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SYNCing Guidelines- Catanzaro
1. Guideline Summary:
When to Start ART
Guidelines for the Use of
Antiretroviral Agents
in Adults and Adolescents
Andy Catanzaro, MD
Infectious Diseases
acatanzaro@unityhealthcare.org
March 2012
2. Outline
Overview of HIV therapy
Initiation of Therapy
Special Issues
2 October 2011 www.aidsetc.org
3. HIV Terms/Acronyms
Terms
ART: Antiretroviral Therapy
HIV Viral Load: amount of virus in the blood
Undetectable Viral Load: Goal of Therapy
CD4 Count: Immune Marker
Genotype: Sensitivity of the Virus to
Medications
3 October 2011 www.aidsetc.org
5. What are ‘The Guidelines’ for HIV Therapy
Independent panel of experts
Review Current Literature on HIV
Make Recommendations
Strength of Evidence given for each
guidance
(www.aidsinfo.nih.gov)
October 2011 www.aidsetc.org
6. What the Guidelines Address
Baseline evaluation
Laboratory testing
When to initiate & change therapy
Therapeutic options
ART-associated adverse effects
6
7. What the Guidelines Address
Treatment of acute HIV infection
Special considerations (pregnant,
injection drug users, coinfected with
HBV, HCV, or TB)
Preventing secondary transmission
7
8. Websites to Access the Guidelines
http://aidsinfo.nih.gov
http://www.aidsetc.org
8
9. Goals of Treatment
Improve quality of life
Reduce HIV-related morbidity and
mortality
Restore and/or preserve immunologic
function
Suppress HIV viral load
Prevent HIV transmission
9
10. Use of CD4 Cell Levels to Guide
Therapy Decisions
CD4 count
The major indicator of immune function
Most recent CD4 count is best predictor of
disease progression
A key factor in decision to start prophylaxis
Important in determining response to ART
Adequate response: CD4 increase 50-150 cells/µL per year
*
10
11. Studies in patients CD4>500
Favor Treatment Neutral on Treatment
NA-ACCORD ART-CC
CASCADE
11
12. ART in Treatment Recommended for
All Patients
CD4 count Strength of the Evidence for the
Recommendation Recommendation
<350 Strong Data from randomized clinical trials
350-500 Strong Data from non-randomized clinical
trials
>500 Moderate Expert Opinion
12
13. Use of HIV RNA Levels to Guide
Therapy Decisions
HIV RNA
May influence choice of ART
Critical in monitoring response to ART
Goal of ART: HIV RNA below limit of detection
(ie, <20-75 copies/mL, depending on assay)
13
14. Use of HIV RNA Levels to Guide
Therapy Decisions (2)
RNA monitoring
Check at baseline
Before initiating ART
2-4 weeks (not more than 8 weeks) after start or change of
ART, then every 4-8 weeks until suppressed to <200
copies/mL
Every 3-4 months with stable patients; may consider every 6
months for stable adherent patients with VL suppression >2-3
years
Isolated “blips” may occur (transient low-level RNA, typically
<400 copies/mL), are not thought to predict virologic failure
ACTG defines virologic failure as confirmed HIV RNA >200 copies/
mL
14
15. When to Start ART
Potent ART may improve and preserve immune
function in most patients with virologic suppression,
regardless of baseline CD4 count
ART indicated for all with low CD4 count or symptoms
Earlier ART may result in better immunologic responses
and better clinical outcomes
Reduction in AIDS- and non-AIDS-associated morbidity and
mortality
Reduction in HIV-associated inflammation and associated
complications
Reduction in HIV transmission
Recommended ARV combinations are considered to be
durable and tolerable
15
16. When to Start ART
Exact CD4 count at which to initiate therapy not known,
but evidence points to starting at higher counts
Current recommendation: ART for all patients with CD4
Randomized control trial (RTC) data support benefit of ART if
CD4 count ≤350 cells/µL
No RTC data on benefit of ART at CD4 counts of >350 cells/µL,
but observational cohort data exist
Currently available ARVs are effective and well tolerated
16
17. Potential Benefits of Early Therapy
(CD4 count >500 cells/µL)
Cohort study data show survival benefit if ART
initiated at CD4 count >500 cells/µL
Earlier ART may prevent HIV-related end organ
damage; deferred ART may not reliably repair
damage acquired earlier
Increasing evidence of direct HIV effects on various
end organs and indirect effects via HIV-associated
inflammation
End organ damage occurs at all stages of infection
17
18. Potential Benefits of Early Therapy
(CD4 count >500 cells/µL) (2)
Potential decrease in risk of many
complications, including:
HIV-associated nephropathy
Liver disease progression from hepatitis B or
hepatitis C
Cardiovascular disease
Malignancies (AIDS defining and non-AIDS defining)
Neurocognitive decline
Blunted immunological response owing to ART
initiation at older age
Persistent T-cell activation and inflammation
18
19. Potential Benefits of Early Therapy
(CD4 count >500 cells/µL) (3)
Prevention of sexual and blood borne
transmission of HIV
Prevention of mother-to-child
transmission of HIV
Prevention of transmission to a sexual
partner
19
20. Potential Limitations of Early Therapy
(CD4 count >500 cells/µL)
ARV-related toxicities
Drug resistance
Non-adherence to ART
Cost
20
21. Recommendations for Initiating ART (3)
Patients may choose to postpone ART
Providers may elect to defer ART, based on
patients’ clinical or psychosocial factors
caveat: do we really know who is ready?
