Cco Aids 2012 Slides

Highlights of AIDS 2012
CCO Official Conference Coverage

of the XIX International AIDS Conference
July 22-27, 2012 Washington, DC
This program is supported by educational grants from

clinicaloptions.com/hiv
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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
Ian M. Sanne, MBBCH, FCP(SA)

Clinical Director Clinical HIV Research Unit University of the Witwatersrand Johannesburg, Republic of South Africa

Faculty Disclosures
Joel E. Gallant, MD, MPH, has disclosed that he has received consulting fees from Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline, Janssen, Merck, and Sangamo BioSciences and has received funds for research support from Gilead Sciences.
Ian M. Sanne, MBBCH, FCP(SA), has disclosed that he has received consulting fees from Merck and funds for research support from Pfizer.
Please review the slide notes for a complete discussion of each study by expert faculty Joel E. Gallant, MD, MPH, and Ian M. Sanne, MBBCH, FCP(SA)
Updated US Treatment Guidelines

DHHS Guidelines, March 2012: When to Start

Antiretroviral therapy recommended for all HIV-infected pts; strength of recommendation varies according to CD4+ cell count or condition
CD4+ Cell Count or Clinical Condition CD4 + count < 350 cells/mm (AI) CD4 + count 350-500 cells/mm (AII) CD4 + count > 500 cells/mm (BIII) History of AIDS-defining illness (AI) Pregnancy (AI) HIV-associated nephropathy (AII) HBV coinfection (AII) At risk of transmitting HIV to sexual partners (AI, heterosexuals; AIII, others
DHHS Guidelines for Antiretroviral Therapy in Adults and Adolescents. March 27, 2012.

IAS-USA Guidelines, July 2012: When to Start

Antiretroviral therapy recommended for all HIV-infected pts; strength of recommendation varies according to CD4+ cell count or condition
CD4+ Cell Count or Clinical Condition CD4+ cell count 500 (AIa) CD4+ cell count > 500 (BIII) Pregnant women (AIa) Older than 60 yrs of age (BIIa) Active HBV coinfection (AIIa) HCV coinfection (CIII)* HIV-associated nephropathy (AIIa) Primary infection (BIII)
*Pts with HCV coinfection and CD4+ count > 500 cells/mm may delay antiretroviral therapy until after completion of HCV treatment. Regardless of symptoms.
Thompson MA, et al. JAMA. 2012;308:387-402

IAS-USA Guidelines, July 2012: What to Start

Recommended Regimens NNRTI based Boosted PI based INSTI based Alternative Regimens EFV/TDF/FTC or EFV + ABC/3TC* ATV/RTV + TDF/FTC or ATV/RTV + ABC/3TC* DRV/RTV + TDF/FTC RAL + TDF/FTC NVP + TDF/FTC or NVP + ABC/3TC* RPV/TDF/FTC or RPV + ABC/3TC* DRV/RTV + ABC/3TC LPV/RTV + TDF/FTC or LPV/RTV + ABC/3TC* RAL + ABC/3TC* EVG/COBI/TDF/FTC
NNRTI based
Boosted PI based INSTI based
*HLA-B*5701 screening is recommended before ABC administration to reduce the risk of hypersensitivity reaction. Avoiding the use of ABC or LPV/RTV might be considered for pts with or at high risk of cardiovascular disease. ZDV/3TC is an alternative NRTI component of NNRTI-, PI/RTV-, and RAL-based regimens, but toxicity profile of ZDV reduces its utility.
Thompson MA, et al. JAMA. 2012;308:387-402.
Epidemiology

High HIV Prevalence Among Young MSM in 5 US Cities

Pooled analysis of serial cross-sectional data from young MSM (18-29 yrs) from 5 cities (Baltimore, Miami, LA, NYC, SF) included in 4 different cohorts over various periods from 1994-2008
HIV prevalence
18-22 yrs of age: 11% (stable) 23-29 yrs of age: 16% (slightly increasing)
HIV testing increased significantly over time in both age groups (P < .0001)
Oster AM, et al. AIDS 2012. Abstract MOAC0104.

CDC: Differences in Continuum of Care in HIV-Infected Patients

CDC study shows that only ~ 25% of US patients with HIV have suppressed HIV-1 RNA
82 80 Patients, % 60 40 20 0 66 80 60
72 56 41 31 35 31 22 43 39 31 46 42 36 35 33 27
Individuals 25-34 yrs of age less engaged in each stage of care compared with all older age groups
85 70 89 75 89 89 73
100
100
74
37
33
25
40 20 0
28 22 15
13-24 25-34 35-44 45-54 55-64 Diagnosed Linked to care Retained in care
65
Study further evaluated continuum of care in US by sex, age, race, and transmission category
Prescribed ART Viral suppression
Hall HI, et al. AIDS 2012. Abstract FRLBX05. Graphics reproduced with permission.

