Cco retroviruses_2013_art_slides

March 3-6, 2013Atlanta, Georgia

Highlights of Atlanta 2013: ART as Treatment and PreventionCCO Independent Conference Coverageof the 2013 Conference on Retroviruses and Opportunistic Infections*

*CCO is an independent medical education company that provides state-of-the-art medical information to healthcare professionals through conference coverage and other educational programs.

This program is supported by educational grants from

clinicaloptions.com/hivClinical Impact of New Data From Atlanta 2013

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Faculty

Joel E. Gallant, MD, MPHProfessor of Medicine and Epidemiology Associate Director, Johns Hopkins AIDS ServiceDivision of Infectious DiseasesJohns Hopkins University School of MedicineBaltimore, Maryland

Kathleen E. Squires, MDProfessor of Medicine Director, Division of Infectious DiseasesJefferson Medical CollegeThomas Jefferson UniversityPhiladelphia, Pennsylvania

Andrew R. Zolopa, MDAssociate Professor of MedicineDirector, Stanford Positive Care ProgramPrincipal Investigator, Stanford AIDS Clinical Trials UnitStanford University School of MedicineStanford, California


Disclosures

Joel E. Gallant, MD, MPH, has disclosed that he has received consulting fees from Bristol-Myers Squibb, Gilead Sciences, Janssen, Merck, and Takara Bio and funds for research support from Gilead Sciences.

Kathleen E. Squires, MD, has disclosed that she has received funds for research support from Biocryst, Gilead Sciences, Merck, and Vertex; has served on advisory boards for Abbott, Gilead Sciences, Janssen, Merck, Tobira, and ViiV; has received consulting fees from Tobira; and has served on a data and safety monitoring board for Pfizer.

Andrew R. Zolopa, MD, has disclosed that he has received funds for research support from Gilead Sciences, Pfizer, and Vertex and consulting fees from Bristol-Myers Squibb, Gilead Sciences, and Janssen.

DHHS Guideline Update


2013 Update: DHHS Guidelines on ART for HIV-Infected Adults and Adolescents ART is recommended for all HIV-infected, ART-naive pts to reduce

risk of disease progression and transmission

– Strength of recommendation varies by CD4+ cell count and risk group (perinatal, heterosexual, other)

– Pts should be ready to commit to ART and understand benefits and risks of therapy and importance of adherence; individual pts may elect to defer ART

Regarding alternative regimens for ART-naive patients

– RPV-based regimens recommended alternatives only for patients with baseline HIV-1 RNA ≤ 100,000 copies/mL

– Fixed-dose EVG/COBI/TDF/FTC recommended for patients with CrCl > 70 mL/min

– 3-NRTI regimens no longer recommendedDHHS Guidelines. February 2013.


2013 Update: DHHS Guidelines on ART for HIV-Infected Adults and Adolescents Pts failing INSTI-based regimens should undergo genotypic

assay for INSTI resistance to determine future utility of class

Genotypic tropism assay now available as potential alternative test prior to initiating CCR5 antagonist regimens

Patients with early infection should be offered ART

– “Early” HIV infection now refers to acute (after infection, prior to seroconversion) and recent (< 6 mos) infections

EFV may be continued in pregnant women with virologic suppression

New data on roles/mechanisms of RTV and COBI as pharmacokinetic enhancers

DHHS Guidelines. February 2013.

Cure Research


Very Early Triple-Drug ART Elicits “Functional Cure” in HIV-Infected Child Infant born to untreated HIV-infected mother at 35 wks’

gestation via spontaneous vaginal delivery[1]

– Maternal HIV infection identified during labor via ELISA and Western blot

– Infant HIV infection confirmed via HIV-1 DNA PCR, HIV-1 RNA analysis of 2 separate samples at 30 and 31 hrs of age[2]

– ZDV/3TC + NVP (at therapeutic dose) initiated at 31 hrs of age, continued for 7 days

