20 rape
Transmission via sexual assault
Study of men incarcerated in 40% of assaulted women (70% of
Rhode Island nulliparas) had vaginal
lacerations, compared with 5%
1% of convicted rapists were after consensual sex
HIV infected (3% of all prisoners
sexual assault survivors often
and 0.3% of the general males)
decline nPEP
multiple characteristics increase many who do take it do not
risk for HIV transmission. Study complete the 28-day course.
of 1,076 cases: In Vancouver
20% multiple assailants 71/258 assault survivors accepted
39% strangers the 5-day starter pack of nPEP
83% of females were vaginally 29 returned for additional doses
penetrated 8 completed 4 weeks.
17% sodomized. Those with the highest risk for HIV
Genital in 53% exposure more likely to begin and
complete nPEP.
sperm or semen was detected
in 48%
Nonoccupational Exposure (nPEP)
•Known HIV +
•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
increases in risk behavior-not supported
by data
Toxicity
Selection of resistance
Cost effectiveness
MMWR January 21, 2005 / 54(RR02);1-20
Toxicity
PEP registry
492 health-care workers. Six (1.3%) reported severe
76% reported certain adverse events.
symptoms (i.e., nausea Four stopped PEP because
[57%] and fatigue or of side effects.
malaise [38%]). Of 68 workers who stopped
8% had laboratory taking PEP despite exposure
abnormalities. to a source person known to
All resolved promptly at the be HIV-positive, 29 (43%)
end of antiretroviral stopped because of side
treatment. effects.
MMWR January 21, 2005 / 54(RR02);1-20
Toxicity
U.S. nPEP surveillance Nevirapine 1997--2000.
registry, among. 22 severe ADRs for PEP or
107 exposures. nPEP reported to FDA.
initial regimen stopped or 12 severe hepatotoxicity
modified in 22%; 50% due (one transplant), 14 severe
to side effects. skin reactions, 4 both.
serious side effects have risk of nevirapine-
been reported (e.g., containing regimen for
nephrolithiasis and occupational PEP
hepatitis). outweighs benefits.
nevirapine should not be
used for nPEP.
MMWR January 21, 2005 / 54(RR02);1-20
Selection of Resistance
“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
US study British Columbia study
cost-effective only with known (already doing nPEP)
HIV+ source or after >50% did not fit criteria (e.g.,
unprotected receptive anal for exposure to intact skin).
intercourse with a
use of nonindicated nPEP
homosexual or bisexual man
of unknown serostatus. doubled the cost per HIV
infection prevented ($530,000
French study vs. $230,000)
nPEP cost-saving for Even if nPEP is cost-effective
unprotected receptive anal for highest risk exposures,
intercourse with known HIV + behavioral interventions more
partner and for receptive anal
intercourse with a cost-effective.
homosexual or bisexual Emphasizes the importance of
partner of unknown providing risk-avoidance and
serostatus risk-reduction counseling to
not cost-effective for penile- reduce the occurrence of future
vaginal sex, insertive anal HIV exposures.
intercourse, or other exposures
considered.
MMWR January 21, 2005 / 54(RR02);1-20
Barriers to nPEP
Failure to report
Cost to patient
Harder to test source
Evaluation of Exposure
Blood is key source Facilitate adherence
Infected saliva very low Frank, nonjudgemental
risk counseling about risk
Rapidly test and interview behaviors
source (?viral load, Treatment for other blood
HAART, prior resistance) borne or sexually
If experts not immediately transmitted infections
available, do not delay 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
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 ring-
enhancing 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) Add ethambutol
b) Substitute tenofovir for abacavir
c) Lymph node biopsy
d) Thoracentesis
e) 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. Begin 3 drug HAART immediately and continue for 2 months
2. Wait on results of testing
3. Begin 3 drugs then stop if negative
4. Obtain viral load testing on source and employee now and in 6
weeks
5. 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?
All 3 prophylactic drugs.
Question
What virus presents as a rash in kids, arthritis in
adults? How does it present in HIV patients?
Parvovirus B19
Severe anemia
Name that HIV drug…
Causes bone marrow
suppression? Zidovudine
Pancreatitis? Didanosine, stavudine
Absolutely contraindicated in
pregnancy? Efavirenz
Severe flu-like hypersensitivity
reaction, fatal on rechallenge? Abacavir
diabetes PIs
Rash and hepatitis? Nevirapine
Peripheral neuropathy? Didanosine, stavudine
Nightmares? Efavirenz
Nephrolithiasis? Indinavir
Lactic acidosis? Stavudine, didanosine, etc.
Lipodystrophy? PIs and RTIs
Ingrown toenails? indinavir
Worst diarrhea? Nelfinavir
hyperlipidemia PIs