Care for HIV infected patients: Looking beyond HIV and HAART

Care for HIV infected patients:
Looking beyond HIV and
HAART
Timothy P. Flanigan, MD
Professor of Medicine
Brown Medical School

HIV Care @ Miriam Hospital 6/07
• A 52 yo man with hepatitis C infection is
admitted with fever, hyptotension, and
SOB…CD4 220 (CD4% is 34%)
• 44 yo patient of mine with HIV > 12 yrs is
admitted with bronchitis and severe asthma to
the ICU…CD4 512
• A 46 yo man is admitted with chest pain and a
severe family history of heart disease.CD4 490
• A 38 yo woman is admitted with abdominal pain,
a rash, and is homeless and using crack
cocaine…CD4 5

What is the underlying
process?
• All 4 patients have had HIV for >10 years.
• All 4 patients are older: the epidemic is aging. None of
these admissions are due to HIV!!!!
• The 52 yo with sepsis with hepatitis C is ill due to liver
failure. PVL < 75
• The 44 yo with bronchitis with severe asthma is ill due to
smoking. PVL < 75
• The 46 yo with angina has CAD. PVL < 75
• The 38 yo with substance abuse has severe physical,
psychological, and social comorbidity. PVL > 120,000
with no PI resistance

Percent
40
35
30
25
20
15
10
5
0
Common Medical Conditions in
HCV
34
Hypertension
32
Bacterial Pneumonia
27
Herpes Simplex
21
Herpes Zoster
16 16
PCP
Diabetes
HIV
13
Obstructive Pulmonary Disease
12
Wasting
9
NonAIDS Cancers
7 7 7
MI/CAD
TB
Congestive Heart Failure
5

Percent of All Deaths
Causes of Death in HIV
16
14
12
10
8
6
4
2
0
Hepatitis/cirrhosis
14
"AIDS"
13
Wasting
11
Lymphoma
9
NonAIDS Cancer
8
6 6
6 6 5
Recurrent Pneumonia
Sepsis
Disseminated MAC
CMV
Violence
Dementia
Sudden Death
5
Cardiovascular Disease
4 4 4 4
PCP
KS
Cryptococcosis
Cause of Death- (Major Non-HIV Causes in Red)
CHORUS, n=626 deaths from 1999-2005 (92% of all deaths recorded)
3

Hepatitis: What causes
elevated LFT’s in your patient?
• Hepatitis A: Acute, can be bad, preventable
• Hepatitis B: Antibody is v common. Chronic
active disease (ie Hep B Sag+)

Increasing ESLD Mortality
• Retrospective analysis
COD of HIV+ pts
• ESLD leading COD 1998
(P = .003).
• > 1/2 who died of ESLD
had no detectable VL or
CD4 >200/mm 3 6 mos
prior to death
• Of the pts that died in
1998: 91% tested for
HCV, all HCV+
in Patients With HIV
ESLD-Related Deaths (%)
Bica CID 2001
50
40
30
20
10
0
11
14
50
1991
1996
1998

What is the most effective
approach to prevent cirrhosis in
your Hepatitis C infected patient?
• Alcohol cessation!!!!
• Alcohol in a dose dependent manner is
the strongest cofactor in progression of
Hepatitis C liver disease progressing to
cirrhosis…The vast majority of Hepatitis
C infected patients that do not drink
alcohol will never have clinically
significant liver disease.

Non-AIDS Defining Cancer
• People with HIV have higher incidence
of some AIDS-defining cancers such as
Kaposi’s sarcoma (KS), Cervical Cancer
and non-Hodgkin lymphoma (NHL)
• HIV+ individuals appear to be at higher
risk for other non-AIDS defining cancers
and may require enhanced screening
strategies.

Estimated cancer incidence rates
(per 100 000)
900
800
700
600
500
400
300
200
100
0
Incidence of Non-AIDS
Oral
Digestive
Defining Cancers
Anal
Respiratory
Soft Tissue
Skin
Brain
McGinnis K et al. 41 st ICAAC, Chicago, 2001, #I-249
Veterans with HIV cohort study
VA electronic medical records
Male genital

Pulmonary
• Upper and lower respiratory tract
infections are the #1 cause of hospital
admissions�bacterial pneumonia,
bronchitis, asthma, sinusitis, PCP, and
TB.