– ZDV/3TC + LPV/RTV continued from 7 days to 18 mos of age

– HIV-1 RNA undetectable by Day 30

– Mother removed patient from care at 18 mos of age

1. Persaud D, et al. CROI 2013. Abstract 48LB. 2. DHHS Pediatric Guidelines. 2012.


“Functional Cure” Child: Standard HIV-1 Assays Undetectable to Age 26 Mos

Assessments at Mos 24 and 26

– Western blot negative

– No HIV-specific CD8+ or CD4+ T-cell responses

– Standard HIV-1 RNA and HIV-1 DNA undetectable

– By ultrasensitive assays

– Mo 24: HIV-1 RNA 1 c/mL; HIV-1 DNA < 2.7 c/million PBMCs

– Mo 26: HIV-1 DNA 4 c/million PBMCs

Clinical trials of exposed infants treated with ART recommended

Persaud D, et al. CROI 2013. Abstract 48LB.

ART regimens: ZDV/3TC + NVP (31 hours – 7 days)

ZDV/3TC + LPV/RTV (7 days – 18 months)

Plasma VL on ART displayed typical biphasic decay from baseline VL 19,812 c/mL

– VL undetectable by < 30d of age

– VL remained undetectable though > 80d of age


Early Treatment of Pts With Acute HIV Infection Restricts Seeding of Reservoirs RV254/SEARCH 010: ongoing, prospective, open-label study of subjects

seeking voluntary HIV testing (n = 75 with Fiebig stage I-III acute infection)

Before ART, HIV reservoir seeding limited

– Integrated HIV-1 DNA undetectable in PBMCs (92%) and sigmoid colon (88%) of most Fiebig I pts

– Lower infection frequencies of central memory CD4+ T cells vs other memory cells

After ART, decline in HIV reservoir size

– Integrated HIV-1 DNA undetectable in PBMCs in 90% of pts at 1 yr

– Reservoir primarily in transitionaland effector memory CD4+ T cells

Suggests very early ART may prevent seeding of reservoirs

Fiebig Stages

Fiebig I: RNA+, p24R neg, 3rd-gen ELISA neg

– Would not be detected by 4th-gen ELISA

Fiebig II: RNA+, p24+, 3rd-gen ELISA neg

Fiebig III: 3rd-gen ELISA+, WB neg

Ananworanich J, et al. CROI 2013. Abstract 47.


Vorinostat Activates HIV Transcription in Latently Infected CD4+ T Cells Vorinostat investigated as possible

strategy to eliminate latent HIV infection in pts on stable ART

– Histone deacetylase inhibitor approved for cutaneous T-cell lymphoma

– Single dose ↑ HIV-1 RNA expression in resting memory CD4+ cells of HIV-infected patients

– Activation may result in elimination of latently infected T cells

Current study is a single-arm trial of vorinostat 400 mg QD for 14 days (N = 20) in pts on stable ART, CD4+ count > 500 cells/mm3

18/20 pts had significant increase in cell-associated unspliced HIV-1 RNA on ≥ 2 occasions while on drug

– Mean 2.65-fold increase

All AEs mild (grade 1/2)

– Most common: diarrhea, lethargy, thrombocytopenia, dysgeusia

No significant changes in HIV-1 DNA in PBMCs or rectal tissue

– Suggests vorinostat alone not likely to eliminate latent infected cells

Elliott EJ, et al. CROI 2013. Abstract 50LB.


PrEP Trials to Date

Trial Population/Setting InterventionReduction in

HIV Infection Rate, %

CAPRISA[1]

(N = 899)High-risk women in

South Africa Coitally applied

vaginal TFV gel39

iPrEX[2] (N = 2499)

MSM, transgender women, 11 sites in US, South America,

Africa, Thailand Daily oral TDF/FTC 44

Partners PrEP[3] (N = 4747)

Serodiscordant couples in Africa

Daily oral TDF Daily oral TDF/FTC

Women: 71; men: 63 Women: 66; men: 84

TDF2[4]

(N = 1219)Heterosexual males and

females in Botswana Daily oral TDF/FTC 62*

FEM-PrEP[5]

(N = 2120)High-risk women in Africa Daily oral TDF/FTC

Equal numbers of infections in active and control arms

Study stopped for lack of efficacy

1. Abdool Karim Q, et al. Science. 2010;329:1168-1174. 2. Grant RM, et al. N Engl J Med. 2010;363: 2587-2599. 3. Baeten JM, et al. N Engl J Med. 2012;367:399-410. 4. Thigpen MC, et al. N Engl J Med. 2012;367:423-434. 5. Van Damme L, et al. N Engl J Med. 2012;367:411-422.

