Transcript ARV guidelines

Antiretroviral Therapy
DHHS Guidelines
Guidelines for the Use of
Antiretroviral Agents in Adults
and Adolescents
II. Background and Principles:
Contents
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Goals of therapy
Adherence
Risks and benefits of early or
delayed therapy
Testing viral load and CD4+ T cell
Resistance testing
Risks and Benefits of Delayed
Initiation of Therapy
BENEFITS
 Avoid negative effects
on quality of life
 Avoid drug-related
adverse events
 Delay in development
of drug resistance
 Preserve maximum
number of available
and future drug
options when HIV
disease risk is highest
RISKS
 Possible risk of
irreversible immune
system depletion
 Possibly greater
difficulty in
suppressing viral
replication
 Easier to transmit HIV
to others
Risks and Benefits of Early
Therapy
BENEFITS
 Control of viral
replication easier to
achieve and maintain
 Delay or prevention of
immune system
compromise
 Lower risk of
resistance with
complete viral
suppression
 Decreased risk of HIV
transmission
RISKS
 Drug-related
reduction in quality of
life
 Greater cumulative
drug-related adverse
events
 Earlier development
of drug resistance, if
viral suppression is
sub optimal
 Limitation of future
antiretroviral
100%
80%
60%
40%
CD4 < 200
20%
CD4 201-350
HIV-1 RNA (copies/mL)
by RT-PCR
<1500
1.5K-7K
CD4 >350
7K-20K
20K-55K
0%
>55,000
Risk of Disease Progression
Risk of Progression to an AIDSDefining Illness in 3 Years by
Baseline HIV RNA and CD4
Mellors J, et al. Science, 1996; 272:1167-1170.
Risk of Progression to an AIDSDefining Illness in 3 Years by
Baseline HIV RNA and CD4
Guidelines
recommend
treatment
Guidelines
recommend
observation
80%
60%
40%
CD4 < 200
20%
CD4 201-350
<1500
1.5K-7K
CD4 >350
7K-20K
20K-55K
0%
>55,000
Risk of Disease
Progression
100%
HIV-1 RNA (copies/mL)
Mellors J, et al.
by RT-PCR
Science, 1996; 272:1167-1170.
Testing
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Viral load
CD4+ T cells
Resistance testing
Decision Making
Initiating and Changing Therapy
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Plasma HIV RNA (viral load)
CD4+ T cell count
Clinical condition of the patient
Measuring Plasma HIV RNA
and CD4+ T Cells
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At the time of diagnosis
Every 3-4 months in the untreated
patient
Immediately prior to initiating
therapy
2-8 weeks after initiating therapy
Every 3-4 months in patients on
therapy
As indicated in the opinion of the
provider
Factors Affecting the Rate of
Plasma HIV RNA Decline
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Baseline CD4+ T cell count
Initial viral load
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Potency of the regimen
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Adherence to the regimen
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Prior exposure to antiretroviral agents
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Resistance
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Presence or history of opportunistic
infections
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III - Initiation of
Therapy
III. Initiation of Therapy:
Contents
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Goals of Therapy and Tools to Achieve
Them
ART in the chronically HIV infected
Treatment options
Adherence
Drug interactions
Toxicities
Goals of Therapy
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Eradication of HIV? Not yet…
“…in spite of plasma RNA below
detection there is evidence of genetic
evolution in reservoirs.”
Goals of Therapy and Tools To Achieve
Goals
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Maximal and durable
suppression of viral
load
Restoration and/or
preservation of
immunologic function
Improvement of
quality of life
Reduction of HIVrelated morbidity and
mortality
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Maximize adherence
Rational sequencing
of therapy
Preservation of future
treatment options
Use of resistance
testing in selected
clinical settings
Before Initiating Therapy...
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Confirm HIV results
Complete H&P
CBC, chemistry profile
CD4 and T lymphocyte count
Plasma HIV RNA measurement
Assess “readiness” for rx &
adherence
Additional tests
Before Initiating Therapy
Additional Tests
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VDRL
PPD
Chest x-ray
Hepatitis A,B,C
serology
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Gynecology exam
with pap smear
Ophthalmology
exam (CD4+ T cell
<100)
Toxoplasma titer
CMV serology (if
indicated by
history)
Considerations in Initiating Therapy
HIV Asymptomatic
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Theoretical benefit
No proven long-term clinical benefit
for CD4 >200 cells/ml3
Expert opinion advises initiation of
therapy for CD4 <350 cells/ml3 at any
viral load
— Consider the viral load when > 350
cells/ml3 CD4+ T cell
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The “downside” of antiretroviral
regimens
Considerations in Initiating Therapy
HIV Asymptomatic
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Willingness of patient to begin and
the likelihood of adherence
Degree of immunodeficiency
Plasma HIV RNA
Risk of disease progression
Potential risks and benefits
Indications for ART in the
Chronically HIV-Infected Patient