Smoking and HIV
• Patients that smoke are 5x more likely
to have bacterial pneumonia. Primary
and secondary smoking increase risk of
all of the above infections!

HIV Mortality Rate by Smoking Status
6
5
4
3
2
1
0
5.4
Mortality Rate =Deaths/100 Person Years p

• FIVE A’S!
Smoking cessation
• NRT (nicotine replacement therapy) �
the patch…gum…lozenges
• Pharmacological therapy

Cardiovascular Disease
• Patients are aging
• HIV itself as well as HAART decreases HDL and
increases LDL…PI therapy may cause insulin
resistance.
• Smoking is very common (70% of our patients
smoke).
• Bad lipid profile, hyperglycemia, smoking…and
often hypertension (particularly in African
American patients)� Set up for CVD
• Treatment: Lipid control, diabetes treatment,
smoking cessation, HTN treatment, exercise,
baby ASA a day!

Prevalence of Diabetes in HIV+ vs HIV- HIV Men:
1999-2003 1999 2003 (n=1107, men)
%
15
10
5
0
Brown et al. CROI 2004
Age-BMI-adjusted
OR=4.4, CI 2.6-7.4
Non-HIV HIV + HAART

CVD on ART:
Update from the D:A:D Study
• n=23,441; 11 cohorts
• 76,577 pt-years follow-up
• Mean ARV exposure = 4.5
years
• 24% women
• At baseline: 42%
dyslipidemic, 47% smokers,
16% ex-smokers
• 277 first MI; 3.6/1000 pt-years
• 28.5% fatal
• RR 1.17/year cART
(95% CI 1.08–1.26)
Incidence/1000 PY (95% CI)
El-Sadr W, et al. 12th CROI, Boston 2005, #42; Friis-Moller et al NEJM, Nov 2003
8
6
4
2
0
Incidence of MI by ART exposure
p

Substance Abuse
• A chronic relapsing disease!
• Treatment does work…but is often not
curative.
• Polysubstance use is the rule not the
exception…look out for it.
• Become comfortable doing tox screens,
writing contracts, talking to your patients
about their substance use and what has
worked and not worked for them in the past.
• Use AA…NA…CA…every treatment modality
• Be on the look out for mental health disease
and try to treat

South Providence

Substance Abuse
• Our patients are “wiley”…they’re good
at it because they have to be.
• DON’T TAKE IT PERSONALLY…BUT
TRY NOT TO GET SUCKED IN.

Different treatments work for
different folks
• Multiple treatment modalities can work
together
• Treat depression…bring in family
allies…encourage spiritual or religious
support…substance abuse counseling…tox
screens…opiate replacement therapy
• Get help�case manager/social
worker/counselor for your patient (and for you
to commiserate with…)

Picture Slides

Buprenorphine for opiate
addiction treatment
• Buprenorphine is a partial agonist and is
appropriate for office-based treatment of
opioid dependence.
• Buprenorphine reaches a ceiling effect at
only half the levels of methadone or
morphine, limiting the likelihood of
overdose
• Suboxone, the coformulation of
buprenorphine and naloxone, also
minimizes diversion for injection.

Buprenorphine Maintenance Therapy
• The efficacy of buprenorphine maintenance treatment
has been found to be:
– similar to moderate dose methadone (60 -100 mg
qd) in terms of retention in care and opioid-free
toxicology screens
– superior to placebo in a randomized controlled
trial, and
– to have significantly greater retention to care and
opioid-free urine samples when administered in a
primary care setting than when administered in a
methadone maintenance program
• buprenorphine maintenance therapy associated with
higher adherence to HAART

Methadone Treatment works for HIV+
% seropositive
45
40
35
30
25
20
15
10
5
0
patients and Decreases
HIV Seroincidence
Metzger et al. JAIDS 1993;6:1049.
Methadone Out-of-treatment
Baseline 1 yr. 2 yr. 3 yr.