Highlights for clinical practice HIV International Congress of

Highlights for clinical practice HIV International Congress of

Highlights for clinical practice HIV International Congress of Drug Therapy in HIV Infection Glasgow, UK 23-26 October 2016 About the slide deck Goal How to reach the goal? Bringing newest insights/research data to the healthcare professional community in HIV, with context and clinical relevance Peer-reviewed slide deck on abstracts with impact on clinical practice - Presented as poster or orally - Selected by reporter in cooperation with editorial board - Reviewed by reporter and editorial board Structure of slide deck First slide

Topic (title of the abstract) + reference Second slide Following slide(s): Final slide: Clinical question + background of the question Description of study design + main data Repetition of clinical question + answer (take home message) Disclaimer This scientific material was prepared by e-HIMS; content selection and review was performed by:

Dr. Eric Florence, ITG Antwerp (editorial board) Dr. Agns Libois, CHU St Pierre, Brussels (medical reporter) Dr. Charlotte Martin, CHU St Pierre, Brussels (medical reporter) Dr. Eric Van Wijngaerden, UZ-KULeuven, Leuven (editorial board) The information on the slides included is not intended to replace professional guidelines or established clinical practice Concerning medical treatment options, the approved summary of product characteristics should be used for guidance Disclaimer terms of use 2016 These slides may not be published or posted online without permission from the publisher e-HIMS (request by email [email protected]) The slides may be re-used in personal presentations and in meetings organised by the industry partner with a license agreement (ViiV Healthcare Belgium), upon appropriate referencing to the source as Derived from FORUM HIV - 2016 e-HIMS Overview PEP/PrEP Diagnosis Co-morbidities & ageing ARV safety Treatment simplification Switch strategies

Co-infections New ARVs PEP/PrEP InterPrEP: internet-based PrEP with generic TDF/FTC in London analysis of PK, safety and outcomes Wang X. J Int AIDS Soc 2016;19(Suppl 7):15(abs.O315) ? Are drug concentrations of bioequivalent generic forms of TDF/FTC consistent with the FDAapproved TDF/FTC for PrEP? FDA- and WHO-approved forms of TDF/FTC are available via the internet (eg www.iwantprepnow.co.uk) There are concerns about the authenticity of medicines purchased online Population and assessments o Plasma TFV/FTC therapeutic drug monitoring in 234 HIV-negative individuals on generic PrEP

o Evaluation of renal function at baseline and every 3 months o HIV and STI testing at baseline and every 3 months Population characteristics MSM (%) Median age (yr) Chemsex (%) PrEP dosing schedule (% pts) Company Online suppliers N=234 100 37 35 Event-driven: 15% Daily: 85% Cipla: N=181 Emcure: N=2 Mylan: N=1 Not reported: N=50

www.iwantprepnow.co.uk: 92% www.alldaypharmacy.co.uk: 6% Other: 2% Wang X. J Int AIDS Soc 2016;19(Suppl 7):15(abs.O315) poster & oral presentation Outcome Pharmacokinetics Efficacy and safety N=212 Plasma concentrations No HIV infections observed (FU on N=201) Normal renal function at baseline and FU Median (ng/mL) Range (ng/mL) Median time post dose (h) TFV FTC 103

142 21-597 17-1,876 15.5 15.5 Repeated for 12 individuals: adequate plasma concentrations of TFV non-TDF and FTC Wang X. J Int AIDS Soc 2016;19(Suppl 7):15(abs.O315) poster & oral presentation Are drug concentrations of bioequivalent generic forms of TDF/FTC consistent with the FDA-approved TDF/FTC for PrEP? TAKE HOME MESSAGE In this cohort there appears to be no concerns about the pharmacokinetic properties of generic TDF/FTC purchased online

Risk perception in MSM taking PrEP Boccino S. J Int AIDS Soc 2016;19(Suppl 7):28(abs.P012) ? How does PrEP influence risk perception of MSM? PrEP is recommended in adults at high risk of acquiring HIV infection when condoms are not used consistently PrEP does not protect against other STIs and should be used in combination with other preventive interventions Feeling on risk of acquiring other STIs after starting PrEP Survey The same; 78.00% o MSM attending a central London sexual health clinic for PrEP monitoring (Febr-June 2016) o Self-reported anonymous paper

questionnaire Completed questionnaires (N) MSM respondents (N) PrEP adherence (%) Daily Event-driven Not specified Median time on PrEP (mo) 100 100 77 19 4 3 More relaxed; 2.00% Less relaxed; 20.00% 83% more relaxed about risk of acquiring HIV Boccino S. J Int AIDS Soc 2016;19(Suppl 7):28(abs.P012)

Change in self-reported condomless sexual activity Decreased No change Increased 70 63 % MSM 60 50 40 41 P=0.049 vs <4 mo on PrEP 30 30 22

18 20 12 10 3 0 4 mo on PrEP *2 pts no data on PrEP duration 2 <4 mo on PrEP 5 Total * Boccino S. J Int AIDS Soc 2016;19(Suppl 7):28(abs.P012) How does PrEP influence risk perception of MSM? TAKE HOME MESSAGE There appears to be an association between

length of time on PrEP and increased condomless sexual activity MSM taking PrEP seem less afraid about acquiring HIV but less so about acquiring other STIs Compliance of fixed-dose single tablet EVG/COBI/FTC/TDF regimen vs LPV/r / d4T/3TC for PEP in sexual assault victims: a retrospective sequential period study De Wit S. J Int AIDS Soc 2016;19(Suppl 7):27(abs.P010) ? Is PEP compliance in sexual assault victims higher with a single-tablet versus a multitablet regimen? Although PEP is often recommended in sexual assault cases, compliance is poor (~40%) A single-tablet PEP regimen showed high levels of adherence and completion in a recent study Retrospective sequential period analysis (2011-2015)

o Prospective PEP registry o Compliance = pts taking PEP for 28 d Extracted from medical records Calculated from pharmacy records Variable Value Received PEP / Consulted for PEP (N) 283/368 Female (%) 92 Migrants (%) 50 Mean age (yr) 27 Exposure (%)

