The document provides guidelines for initiating antiretroviral therapy (ART) including: - ART is recommended for all patients with a CD4 count ≤350 cells/μL, and is moderately recommended for those with a CD4 count >500 cells/μL. - Earlier ART may prevent end organ damage, improve clinical outcomes, and reduce HIV transmission. However, there are also risks of drug toxicities and resistance with early treatment. - Preferred initial ART regimens include combinations of two nucleoside reverse transcriptase inhibitors (NRTIs) plus an integrase inhibitor, non-nucleoside reverse transcriptase inhibitor (NNRTI), or protease inhibitor (PI). Guidelines are updated

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
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4. Goal of HIV Therapy: Stop the Virus!

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
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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
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8. Websites to Access the Guidelines
 http://aidsinfo.nih.gov
 http://www.aidsetc.org
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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
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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
*
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11. Studies in patients CD4>500
 Favor Treatment  Neutral on Treatment
 NA-ACCORD  ART-CC
 CASCADE
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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
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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)
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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
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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
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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
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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
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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
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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
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20. Potential Limitations of Early Therapy
(CD4 count >500 cells/µL)
 ARV-related toxicities
 Drug resistance
 Non-adherence to ART
 Cost
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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?
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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
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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
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24. Initial ART Regimens: DHHS Categories
 Preferred
 Randomized controlled trials show optimal efficacy and
durability
 Favorable tolerability and toxicity profiles
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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)
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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)
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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.

28. Drug-Drug Interactions
Too Common
Always check new medications
Resources: Guidelines, Uptodate,
Epocrates
October 2011 www.aidsetc.org

29. Websites to Access the Guidelines
 http://www.aidsetc.org
 http://aidsinfo.nih.gov
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