21
22. Consider More Rapid Initiation of ART
(e.g. before the genotype is available)
Pregnancy
Acute opportunistic infection
Lower CD4 count (eg, <200 cells/µL)
Rapid decline in CD4
Higher viral load
HIV Associated Nephropathy
HBV coinfection when HBV treatment is indicated
22
23. Consider Deferral of ART
Clinical or personal factors may support deferral
of ART
If CD4 count is low, deferral should be considered
only in unusual situations, and with close follow-up
When there are significant barriers to adherence
If comorbidities complicate or prohibit ART
“Elite controllers” and long-term nonprogressors
23
24. Initial ART Regimens: DHHS Categories
Preferred
Randomized controlled trials show optimal efficacy and
durability
Favorable tolerability and toxicity profiles
24
25. Initial Treatment: Choosing Regimens
3 main categories:
1 Non-nucleoside Reductase Inhibitor + 2 Nucleside
Reductase Inhibitor (NRTI)
1 Protease Inhibitor + 2 NRTIs
1 Integrase Inhibitor + 2 NRTIs
Combinations preferred for most patients
(Bias: Once Daily Preferred by patients)
25
26. Initial Therapy: Fixed Dose Combinations
Preferred: Once-daily dosing
High virologic efficacy
TDF/FTC Active against HBV
(Truvada) Potential for renal toxicity
Alternative: Once-daily dosing
Risk of hypersensitivity reaction if positive for
ABC/3TC HLA-B*5701
(Epzicom) Possible inferior efficacy if baseline HIV RNA
>100,000 copies/mL
Active against HBV
Acceptable: Twice-daily dosing
Preferred for pregnant women
ZDV/3TC More toxicities than TDF/FTC or ABC/3TC
(Combivir)
26
27. Initial Regimens: Preferred
NNRTI based EFV/TDF/FTC (Atripla) 1,
Protease ATV/r (Reyataz/Norvir) + TDF/
Inhibitor FTC (Truvada)
based DRV/r (Prezista/Norvir) + TDF/
FTC (Truvada)²
Integrase RAL (Isentress BID) +
Inhibitor based TDF/FTC (Truvada)
Pregnant women LPV/r (Kaletra BID) +
ZDV/3TC (Combivir)²
1. EFV should not be used during the first trimester of pregnancy or in
women trying to conceive or not using effective and consistent
27 contraception.
29. Websites to Access the Guidelines
http://www.aidsetc.org
http://aidsinfo.nih.gov
29
Notas do Editor
Summary of Recommended Regimens The most extensively studied combination antiretroviral regimens for treatment-naïve patients generally consist of two NRTIs plus either one NNRTI or a PI (with or without ritonavir boosting). A list of Panel-recommended components for initial therapy in treatment-naïve patients can be found in Table 6 . Potential advantages and disadvantages of the components recommended as initial therapy for treatment-naïve patients are listed in Table 7 to guide prescribers in choosing the regimen best suited for an individual patient. A list of agents or components not recommended for initial treatment can be found in Table 8 . Some agents or components that are not recommended for use because of lack of potency or potential serious safety concerns are listed in Table 9