CDC: Differences in Continuum of Care in HIV-Infected Patients (contd)

Blacks less likely than Hispanics/ Latinos or whites to be engaged in care
100 81 80
IDUs more aware of HIV dx vs those who acquire HIV through sexual contact Male IDUs < female IDUs to be engaged in care Male heterosexuals < female heterosexuals to be diagnosed or engaged in care
90 79 63 91 73 44 39 28 91 76 76 60 32 29 22 39 35 26 29 26 19 40 34 25 82 68
85
67 71
80
Patients, % 60 40 20 0
62
34
29 21
37
33
38 35
100 30 80 60
26
70
Black
Hispanic or Latino
White
40 20 0
36 33 27
Diagnosed Linked to care Retained in care
Prescribed ART Viral suppression
MSM
IDU, Male
IDU, Female
MSM/ IDU
Hetero- Heterosexual sexual Male Female
Hall HI, et al. AIDS 2012. Abstract FRLBX05. Graphics reproduced with permission.
Laboratory Monitoring

Frequent CD4+ Count Monitoring Not Necessary for Pts With CD4+ > 300
Retrospective review of VA laboratory database of > 25,000 paired VL and CD4+ counts from 1821 unique pts (1998 -2011) Eligible pts had sequences: consecutive VL/CD4+ pairs with
VL < 200 copies/mL CD4+ count > 200 cells/mm3 Probability %CD4+ > 14 < 390 days between CD4+ counts
Virologically suppressed pts with CD4+ > 300 extremely unlikely to have CD4+ count dip < 200 CD4+ testing may be undertaken less frequently in these pts
Probability of Maintaining CD4+ > 200 During Viral Suppression 1.0 0.9 0.8 0.7 0.6 0.5 0 1 2 3 4 5 6 Viral Suppression (Yrs)
CD4+ Count 350 300-349 250-299 200-249
Analysis of pts with sequences (n = 846) who experienced CD4+ dips < 200 during periods of virologic suppression (n = 61)
24 with clinical causes of lymphopenia
Gale H, et al. AIDS 2012. Abstract WEPDB0101. Graphic reproduced with permission.

Low-Level Viremia Not Associated With Short-term Risk of Virologic Failure

Retrospective study of 656 pts at 1 institution
Stable ART for 6 mos 3 VL tests in 1 yr (inclusion period), all < 50 copies/mL During follow-up, no difference in frequency of VF between LLV- and LLV+ groups
4% vs 8%, respectively (P = 0.32)
LLV(n = 413) All VL < 20,% VL 20-50 on 2 occasions, % 2 consecutive VL > 50, % 65 2 4 LLV+ (n = 25) 44 16 8 P Value .053 .002 .320
3 VL tests in following 12 mos
Comparison of virologic outcomes among 2 groups of pts:

LLV- : No low-level viremia during follow-up; VL consistently < 20 copies/mL LLV+: VL 20-50 copies/mL on 2 occasions
ART regimens did not differ between LLV- and LLV+ groups
Charpentier C, et al. AIDS 2012. Abstract WEPDB0102. Table reproduced with permission.
Antiretroviral Therapy

Cobicistat-Boosted vs Ritonavir-Boosted Atazanavir in Treatment-Naive Patients

Randomized, multicenter, placebo-controlled phase III trial
Primary endpoint: VL < 50 c/mL at Wk 48 (FDA snapshot analysis)
Stratification by HIV-1 RNA vs > 100,000 copies/mL
Wk 48 Primary endpoint
Wk 96
Antiretroviral-naive patients, HIV-1 RNA 5000 copies/mL, eGFR 70 mL/min (N = 692)
Atazanavir/Cobicistat* + Tenofovir/Emtricitabine (n = 344) Atazanavir/Ritonavir + Tenofovir/Emtricitabine (n = 348)
Gallant J, et al. AIDS 2012. Abstract TUAB0103.

ATV/COBI vs ATV/RTV: Noninferior Virologic Suppression at Wk 48

HIV-1 RNA < 50 copies/mL at Wk 48 (Snapshot Analysis)
-2.2% (-7.4 to 3.0) 100 Patients (%)
ATV/COBI
P = NS 88 84 86
ATV/RTV
86 P = NS 90 90 P = NS 81 85
P = NS
85
87
80
60 40 20 0 n = 344 348 Overall 179/ 181/ 212 205 Baseline VL 100K 114/ 123/ 132 143 Baseline VL > 100K 156/ 164/ 174 183 Baseline CD4+ 350
137/ 140/ 170 165 Baseline CD4+ > 350
CD4+ count gain: +213 with ATV/COBI vs +219 with ATV/RTV Among 24 pts with suboptimal virologic response and genotype: no primary PI or TDF resistance; M184V/I in 2 pts in COBI arm, 0 in RTV arm
Gallant J, et al. AIDS 2012. Abstract TUAB0103. Graphic reproduced with permission.

ATV/COBI vs ATV/RTV: Changes in Serum Creatinine and eGFR

COBI serum creatinine and eGFR by inhibiting renal creatinine secretion[1] COBI does not affect actual glomerular filtration rate[2] Change in Serum Creatinine, Median (IQR) 0.4 0.3 ATV/COBI ATV/RTV mL/min 0 -10 Change in eGFR, Median (IQR)
mg/dL
0.2
0.1
-20
-30 -40 ATV/COBI ATV/RTV BL 8 16 24 Wk 32 40 48
0.0
BL 8 16 24 Wk 32 40 48
6 pts in COBI arm and 5 in RTV arm discontinued therapy due to renal abnormalities[3] Higher proportion with hyperbilirubinemia with COBI but discontinuations similar by arm 5 of 6 in COBI arm vs 2 of 5 in RTV arm with proximal tubulopathy discontinued therapy
1. Lepist EI, et al. ICAAC 2011. Abstract A1-1724. 2. German P, et al. J Acquir Immune Defic Syndr. 2012;[Epub ahead of print]. 3. Gallant J, et al. AIDS 2012. Abstract TUAB0103. Graphics reproduced with permission.