*Underpowered to detect differences between sexes


VOICE: Oral TDF, Oral TDF/FTC, Vaginal TFV Gel as PrEP in African Women Phase IIB placebo-controlled trial of > 5000 women in South Africa, Uganda,

and Zimbabwe of daily oral TDF, daily oral TDF/FTC, daily vaginal TFV 1% gel as PrEP

– DSMB stopped daily oral TDF arm in September 2011 and daily vaginal gel arm in November 2011, both for lack of efficacy; daily oral TDF/FTC arm continued

– 334 infections seen across 5 arms; 22 infected at enrollment

Primary Efficacy Results (mITT)

TDF*(n = 1007)

Oral Placebo*

TDF/FTC(n = 1003)

Oral Placebo

TFV Gel(n = 1007)

GelPlacebo

Infections, n 52 35 61 60 61 70

Infections/100 PY 6.3 4.2 4.7 4.6 5.9 6.8

Protective Efficacy vs Placebo

HR (95% CI) 1.49 (0.97-2.30) 1.04 (0.7-1.5) 0.85 (0.6-1.2)

P value .07 > .2 > .2

*Censored when sites took women off TDF and TDF placebo. Total n = 1009.Marrazzo J, et al. CROI 2013. Abstract 26LB.


VOICE: Lack of Detectable TFV in Plasma; High Rate of Infection in Younger Women

Despite high self-reported adherence, < 40% of women had detectable plasma TFV at first study visit

TFV detected in mean of ≤ 30% of samples in each arm

– ≥ 50% of women in each arm had no TFV detected in any sample

TFV detection less likely if unmarried, younger than 25 yrs, partner younger than 28 yrs

– Highest rates of HIV acquisition in unmarried, younger than 25 yrs

Marrazzo J, et al. CROI 2013. Abstract 26LB. Graphic used with permission.

Pts

Wit

h D

etec

tab

le T

FV

* (%

) 100

80

60

40

20

1 2 3 4 5 6

TDF/FTCTDFTFV 1% gel

TDF/FTCTDF TFV 1%

0

123119156

11180

107

1175682

952852

611630

Quarterly Visits

Plasma TFV Detection in Random Cohort Sample

*Level of TFV detection: ≥ 0.3 ng/mL.

Pts at Risk, n

135147166


Additional Data on PrEP

GSK1265744, dolutegravir analogue packaged in nanoparticles (GSK744LAP), permitting monthly or quarterly dosing in humans by IM injection

– 8/8 macaques injected with GSK744LAP and rectally challenged with SHIV protected from infection; 8/8 controls became infected (P < .0001)[1]

Intravaginal rings containing TDF protected against SHIV infection in 6/6 macaques; 11/12 controls became infected (P < .0004)[2]

Among iPrEX participants stopping PrEP before entry into open-label extension (iPrEX OLE), incidence of HIV similar among participants originally on TDF/FTC PrEP and those originally on placebo (P = .43)[3]

– Similarities indicate that although high-risk behaviors continued, there was lack of compensatory increase in high-risk behavior after PrEP discontinued

– HIV incidence after stopping PrEP remained high

1. Andrews C, et al. CROI 2013. Abstract 24LB. 2. Smith J, et al. CROI 2013. Abstract 25LB. 3. Grant R, et al. CROI 2013. Abstract 27.