Vaginal receptive Anal receptive Oral receptive 84 29 27 De Wit S. J Int AIDS Soc 2016;19(Suppl 7):27(abs.P010) poster Compliance for PEP in sexual assault victims Jan 2011 Multi-tablet regimen LPV/r /d4T/3TC 42% (N=212) Jan 2015 Compliance Single-tablet regimen EVG/COBI/FTC/TDF

Dec 2015 52% (N=71) P=0.152 De Wit S. J Int AIDS Soc 2016;19(Suppl 7):27(abs.P010) poster Is PEP compliance in sexual assault victims higher with a single-tablet versus a multi-tablet regimen? TAKE HOME MESSAGE Switching to a well-tolerated single-pill regimen (EVG/COBI/FTC/TDF) does not seem to significantly improve compliance in sexual assault victims Diagnosis Targeting HIV testing at a population level: costeffectiveness of three approaches Gomez Ayerbe C. J Int AIDS Soc 2016;19(Suppl 7):230-2(abs.P328)

? What is the most costeffective targeted HIV testing approach to predict HIV infection? Targeted HIV testing by filling in a self-administered Risk Exposure & Clinical Indicators (RE&CI) questionnaire and testing only subjects with a positive questionnaire seems as efficient as a non-targeted routine testing in the DRIVE 01 study Study design: non-targeted HIV testing programme in the emergency department and primary care centre - DRIVE 01 study RE&CI questionnaire 6 questions for risk of exposure 14 questions for HIV-associated clinical indicators One affirmative item = positive* test Denver HIV Risk Score (DHRS) Demographics (age, sex, race, ethnicity) Risk behaviour History of HIV testing Cut-off >30 = positive* test HIDES 14 clinical indicators One clinical indicator = positive* test

*being at increased risk of HIV infection Analysis Predictive performance Cost per new HIV diagnosis Incremental costeffectiveness ratio (ICER) Gomez Ayerbe C. J Int AIDS Soc 2016;19(Suppl 7):230-2(abs.P328) poster Population characteristics (N=5,329) Predictive performance of targeted HIV tests o Women: 50% o Median age: 37 yr Routine testing as ref o Positive RE&CI questionnaire: 52%

DHRS: 40% HIDES: 27% o NHD confirmed by enzyme immunosassay/western blotting 0.4% Sens Spec PPV NPV RE&CI questionnaire 100 49 1 100 DHRS

73 60 1 100 HIDES 91 74 1 100 Routine testing RE&CI questionnaire DHRS HIDES NHD/MHI

22/0 22/0 N tests avoided 0 2,601 N test for 1 pos result 242 124 16/6 20/2 3,212 3,948 132 69 NDH: new HIV diagnosis; MHI: missed HIV infections Gomez Ayerbe C. J Int AIDS Soc 2016;19(Suppl 7):230-2(abs.P328) poster Cost and cost-effectiveness Gomez Ayerbe C. J Int AIDS Soc 2016;19(Suppl 7):230-2(abs.P328) poster

What is the most cost-effective targeted HIV testing approach to predict HIV infection? TAKE HOME MESSAGE While the RE&CI questionnaire detected all HIV-infected subjects from the routine strategy, the HIDES test seems to avoid the highest number of tests and has a high sensitivity as well Co-morbidities & ageing Neuro+3 study: cognitive evolution in HAND after 96 wk of treatment intensification with higher CNS penetration score Force G. J Int AIDS Soc 2016;19(Suppl 7):161(abs.P217) ? Does treatment intensification with higher CNS penetration score improve cognitive results in virologically controlled pts? HIV infection can result in neurocognitive disorders (HAND)

Some reports suggest that the use of ART with good CNS penetration leads to better neurocognitive outcomes Study design: Open-label pilot study 63 pts screened in 8 investigational centres 2 ability domains altered 31 pts included* ARV changed to new combination with higher CNS penetration effectiveness (CPE) (3 point score improvement and total score of 9) Raw test score Cognitive Complaint Questionnaire score Global deficit score HAND level classification Grooved Pegboard, Verbal Fluency, CVLT, Digit span, PASAT, Digit symbol, Wisconsin Card Scoring Test (6 domains) *Exclusion criteria: drug/alcohol abuse, HBsAg or HCV positivity, hypothyroidism, vitamin B deficiency, psychiatric problems

Force G. J Int AIDS Soc 2016;19(Suppl 7):161(abs.P217) poster Tx intensification with INSTI (64.5%), CCR5 inhibitor (32.3%) or NNRTI (19.4%) Evolution of cognitive results (N=31) HAND classification (N=31) HIV-associated dementia Cognitive Complaint Questionnaire score 4 Median score I m p r o v e m n t Number of pts

Global Deficit Score Mild neurocognitive impairment 20 16 12 P=0.009 0 Day 0 Week 48 *7 pts with one altered domain **2 pts with one altered domain and 3 pts with normal tests Week 48 vs Day 0: P=0.002 Week 96 vs Day 0: P<0.001 8 P<0.001 2

