Cco retroviruses_2013_art_slides

March 3-6, 2013
Atlanta, Georgia
Highlights of Atlanta 2013:
ART as Treatment and Prevention
CCO Independent Conference Coverage
of 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/hiv
Clinical Impact of New Data From Atlanta 2013
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Faculty
Joel E. Gallant, MD, MPH
Professor of Medicine and
Epidemiology
Associate Director, Johns Hopkins
AIDS Service
Division of Infectious Diseases
Johns Hopkins University
School of Medicine
Baltimore, Maryland
Kathleen E. Squires, MD
Professor of Medicine
Director, Division of Infectious
Diseases
Jefferson Medical College
Thomas Jefferson University
Philadelphia, Pennsylvania
Andrew R. Zolopa, MD
Associate Professor of Medicine
Director, Stanford Positive Care
Program
Principal Investigator, Stanford AIDS
Clinical Trials Unit
Stanford University School of Medicine
Stanford, 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.

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 recommended
DHHS 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.

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 transitional
and effector memory CD4+ T cells
 Suggests very early ART may
prevent seeding of reservoirs
Fiebig Stages
Fiebig I: RNA+, p24 neg, 3rd-gen ELISA neg̶
– 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 Intervention
Reduction in
HIV Infection Rate, %
CAPRISA[1]
(N = 899)
High-risk women in
South Africa
 Coitally applied
vaginal TFV gel
39
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)
Gel
Placebo
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.
PtsWithDetectableTFV*(%)
100
80
60
40
20
1 2 3 4 5 6
TDF/FTC
TDF
TFV 1% gel
TDF/FTC
TDF
TFV 1%
0
123
119
156
111
80
107
117
56
82
95
28
52
61
16
30
Quarterly Visits
Plasma TFV Detection
in Random Cohort Sample
*Level of TFV detection: ≥ 0.3 ng/mL.
Pts at Risk, n
135
147
166

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-1RNA<50copies/mL(%)
100
80
60
40
20
0
BL 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 + OBR
Raltegravir + 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
Female
Male
< 50 yrs
≥ 50 yrs
White
Black
SPRING-2
0% 50% 100%
DTG
RAL
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
Female
Male
< 50 yrs
≥ 50 yrs
White
Black
SINGLE
0% 50% 100%
DTG + ABC/3TC
TDF/FTC/EFV
30%20%10%0%-20% -10%
Difference (DTG-EFV) and 95% CI
In 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 + RAL
LPV/RTV + 2-3 NRTIs
60
0 12 24 36 48
HIV-1RNA<200c/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 1
Primary Endpoint
Yr 2
Secondary 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 NRTIs
TDF + FTC (3TC)
ZDV + TDF + FTC (3TC)
Other
Regimen
RAL + DRV/RTV + ETR
RAL + DRV/RTV + MVC
RAL + DRV/RTV + ETR + MVC
RAL + ETR + MVC
RAL + DRV/RTV + ETR + ENF
Other
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 NRTIs
Not 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-1RNA<50c/mL(%)
Wks
0
ITT, M = F Analysis
89.7%
87.5%
With TAF:
PBMC TFV-DP exposure 5.3 x
higher than TDF
Plasma 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
Mean%ChangeinBMD
0 12 24
Wks
-0.8
-2.5
P = .002
2
0
-2
Hip
0 12 24
Wks
-0.3
-2.0
P < .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.
ChangeinHIV-1RNA(log10)
0.3
0.0
-0.3
-0.6
-0.9
-1.2
-1.5
-1.8
1 2pre 3pre 4pre 5pre 6pre 7pre 724hr
Dayshr From First Dose
Placebo QD
MK-1439 25 mg QD
MK-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 48
final analysisStratified by BL HIV-1 RNA
< 100,000 or ≥ 100,000 copies/mL
Wk 24
primary 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-1RNA<50c/mL(%)
Wks
ITT (FDA Snapshot Analysis)
CVC 100
CVC 200
EFV
100
80
60
40
20
0
BL 4 8 12 16 24201 2
76
73
71
0
2
0
3
2
4
11
4
5
25
17
12
37
28
16
44
33
18
42
40
19
45
41
20
CVC 100
CVC 200
EFV
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.

Go Online for More CCO
Coverage of CROI 2013!
Capsule Summaries of key studies
Additional downloadable slideset on Coinfection and Comorbidities
Coming soon! CME-certified slidesets
with expert faculty commentary
on all key studies
clinicaloptions.com/atlanta2013

Cco retroviruses_2013_art_slides

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