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.

5From 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 co

pies

/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 MTR507 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.

Prob

abili

ty o

f Sur

vivi

ng W

ithou

tD

eath

/New

AID

S-D

efin

ing

Even

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

EarlyDeferred

Time to Death/New AIDS-Defining Event(weeks)

11From CB Hicks, MD, at Chicago, IL: May 20, 2013, IAS-USA.