Therapeutic Regimens in

HIV/AIDS

J. Peter Figueroa
Chief, Epidemiology & AIDS
Presented by T. Hylton-Kong
Blue Cross Symposium, November 16, 2003
Acknowledgement
Resource material includes slides
from:
Dr. John Bartlett
Dr. Christopher Behrens
Dr. Robert Redfield
Reference to:
Regional ARV guidelines meeting in
May 2003
Clinical guidelines for Jamaica (in
press)
HIV/STD Control in Jamaica
Achievements
High awareness of HIV/AIDS
Increased use of condoms
Decline in syphilis & gonorrhea
Decline in congenital syphilis cases
Protection of the blood supply
Slowed HIV spread
Averted over 100,000 HIV
infections

Despite the achievements :


HIV and AIDS
continue to spread
in Jamaica

24% of men & 34% of women
having sex with a non-regular partner
do not use a condom in Jamaica







HIV/AIDS IN JAMAICA
Sero-prevalence among adults 1.5%
Estimated No. with HIV/AIDS 22,000
No. of persons in need of ARV 8,000
No. of persons currently on ARV 400
Improving access to
Antiretroviral Drugs
Submission to the Global Fund
US$23million over 5 years
National Health Fund
Cost recovery

MAJ AIDS Fund
Initial Health Care
History and examination
Laboratory Investigations
HIV education and counseling
Treatment of current conditions
Vaccination Hep B, HZ, `Flu
Case notification
Partner notification
Refer as necessary

Healthy Lifestyle
Good nutrition, care re eating
Rest, relaxation, exercise
Avoid crowds, hospitals and pets
Stop smoking, alcohol, drugs
Family planning
Condom use
Family, friends and social support
Spiritual health
HIV disease
Treatment Principles
Suppress the virus
Restore the immune system
Treat the complicating illnesses
Minimize the risk of resistance & toxicity
Improve the quality of life & clinical
outcome
TREAT THE WHOLE PERSON, not just
the diseases they have
Laboratory Tests:
Jamaican Guidelines
Must do: HIV, CBC (Hb, WBC, diff,
platelets), VDRL, urinalysis

Should do: CD4, renal, LFTs, lipids,
CXR, HBsAg, Pap smear,

As indicated: glucose, pregnancy,
amylase

Optional: HIV viral load
1
10
100
1,000
10,000
100,000
1,000,000
10,000,000
P
l
a
s
m
a

H
I
V

R
N
A
Viral Load
CD4 Cells
4-8 Weeks Up to 12 Years 2-3 Years
C
D
4

C
e
l
l

C
o
u
n
t

1,000
500
Intermediate Stage
AIDS
Primary
Infection
Sero-
conversion
CD4 Count, Viral Load and
Clinical Course
WHEN TO START: WHO
CD4 count available
WHO stage IV (AIDS)
WHO stages I-III + CD4 <200

CD4 not available
WHO stage IV (AIDS)
WHO stage II or III + Total
Lymphocyte Count <1,000-1,200
When Should HAART be Initiated?
DHHS Guidelines
Clinical Category
CD4 count Viral Load Recommendation
Symptomatic (AIDS,
severe Sx)
Any value Any value Treat
Asymptomatic, AIDS < 200/mm
3
Any value Treat
Asymptomatic > 200/mm
3
but < 350
Any value Treatment should
generally be
offered
Asymptomatic > 350/mm
3
> 55,000
copies/mL
Some experts
would recommend
initiating treatment
Asymptomatic > 350/mm
3
< 55,000
copies/mL
Many experts
would defer
therapy and
observe

DHHS Guidelines for the Use of Antiretroviral Agents in HIV-Infected Adults and
Adolescents, February 4, 2002, Table 6.
Improving Adherence:
before Initiation of Therapy
Assess patient's understanding and
acceptance of the regimen: negotiated
plan
Investigate and manage medical
barriers to adherence
Try to use simple regimens
bid or better
without food requirements if possible

Adapted from: Miller et al., The AIDS Reader 10(3):177-185, 2000.
Adapted from: Walker B. IDSA 1998
Classes of Antiretroviral Agents
RNA
DNA
HIV
Nucleus
Host Cell
Nucleoside Analogues (NRTIs)
Non-Nucleosides (NNRTIs) Protease Inhibitors (PIs)
RT
Highly Active Antiretroviral
Therapy (HAART)
Combination of at least 3 drugs, usually:
NNRTI - based regimens (2 NRTIs + 1
NNRTI)
NRTI - based regimens (3 NRTIs)
PI - based regimens (2 NRTIs + 1-2 PIs)

Therapy with only one or two ARV drugs
allows HIV to overcome therapy through
resistance mutations
WHAT TO START
2NRTI + 1NNRTI 3 NRTIs PI
AZT/3TC + NVP
AZT/3TC or EFV
d4T/3TC
d4T/ddI
AZT/3TC*/ABC AZT/3TC* + IDV
or NFV
or LPV/r or
IDV/r or SQV/r
*d4T/3TC or d4T/ddI
AZT = ZDV = Zidovudine NVP=Nevirapine IDV=Indinavir
3TC = LMV = Lamivudine EFV=Efavirenz NFV=Nelfinavir
d4T = STV = Stavudine ABC=Abacavir
LPV/r=Lopinavir/ritonavir SQV/r=Saquinavir/ritonavir
Choice of initial regimen
by baseline Viral Load (VL)
VL > 100,000
Proven
Kaletra + 2 NRTIs
Efavirenz + 2 NRTIs
Unproven
Boosted PI + 2
NRTIs
3 NRTIs + PI
3 NRTIs +
Nevirapine
NRTI/NNRTI/PI
VL < 100,000

