Transcript Case

Is It “Harm Reduction” or
“First Do No Harm” ?
James M Sosman, MD
Section of General Internal medicine
University of Wisconsin School of Medicine
and Public Health
Case
ID: AK is a 52 yo man who presents
 CC: routine 6 month follow up for HIV
 HPI: AK was diagnosed HIV+ 5/05 during routine
STD/HIV screening. He has been Asx. He reports
that he would like to start a relationship with a
HIV+ man who is on ART. AK has been reading
and talking to others and learned that if he starts
ART his risk of transmitting HIV may be “zero”. He
inquires about the possibility of starting ART to
reduce this risk, preferably with the new single pill
ART.

Case
 PMHx:
—No history of STD or genital warts
—No medical problems
—Hx of abdomenal liposuction
 NKAD
 Medications: none
Case

SHx:
—Worked as administrator
—Lives alone, occasional ETOH no IDU no illicit
drug use
—Divorced and considers himself homosexual
—Multiple prior sexual partners. He mostly used
condoms but not with his previous main partner.

ROS: denies urethral, anal or oral discharge, pain or
trauma/bleeding
Case
 PE:
AK is in NAD and looks
younger than stated age.
 VS: 115/70, 70, 18, wt 170lbs
 Remainder of exam WNL
Case
DATE
5/05
CD4#
(cells/ul)
959
HIV Viral Load
(cps/ml)
33,000
10/05
1008
14,600
3/06
700
78,000
10/06
1150
91,000
Case
Should
we start AK on
antiretroviral medication
for the reasons he statedto reduce the risk of HIV
transmission?
Dramatic Declines in AIDS Mortality
Rates: 1996-2001
Mortality vs. ART utilization
Deaths per 100 person-years
Percentage of P
35
USE OF ART
30
25
Percentage of patient-days on ART
100
40
75
DEATHS
20
50
15
10
25
Deaths per 100 Person-Years
5
0
1995
1996
1997
1998
1999
2000
0
2001
Palella F et al. 8th CROI 2001; abstract 268b.
IMMUNE RECONSTITUTION
1000
750
500
100,000
250
CD4 Counts (cells/cubic ml)
Viral Load (Copies/cc)
>750,000
Detectable
0
Increased
Risk OI
1
2
3
4
5
12
Time (Weeks)
24
48
0
Decreased
Risk OI
CD4 Cell Counts Increase through 7 Years of
HAART Regardless of Baseline CD4 Cell Count
700
Mean absolute value at year 7 = 776 cells/mm3
600
+501
cells/mm3
(n=60)
Cells/mm3
500
400
300
All Patients
Baseline <50 (n=17)
Baseline 50-200 (n=19)
Baseline 200-350 (n=19)
Baseline 350-500 (n=19)
Baseline >500 (n=26)
200
100
0
0
60
120
180
240
300
360
Week
Murphy R. et al., 10th EACS, Dublin, Ireland, November 2005, #P7.9/3
Study 720
A Common Choice in Initial
Once Daily HIV Treatment
Tenofovir+FTC
Or
Abacavir+3TC
Efavirenz
Plus
Or
One of several daily ritonavir
boosted protease inhibitors:
Atazanavir/rtv, Fosamprenavir/rtv, Kaletra
LPV/rtv
When to Initiate Treatment?

“Decision to begin therapy in the asymptomatic
patient ... is complex”

Immune reconstitution impressive when starting at
a CD4 > 200 cells/mm3
— Consensus that this is lower limit
— CD4 <200 cells/mm3 is associated with opportunistic
infections, disease progression, and mortality

Adherence fatigue

Risk of resistance

Risk of side effects and long term toxicity

Delay = increased rates of transmission?
DHHS Guidelines: www.hivatis.org.
Consequences of Anti-retroviral
Treatment




Resistance can develop with as little
as 30% dose reduction
Prominent cause of HAART failure
Transmission of multi-drug resistant
HIV now documented
Public health consequences
Increasing Prevalence of Drug Resistance
in Primary HIV Infection
Little et al NEJM 2002
2006 DHHS Guidelines
CD4
HIV RNA
<200
Any Value
Treat
>200, <350
Any Value
Treatment may
be offered, though
controversy exists
>350
>100,000K
Possibly initiate due to high
HIV RNA; may defer until
lower CD4; clinical outcomes
data lacking
>350
<100,000K
Generally defer
DHHS Guidelines. 2006
Recommendation
3-Year Risk of
AIDS With No
Treatment
3-Year Probability of AIDS
HIV and ART: Risk vs Benefit
100%
80%
60%
40%
< 200
201 - 350
351 - 500
501 - 750
> 750
20%
0%
> 55K
20-55K
7-20K
1.5-7K
< 1.5K
CD4 count
(cells/μL)
3-Year Risk of
AIDS With First
HAART
3-Year Probability of AIDS
HIV-1 RNA Concentration (copies/mL)
100%
80%
60%
40%
20%
0%
> 55K
20-55K
7-20K
1.5-7K
< 1.5K
HIV-1 RNA Concentration (copies/mL)
Mellors JW et al. Ann Intern Med. 1997;126:946-954.
Egger M et al. Lancet. 2002;360:119-129.
< 200
201 - 350
351 - 500
501 - 750
> 750
CD4 count
(cells/μL)
Case
 Based
on immunologic guidelines, I
would recommend continued watchful
waiting for AK. He may be able to
avoid initiating ART for 3-6 years.
 However,
AK still wants to start ART
to reduce his sexual risk of
transmission
Transmission of HIV
 Infectious Body Fluids
—Blood, Semen, Vaginal Fluids, Breast milk
 Routes of Transmission
—Unprotected sexual intercourse (oral,
vaginal, and anal)
—Exchange of Blood or Blood Products
(ie, sharing needles, body piercing/tattoo)
—Perinatal transmission during pregnancy
and delivery, or after birth through breast
feeding
Risk of Specific Exposures
Per Contact Transmission Rate