Antiretroviral Therapy Trials:Current Agents


SAILING: Dolutegravir vs Raltegravir in ART-Exp’d, Integrase Inhibitor–Naive Pts Phase III randomized, double-blind, double-dummy,

noninferiority study

Pozniak A, et al. CROI 2013. Abstract 179LB.

Treatment-experienced, integrase inhibitor–naive patients with HIV-1 RNA

> 400 copies/mL and ≥ 2 class resistance

(N = 715)

Dolutegravir 50 mg QD + OBR(n = 354)

Raltegravir 400 mg BID + OBR(n = 361)

Stratified by number of fully active background agents, use of DRV,

screening HIV-1 RNA ≤ vs > 50,000 copies/mL

Wk 24 interim analysis Wk 48


SAILING: Higher Rate of Virologic Suppression With DTG vs RAL at 24 Wks

Lower incidence of integrase resistance at VF with DTG

– R263K at VF in 2 DTG pts; first report of treatment-emergent resistance on DTG

– < 2-fold change in IC50 for both DTG and RAL

– Y143, Q148, and/or N155 at VF in 9 RAL pts; consistent with previous studies

– High-level resistance to RAL

Both regimens well tolerated with similar AE profiles

Pozniak A, et al. CROI 2013. Abstract 179LB. Graphic used with permission.

HIV

-1 R

NA

< 5

0 co

pie

s/m

L (

%)

100

80

60

40

20

0BL 4 8 12 16 24

Wk

Wk 24 adjusted difference in response: +9.7 in favor of DTG (95% CI: 3.4% to 15.9%; P = .003)

79%

70%

Dolutegravir + OBRRaltegravir + OBR


Dolutegravir Efficacy in Phase III Studies in ART-Naive Pts: Subgroup Analyses Retrospective analysis of phase III trials in treatment-naive pts [1]

– SPRING-2[2]: DTG noninferior to RAL at Wk 48, each combined with investigator-selected NRTIs (TDF/FTC or ABC/3TC)

– SINGLE[3]: DTG + ABC/3TC superior to TDF/FTC/EFV at Wk 48

In both trials, activity of DTG-based regimens similar in subgroup analyses by HIV risk factor, baseline HIV-1 RNA, CD4+ cell count, sex, age, race

In SINGLE, higher rates of HIV-1 RNA < 50 copies/mL with DTG-based therapy across patient subgroups

In both trials, no apparent subgroup differences in AEs or discontinuations

1. Brinson C, et al. CROI 2013. Abstract 554. 2. Raffi F, et al. Lancet. 2013;381:735-743.3. Walmsley S, et al. ICAAC 2012. Abstract H-556b.


Subgroup Analyses of SPRING-2 and SINGLE: Virologic Suppression at Wk 48

Brinson C, et al. CROI 2013. Abstract 554. Graphic used with permission.

≤ 100,000 c/mL> 100,000 c/mL< 350 cells/mm3

≥ 350 cells/mm3

FemaleMale

< 50 yrs≥ 50 yrs

WhiteBlack

SPRING-2

0% 50% 100%

DTGRAL

30%20%10%0%-20% -10%

Difference (DTG-RAL) and 95% CI

In favor of RAL In favor of DTG

≤ 100,000 c/mL> 100,000 c/mL< 350 cells/mm3

≥ 350 cells/mm3

FemaleMale

< 50 yrs≥ 50 yrs

WhiteBlack

SINGLE

0% 50% 100%

DTG + ABC/3TCTDF/FTC/EFV

30%20%10%0%-20% -10%

Difference (DTG-EFV) and 95% CIIn favor of DTGIn favor of EFV


SECOND-LINE: LPV/RTV + RAL vs LPV/RTV + NRTIs After First-line VF Randomized, open-label, international, multicenter trial

Humphries A, et al. CROI 2013. Abstract 180LB.