Asymptomatic neurocognitive impairment 4 Week 96 0 Day 0 Week 48* Week 96** Force G. J Int AIDS Soc 2016;19(Suppl 7):161(abs.P217) poster Does treatment intensification with higher CNS penetration score improve cognitive results in virologically controlled pts? TAKE HOME MESSAGE Treatment intensification by NNRTI, INSTI and/or CCR5 inhibitor seems to be associated with a statistical improvement in cognitive test after 48 and 96 weeks, with enhanced GDS and HAND classification

The relative impact of ARV drugs and baseline immune status on bone quality in HIV-positive subjects: results from the HIV UPBEAT cohort McGinty T. J Int AIDS Soc 2016;19(Suppl 7):130-1(abs.P169) ? What is the effect of HIVspecific factors on bone microstructure? In pts with similar bone mineral density (BMS), the trabecular bone score (TBS) can non-invasively detect differences in bone quality HIV-positive subjects have a lower TBS compared with HIV-negative persons, which appears to be driven by current smoking status Study design o N=201 HIV-positive patients from HIV UPBEAT cohort o BMD: measured by dual X-ray absorptiometry (DXA) o TBS: derived from baseline lumbar spine DXA images using TBS Insight software

Baseline characteristics Mean age (yr) Value 39 Male (%) 59.2 Duration HIV disease (yr) 4.5 Nadir/current CD4 count (cells/mm) 211/471 Cumulative ART exposure (yr) 2.7 Current smoker (%) 35.8

Homosexual/heterosexual sex/IVDU (%) 31/52/17 McGinty T. J Int AIDS Soc 2016;19(Suppl 7):130-1(abs.P169) poster & oral presentation Results Patient characteristics significantly affecting TBS Multivariate analysis* - final model that best predicts lower TBS in HIV-positive pts Variable Current smoker Nadir CD4 count (per 50 cells/mm higher) PI-containing ART Effect on TBS -0.047 95% CI P

-0.085, -0.008 0.02 0.005 0.003, 0.011 0.04 -0.045 -0.079, -0.011 0.009 *Adjusted for lumbar spine BMD, ethnicity, age, gender, BMI and current smoking status TDF treatment status did not affect TBS McGinty T. J Int AIDS Soc 2016;19(Suppl 7):130-1(abs.P169) poster & oral presentation What is the effect of HIV-specific factors on bone microstructure?

TAKE HOME MESSAGE In addition to smoking, also baseline immune status and exposure to PI (rather than TDF) seem significantly associated with lower TBS and related bone quality in HIV-positive subjects HIV patients today and 10 yr ago: do they have the same needs? Results from cross-sectional analysis of ANRS CO3 Aquitaine cohort Bonnet F. J Int AIDS Soc 2016;19(Suppl 7):9(abs.O212) What is the evolution of chronic non-HIV-related diseases and risk factors over 10 yr? ? People living with HIV live longer due to effective ART Due to ageing, risk factor exposure, ART and HIV-related factors, HIVinfected people are more likely to develop co-morbidities Study design: longitudinal crosssectional study of the prospective ANRS

CO3 Aquitaine cohort Bonnet F. J Int AIDS Soc 2016;19(Suppl 7):9(abs.O212) oral presentation Male Median age (yr) Age >50 yr Median BMI MSM Heterosexual 2004 2014 71% 42 52 20% 62% 22 23 40% 33% HIV and ART characteristics (N=2,138) 2004 % pts

Population characteristics (N=2,138) 100 80 60 P<0.0001 72.0 2014 91.5 P<0.0001 50.9 43.6 40 20 0 CD4 count 500 HIV-RNA <50 c/mL

ART drug class (% pts) 2004 2014 2 NRTIs + 1 PI/r 24 32 2 NRTIs + 1 NNRTI 22 32 2 NRTIs + INTI 0 7 Other tx

35 26 No tx 19 3 Bonnet F. J Int AIDS Soc 2016;19(Suppl 7):9(abs.O212) oral presentation Co-morbidities, co-treatments and risk scores % pts (N =2,138) Significant (P<0.0001) increase over 10 yr: 2004 60 50 40 30 20 10

0 56.3 54.5 24.0 14.3 2014 9.2 50.7 29.9 22.7 18.7 6 14.0 3.6 19.9 5.3

18.3 3.6 18.5 8.4 2.4 5.8 1.3 3.7 0.7 7.0 Tobacco use (~ 40%) and antidepressant drug use (~ 10%) stable over 10 yr Bonnet F. J Int AIDS Soc 2016;19(Suppl 7):9(abs.O212) oral presentation What is the evolution of chronic non-HIV-related diseases and risk factors over 10 years? TAKE HOME MESSAGE Significant improvement in HIV markers over 10 years Higher prevalence of co-morbidities over time, especially dyslipidaemia and

hypertension, with increased associated risk factors and co-treatments Future challenges for clinical care of an ageing population infected with HIV: a geriatric HIV modelling study De Francesco D. J Int AIDS Soc 2016;19(Suppl 7):118-9(abs.P155) ? How will the HIV population evolve and what are the implications? According to a modelling study, multimorbidity in HIV patients will be the norm 15 years from now Frailty, geriatric syndromes and disability will be relevant clinical outcomes in this context Individual-based model of ageing HIV population - Italy Data from Modena HIV Metabolic Clinic collected between 2009-2015* N=2,982 Frailty index