Elvitegravir/Cobicistat/TDF/FTC vs EFV/TDF/FTC: Subgroup Responses

Randomized, double-blind phase III trial (N = 700)[1,2]
Primary endpoint results: EVG/COBI/TDF/FTC noninferior to EFV/TDF/FTC at Wk 48[2]
HIV-1 RNA < 50 copies/mL at Wk 48
EVG/COBI -3.6% (-1.6 to 8.8) 100 88 84 P = .15 90 85 P = .47 84 EFV P = .68 86 79 90 P = .40 82 P = .68 87 P = .039 91
84
84
80
Patients (%) 60 40 20 0 n = 348 352 206/ 201/ 230 236 Baseline VL 100K 81/ 97
74
69/ 87
18/ 21
26/ 29
32/ 43
42/ 51
97/ 112
81/ 96
176/ 173/ 193 205 Baseline CD4+ > 350
Overall
Baseline VL > 100K-400K
Baseline VL > 400K
Baseline CD4+ 200
Baseline CD4+ > 201-350
1. Sax P, et al. AIDS 2012. Abstract TUPE028. 2. Sax P, et al. CROI 2012. Abstract 101. Graphic reproduced with permission.

Elvitegravir/Cobicistat/TDF/FTC vs ATV/RTV + TDF/FTC: Subgroup Responses

Randomized, double-blind phase III trial (N = 708)[1,2]
Primary endpoint results: EVG/COBI/TDF/FTC noninferior to ATV/RTV + TDF/FTC at Wk 48[2]
EVG/COBI 3.0% (-1.9% to 7.8%) 100 80 Patients (%) 60 40 20 188/ 192/ 203 214 Baseline VL 100K 99/ 117 91/ 112 29/ 33 25/ 29 Baseline CD4+ 200 Baseline CD4+ > 201-350 Baseline CD4+ > 350 88 P = .30 93 90 P = .50 85 81 ATV/RTV P = .85 P = .71 80 85 P = .20 93 86 89 P = .25 90 86
84
88
n = 353 355 Overall
Baseline VL > 100K-400K
Baseline VL > 400K
1. DeJesus E, et al. AIDS 2012. Abstract TUPE043. 2. DeJesus E, et al. CROI 2012. Abstract 627. Graphic reproduced with permission.

SPRING-2: Dolutegravir QD vs Raltegravir BID in Treatment-Naive Pts at 48 Wks

Randomized, double-blind, placebo-controlled phase III trial
Primary endpoint: VL < 50 c/mL at Wk 48 (FDA snapshot analysis)
Stratified by screening HIV-1 RNA ( vs > 100,000 copies/mL) and NRTI backbone
Wk 96
Antiretroviral-naive pts, VL 1000 c/mL (N = 822)
Dolutegravir 50 mg QD + 2 NRTIs* (n = 411)
Raltegravir 400 mg BID + 2 NRTIs* (n = 411)
*Investigator-selected NRTI backbone: either TDF/FTC or ABC/3TC. Raffi F, et al. AIDS 2012. Abstract THLBB04.

SPRING-2: Dolutegravir Noninferior to Raltegravir at 48 Wks

100 Pts With VL < 50 c/mL (%) 80
88% 85% DTG 50 mg QD (n = 411) RAL 400 mg BID (n = 411)
2.5% (95% CI: -2.2% to 7.1%)
60
40 20 0
Per protocol response: 90% (DTG) vs 88% (RAL) by snapshot analysis; 1.6% (95% CI: -2.7% to 5.9%)
No significant differences between arms in virologic response by baseline VL or NRTI backbone CD4+ gain of +230 cells/mm3 from BL in both arms
BL
12
16
24 Wk
32
40
48
Raffi F, et al. AIDS 2012. Abstract THLBB04. Graphic reproduced with permission.

SPRING-2: Safety and Resistance

Lower rate of confirmed virologic failure at or after Wk 24 with DTG vs RAL (5% vs 7%)
DTG 50 mg QD (n = 411) 20 0/8 0/12 RAL 400 mg BID (n = 411) 28 1/18 4/19
Patients Subjects with protocol-defined virologic failure, n Resistance, n/N INSTI resistance mutations NRTI resistance mutations
DTG had favorable safety profile, comparable to RAL

Few AEs necessitating treatment discontinuation (2% in each arm) Greater increase in creatinine with DTG vs RAL (+0.139 vs +0.053 mg/dL)
DTG increases serum creatinine by inhibiting renal creatinine secretion but does not affect actual glomerular filtration rate[2]
No premature discontinuation for renal events

1. Raffi F, et al. AIDS 2012. Abstract THLBB04. 2. Koteff J, et al. ICAAC 2011. Abstract A1-1728.

STARTMRK: Final 5-Yr Phase III Results of Efavirenz vs Raltegravir in ART-Naive Pts
Double-blind phase III trial of EFV vs RAL, each with TDF/FTC, in treatmentnaive patients
Noninferior at Wk 48 primary endpoint
CD4+ gain: +374 (RAL) vs +312 (EFV) Generally consistent virologic and immunologic effects in various demographic and prognostic subgroups (eg, baseline CD4+/VL, age, sex, race, etc)
Pts With VL < 50 c/mL (%)
At Wk 240 analysis, RAL superior to EFV by VL < 50 c/mL (ITT, NC = F)