Receptive Anal
Insertive Anal
Receptive Vaginal
Insertive Vaginal
Shared Needles
Occupational NS
Receptive Oral
0.8 - 5%
< 0.1 - 1%
< 0.1 - 1%
0.01 - 5.6%
0.67 - 10%
0.3%
???
Effect of viral load on HIV
transmissibility
Ratios of Risk for Transmission and Acquisition of
HIV Among Discordant Couples
 <3,500
Referent
 3500-9999
5.8
 10,000-49,999
6.91
 >50,000
11.87
 Per log increment in VL=
2.45
•See MMWR, July 18, 2004.
HIV superinfection




Superinfection recently described
in the literature1−4
3 of 78 (4.1%) patients in the first 6
to 20 months of infection in San
Diego and Los Angeles5
1 of 32 (3.1%) newly infected
subjects from the MACS6
— CD4+ progressed to <200
cells/mm3 2.4 years
postinfection
Implications:
— Counseling of HIV-infected
partners
Mean change in HIV RNA and CD4+
6 months after superinfection
+1.6 log10 c/mL
–132 cells/mm3
ΔRNA
(log10 c/mL)
ΔCD4+
(cells/mm3)
p=0.05 vs controls without superinfection
1. Altfeld M, et al. Nature 2002;420:434; 2. Jost S, et al. NEJM 2002;347:731; 3. Koelsch K, et al. AIDS 2003;17:F11;
4. Ramos A, et al. J Virol 2002;76:7444; 5. Smith D, et al. 11th CROI, San Francisco 2004, #21;
6. Gottlieb G, et al. ibid, #454
Increasing rates of high-risk behavior
and STDs in San Francisco
Percent
STDs, high-risk behavior,
in MSM1
Unprotected anal sex
40
35
30
25
20
15
10
5
0

Unprotected anal sex,
multiple partners
97
98
99
2000
2001
250
No. patients
Predictors of high-risk behavior
among HIV+ individuals2
200
Rectal gonorrhea
150

Belief that undetectable
VL reduces transmission
vs no change in
transmission: AOR 5.9
(95% CI 1.9–19)
Most recent VL
undetectable vs
detectable: AOR 9.3
(95% CI 2.3–37)
100
50
Early syphilis
0
97
98
99
2000
2001
1. Gibson S, et al. XIV Int AIDS Conference, 2002, #3430; 2. Colfax G, et al. ibid, #3445
Primum Non Nocere- First Do No
Harm

So-called Hippocratic injunction
— Axiom central to medicine
— Balance of harms vs the benefits of therapy
— Growth of use and relevance




Mostly in 20th century especially after Nazi atrocities
Used in almost all medical schools as a graduation oath
IOM concern study about medical errors (1999)
Contemporary focus on risk/benefit and cost/benefit
analysis
— Concern that the directive emphasizes errors of
commission over errors of omission
Harm Reduction

Relatively new social policy (1920’s
England, 1950s Canada, 1960s USA)
— Methadone maintenance to reduce harm
associated with heroin

1990s
— Needle exchange programs for IDUs

Pragmatic approaches that focus on the
consequences of harmful behavior and
not whether the behavior is “right” or
“wrong”
— Neither condones nor condemns behavior
Marlatt, 1999
Harm Reduction

Harm reduction
— Traditional strategies
have limited effect, with
unattainable goals
— Recognizes the
structural inadequacies
in society (poverty,
access to care,
discrimination)
— Compatible with health
promotion
— Patient centered and
“user-friendly”
— “Low threshold” access
to treatment

Abstinence model
— Goals are clearly stated
— Avoids ambiguous
recommendations
— Avoids condoning
unhealthy choices
— Based on moral
idealism?
Case
Harm Reduction Vs First Do No Harm

To start ART
— Reduces progression
to AIDS
— May reduce the risk of
HIV transmission and
acquiring a HIV superinfection
— May encourage riskier
behaviors
— Exposes patient to
side effects, toxicity,
and potential
development of
resistance

To delay ART
— Prevents side effects
and toxicity from ART
— Avoids potential to
develop resistant
virus
— Avoids “Exhausting”
available treatments
before they may have
their greatest
value/need
— May be at greater risk
to transmit HIV or
acquire a
superinfection
Any thoughts on which
approach to employ?
Case



AK was offered ART and elected to
start Atripla (Tenofovir,
Emtricidabine, Effaverenz) one pill
PO qhs.
AK was counseled regarding the
risks and side effects of ART
AK was counseled regarding the
continued need for safer sexual
practices
Case


AK called 10 days later complaining
of acute onset of an erythematous
pruritic rash on his back progressing
to chest and legs.
Diagnosed with drug erruption
— Atripla discontinued
— Prescribed Prednisone and H1-blocker

AK was anxious to start another ART
regimen