Lopinavir/Ritonavir 400/100 mg BID +Raltegravir 400 mg BID

(n = 270)

Lopinavir/Ritonavir 400/100 mg BID + 2-3 NRTIs QD or BID

(n = 271)

HIV-infected pts with virologic failure on first-line

regimen of 2 NRTIs + NNRTI(N = 541)

Stratified by clinical site, baseline HIV-1 RNA

(≤ or > 100,000 copies/mL)

Wk 48 primary endpoint


SECOND-LINE: Noninferiority of LPV/RTV + RAL vs LPV/RTV + NRTIs

Pooled pt data from ACTG A5142, A5202, A5208 of those failing first-line boosted PI regimens found 131/200 (66%) remained on same regimen[2]

– Various regimen changes: n = 69

– HIV-1 RNA < 400 c/mL at Wk 24 similar between pts who maintained same regimen and those who switched

– Pts with highest resuppression rates were those with higher CD4+ counts at regimen change and those who had ever responded to first regimen

– Suggests better adherence

0

20

40

80

100

Wk

LPV/RTV + RALLPV/RTV + 2-3 NRTIs

60

0 12 24 36 48

HIV

-1 R

NA

< 2

00 c

/mL

(%

)

Similar high levels of virologic suppression with each strategy in primary mITT analysis[1]

82.6

80.8

P = .59

1. Humphries A, et al. CROI 2013. Abstract 180LB. Graphic used with permission.2. Zheng Y, et al. CROI 2013. Abstract 558.


OPTIONS: NRTIs vs No NRTIs in Regimens for Highly ART-Experienced Pts Randomized, noninferiority, multicenter trial (ACTG A5241)

– Primary endpoint: regimen failure (VF or divergence from NRTI assignment, whichever occurred first)

NRTI-Omitting Individualized Optimized Regimen*

(n = 179)

NRTI-Including Individualized Optimized Regimen*

(n = 181)

Treatment-experienced pts failing on PI-based regimen

with NRTI, NNRTI experience and/or resistance

(N = 360)

Stratified by choice of MVC-containing regimen and

previous enfuvirtide or integrase inhibitor experience

*20 potential 3- to 4-drug combinations including DRV/RTV, ENF, ETR, MVC, RAL, TPV/RTV. Individualized selection of regimens with PSS > 2.

Tashima K, et al. CROI 2013. Abstract 153LB.

Yr 1Primary Endpoint

Yr 2Secondary Endpoint


OPTIONS: Pt-Specific Regimen Selected Then Randomized to ± NRTI

Tashima K, et al. CROI 2013. Abstract 153LB. Graphic used with permission.

Chosen Regimen and NRTI Combinations Add NRTIsTDF + FTC (3TC)ZDV + TDF + FTC (3TC)Other

RegimenRAL + DRV/RTV + ETRRAL + DRV/RTV + MVCRAL + DRV/RTV + ETR + MVCRAL + ETR + MVCRAL + DRV/RTV + ETR + ENFOther

Randomization

Omit NRTIs

6%

12%

82%6%

56%

7%

8%

14%

9%

Add NRTIs


OPTIONS: Omitting NRTIs Noninferior to Adding NRTIs to Optimized Regimen

Similar virologic suppression (HIV-1 RNA < 50 c/mL) in each arm (~ 65%)

Similar CD4+ cell count increases in each arm (90-106 cells/mm3)

No significant difference in any safety outcome when globally evaluating symptoms and laboratory abnormalities

– However, mortality significantly higher in NRTI-added arm (P < .001)

– 6 deaths in NRTI arm, 2 possibly due to ART drug

Tashima KT, et al. CROI 2013. Abstract 153LB. Graphic used with permission.

Primary Efficacy Outcome Comparisons

Outcome, n (%)

Regimen failure

Virologic failure

Stop NRTI assignment

Omit NRTIs(n = 179)

53 (30)

44 (25)

19 (8)

Add NRTIs(n = 181)

48 (26)

45 (25)

10 (6)

-30 -15 0 15 30% Difference (Omit - Add) at 1 Yr (95% CI)

Omitting NRTIsNot Inferior Inferior

3.2 (-6.1 to 12.5)

-0.4 (-9.4 to 8.7)

3.6 (-1.7 to 9.0)

Antiretroviral Therapy Trials:Investigational Agents


Tenofovir Alafenamide (TAF) vs Tenofovir DF in ART-Naive Pts TAF (GS-7340), investigational

prodrug of tenofovir with lower plasma concentrations, increased delivery to hepatocytes, lymphoid cells

Randomized, placebo-controlled phase II trial of TAF vs TDF, each coformulated with FTC/EVG/COBI, in ART-naive patients

Zolopa A, et al. CROI 2013. Abstract 99LB. Graphic used with permission.