100 80 82 60 40 20 0 0 12 24 48
280 281
86
81 79
75 69 76 67 71
Low levels of genotypic resistance among patients with VF and VL > 400 c/mL in both arms
RAL, n = 7; EFV, n = 12
61
Wk 240 = +9.5 (95% CI, 1.7-17.3) Noninferiority P < .001 72

281 282
RAL EFV
Fewer pts with drug-related adverse events in RAL arm Significantly smaller increases in TC, HDL-C, LDL-C, and TG levels with RAL vs EFV
96 120 144 168 192 216 240 Wks

281 282 277 281 280 281 281 282 281 282 277 282 279 279
Pts, n 281 278 279

282 282 282
Rockstroh J, et al. AIDS 2012. Abstract LBPE19. Copyright 2012 Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Whitehouse Station, N.J., U.S.A. All Rights Reserved.

SPIRIT: Switch to RPV/TDF/FTC From Boosted-PI Regimens in Suppressed Pts

Multicenter, randomized, open-label switch study
Primary endpoint: maintenance of VL < 50 c/mL at Wk 24 (FDA snapshot analysis)
Randomized 2:1
Wk 48
Pts with VL < 50 c/mL on stable ritonavirboosted PI + 2 NRTIs for 6 mos, no previous NNRTI use (N = 476)
Rilpivirine/Tenofovir/Emtricitabine (n = 317) Ritonavir-Boosted PI* + 2 NRTIs (n = 159) Rilpivirine/ Tenofovir/Emtricitabine (n = 159)
*PIs: ATV/RTV, 37%; LPV/RTV, 33%; DRV/RTV, 20%; FPV/RTV, 8%; SQV/RTV, 2%. Palella F, et al. AIDS 2012. Abstract TUAB0104.

SPIRIT: Switch to RPV/TDF/FTC Noninferior to Continued Boosted PI

Switch to RPV/TDF/FTC noninferior to maintaining boosted-PI regimen at Wk 24
93.7% vs 89.9% with VL < 50 c/mL
Pts With VL < 50 c/mL (%)

RPV/TDF/FTC 3.8% (-1.6 to 9.1) 100 80 60 40 20 0 n = 317 159 152/ 160 83/ 93 128/ 134 48/ 52 93.7 89.9 Boosted PI 3.2% (-4.8 to 11.3) 95.5 92.3
5.9% (-1.4 to 12.9) 95.0 89.2
Noninferiority observed regardless of pretreatment (naive) VL stratum
All 17 pts with baseline K103N who switched to RPV/TDF/FTC maintained virologic suppression Significant reductions in TC, LDL, TG, HDL, TC:HDL ratio (P < .001) and in 10-yr Framingham score (P = .001) at Wk 24 among RPV/TDF/FTC switch pts
Overall
< 100K 100K Baseline VL (When Naive)*
*Excludes 23 RPV and 14 boosted PI pts lacking baseline VL while ARV naive.
Palella F, et al. AIDS 2012. Abstract TUAB0104. Graphic reproduced with permission.

Elvitegravir QD vs Raltegravir BID in ART-Exp Pts: Phase III Results at Wk 96

Randomized, double-blind, placebo-controlled phase III trial
Primary endpoint: VL < 50 c/mL at Wk 48
Wk 48 Primary endpoint Wk 96
Pts with VL 1000 c/mL, resistance or 6 mos of exposure to 2 antiretroviral classes (N = 702)
Elvitegravir 150 mg (or 85 mg) QD* + Boosted PI + Third Agent (n = 351)
Raltegravir 400 mg BID + Boosted PI + Third Agent (n = 351)
*EVG dose reduced to 85 mg QD for patients taking ATV/RTV or LPV/RTV as part of background regimen. Background regimen to include fully active ritonavir-boosted PI, selected using resistance testing. Third active agent selected from ENF, ETR, MVC, or NRTI. Option of also adding FTC or 3TC for patients with M184V/I.
Molina JM, et al. Lancet Infect Dis. 2012;12:27-35.

Elvitegravir Comparable to Raltegravir in Treatment-Experienced Pts at Wk 96

100
CD4+ gain: +205 (EVG) vs +198 (RAL) at Wk 96

EVG (n = 351) RAL (n = 351)
59 58 48 45
80
Patients (%) 60 40 20 0
22 23 26
Similar rates of treatmentemergent integrase resistance in each arm (7%)
Similar rates of AEs overall

29 19 19 26 26
More diarrhea with EVG vs RAL (13% vs 8%) More liver-related AEs leading to study d/c with RAL (1.7% vs 0.8%)
*Includes never suppressed, rebound, switch of background regimen, and discontinuation due to lack of efficacy Includes death, discontinuation due to AE, investigators discretion, lost to follow up, pregnancy, protocol violation, noncompliance, withdrawal of consent.
Wk 48 Wk 96 Wk 48 Wk 96 Wk 48 Wk 96
HIV-1 RNA < 50 c/mL
Virologic Failure*
Others
Elion R, et al. AIDS 2012. Abstract TUAB105.

