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Slide 1 of 11
From CB Hicks, MD, at Chicago, IL: May 20, 2013, IAS-USA. IAS–USA
Charles B. Hicks, MDProfessor of Medicine
Duke University Medical CenterDurham, North Carolina
New Guidelines, Strategies, and Drugs for Initiation of
Antiretroviral Therapy 2013
From CB Hicks, MD, at Chicago, IL: May 20, 2013, IAS-USA.
clinicaloptions.com/hivImproving Practical Skills for Primary Care of HIV-Infected Patients Slide 2 of 11
From CB Hicks, MD, at Chicago, IL: May 20, 2013, IAS-USA.
Goals of Antiretroviral Therapy
Reduce HIV-associated morbidity and prolong duration and quality of survival
Restore and preserve immunologic function
Maximally and durably suppress HIV-1 RNA
– Persistently below level of detection (< 20-75 copies/mL, depending on the assay used)
– Isolated “blips” not uncommon in successfully treated patients and not thought to predict virologic failure
Prevent HIV transmissionDHHS Guidelines for Antiretroviral Therapy in Adults and Adolescents. March 2012.
clinicaloptions.com/hivImproving Practical Skills for Primary Care of HIV-Infected Patients Slide 3 of 11
From CB Hicks, MD, at Chicago, IL: May 20, 2013, IAS-USA.
Changing Criteria for Antiretroviral Therapy Initiation in DHHS GuidelinesCD4+ Count, cells/mm3
1998 2001 2006 2008 2009 2012
> 500 Offer if VL > 20K
Offer if VL > 55K
Consider if VL ≥ 100K
Consider in certain groups*
Consider† Treat
110-500 Offer if VL > 20K
Consider if VL > 55K
Consider if VL ≥ 100K
Consider in certain groups*
Treat Treat
200-110 Offer if VL > 20K
Offer, but controversy
exists
Offer after discussion with patient
Treat Treat Treat
< 200 or symptomatic Treat Treat Treat Treat Treat Treat
*Pregnant women, patients with HIV-associated nephropathy, and patients with HBV that requires treatment.†50% of panel members recommended starting antiretroviral therapy; 50% of members viewed treatment as optional.
Wilkin T, et al. Available at: http://inpractice.com.
Slide 4 of 11
From CB Hicks, MD, at Chicago, IL: May 20, 2013, IAS-USA.
• CD4 cell count <110 cells/mm3 (AI)• CD4 cell count 110-500 cells/mm3 (AII)• CD4 cell count >500 cells/mm3 (BIII)
• Pregnancy (AI)• History of an AIDS-defining illness (AI)• HIV-associated nephropathy (AII)• HIV/HBV coinfection (AII)
When to Start: 2013 DHHS Guidelines
ART is recommended for all HIV-infected individuals;
strength of recommendation varies according to CD4 cell
count.
ART is strongly recommended for
individuals with the following conditions regardless of
CD4 cell count.
HBV = hepatitis B virus.DHHS guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. February 12, 2013. Available at: http://aidsinfo.nih.gov. Accessed February 21, 2013.
Changes reflect increasing evidence of the harmful impact of ongoing HIV replication on AIDS and non-AIDS disease progression and
the benefit of effective ART in preventing secondary transmission of HIV.
4
Slide 5 of 11
From CB Hicks, MD, at Chicago, IL: May 20, 2013, IAS-USA.
When to Start: IAS-USA 2012 Guidelines
• “When HIV is allowed to replicate uninhibited by ART, resultant immune activation and inflammation are associated not only with immune destruction and opportunistic infections but also increased rates of cardiovascular, renal, hepatic, and neurologic diseases; malignancies; and other serious non-AIDS diseases”
• “Evidence from clinical trials, observational cohorts, and pathogenesis studies all point toward the health benefits of earlier ART”
All adults with HIV infection should be offered ART regardless of CD4 cell count.
IAS-USA = International Antiviral Society-USA.Thompson MA et al. JAMA. 2012;308:387-402.
5
From CB Hicks, MD, at Chicago, IL: May 20, 2013, IAS-USA.
Slide 6 of 11
From CB Hicks, MD, at Chicago, IL: May 20, 2013, IAS-USA.