TREAT ALL
(regardless of viral load)
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Symptomatic (AIDS, severe
symptoms)
Asymptomatic, CD4+ <200 cells/mm3
Asymptomatic, CD4+ >200/mm3 but
<350 cells/ mm3 *
* Treatment should generally be offered, though controversy
exists
Indications for ART in the
Chronically HIV-Infected Patient
TREAT
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Asymptomatic
CD4+ >350/mm3
HIV RNA>30,000(bDNA)/55,000(RT-PCR)*
* Some experts would recommend initiating therapy, recognizing that the 3
year risk of developing AIDS in untreated patients is >30%. In the
absence of very high levels of plasma HIV RNA, some would defer
therapy and monitor the CD4+ and level of plasma HIV RNA more
frequently. Clinical outcomes data after initiating therapy are lacking.
Indications for ART in the
Chronically HIV-Infected Patient
DEFER TREATMENT
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Asymptomatic
CD4+ cells > 350/mm3
HIV RNA <30,000(bDNA)/55,000(RTPCR)*
* Many experts would defer therapy and observe, recognizing that
the 3 year risk of developing AIDS in untreated patients is <15%.
Indications for ART in the
Chronically HIV-Infected Patient
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Clinical benefit has been demonstrated for
patients w/ CD4 <200 mm3. However, most
experts would offer therapy at a CD4 threshold
<350 mm3.
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All decisions should be based on prognosis for
disease-free survival in the absence of treatment,
as determined by the CD4 count and viral load
(Table V), the potential benefits and risks of
therapy (Table IV), and the willingness of the
patient to accept therapy. For further information,
see text.
WHO HIV Staging System
WHO HIV Staging System
WHO Guidelines for ARV Therapy in
Resource Limited Settings
Scaling Up Antiretroviral Therapy In Resource-limited Settings Guidelines For A
Public Health Approach- WHO 2002
WHO Guidelines for ARV Therapy in
Resource Limited Settings
Scaling Up Antiretroviral Therapy In Resource-limited Settings Guidelines For A Public Health Approach- WHO 2002
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
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Amprenavir
Atazamavir
Fosamprenavir
Indinavir
Lopinavir
Nelfinavir
Ritonavir
Saquinavir
— soft gel
— hard gel
APV
ATV
FPV
IDV
LPV
NFV
RTV
SQV
SGC
HGC
NNRTI
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Delavirdine
Efavirenz
Nevirapine
DLV
EFV
NVP
Fusion Inhibitor
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Enfuvirtide
T-20
Antiretroviral Activity:
An Historical Perspective
HIV RNA change (log10 c/mL)
1987: AZT
Monotherapy
1994:
Two-Drug Therapy
1997:
HAART
0
0
0
-0.5
-0.5
-0.5
-1
-1
-1
-1.5
-1.5
-1.5
-2
-2
-2
-2.5
-2.5
-2.5
-3
24-week response
-3
24-week response
Fischl, NEJM, 1987
Katzenstein, NEJM, 1996
Eron, NEJM, 1995;
Hammer, NEJM, 1996
-3
24-week response
Gulick, NEJM, 1997;
Cameron, Lancet, 1998
Goal of ARV Therapy: Prolonged
Virologic Suppression
% With VL BLQ
Past
Present
(Two-Drug Therapy) (Three-Drug Therapy)
Future
100
100
100
80
80
80
60
60
60
40
40
40
20
20
20
0
0
0
Weeks
MonthsYears
Decades
Antiretroviral Components in
Initial Therapy: NNRTIs
ADVANTAGES
 Less fat
maldistribution and
dyslipidemia than
PI-based regimens
 PI options
preserved for future
use
DISADVANTAGES
 Resistance - single
mutation
 Cross resistance
among NNRTIs
 Rash
 Potential drug
interactions
(CYP450)
Antiretroviral Components in
Initial Therapy: PIs
ADVANTAGES
 NNRTI options
preserved for future
use
 Longest prospective
data
DISADVANTAGES
 Metabolic
complications (fat
maldistribution,
dyslipidemia, insulin
resistance)
 Greater potential for
drug interactions
(CYP3A4)
Antiretroviral Components in
Initial Therapy: NRTIs
ADVANTAGES
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DISADVANTAGES
Established backbone
 Lactic acidosis
of combination therapy
reported with most
Limited cross
NRTIs
resistance within the
 Triple NRTI regimens
class
show inferior virologic
Minimal drug
response compared to
interactions
efavirenz-based and
Triple NRTI regimen of
indinavir-based
abacavir + lamivudine +
regimens
zidovudine (or
stavudine)* spares PI
and
NNRTI
fortriple
future
*This
is the only
NRTI regimen considered acceptable (as
an “alternative” regimen)
options
Initial Treatment: NNRTIBased Regimens
#pills
/day
Preferred
Regimen
Efavirenz +lamivudine + (zidovudine or
tenofovir or stavudine)*
*Avoid in pregnant women or women with pregnancy potential
3-5
Initial Treatment: NNRTIBased Regimens
#pills
/day
Alternative
Regimens
Efavirenz
+ emtricitabine +
(zidovudine or tenofovir or stavudine)*
3-4
Efavirenz
3-5
+ (lamivudine or
emtricitabine) + didanosine*
Nevirapine
+ (lamivudine or
emtricitabine) + (zidovudine or
stavudine or didanosine)
*Avoid in pregnant women or women with pregnancy potential
4-6
Initial Treatment: PI-Based
Regimens
#pills
/day
Preferred
Regimen
Lopinavir/ritonavir (Kaletra) + lamivudine +
(zidovudine or stavudine)
8-10
Initial Treatment: PI-Based
#pills
Regimens
/day
Amprenavir/ritonavir
+ (lamivudine or
emtricitabine) + (zidovudine or stavudine)
Alternative
Regimens
Atazanavir + (lamivudine or emtricitabine) +
(1)
(zidovudine or stavudine)
Indinavir
+ (lamivudine or emtricitabine) +
(zidovudine or stavudine)
Indinavir/ritonavir
+ (lamivudine or