Study A4001078: Wk 96 Data With ATV/RTV Plus MVC or TDF/FTC

Open-label phase IIb pilot study
Not powered to show treatment difference
Wk 96
Antiretroviral-naive pts, R5 only, VL 1000 c/mL*, CD4+ 100 cells/mm3, no resistance to ATV/RTV, TDF, or FTC (N = 121)
Maraviroc 150 mg QD + Atazanavir/Ritonavir 300/100 mg QD (n = 60)
Tenofovir/Emtricitabine 300/200 mg + Atazanavir/Ritonavir (n = 61)
*16 pts (27%) in NRTI-sparing arm and 22 pts (36%) in TDF/FTC arm had VL > 100,000 c/mL Mills A, et al. AIDS 2012. Abstract TUAB0102.

A4001078: Virologic Suppression at Wk 96

Pts With VL < 50 c/mL (%)[1] 100 80 60 40 20 0 0 n = 61 59 4 8 12 16 20 24 54 48 32 40 48 Wk 51 44 50 40 60 72 84 96 TDF/FTC + ATV/RTV MVC + ATV/RTV ITT, NC = F 82.0% 67.8%
All pts with detectable viremia at Wk 96 had intermittent periods of virologic suppression Grade 3 or 4 hyperbilirubinemia: 70% in MVC arm vs 56% in TDF/FTC arm
Mills A, et al. AIDS 2012. Abstract TUAB0102.

Cost-effectiveness Modeling of Generic First-line Antiretroviral Therapy

Cost-effectiveness model comparing
No ART Generic ART (branded TDF + generic 3TC + generic EFV) Branded ART single-pill TDF/FTC/EFV
Branded vs generic ART results in

$42,500 higher lifetime costs/pt
$342,800 vs $303,300, respectively
0.37 QALYs gained

12.45 vs 12.08, respectively
Regimen assumptions
Generic ART: 78% with suppression at 24 wks; 5.41/100 pt-yrs with virologic failure after 24 wks; $9200 regimen cost per yr Branded ART: 85% with suppression at 24 wks; 2.52/100 pt-yrs with virologic failure after 24 wks; $15,300 regimen cost per yr
Estimated yearly savings of $920 million if all eligible patients in US switched to generic ART
Walensky R, et al. AIDS 2012. Abstract FRLBX06.

D:A:D: Changes in Causes of Death Over Time, 1999-2011

D:A:D: collaboration of 11 cohorts of HIV-infected persons from Europe, US, and Australia (N = 49,734) Prospective follow-up assessing causes of death
32% 34%
8% 10%
1999-2000 (N = 255)
16% Liver related NADM
3802 deaths occurred in 49,734 HIV+ individuals followed for 304,695 ptyrs (rate: 12.5/1000 pt-yrs [95% CI: 12.112.9])
Proportion of deaths attributed to AIDSrelated causes fell from 1999-2000 to 2009-2011
Largely due to increase in CD4+ cell counts
AIDS related CVD related Other/unknown
22%
2009-2011 (N = 548)
39% 9% 20% 10%
Proportion of deaths attributed to nonAIDS defining malignancies (NADM) increased from 1999-2000 to 2009-2011
Weber R, et al. AIDS 2012. Abstract THAB0304.
AIDS related CVD related Other/unknown
Liver-related NADM
Treatment as Prevention

HPTN 052: Immediate vs Delayed ART in Serodiscordant Couples

HIV-infected, sexually active serodiscordant couples; CD4+ cell count of the infected partner: 350-550 cells/mm3 (N = 1763 couples) Immediate ART Initiate ART at CD4+ cell count 350-550 cells/mm3 (n = 886 couples) Delayed ART Initiate ART at CD4+ cell count 250 cells/mm3* (n = 877 couples)
*Based on 2 consecutive values 250 cells/mm3.
Primary efficacy endpoint: virologically linked HIV transmission Primary clinical endpoints: WHO stage 4 events, pulmonary TB, severe bacterial infection and/or death Couples received intensive counseling on risk reduction and use of condoms
Cohen MS, et al. N Engl J Med. 2011;365:493-505.

HPTN 052: HIV Transmission Reduced by 96% in Serodiscordant Couples

Total HIV-1 Transmission Events: 39 (4 in immediate arm and 35 in delayed arm; P < .0001)
Linked Transmissions: 28
Unlinked or TBD Transmissions: 11
Delayed Arm: 27
Immediate Arm: 1
Single transmission in patient in immediate ART arm believed to have occurred close to time therapy began and prior to HIV-1 RNA suppression
P < .001
Cohen MS, et al. N Engl J Med. 2011;365:493-505.

HPTN 052: Decrease in AIDS-Related Events in Immediate vs Delayed ART Arms

Time to First AIDS-Defining Disease
0.25 Failure Probability 0.20 Logrank P = .03
Immediate ART Delayed ART Subjects Experiencing 1 AIDS-Related Event Tuberculosis, n (%) Serious bacterial infection, n (%) WHO stage 4 event, n (%) Esophageal candidiasis, n Cervical carcinoma, n Cryptococcosis, n Delayed 34 (4) 13 (1) 19 (2) 2 2 0 1 8 1 1 1 0 2 1 Immediate 17 (2) 20 (2) 9 (1) 2 0 1 0 2 1 0 0 1 0 2
0.15
0.10
0.05
0 0 1 2 3 4 5 Yrs Since Randomization
829 822 454 435 169 165 35 31 35 29
HIV-related encephalopathy, n Herpes simplex (chronic), n Kaposis sarcoma, n CNS lymphoma, n Pneumocystis pneumonia, n Septicemia, n HIV wasting, n Bacterial pneumonia, n
Pts at Risk, n 886 875
Non-AIDS events infrequent, with similar numbers of events in each arm
Grinsztejn B, et al. AIDS 2012. Abstract THLBB05. Graphic reproduced with permission.