= Proportion of deficits present (total of 37) <0.3: not frail 0.3-0.4: frail 0.4: most frail Geriatric syndrome = Patient-reported fall frequency in the past year (1) Disability = Impairment in 1 IADL** *Model follows pts enrolled up to 2015 and generates new entries on a yearly basis up to 2030 with the relationship between age, gender, geriatric syndrome and disability being constant over time **Housekeeping, money management, cooking, transportation, telephone use, shopping, laundry, medication management De Francesco D. J Int AIDS Soc 2016;19(Suppl 7):118-9(abs.P155) poster Model outcomes Population characteristics HIV-positive pts 2015 2030

Median age (yr) 49 59 >50 yr (%) 42 95 Frailty index Frail (%) Most frail (%) 26 24 28 48 Geriatric syndrome (%) NA

30 Disability (%) NA 34 De Francesco D. J Int AIDS Soc 2016;19(Suppl 7):118-9(abs.P155) How will the HIV population evolve and what are the implications? TAKE HOME MESSAGE The increasing number of older patients with frailty, geriatric syndromes and disability seems to depict a geriatric HIV scenario in 15 years Tailored screening and clinical protocols adapted to a geriatric hiv population are needed Epidemiologic snapshot of the HIV-positive population in Belgium, 2014 to 2016 Callens S. J Int AIDS Soc 2016;19(Suppl 7):129-30(abs.P167)

? How is the current Belgian HIV population composed and what is the prevalence of the main non-infectious co-morbidities? HIV care in Belgium: 11 AIDS reference centres and 7 HIV reference laboratories in Belgium 14,000 HIV cases in 2014; 3 new cases per day Of HIV individuals diagnosed in 2006-2008: 98.2% linked to care and 90.8% retained in HIV care Cross-sectional analysis of cohort data o 4 Belgian HIV reference centres o N=5,785 HIV-positive individuals with 1 FU care (June 2014 July 2016) Baseline characteristics Mean age (yr) Female (%) Mean nadir/recent CD4 count (cells/mm) Started HIV treatment (%)

Risk factors Smokers, former or current (%) Hypertension (%) HCV-RNA positive (%) Value 46.6 37.6 268.8/651.3 94.9 37.9 17.4 3.1 Callens S. J Int AIDS Soc 2016;19(Suppl 7):129-30(abs.P167) poster Outcomes NCIMs All ages (N=5,785) 40 yr 41-50 yr 51-60 yr

60 yr Diabetes mellitus 5.9 1.8 4.5 10.4 12.2 CVD* 2.9 0.6 1.5 4.9 8.3

CKD 7.7 1.7 5.3 10.6 24.9 Other** 0.8 0.4 0.6 1.7 0.9

Clinical diagnoses, or Prescription of anti-diabetic drugs or insulin Myocardial infarction Cerebrovascular accident, or Invasive cardiovascular procedure Confirmed eGFR <60 mL/min/1.73 m when baseline eGFR >60, or Confirmed 25% eGFR decline when baseline eGFR <60 *Data from 3 centres **Anal cancer and Hodgkins lymphoma Callens S. J Int AIDS Soc 2016;19(Suppl 7):129-30(abs.P167) poster

How is the current Belgian HIV population composed and what is the prevalence of the main non-infectious co-morbidities? TAKE HOME MESSAGE Almost 40% of the HIV-infected population is 50 years Higher prevalence of NICMs, especially CKD and diabetes mellitus in the elderly, warrants the need for careful patient management ARV safety Higher rates of neuropsychiatric adverse events leading to DTG discontinuation in women and older pts Sabranski M. J Int AIDS Soc 2016;19(Suppl 7):10(abs.O214) ? Is there a need for concern about potential neuropsychiatric adverse events related to DTG?

Recent reports of DTG have raised concerns about the safety of DTG in real-life practice with regard to neuropsychiatric AEs Study design: retrospective analysis of HIV pts from 2 German centres Sabranski M. J Int AIDS Soc 2016;19(Suppl 7):10(abs.O214) oral presentation Discontinuation rate on DTG N=985, median FU 11.5 mo (range 0-25.4 mo) Estimated AE discontinuation rate at 12 mo Total discontinuation rate: 9% Reasons: 0.1 6.8 RAL (N=678) *P<0.0001 between DTG and other INSTI 0.9 1

EVG (N=287) 8 7.6 7.6 % pts 0.2 DTG (N=985) 5.6 4 3.3 1.9 Virological failure Death 0.7

Other reasons ART simplification 0 Any AE Neuropsychiatric AE* AEs (any) 5% neuropsychiatric AEs: mostly insomnia, sleep disturbances No hospitalisation for symptoms; quick disappearance of symptoms after discontinuation Sabranski M. J Int AIDS Soc 2016;19(Suppl 7):10(abs.O214) oral presentation Variables associated with DTG discontinuation due to neuropsychiatric AEs Multivariate Cox regression analysis RH (95% CI) P

Female vs male 2.64 (1.23-5.65) 0.0122 >60 yr vs younger 2.86 (1.42-5.77) 0.0033 ABC with DTG initiated vs no ABC 2.42 (1.38-4.24) 0.002 11.36 (4.31-29.41) <0.0001 DTG start in 2016 vs 2014/5 Likely due to increased awareness of treating physicians

No association with ethnicity, centre, CD4 cell count, prior AEs with other ARTs Neuropsychiatric symptoms reproducible in 6 cases upon re-exposure to DTG 86% of DTG discontinuers had no tolerability problems with the subsequent ART (FU >3 mo) Sabranski M. J Int AIDS Soc 2016;19(Suppl 7):10(abs.O214) oral presentation Is there a need for concern about potential neuropsychiatric adverse events related to DTG? TAKE HOME MESSAGE In this retrospective cohort study, the DTG tx discontinuation rate due to neuropsychiatric AEs is relatively high (6% at 12 mo) Women, older pts and pts on ABC co-initiation tx had a 2-3 fold higher risk of DTG tx discontinuation due to neuropsychiatric AEs These AEs were reversible and not severe (mostly sleep disturbances) Psychiatric AEs from the DTG ART-nave phase III clinical trials Quercia R. J Int AIDS Soc 2016;19(Suppl 7):155-6(abs.P210) ? Does DTG have psychiatric side effects in treatment-nave subjects?