NA-ACCORDRisk of death associated with deferral of ART, according to CD4+ count at baseline, adjusted for HIV RNA level, age, and sex*
Deferred ART was associated with a 69% increase in risk of death versus early initiation in patients with CD4 111-500; 94% increase in risk of death for patients with CD4 >500
Kitahata MM, Gange SJ, Abraham AG, et al. N Engl J Med. 2009;360(18):1815-1826.
Slide 7 of 11
From CB Hicks, MD, at Chicago, IL: May 20, 2013, IAS-USA.
CNICS: Viremia Copy-Years Predicts Mortality
“Viremia copy-years, a measure of
cumulative plasma HIV RNA exposure and de novo viral
replication, demonstrated a
strong association with all-cause
mortality in a large sample of HIV-
infected patients who started ART.”
Mugavero MJ, Napravnik S, Cole SR, et al. CID. 2011;53:927-911.
Slide 8 of 11
From CB Hicks, MD, at Chicago, IL: May 20, 2013, IAS-USA.
HPTN 052: 96% Reduction in HIV Transmission
Cohen, MS et al. N Engl J Med. 2011;365:493-505.
Kaplan–Meier estimate for the cumulative probabilities of linked HIV-1 transmission between partners among participants in the early-therapy and delayed-therapy groups
clinicaloptions.com/hivImproving Practical Skills for Primary Care of HIV-Infected Patients Slide 9 of 11
From CB Hicks, MD, at Chicago, IL: May 20, 2013, IAS-USA.
When to Start Therapy: Balance Now Favors Earlier Antiretroviral Therapy
Drug toxicity Preservation of limited Rx
options Risk of resistance (and
transmission of resistant virus)
↑ potency, durability, simplicity, safety of current regimens
↓ emergence of resistance ↓ toxicity with earlier therapy ↑ subsequent treatment options Risk of uncontrolled viremia Near normal survival if CD4+ > 500 ↓ transmission
Early Antiretroviral Therapy
Delayed Antiretroviral TherapySlide from Joel E. Gallant, MD, MPH.
Slide 10 of 11
From CB Hicks, MD, at Chicago, IL: May 20, 2013, IAS-USA.
-24 -12 0 12 24 36 480
2
4
6
8
Percentage with VL≥50 copies/ml and 95% CI at 12 week intervals before and after the switch from STR to MTR
VL
≥5
0 c
op
ies
/ml (
%)
Conclusion: In a well-organized health care setting (free access to ART), switch from TDF/FTC/EFV to a MTR did not change virologic response Caveats: Generalizability may be limited by single population, observation time
Change from STR to Multi-tablet Regimen (MTR) After Virologic Suppression
509 patients on STR (TDF/FTC/EFV); 478 (94%) switched to TDF + 3TC + EFV (MTR)
Eligibility STR - first cART regimen in 215 (42%)On TDF/FTC/EFV ≥ 1 year prior to the change to MTRNo known compliance problems
Engsig F, et al. 20th CROI; Atlanta, GA; March 3-6, 2013. Abst. 579.
Number a risk: Weeks before and after the switch to MTR
507 508 509 504 498 486 470
Switched from STR to MTR
P=ns for change in %VF from wk 0-48
Slide 11 of 11
From CB Hicks, MD, at Chicago, IL: May 20, 2013, IAS-USA.
Early ART in Patients With Acute OIs Reduces Risk of AIDS Progression or Death• Randomized strategy trial of
early vs deferred ART in patients with acute OIs
• Results:– 282 enrolled, median
CD4 29; OIs: PCP 63%, bacterial infection 12%
– Early ART associated with reduced risk of new AIDS complications or death
• Supports starting ART within 14 days of OI diagnosis
OI = opportunistic infection; PCP = Pneumocystis jiroveci pneumonia.
Zolopa A et al. PLoS ONE. 2009;4:e5575.
Pro
ba
bil
ity
of
Su
rviv
ing
Wit
ho
ut
De
ath
/Ne
w A
IDS
-De
fin
ing
Ev
en
t
1.00.90.80.70.60.50.40.30.20.1
0 4 8 12 16 20 24 28 32 36 40 44 48
Early Deferred
No. at Risk141141
129117
124108
11998
11694
Early
Deferred
Time to Death/New AIDS-Defining Event(weeks)
11
From CB Hicks, MD, at Chicago, IL: May 20, 2013, IAS-USA.