HPTN-052: Decrease in Risk Behavior Over Study Duration

As part of HPTN-052, all participants received extensive risk counseling, condoms, and STD testing and treatment[1]
Recounseled at every 3-mo visit
Heterosexual pts with detectable VL and having unprotected sex at 24 mos

Immediate arm: 1%; delayed 3%
10 8 6 4 2 0 Heterosexual Pts With Detectable VL Who Reported Unprotected Sex, % Delayed ART Immediate ART
Substudy assessed time trends of risk behaviors and compared the change between the 2 treatment arms, adjusting for baseline characteristics including sex, region, substance use, and HIV-1 RNA level[2]
Pts at Risk, Delayed n Immediate
855 865
829 826 840 825
822 816
807 812
741 750
651 636
563 555
463 460
1. Cohen MS, et al. N Engl J Med. 2011;365:493-505. 2. Mayer K, et al. AIDS 2012. MOPDC0106. Graphic reproduced with permission.

HPTN-052: Cost-effectiveness of Early vs Delayed Therapy in South Africa and India

Cost-effectiveness* model using HPTN-052 data on transmission and clinical and resource utilization data from South Africa and India In South Africa, early ART projected to increase survival, decrease transmission events, and be cost saving at 5 yrs and very costeffective on lifetime horizon
In India, early ART also projected to increase survival, dramatically decrease HIV transmissions, and be cost-effective at 5 yrs and very cost-effective on lifetime horizon
*WHO thresholds: very cost-effective: < 1 x per capita GDP; cost-effective: < 3 x per capita GDP. Assumptions: mean CD4+ cell count 449 cells/mm3; HIV-1 RNA suppression at Wk 48: 92%; lost to follow-up: 3.4 per 100 pt-yrs; average partners: 1.011/mo; transmission rate: 0.103-1.483/100 pt-yrs; GDP South Africa: US$8100; India: US$1400. Walensky R, et al. AIDS 2012. Abstract FRLBC01.

Home HIV Testing and Increased HIV Screening of High-Risk MSM

Home HIV Testing[1]
Structured assessment and follow-up interviews of 27 MSM at high risk of HIV infection 16 home HIV tests given to each participant Subjects used home HIV test to seroscreen potential sex partners
Mutual testing often took place
Increased HIV Screening[2]

Current CDC testing guidelines call for HIV testing at least annually for sexually active MSM[3] Cost-effectiveness model of HIV testing at 3- and 6-mo intervals vs annually for a cohort of 10,000 MSM aged 14-64 yrs
Testing Q3 or Q6 mos was cost saving vs Q12 mos (Estimated cost-effectiveness as program costs minus treatment costs averted per QALY gained)
No intercourse took place when a partner tested positive

Subjects reported using condoms with partners who refused HIV tests
1. Carballo-Diguez A, et al. AIDS 2012. Abstract TUPDC0304. 2 Hutchinson AB, et al. AIDS 2012. Abstract THAB0302. 3. Branson BM, et al. MMWR Recomm Rep. 2006;55(RR-14):1-17.
HPV Vaccine in HIV-Infected Patients

Immunogenicity of HPV Vaccine in HIV-Infected Women

Open-label, 48-wk phase II trial in HIV+ women, age 16-23 yrs (n = 99)
Group A: ART naive or no ART for 6 mos Group B: on ART for 6 mos, with 2 VL < 400 c/mL Historical controls: HIV- women aged 16-23 yrs (n = 267) Seroconversion at Wk 48 (%) 100 80 60 40 20 0
22 95.8
High levels of vaccine seroconversion in both groups at 48 wks

Group A Group B
100 97.4 100 100 97.1 P < .05 87.5 73.9
All pts received quadrivalent HPV vaccine at vaccine at Day 1, Wk 8, and Wk 24, then followed for 24 wks No AEs > grade 3 evaluated as related to vaccine
HPV-6
HPV-11
HPV-16
HPV-18
Kahn J, et al. AIDS 2012. Abstract WEAB0202.

ACTG 5240: HPV Vaccine in HIV-Infected Women

Open-label phase II trial in HIV+ women age 13-45 yrs (n = 319) from US, Brazil, and South Africa
Stratum A: CD4+ > 350 (n = 130) Stratum B: CD4+ 200-350 (n = 95) HPV-6 HPV-11 Seroconversion, % Stratum A 96 (n = 50) 97.6 (n = 82) Stratum B 100 (n = 48) 98.3 (n = 58)
Stratum C: CD4+ 200 (n = 94)
HPV-16
HPV-18
All pts received quadrivalent HPV vaccine at Day 1, Wk 8, and Wk 24

Titers assessed 4 wks after last dose
98.4 (n = 64)
90.7 (n = 75)
98.2 (n = 55)
84.3 (n = 70)
*Stratum C not reported.
High rates of seroconversion at Wk 28 in Strata A and B who were seronegative at BL*
3 subjects with grade 3 or higher AEs possibly related to vaccine

1 each with chest pain, back pain, rash
Kojic EM, et al. AIDS 2012. Abstract WEAB0203.
Tuberculosis

Isoniazid Preventive Therapy in HIV-Infected Pts With TB

Randomized, double-blind, placebo-controlled trial in Khayelitsha, Cape Town, South Africa
Primary endpoint: incident TB (definite, probable, or possible)
Yr 1
HIV-1-infected pts on established ART or initiating ART (N = 1329)*
Isoniazid 5 mg/kg/day (n = 662)
Pts followed for 1-3 additional yrs
Placebo (n = 667)
*40 additional pts randomized but excluded from analysis due to presence of culture-positive TB (n = 39) or failure to receive study drug (n = 1). Maximum of 300 mg; coadministered with pyridoxine. Rangaka MX, et al. AIDS 2012. Abstract THLBB03.