INSTIs are one of the classes recommended for pts starting ART due to their favourable safety and tolerability profile Psychiatric AEs (pAEs) have been reported in INSTI-treated pts, but at lower frequency than in EFV-treated pts Data analysis o Phase III/IIIb trials in tx-nave subjects on DTG 50 mg qd with 48 wk of data as of April 2016 pAEs* grouped in 5 categories SPRING-2, FLAMINGO, SINGLE studies: 96 wk FU data ARIA study: 48 wk FU data o N=1,315 with DTG *Defined according to MedDRA Quercia R. J Int AIDS Soc 2016;19(Suppl 7):155-6(abs.P210) poster & oral presentation pAEs (N=2,634)

Insomnia Suicidality Anxiety Nightmares/Abnormal dreams Depression 21 20 17 Pts with pAEs (%) 15 12 10 5 8 7

6 5 4 0 1* DTG SPRING-2 *Values <1 11 10 5 6 5 7

7 5 1 RAL 2 7 4 2 2 DTG FLAMINGO 8 7 5 4

1* 1 DRV/r 2 1* DTG EFV SINGLE 4 2 3 3 1 1 DTG 4 2 ATV/r

1* ARIA Quercia R. J Int AIDS Soc 2016;19(Suppl 7):155-6(abs.P210) poster & oral presentation Characteristics of pAEs % of AEs Insomnia Drug related (%) Severe or grade 3/4 (%) Anxiety Drug related (%) Severe or grade 3/4 (%) Depression Drug related (%) Severe or grade 3/4 (%) Suicidality Drug related (%) Severe or grade 3/4 (%) SPRING-2 DTG* RAL* (N=411)

(N=411) FLAMINGO DTG* DRV/r* (N=242) (N=242) SINGLE ARIA DTG (N=414) EFV (N=419) DTG (N=248) ATV/r (N=247) 24 0

15 0 20 0 31 0 61 4 54 0 50 10 13 0 6 6 9

0 8 0 0 0 14 0 37 10 0 0 13 25 3 3 10 5

0 19 0 8 37 14 43 18 11 0 9 9 0 75 0 83 25 75

0 0 0 67 57 71 33 0 0 25 Majority of pAEs were low grade and few leading to tx discontinuation Co-medication with *2NRTIs; ABC/3TC; TDF/FTC; DTG/3TC Quercia R. J Int AIDS Soc 2016;19(Suppl 7):155-6(abs.P210) poster & oral presentation Does DTG have psychiatric side effects in treatment-nave subjects? TAKE HOME MESSAGE DTG once daily seems to be well tolerated

with a low rate of pAEs, the majority of which were low grade, as reported from clinical trials Treatment simplification Non-inferiority of dual therapy with DRV/r + 3TC vs triple therapy with DRV/r + TDF/FTC or ABC/3TC for maintenance of viral suppression: 48-wk results of the DUAL-GESIDA 8014 trials Pulido F. J Int AIDS Soc 2016;19(Suppl 7):16-7(abs.O331) ? Is dual therapy with DRV/r + 3TC non-inferior to triple therapy with DRV/r + 2 N(t)RTIs for maintenance of virological suppression? Dual therapy with a boosted PI and 3TC can have advantages in toxicity and cost Dual therapy with 3TC and LPV/r or ATV/r is non-inferior to triple therapy with 2 N(t)RTIs and LPV/r or ATV/r for maintaining virological suppression Study design: Multi-centre, open-label, non-inferiority RCT

Suppressed HIV patients HIV-RNA <50 c/mL for >6 mo On triple therapy with DRV/r + ABC/3TC or TDF/FTC 2 mo No resistance to DRV, 3TC or FTC HBsAg negative Switch to dual therapy: DRV/r qd + 3TC qd 48 wk; N=129 Continue triple therapy: DRV/r qd + ABC/3TC or TDF/ FTC 48 wk; N=128 Primary endpoint: % of pts with HIV-RNA <50 c/mL at wk 48 cfr FDA snapshot algorithm in exposed ITT population Secondary endpoints: % of pts with HIV-RNA <50 c/mL at wk 48 cfr FDA snapshot algorithm in PP and observed therapy populations % pts with persistently suppressed viraemia, % pts with blips Safety Pulido F. J Int AIDS Soc 2016;19(Suppl 7):16-7(abs.O331) poster & oral presentation Baseline

characteristics similar between groups Primary endpoint: non-inferiority at wk 48 o Male (83%) o 100 wk with suppressed viraemia (median)* o CD4 nadir 246 cells/mL (median) 100 90 89 Dual (N=126) Triple (N=123) 93 80 70 60 % pts

o TDF/FTC use at baseline (75%) o ABC/3TC use at baseline (25%) -3.8% difference (95% CI: -11%, +3.4%) 50 40 30 *80 vs 113 wk for dual vs triple therapy (P=0.014) 20 10 0 3 8 2 HIV-RNA <50 c/mL HIV-RNA 50 c/mL 6 Unknown