HIV-infected, ART-naive

patients(N = 170)

TAF/FTC/EVG/COBI(n = 112)

TDF/FTC/EVG/COBI(n = 58)

Wk 48Wk 24Gut

TFV

TDF

TAF

Plasma

TDF/TFV

TAF

Lymphoid Cells

TAF TFV

TFV-MP

TFV-DP

Cathepsin A


TAF Noninferior to TDF at Wk 24 Primary Endpoint


TDF/FTC/EVG/COBI

TAF/FTC/EVG/COBI

2 4 8 12 16 24

20

40

60

80

100

HIV

-1 R

NA

< 5

0 c/

mL

(%

)

Wks

0

ITT, M = F Analysis89.7%

87.5%

With TAF:PBMC TFV-DP exposure 5.3 x higher than TDFPlasma TFV exposure 91% lower


Change in BMD and Serum Creatinine With TAF vs TDF Smaller change in BMD over 24 wks with TAF vs TDF

Median serum creatinine : TAF 0.07 mg/dL vs TDF 0.12 mg/dL


2

0

-2

Spine

Mea

n %

Ch

ang

e in

BM

D

0 12 24

Wks

-0.8

-2.5P = .002

2

0

-2

Hip

0 12 24

Wks

-0.3

-2.0P < .001

TAF/FTC/EVG/COBI (n = 112)TDF/DTC/EVG/COBI (n = 58)


Short-term Efficacy and Tolerability of MK-1439, Investigational QD NNRTI MK-1439, investigational NNRTI,

dosed QD, active against K103N, Y181C, G190A variants

Randomized phase Ib study in ART-naive pts (N = 18; 6 per arm)

– 7-day monotherapy

Similar activity with MK-1439 25 mg vs 200 mg dose

All AEs mild to moderate

– No rash/CNS events

Pharmacokinetics comparable to HIV-negative pts

Anderson M, et al. CROI 2013. Abstract 100. Copyright © 2013 Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Whitehouse Station, N.J., U.S.A. All Rights Reserved.

Ch

ang

e i

n H

IV-1

RN

A (

log

10)

0.3

0.0

-0.3

-0.6

-0.9

-1.2

-1.5

-1.81 2pre 3pre 4pre 5pre 6pre 7pre 724hr

Dayshr From First Dose

Placebo QDMK-1439 25 mg QDMK-1439 200 mg QD

-1.26

-1.37


Cenicriviroc: Investigational QD Oral CCR5/CCR2 Receptor Antagonist Randomized, double-blind, double-dummy, dose-finding phase IIb trial

Gathe J, et al. CROI 2013. Abstract 106LB.

ART-naive pts with CCR5-tropic HIV-1, no NRTI or NNRTI

resistance(N = 143)

CVC 100 mg + TDF/FTC (n = 59)

CVC 200 mg + TDF/FTC (n = 56)

EFV 600 mg + TDF/FTC (n = 28)

Wk 48final analysisStratified by BL HIV-1 RNA

< 100,000 or ≥ 100,000 copies/mL

Wk 24primary analysis

Complex dosing: 4 pills with breakfast (4 CVC or 4 CVC placebo or 2 of each); 1 pill on empty stomach at bedtime (EFV or EFV placebo); 1 pill taken anytime (open-label TDF/FTC)


Virologic Non-

Response, %

DC Other Than AE,

%

DC Due to AE, %

12 10 0

14 11 2

4 7 18

24-Wk Efficacy and Safety of Cenicriviroc + TDF/FTC vs EFV/TDF/FTC

CVC generally well tolerated with no safety signals

sCD14 decreased with CVC and increased with EFV

Gathe J, et al. CROI 2013. Abstract 106LB. Graphic used with permission..