Isoniazid Preventive Therapy Reduces Incidence of TB

95 TB cases observed, resulting in overall TB rate of 2.9/100 pt-yrs
37% lower rate of incident TB in INH arm vs placebo
2.3 vs 3.6/100 pt-yrs (P = .03)
No significant difference in mortality

0.9 vs 1.2 /100 pt-yrs (P = .32)
More pts receiving INH stopped study therapy due to grade 3 increase in ALT
2.9% vs 1.3% (P = .05)
Rangaka MX, et al. AIDS 2012. Abstract THLBB03.

ANRS REFLATE: EFV- vs RAL-Based ART in HIV/TB-Coinfected Pts

Multicenter, randomized, open-label phase II trial
Primary endpoint: HIV-1 RNA < 50 copies/mL at Wk 24
Wk 24 Primary endpoint Raltegravir 400 mg BID + Tenofovir + Lamivudine (n = 51) Antiretroviral-naive pts initiating rifampincontaining therapy* for TB coinfection (N = 154) Raltegravir 800 mg BID + Tenofovir + Lamivudine (n = 51) Raltegravir 400 mg BID + Tenofovir + Lamivudine Wk 48
Efavirenz + Tenofovir + Lamivudine (n = 52) *Rifampin-containing therapy initiated before ART and consisted of rifampin, isoniazid, pyrazinamide, and ethambutol for 2 mos, followed by rifampin and isoniazid for 4 mos. Grinsztejn B, et al. AIDS 2012. Abstract THLBB01.

REFLATE: Virologic Suppression at Wk 24 by ART Regimen

100
RAL 400 mg RAL 800 mg EFV

78 76 67
Pts with VL < 50 c/mL (%)
80
60 ITT; M = F, D/C = F
40
20
Virologic Failure at Wk 24
VL > 50 c/mL, n (%)
RAL 400 (n = 51)

12 (24) 20
RAL 800 (n = 51)

4 (8) 24
EFV (n = 51)
15 (29)
12 Wks
16
Grinsztejn B, et al. AIDS 2012. Abstract THLBB01. Graphic reproduced with permission.

REFLATE: Adverse Events Through Wk 24

Adverse Events Any AE grade 2, n (%) Grade 3 or 4 clinical AE, n (%) AE leading to drug discontinuation, n Hepatotoxicity* Cutaneous rash Gynecomastia Grade 3 or 4 IRIS, n AIDS-defining events, n (%) Death, n (%) RAL 400 mg (n = 51) 37 (73) 11 (22) 0 0 0 0 1 3 (6) 0 (0) RAL 800 mg (n = 51) 37 (73) 12 (22) 3 2 1 0 3 0 (0) 2 (4) EFV (n = 51) 39 (76) 13 (25) 2 0 1 1 1 2 (4) 2 (4)
*Both related to TB drugs: fulminant hepatitis with liver transplant in 1 patient Causes of death:EFV arm: 1 TB meningitis Wk4, 1 sepsis related to TB Wk6; RAL 800 arm: 1 unknown Wk2, 1 TB meningitis Wk12
Grinsztejn B, et al. AIDS 2012. Abstract THLBB01.

Early Bactericidal Activity of Sutezolid (PNU-100480) in HIV+/- Pts With TB

South African (2 centers), open-label phase IIa trial
Sutezolid, an oxazolidinone antimicrobial
Day 14
HIV- or HIV+ pts with CD4+ > 350 not receiving ART with pulmonary TB and no TB treatment in previous 6 mos (N = 59)
Sutezolid 600 mg BID (n =25)
Sutezolid 1200 mg QD (n = 25) Isoniazid/Rifampin/Ethambutol/Pyrazinamide (HREZ) (n = 9)
Standard TB Tx
Wallis RS, et al. AIDS 2012. Abstract THLBB02.

Early Bactericidal Activity of Sutezolid

Significant log CFU reductions with both sutezolid regimens during the 14-day treatment period
Change in log CFU 600 mg BID: -0.09 log/day (90% CI: -0.06 to -0.11) 1200 mg QD: -0.07 log/day (90% CI: -0.04 to -0.09) Trend toward superior response with BID dosing
-1
-2
600 BID 1200 QD HREZ 0 2 4 6 8 10 12 14
Both dosing schedules generally safe and relatively well tolerated

7/50 sutezolid-treated pts experienced ALT increases to 2-3 ULN
-3
Day
Wallis RS, et al. AIDS 2012. Abstract THLBB02. Graphic reproduced with permission.