Similar results for PP and observed therapy populations Pulido F. J Int AIDS Soc 2016;19(Suppl 7):16-7(abs.O331) poster & oral presentation Safety of dual vs triple therapy Pts (%) Dual Triple (N=126) (N=123) Any AE 70 76 Grade 2 or 4 Any grade 3 or 4 lab AE 12

15 3 3 SAE 5 5 Discontinuation due to AE or intolerance 1 2 No statistically significant difference between groups AEs occurring in Dual Triple

(N=126) (N=123) Respiratory 25 24 Infections and infestations 18 15 Digestive 14 18 Muscular or skeletal 13

18 Neuropsychiatric 10 10 10% of pts (% pts) No statistically significant difference between groups Pulido F. J Int AIDS Soc 2016;19(Suppl 7):16-7(abs.O331) poster & oral presentation Is dual therapy with DRV/r + 3TC non-inferior to triple therapy with DRV/r + 2 N(t)RTIs for maintenance of virological suppression? TAKE HOME MESSAGE Dual therapy with DRV/r + 3TC seems noninferior (and as well tolerated) as DRV/r + TDF/FTC (or ABC/3TC) for maintenance of virological suppression over 48 wk Switching from cART to DTG maintenance monotherapy in virologically suppressed HIV-1

infected adults: a randomised, multi-centre, non-inferiority clinical trial (DOMONO) Wijting I. J Int AIDS Soc 2016;19(Suppl 7):17-8(abs.O333) ? Is DTG monotherapy noninferior to cART in maintaining virological suppression? DTG in cART shows equal or superior virological suppression vs NNRTI, PI or first-generation INSTI in cART Given potential side effects of cART, maintenance therapy with fewer drugs is warranted Only retrospective studies have investigated DTG maintenance monotherapy Study design: Multi-centre, open-label, non-inferiority RCT cART patients

HIV-RNA <50 c/mL for >6 mo HIV-RNA zenith <100,000 c/mL CD4 cells nadir >200 cells/mm3 No resistance, no virological failure HBV-immune or vaccinated >95% estimated compliance Immediate DTG monotherapy (50 mg qd) 48 wk, N=51 Continue cART 24 wk, N=53 Delayed DTG monotherapy (50 mg qd) 48 wk On-treatment analysis: Primary endpoint: virological suppression at 24 wk (% pts with HIV-RNA <200 c/mL) for DTG vs continuous cART Secondary endpoints: Virological suppression at 24 wk (% pts with HIV-RNA <50 c/mL)

% pts on DTG immediate+delayed monotx with virological suppression at 24 and 48 wk Wijting I. J Int AIDS Soc 2016;19(Suppl 7):17-8(abs.O333) poster & oral presentation Baseline characteristics Variable DTG (N=51) cART (N=53) Male (%) 92 91 MSM transmission (%)

80 77 On TDF before switch (%) 86 85 Median time on cART (mo) 35 43 Median HIV-RNA zenith (c/ mL) 22,000 28,000 Median CD4 nadir (cells/L)

% p ts w ith H IV -R N A < 2 0 0 c/m L Primary endpoint Virological suppression at wk 24 in pts on tx Non-inferiority 2% difference (95% CI: +12%, -5%) 100 98 100 80 60 40 320 380 20

0 Switch to DTG monotherapy (N=50) Continue cART (N=53) Wijting I. J Int AIDS Soc 2016;19(Suppl 7):17-8(abs.O333) poster & oral presentation Virological failures (>50 c/mL at wk 24) secondary endpoint At wk 24: Wijting I. J Int AIDS Soc 2016;19(Suppl 7):17-8(abs.O333) data from poster & oral presentations included Is DTG monotherapy non-inferior to cART in maintaining virological suppression? TAKE HOME MESSAGE In a carefully selected HIV population on suppressive cART, switching to DTG maintenance monotherapy: Seems to be non-inferior to cART in virological suppression <200 copies/mL at 24 wk Tends to provide more often lower level viraemias than cART continuation at 24 wk Long-term use of DRV/r qd

monotherapy in daily practice: retrospective observational cohort data of 111 HIV pts in Belgium De Wit S. J Int AIDS Soc 2016;19(Suppl 7):108-9(abs.P137) ? Is DRV/r qd monotherapy a suitable option for virologically suppressed pts? DRV/r 800 mg/100 mg qd in combination therapy with other ARVs, but not as monotherapy, is recommended as first-line option Clinical trials have shown the usefulness of DRV/r monotherapy for pts with stable virological suppression on cART Study design: Multi-centre, retrospective, observational cohort study in Belgium De Wit S. J Int AIDS Soc 2016;19(Suppl 7):108-9(abs.P137) poster Variable Age (yr) Male (% pts) CD4 cells/mm3 (mean)

CD4 nadir (mean) HIV-RNA (% pts) <50 c/mL 50<200 c/mL P r o b a b ilit y o f r e m a in in g o n T x (% ) Baseline characterstics (N=111) Primary endpoint: 25.2% of pts discontinued Tx (median follow-up of 2.6 yr) Value 49.5 65.8 648.1 223.0 90 85 80 75

84.7 7.2 70 65 6 mo 1 yr 2 yr 3 yr Reasons for Tx discontinuation Virological failure 1.8 AEs 11.7 9.9 1.8 Simplification/compliance

Other De Wit S. J Int AIDS Soc 2016;19(Suppl 7):108-9(abs.P137) poster Secondary endpoints De Wit S. J Int AIDS Soc 2016;19(Suppl 7):108-9(abs.P137) poster Is DRV/r qd monotherapy a suitable option for virologically suppressed pts? TAKE HOME MESSAGE Based on long-term real-life data in a Belgian subpopulation, DRV/r qd monotherapy seems to have good efficacy and tolerability in virologically suppressed patients Dual therapy with a boosted PI plus 3TC is an effective maintenance strategy in pts on nd 2 -line ART in Africa: the ANRS 12286/MOBIDIP trial Ciaffi L. J Int AIDS Soc 2016;19(Suppl 7):5(abs.O122) ?