HIV

-1 R

NA

< 5

0 c/

mL

(%

)

Wks

ITT (FDA Snapshot Analysis)

CVC 100CVC 200EFV

100

80

60

40

20

0BL 4 8 12 16 24201 2

76

73

71

020

324

1145

251712

372816

443318

424019

454120

CVC 100 CVC 200EFV

Pts at Risk, n

Additional Data on Epidemiology and

Antiretroviral Trends


ART Initiation Associated With Better Retention in Care in Zambia National ART program at 18

primary care sites in urban Zambia

– ART started when CD4+ cell count < 200 cells/mm³ or WHO stage IV or WHO stage III and CD4+ cell count < 350 cells/mm3

– “Immediate” initiation defined as within 180 days of eligibility; lost to follow-up (LTFU) as ≥ 60 days late

ART started by 75% of 6419 eligible pts with CD4+ 175-225 cells/mm³ and WHO Stage I-II disease

Proportion lost to follow-up greater in those who delayed ART vs those who started ART immediately, P < .001

Pts who started therapy 4x more likely to be retained in care

Factors Associated with LTFU

Adjusted Hazard Ratio (95% CI)

Did not start ART 4.13 (3.69-4.62)

Age 25 yrs or younger

1.85 (1.65-2.07)

CD4+ 175-199 1.16 (1.05-1.29

WHO Stage II 0.82 (0.74-0.90)

Li M, et al. CROI 2013. Abstract 93.


Trends in Genotypic Drug Resistance

Among 1484 ART-naive pts in HOPS cohort, GT testing rate increased from 20.8% in 1999-2002 to 62.8% in 2009-2011[1]

– > 1/3 still not tested in most recent period

No statistically significant increase in transmitted resistance from 1999-2011

– Increased frequency of resistance in black, Hispanic, pts with CD4+ > 500 cells/mm3

17.5% of pts had any major IAS-USA mutation in 2009-2011 (similar to CDC analysis)[2]

– Rates of class resistance: NRTI 10.8%; NNRTI 6.6%; PI 1.8%

Separate study showed major INSTI mutations in 1/5 of pts tested since availability of INSTI GT assay[3]

Additional study showed low rates of DRV resistance among all isolates tested that declined over time[4]

1. Buchacz K, et al. CROI 2013. Abstract 615. 2. Kim D, et al. CROI 2013. Abstract 149. 3. Hurt CB, et al. CROI 2013. Abstract 591. 4. Lathouwers E, et al. CROI 2013. Abstract 590.


ART and Birth Defects in ANRS French Perinatal Cohort French national prospective

multicenter cohort studying PMTCT strategies in HIV-positive women[1]

– N = 17,000 (~ 70% of HIV-positive women in France)

– 13,124 live births exposed to ART in utero

In EFV first trimester-exposed infants, risk for neurologic (but not neural tube) defects but not for overall birth defects

In ZDV first-trimester-exposed infants, risk for both overall birth defects and heart defects

Findings inconsistent with meta-analysis of studies of EFV use[2] in pregnancy and data from the US Antiretroviral Pregnancy Registry[3]

– Both indicate no risk of birth defect with EFV; APR shows no risk with ZDV

Defects With First Trimester Exposure, AOR (95% CI)

EFV(n = 372)

ZDV(n = 3267)

Overall birth defects

1.3 (0.9-1.9) P = .31

1.4 (1.1-1.8) P = .002

Specific organ system defects

3.2 (1.1-9.1) P = .03

2.5 (1.6-4.2) P = .001

1. Siubide J, et al. CROI 2013. Abstract 81. 2. Ford N, et al. AIDS. 2011;25:2301-2304. 3. Antiretroviral Pregnancy Registry. December 2012.

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Capsule Summaries of key studies

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