Early Bactericidal Activity of Novel Combinations of TB Drugs

Phase IIa trial in TB-infected pts
Bedaquiline (TMC 207) (n = 15) Bedaquiline + Pyrazinamide (n = 15) HIV- or HIV+ pts* with newly diagnosed pulmonary smear and culture positive drug sensitive TB (N = 85) Bedaquiline + PA-824 (n = 15) PA-824 + Pyrazinamide (n = 15) Day 14
PA-824 + Pyrazinamide + Moxifloxacin (n = 15)

Isoniazid/Rifampicin/Ethambutol/Pyrazinamide (HREZ) (n = 10)
*6 HIV+ subjects.
Diacon A, et al. Lancet. July 23, 2012[Epub ahead of print]. Everitt D, et al. AIDS 2012. Abstract MOAB0305.

Early Bactericidal Activity of Novel TB Regimens

Log CFU Change From Baseline 0.5 0 -0.5 -1.0 -1.5
-2.0
-2.5 -3.0 0 2 4 6 Day Bedaquiline Bedaquiline + PZA Bedaquiline + PA-824 HREZ PA-824 + PZA PA-824 + PZA + moxifloxacin 8 10 12 14
Diacon A, et al. Lancet. July 23, 2012[Epub ahead of print]. Everitt D, et al. AIDS 2012. Abstract MOAB0305.
Inflammatory Markers

ACTG 5202: Inflammatory Markers and AIDS and Non-AIDS Events

ACTG 5202: TDF/FTC or ABC/3TC plus ATV/RTV or EFV in treatment-naive patients[1,2]
Biomarker substudy[3]
When adjusted for time-updated CD4+ cell count and ART, levels of TNF-alpha and sTNF receptors, but not hsCRP, independently associated with increased risk of AIDSdefining and non-AIDSdefining events
In separate study, 1 wk of aspirin therapy decreased T-cell activation and sCD14 in HIV-infected pts[4]
hsCRP, IL-6, and d-dimer trended downward
1. Sax P, et al. N Engl J Med 2009;361:2230-2240. 2. Daar E, et al. Ann Intern Med. 2011;154:445-456. 3. McComsey G, et al. AIDS 2012. Abstract THLBB06. 4. OBrien M, et al. AIDS 2012. Abstract THAB0202.
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clinicaloptions.com/AIDS2012

Cco Aids 2012 Slides

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Highlights of AIDS 2012

CCO Official Conference Coverage

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Highlights of AIDS 2012

About These Slides

Highlights of AIDS 2012

Ian M. Sanne, MBBCH, FCP(SA)

Highlights of AIDS 2012

Updated US Treatment Guidelines

Highlights of AIDS 2012

DHHS Guidelines, March 2012: When to Start

Highlights of AIDS 2012

IAS-USA Guidelines, July 2012: When to Start

Highlights of AIDS 2012

IAS-USA Guidelines, July 2012: What to Start

Thompson MA, et al. JAMA. 2012;308:387-402.

Highlights of AIDS 2012

High HIV Prevalence Among Young MSM in 5 US Cities

Oster AM, et al. AIDS 2012. Abstract MOAC0104.

Highlights of AIDS 2012

CDC: Differences in Continuum of Care in HIV-Infected Patients

Prescribed ART Viral suppression

Highlights of AIDS 2012

CDC: Differences in Continuum of Care in HIV-Infected Patients (contd)

Diagnosed Linked to care Retained in care

Prescribed ART Viral suppression

Hetero- Heterosexual sexual Male Female

Highlights of AIDS 2012

Highlights of AIDS 2012

Low-Level Viremia Not Associated With Short-term Risk of Virologic Failure

3 VL tests in following 12 mos

Comparison of virologic outcomes among 2 groups of pts:

Highlights of AIDS 2012

Cobicistat-Boosted vs Ritonavir-Boosted Atazanavir in Treatment-Naive Patients

Antiretroviral-naive patients, HIV-1 RNA 5000 copies/mL, eGFR 70 mL/min (N = 692)

Atazanavir/Cobicistat* + Tenofovir/Emtricitabine (n = 344) Atazanavir/Ritonavir + Tenofovir/Emtricitabine (n = 348)

Gallant J, et al. AIDS 2012. Abstract TUAB0103.

Highlights of AIDS 2012

ATV/COBI vs ATV/RTV: Noninferior Virologic Suppression at Wk 48

137/ 140/ 170 165 Baseline CD4+ > 350

Highlights of AIDS 2012

ATV/COBI vs ATV/RTV: Changes in Serum Creatinine and eGFR

Highlights of AIDS 2012

Elvitegravir/Cobicistat/TDF/FTC vs EFV/TDF/FTC: Subgroup Responses

176/ 173/ 193 205 Baseline CD4+ > 350

Baseline VL > 100K-400K

Baseline VL > 400K

Baseline CD4+ 200

Baseline CD4+ > 201-350

Highlights of AIDS 2012

Elvitegravir/Cobicistat/TDF/FTC vs ATV/RTV + TDF/FTC: Subgroup Responses

n = 353 355 Overall

Baseline VL > 100K-400K

Baseline VL > 400K

Highlights of AIDS 2012

SPRING-2: Dolutegravir QD vs Raltegravir BID in Treatment-Naive Pts at 48 Wks

Antiretroviral-naive pts, VL 1000 c/mL (N = 822)

Dolutegravir 50 mg QD + 2 NRTIs* (n = 411)

Raltegravir 400 mg BID + 2 NRTIs* (n = 411)

Highlights of AIDS 2012

SPRING-2: Dolutegravir Noninferior to Raltegravir at 48 Wks

Highlights of AIDS 2012

SPRING-2: Safety and Resistance

DTG had favorable safety profile, comparable to RAL