emtricitabine) + (zidovudine or stavudine)
12-14
4-6
8-10
8-12
Initial Treatment: PI-Based
Regimens
#pills
/day
Lopinavir/ritonavir
(Kaletra) + emtricitabine
+ (zidovudine or stavudine)
Alternativ
e
Nelfinavir + (lamivudine or emtricitabine) +
Regimens (zidovudine or stavudine)
(2)
Saquinavir
(hard or soft gel
capsule)/ritonavir + (lamivudine or
emtricitabine) + (zidovudine or stavudine)
8-9
6-14
14-16
Initial Treatment: NRTI-Based
Regimens* #pills/
day
Alternative Abacavir + lamivudine +
to NNRTI- or zidovudine (or stavudine)
PI-based
regimen
2-6
* To be used only when an NNRTI- or PI-based
regimen cannot or should not be used as first line
therapy
Antiretroviral Medications:
Not Recommended in Initial
Treatment
Modest antiviral
activity
Delavirdine
High pill burden
Amprenavir
Zidovudine
+ zalcitabine
Saquinavir
soft gel capsule
Nelfinavir + saquinavir
High incidence of
toxicities
Stavudine
+ didanosine
Ritonavir used as sole PI
Antiretroviral Medications:
Should not be offered
Regimens not recommended:
—Monotherapy (except in prevention of perinatal
HIV transmission)
—Dual NRTI therapy
—3-NRTI regimen with abacavir + tenofovir
+ lamivudine
—3-NRTI regimen with didanosine +
tenofovir + lamivudine
Antiretroviral Medications:
Should not be offered
Antiretroviral components not recommended:
—Stavudine + didanosine
—Efavirenz in pregnancy
—Saquinavir hard gel capsule (Invirase) as single PI
—Stavudine + zidovudine
—Zalcitabine + stavudine; zalcitabine + didanosine
—Atazanavir + indinavir
—Emtricitabine + lamivudine
—Amprenavir oral solution in pregnancy, in children
<4 years, in renal or hepatic failure, or in patients
treated with metronidazole or disulfiram
—Hydroxyurea
3TC and ZDV Plus Efavirenz or
Indinavir in Naïve Patients: DMP 006
302 HIV-infected
patients
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Open-label study
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Efavirenz 600 mg QD
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Indinavir 800 mg q8h
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Data presented at
48 weeks as % of
patients with viral
load <50 c/ml
EFV
% <50 c/mL
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100
90
80
70
60
50
40
30
20
10
0
IDV
AT
ITT
EFV+IDV arm omitted
Staszewski S, et al. NEJM, 1999;341:1865-1873.
Combivir Plus Nelfinavir or Nevirapine
in Naïve Patients: COMBINE
142 antiretroviralnaïve patients
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Open-label study
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Nelfinavir 1250 mg
BID
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Nevirapine 200 mg
BID
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Data presented at 12
months as % of
patients with viral
load <20 c/ml
NVP arm
% <20 c/mL
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100
90
80
70
60
50
40
30
20
10
0
NFV arm
AT
ITT
Podzamczer D, et al. 1st IAS, 2001: Abst. 7.
ABC/COM is Comparable to IDV/COM
in HIV-1 Infected Antiretroviral-Naïve
Adults: CNA3014
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342 antiretroviralnaïve patients
60
60
Open label study
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Median baseline viral
load: 54,000 c/mL
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48 week data
presented as % of
patients with viral
load <50 c/mL (ITT:
Missing/Switch =
Failure)
50
50
% <50 c/mL
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40
30
20
10
0
ABC
IDV
Vibhagool A, et al. 1st IAS, 2001: Abst. 63.
Lopinavir/r vs Nelfinavir in AntiretroviralNaïve Subjects: M98-863
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p=0.001
Randomized,
double-blind trial
Patients nearly ARTnaïve (n=653)
d4T/3TC plus either
lopinavir/ritonavir
BID or nelfinavir TID
Data analyzed at 60
weeks, ITT, % of
patients with viral
load <20 c/ml
70
63
60
% <20 c/mL
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51
50
40
30
20
10
0
LPV/RTV
NFV
Ruane P, et al. 1st IAS, 2001: Abst. 6.
Predicting Long-Term Suppression in
ARV-Naïve Patients: Evidence-Based Data
ITT Analysis of VL <400 c/mL at Week 48
Dupont 006: EFV + ZDV + 3TC
Dupont 006: IDV + ZDV + 3TC
BMS Start I: IDV + ZDV + 3TC
BMS Start I: IDV + d4T + 3TC
Atlantic: IDV + d4T + ddI
Agouron 542: NFV TID + d4T + 3TC
Agouron 542: NFV BID + d4T + 3TC
Abbott 863: NFV + d4T + 3TC
Abbott 863: LPV/r + d4T + 3TC
Percent: 0
10
20
30
40
50
60
70
Note: Randomized comparative trials with 100 subjects/arm; populations’ entry criteria and
adherence differ for each trial.
80
The Advantage of Sequencing
Drugs
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To extend the overall long-term
effectiveness of the available therapy
options
Delay the risk of certain side effects
uniquely associated with a single
class of drugs
Anticipates up to 50% of failure rate
and preserves future treatment
options
Adherence
Adherence
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“The achilles heel of HAART”
— G. Friedland
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“Drugs don’t work if people don’t
take them.”
— C. Everett Koop
Adherence
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The “rule” of thirds…
— 1/3 take medication as prescribed
— 1/3 are intermittently adherent
— 1/3 take little or no medication
Correlation Between Optimal Therapeutic Response and
Adherence to Protease Inhibitor Therapy