Is addition of 3TC a good strategy to increase efficacy of the maintenance strategy with PI/r, without additional toxicity? PI-based 2nd-line ART is effective in low resource countries BUT long-term toxicities, costs and saving future options request for tx simplification maintenance strategies PI monotherapy maintenance tx may lead to viral escape and low level viraemia Study design: multi-centre, African, randomised, open-label superiority trial ANRS 12286 MOBIDIP ANRS 12169 2LADY >48 wk, N=454 FTC + TDF + LPV/r ANRS 12286 MOBIDIP 96 wk, N=265 Included in MOBIDIP if: LPV/r monotx PI/r

(N=133) ABC + ddI + LPV/r DRV/r monotx FTC + TDF + DRV/r LPV/r + 3TC Viral load 200 c/mL for 6 mo No change in ART in last 3 mo CD4 100 cells/mL Adherence 90% at end of 2LADY trial PI/r + 3TC (N=132) DRV/r + 3TC Primary endpoint:

% pts with tx failure (viral load 500 c/mL confirmed with 1 mo interval, reintroduction of 2 NRTIs, interruption of PI/r) Ciaffi L. J Int AIDS Soc 2016;19(Suppl 7):5(abs.O122) oral presentation Baseline characteristics Median age (yr) Women (%) Viral load <50 c/mL (%) Median CD4 (cells/L) PI = DRV (%) M184V at 1st-line tx failure (%) PI/r (N=133) 41 76 80 498 42 95 PI/r + 3TC

(N=132) 43 70 83 472 33 97 % p t s w i t h t x f a i lu r e Variable Analysis at 48 wk due to premature stop of monotx arm Primary endpoint (ITT): PI/r (N=133) 30 24.8 PI/r + 3TC (N=132) P<0.001 20

10 3.0 0 Pts with Virological failure Reintroduction NRTI for other reasons Death/lost to FU Total* PI/r 28 2 3 33 PI/r + 3TC 3 0 1 4 *All had viral load <200 c/mL in median 10 wk after reintroduction of NRTI backbone Ciaffi L. J Int AIDS Soc 2016;19(Suppl 7):5(abs.O122) oral presentation

AE Pts with Severe AE (%) AIDS-defining events (%) Tuberculosis (N) M e a n c h a n g e fro m b a s e lin e Safety and tolerability at 48 wk Renal and lipid profile PI/r (N=133) 13 5 2 PI/r + 3TC (N=132) 10 2 0 PI/r (N=133)

PI/r + 3TC (N=132) 4 0 0.2 0 0 -0.1 -0.4 0 -4 No tx discontinuations due to intolerance -8 -8.9 -8.7 -12 Ciaffi L. J Int AIDS Soc 2016;19(Suppl 7):5(abs.O122) oral presentation Is addition of 3TC a good strategy to increase

efficacy of the maintenance strategy with PI/r, without additional toxicity? TAKE HOME MESSAGE After virological suppression with PI plus NRTIs in 2nd-line tx in limited resource settings, maintenance with PI/r plus 3TC seems associated with a higher rate of success than PI/r monotherapy Resistance profile analysis of txexperienced HIV-1 infected pts switching to EVG/COBI/FTC/TAF plus DRV Margot N. J Int AIDS Soc 2016;19(Suppl 7):5-6(abs.O123) Is there an influence of the ART regimen or the resistance profile on the outcome of tx simplification in virologically suppressed tx-experienced pts on complex regimens? ? In the study GS-US-292-0119, 94% versus 76% of the virologically suppressed, tx-experienced pts on complex multi-tablet regimens

maintained suppressed when switched to EVG/COBI/FTC/TAF+DRV versus when staying on the DRV-containing baseline regimen Study design: multi-centre, phase III, open-label switch randomised study GSUS-292-0119 EVG/COBI/FTC/TAF+DRV 800 mg qd (SR) 96 wk, N=89 Virologically suppressed HIV pts 4 mo suppressed on ART with DRV 2 prior failures 2-class resistance by historical genotype (no INSTI-resistance or currently on INSTI) K65R or 3 TAMs Exclude: Q151M, T69ins, DRV RAMs 2:1 Baseline regimen (BR) 48 wk, N=46 EVG/COBI/FTC/TAF+DRV 800 mg qd (SR) 48 wk

Primary endpoint: % pts with HIV-RNA <50 c/mL at wk 24 (FDA snapshot analysis) Secondary endpoints: Safety and tolerability over 24 and 48 wk Efficacy at wk 48: HIV-RNA <50 c/mL Margot N. J Int AIDS Soc 2016;19(Suppl 7):5-6(abs.O123) poster & oral presentation Baseline characteristics SR (N=89) 519 BR (N=46) 518 5 70/26 5 74/20 100

80 BR (N=46) P=0.004 between groups 95.0 76.0 60 35 88 95 40 20 20 44 61/11/ 12 56 SR (N=89)

% pts Median CD4 count (cells/L) Median N of pills/d 2/3 classes resistance (%) 2 classes resistance (%) PI NNRTI NRTI Resistance K65R 3 TAMs TDF/ABC/ other NRTI (%) RAL (%) Primary endpoint wk 48 0 2.0 11.0