LPV/RTV + 2 NRTIs
Efavirenz + 2 NRTIs
Nevirapine + 2
NRTIs
1-2 PIs + 2 NRTIs
AZT/3TC/Abacavir
Zidovudine
Dosing: 300 mg bid, or 200 mg tid
Interactions: no food interaction
Toxicity
Sx: Fatigue, insomnia, nausea, abdominal
discomfort, headaches, myalgia
AE: Granulocytopenia, neutropenia,
anemia,pigmentation of nail beds
(melanychia), lactic acidosis, hepatic steatosis
Lamivudine
Dosing: 150 mg bid
Interactions: no food interaction
Toxicity
Sx: Mild abdominal discomfort, occasional
nausea
AE: Minimal
Efavirenz
Dosing: 600 mg qhs
Interactions: take on empty
stomach
(fat increases absorption)
Toxicity
Sx: Insomnia, nightmares, poor
concentration, mood change,
dizziness, rash, nausea,
dysequilibrium
AE: Rash, hepatitis, depression,
psychosis
Nevirapine
Dosing: 2 weeks of 200 mg. qd, then 200
mg bid
Interactions: no food interaction
Toxicity
Sx: Rash, fever, nausea
AE: Rash, Stevens-Johnson syndrome,
hepatitis
Indinavir
Dosing: 800 mg q 8 hours1
Interactions: empty stomach, or with non-fat milk
Toxicity
Sx: Nausea, diarrhea, flank pain, hematuria, dry lips,
dry skin
AE: Hematuria, pyuria, increased creatinine,
hyperbilirubinemia, xerosis, fat redistribution, lipid
abnormalities
Optimal Response to Initial HAART
Steep drop in viral load to
undetectable levels (< 50 copies/mL)

Rise in CD4 count

Immune Restoration
Optimal Response to Therapy
1.0 log drop after 2-8 weeks treatment
Continued 1.0 log drop monthly
Undetectable virus after 4-6 months
treatment
Durable, complete suppression
Antiretroviral Therapy: Optimal
Response
10
100
1000
10000
100000
1000000
0 1 2 3 4 5 6 7 8
Viral Load
HAART Initiated
50 50
Time (months)
C
D
4

c
o
u
n
t

(
c
e
l
l
s
/
m
m
3
)

V
i
r
a
l

L
o
a
d

(
c
o
p
i
e
s
/
m
L
)

Antiretroviral Therapy: Optimal
Response
10
100
1000
10000
100000
1000000
0 1 2 3 4 5 6 7 8
0
100
200
300
400
500
Viral Load
CD4 Count
HAART Initiated
50 50
Time (months)
C
D
4

c
o
u
n
t

(
c
e
l
l
s
/
m
m
3
)

V
i
r
a
l

L
o
a
d

(
c
o
p
i
e
s
/
m
L
)

SWITCHES FOR
VIROLOGIC FAILURE
Initial Regimen New Regimen
AZT/3TC + NVP or EFV ddI/d4T + PI
AZT/3TC/ABC EFV or NVP
LPV/r ddI/d4T
AZT/3TC + PI ddI/d4T/EFV or NVP
Predictors of ARV Success
Low baseline viremia
High baseline CD4+ T cell count
Rapid decline of viremia
Decline of viremia to <50 HIV RNA
copies/mL
Adequate serum levels of
antiretroviral drugs
Adherence to the drug regimen
0
20
40
60
80
100
>95 90-95 8090 70-80 <70
P
a
t
i
e
n
t
s


w
i
t
h

H
I
V

R
N
A

<
4
0
0

c
o
p
i
e
s
/
m
L
,

%

PI adherence, % (electronic bottle caps)
Paterson, et al. 6th Conference on Retroviruses and Opportunistic Infections; 1999; Chicago, IL. Abstract 92.
Virologic Control falls sharply
with diminished adherence

Adherence is a skill to be
learned (Frank, 1997)

Patient must be able to:
Understand the regimen
Believe they can adhere
Remember to take medication
Integrate regimen into lifestyle
Problem solve changes in schedule
& routines
LESSONS FROM HAART
GOOD NEWS 1996-2003
Remarkable benefit: mortality,
hospitalization, AIDS rates 50-80%
Immune reconstitution even with
baseline CD4 count <50/mm
3
Clinical benefit even with virologic
failure
Reduced viral load decreases
transmission: perinatal, occupational
exposure, sexual (IDU?)
LESSONS FROM HAART
BAD NEWS 1996-2003
Cannot cure HIV
Viral replication continues even
with no detectable virus
Long-term toxicity lipodystrophy
Increasing resistance
Treated patients 50%
Untreated patients 10-20%
Adherence 95% rule
Antiretroviral Induced Metabolic
Toxicities
Mitochondrial toxicity
Lactic acidosis
Hepatitis/pancreatitis
Peripheral neuropathy
Myopathy
Hyperlipidemia
hypertriglyeridemia, hypercholesteremia
Redistribution of fat
Insulin resistance
Bone Disorders
osteopenia , osteoporosis, osteonecrosis
Physical Manifestations of
Lipodystrophy
Improve the Care of Persons
Living with HIV/AIDS
- Access to a health provider
- Confidentiality and respect
- Counseling and psychosocial
support
- Quality of clinical management
- Support for home care
- Training of health staff
- Access to anti-retroviral therapy