Prospective, observational study, n = 81
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Subjects’ adherence to PIs assessed electronically
using Medication Event Monitoring System (MEMS)
— Median follow-up: 6 months (range 3 - 15 months)

Baseline demographics
— CD4 count ranged from <50 cells/mm3 (14% of subjects) to
>500 cells/mm3 (27% of subjects)
— HIV RNA ranged from <400 c/mL (30% of subjects) to
>100,000 c/mL (11% of subjects)
Paterson D, et al. Ann Intern Med. 2000;133:21-30.
What Degree of Adherence
Is Needed?
Patients With Virologic Failure (%)
Adherence to a PI-Containing Regimen Correlates
With HIV RNA Response at Median 6 Months
100
82.1
80
66.7
71.4
54.6
60
40
21.7
20
0
<70
70-80
80-90
Adherence (%)
Paterson. Ann Intern Med 2000;133:21.
90-95
>95
What Happens
to Adherence Over Time?
Adherence Declines Over Time (Treatment Fatigue)
100%
80
80%-100%
0%-80%
70
Patients (%)
60
50
40
30
20
10
0
1 Month
4 Months
Mannerheimer. 13th IAC; 2000; Durban. Abstract 421.
8 Months
CPCRA 057, 058
Duration of Antiretroviral Adherence
Predicts Biologic Outcomes
in Clinical Trials
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Randomized clinical trials (n = 732 subjects)
— Patients had 1 month follow-up
— Adherence measured using confidential, self-report, 7-day
recall questionnaires

Results up to 12 months
Adherence
 HIV RNA
(log10 c/mL)
% HIV RNA
<50 c/mL
 CD4
(cells/mm3)
0 - 79%
80 - 99%
100%
-0.65
-2.27
-2.72
19%
46%
70%
41
175
152
Friedland GH, et al. 1st IAS, 2001: Abst. 33.
Virologic Response by Daily
Pill Burden
Size of symbol is directly
proportional to weight of
data point in the analysis
Bartlett JA, et al. AIDS, 2001; 15:1369-1377.
Who Will Be Adherent?

Age, race, sex, socioeconomic level
educational level, socioeconomic
status, and a past history of
alcoholism or drug use are not
reliable predictors of poor adherence

Active drug use or alcoholism,
unstable housing, mental illness, and
major life crises ARE predictors of
poor adherence
Adherence – Predicting Success

The more severe the symptoms or
illness the better adherence

Improved adherence if patients
believe in efficacy of treatment
Adherence – Keep It Simple
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Once daily therapy - 90% adherence
Twice daily therapy - 80% adherence
Three or more times daily - 65%
adherence
Improving Adherence

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A trusting provider-patient
relationship
Education
Development of treatment plan with
patient
Social support network
Simple regimen
Adherence in Special Populations
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Flexible clinic hours
Accessible clinical staff
Incentives
Bilingual staff
Adherence discussion during
support groups
Individualized adherence programs
Others?
Adherence Strategies
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Negotiate a treatment plan
Assess patient readiness
Educate
Reminder devises
Social support
Others?
Poor Adherence – Now What?

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Increase the intensity of clinical
follow up
Shorten the follow up interval
Recruit additional health team
members
— Mental health
— Chemical dependency counselor
— Others


Involve family and friends
Take a break
Simplified Dosing Strategies NRTIs
Initially
recommended dose (mg)
Amended
dose (mg)
ddI
200 BID
400 QD
(pill, suspension)
AZT
100 five times a day
300 BID
AZT + 3TC
AZT 300 BID
3TC 150 BID
1 (300/150) pill BID
(Combivir)
AZT + 3TC + ABC
AZT 300 BID
3TC 150 BID
ABC 300 BID
1 (300/150/300) pill BID
(Trizivir)
IV - Changing Therapy
AETC NRC Slide Set
Version 1.0, February 2001
IV. Changing Therapy:
Contents
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Considerations
Patterns of change
Criteria for change
Alternatives
Monitoring
Testing for resistance
Treatment interruption
Changing Therapy:
Considerations
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Recent clinical history and physical
examination
Two plasma HIV RNA levels
CD4+ T cell count
Remaining treatment options
Assessment of adherence
Patient education
Changing Therapy
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Drug failure or drug toxicity?
Medication adherence
Pharmacology & drug interactions
Testing for antiretroviral drug
resistance
Changing Therapy
Three Different Patients - 1
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Individuals who are receiving
incompletely suppressive
antiretroviral therapy with detectable
or undetectable plasma viral load
Changing Therapy
Three Different Patients - 2

Individuals who have been on potent
combination therapy and whose
viremia was initially suppressed to
undetectable levels but has again
become detectable
Changing Therapy
Three Different Patients - 3

Individuals who have been on potent
combination therapy and whose
viremia was never suppressed to
below detectable limits.
Criteria for Changing Therapy

Less than a 0.5-0.75 log reduction in
plasma HIV RNA by 4 weeks
following initiation of therapy, or less
than a 1 log reduction by 8 weeks
(CIII)
Criteria for Changing Therapy

Failure of a 1st or 2nd line regimen to
suppress plasma HIV RNA to undetectable
levels within 4-6 months of initiating
therapy (BIII)

Repeated detection of virus in plasma
after initial suppression to undetectable
levels, suggesting the development of
resistance (BIII)
Criteria for Changing Therapy

Any reproducible significant
increase, defined as 3-fold or greater,
from the nadir of plasma HIV RNA in
two or more consecutive viral loads
not attributable to intercurrent
infection, vaccination, or test
methodology except as noted above
(BIII)
Criteria for Changing Therapy

Undetectable viremia in the patient
receiving double nucleoside therapy
(BIII)

Persistently declining CD4+ T cell
numbers, as measured on at least
two separate occasions (CIII)

Clinical deterioration (DIII)
Changing Therapy
Other Considerations




Adherence
Results of resistance testing
Limited choices
Reduction of future choices
Change Options
Patient With Intolerance to One Drug



Substitute for offending drug
Use agent in same class
Changing other medications
unnecessary
Change Options
Patient on Non-preferred Regimen
Viral Load below detection
 Continue treatment and carefully
monitor* or
 Add drugs to the current regimen
(intensify) in limited defined setting
*most authorities feel that treatment with regimens not in the strongly
recommended category is associated with eventual failure and
recommend the latter tactic.
Change Options
Patient on Recommended Regimen




Few specific
strategies
Theoretical
considerations
should guide
decisions
Broad crossresistance among
drugs within a
class
Reinforcement of
adherence




Guided by
resistance testing
Option to delay
changing therapy
Consult an
experienced
clinician
Evidence of better
outcomes with
using a new class
Implications of Treatment Failure
at 2 Years
EuroSIDA Cohort (n = 8507)
Regimen
cohort
Virologic
failure (VL >
500 c/mL)
Immune and
clinical
Clinical
failure
events
20%
5%
1st HAART
40%
2nd HAART
50%
30%
24%
3rd HAART
67%
40%
25%
Mocroft A, et al. Antivir Ther, 2000.
Interruption of
Antiretroviral Therapy





Intolerable side effects
Drug interactions
First trimester pregnancy
Unavailability of drugs
Numerous other possible causes
Interruption of
Antiretroviral Therapy

Stop all antiretroviral medications at
once
V - Special Issues
V. Special Issues:
Contents





Acute HIV infection
Advanced HIV infection
Adolescents
Interruption of therapy
Adherence
Early Intervention Theory







Should be limited to the clinical trial
setting
Suppress the initial burst of viral
replication
Decrease the severity of acute
disease
Alter the viral “set point”
Reduce the rate of mutation
Reduce risk of viral transmission
Preserve immune function
Risks and Benefits of Delayed
Initiation of Therapy
BENEFITS
 Avoid negative effects
on quality of life
 Avoid drug-related
adverse events
 Delay in development
of drug resistance
 Preserve maximum
number of available
and future drug
options when HIV
disease risk is highest
RISKS
 Possible risk of
irreversible immune
system depletion
 Possibly greater
difficulty in
suppressing viral
replication
 Easier to transmit HIV
to others
Risks and Benefits of Early
Therapy
BENEFITS
 Control of viral
replication easier to
achieve and maintain
 Delay or prevention of
immune system
compromise
 Lower risk of
resistance with
complete viral
suppression
 Decreased risk of HIV
transmission
RISKS
 Drug-related
reduction in quality of
life
 Greater cumulative
drug-related adverse
events
 Earlier development
of drug resistance, if
viral suppression is
sub optimal
 Limitation of future
antiretroviral
The Patient With Advanced
Disease
Treatment of the Patient With
Advanced HIV Disease

Offer to all with AIDS and patients
with symptomatic HIV infection with
thrush or unexplained fever
Clinical Issues in the Patient With
Advanced HIV Disease




Drug toxicity
Ability to adhere
Drug interactions
Laboratory abnormalities
Advanced HIV Infection



Often complicated drug regimens
Wasting and anorexia
Co-infection
Treatment of the Patient with
Advanced HIV Disease

Recovery of immune function

Immune reconstitution syndromes :
Immunologic response to subclinical pathogen, e.g.: MAC or CMV

Immune reconstitution syndromes
are different from clinical failure

Treat new opportunistic infections
The HIV Infected Adolescent


Timing of infection; perinatal vs.
acquired as an adolescent
Early intervention
The HIV Infected Adolescent



Normal adolescent development
Drug pharmacology in puberty
Dosing based on Tanner stages