3.0 13.0 54/11/ 13 50 Switching to SR was non-inferior/superior to staying on BR Margot N. J Int AIDS Soc 2016;19(Suppl 7):5-6(abs.O123) poster & oral presentation Outcome at wk 48 influence of baseline factors Virological suppression was similar in each arm, regardless of DRV dosage at baseline Switching to SR was statistically superior to staying on BR Switching to SR was non-inferior/statistically superior to staying on BR SR 100 80

BR % p t s w it h v ir o lo g ic a l s u c c e s s Genotypic Sensitivity Score (GSS) % p t s w i t h v ir o l o g i c a l s u c c e s s DRV dosage at baseline SR 100.0 BR 91.0 78.6 75.0 60 80 40

60 20 40 0 20 0 95.1 93.8 100 66.7 84.2 70.8 No pts <2; 0.0 <2

2 and <3 GSS 3 Margot N. J Int AIDS Soc 2016;19(Suppl 7):5-6(abs.O123) poster & oral presentation Is there an influence of the ART regimen or the resistance profile on the outcome of tx simplification in virologically suppressed txexperienced pts on complex regimens? TAKE HOME MESSAGE Strategic simplification of tx-experienced pts taking ~5 pills/d to EVG/COBI/FTC/TAF+DRV (2 pills qd) was statistically superior in virological suppression to staying on baseline regimen, regardless of baseline DRV dose or GSS Efficacy of antiretroviral drugs during intermittent maintenance treatment with a 4-days-a-week regimen despite low plasma concentrations (ANRS 162-4D trial)

Alvarez JC. J Int AIDS Soc 2016;19(Suppl 7):69(abs.P081) ? Is it feasible to maintain virological suppression with an intermittent tx regimen? An intermittent tx regimen could be an alternative for HIV pts who have to take medication all life-long Study design: Prospective multi-centre, open-label, single-arm, 48-wk French study with 4-consecutive days on tx - 3 days off tx strategy Primary endpoint: virological suppression at wk 48 Alvarez JC. J Int AIDS Soc 2016;19(Suppl 7):69(abs.P081) poster Baseline characteristics (N=100) Variable Median age (yr) Median duration

of virological suppression (<50 c/mL, yr) Baseline ART regimen TDF + FTC (N) ABC + 3TC (N) ABC + TDF (N) 2 NRTIs + NNRTI (%) EFV ETV RPV 2 NRTIs + PI/r DRV ATV LPV Value 47 4.0 89 10 1 71 40 5 26

29 15 13 1 Alvarez JC. J Int AIDS Soc 2016;19(Suppl 7):69(abs.P081) poster 4,000 3,500 3,000 2,500 2,000 1,500 1,000 500 0 ON (292 samples) OFF (585 samples) -100% Efficacy cut-off -99%; P<0.0001

-69%; P<0.0001 -96%; P=0.0005 -47%; EFV -63%; (N=38); 692 P=0.06 ETV RPV (N=5); 269 P<0.0001 (N=26); 39 EFV (N=38) ETV (N=5) RPV (N=26) ATV

(N=12); 52 ATV (N=12)

High adherence: Questionnaire: 95-100% in >90% pts MIMSCaps (N=26 pts): 100% in dosage timing 4-d-a-wk for median 44 of 51 wk per patient Alvarez JC. J Int AIDS Soc 2016;19(Suppl 7):69(abs.P081) poster Is it feasible to maintain virological suppression with an intermittent tx regimen? TAKE HOME MESSAGE Almost all pts with UNDETECTABLE viraemia remained virologically suppressed at 48 wk when applying a 3-d tx interruption on a 4-d-awk regimen, despite low plasma concentrations of PIs or NNRTIs, especially in off periods Switch strategies Long-term (96-wk) efficacy and safety after switching from TDF to TAF in HIV-infected, virologically suppressed adults Raffi F. J Int AIDS Soc 2016;19(Suppl 7):6-7(abs.O125) ? Is FTC/TAF non-inferior to FTC/TDF to maintain virological suppression

in combination with a variety of 3rd agents on the long term? A recent study has shown similar efficacy of FTC/TAF vs FTC/TDF with other 3rd agents, albeit with less renal and bone toxicities, over 48 wk Study design: Double-blind/doubledummy RCT Suppressed HIV patients HIV-RNA <50 c/mL On therapy with FTC/TDF + 3rd agent eGFR 50 mL/min Primary endpoint: HIV-RNA <50 c/mL at 48 wk Secondary endpoints: HIV-RNA <50 c/mL at 96 wk Safety and tolerability FTC/TDF qd + FTC/TAF placebo qd* + Continue 3rd agent 96 wk; N=330 FTC/TAF qd* +

FTC/TDF placebo qd + Continue 3rd agent 96 wk; N=333 *Dose: 200/10 mg with boosted PI; 200/25 mg with unboosted 3rd agent Raffi F. J Int AIDS Soc 2016;19(Suppl 7):6-7(abs.O125) oral & poster presentation Virological suppression Baseline characteristics Female (% pts) Median CD4 count (cells/mm3) Median eGFR (mL/min) Median duration on FTC/TDF (yr) Boosted PI as 3rd agent (% pts) FTC/TDF (N=330)

16 624 FTC/TAF (N=333) 14 663 FTC/TDF FTC/TAF 1.3% (95% CI: -2.5%, +5.1%) -0.5% (95% CI: -5.3%, +4.4%) % pts Variable HIV-RNA <50 c/mL (FDA snapshot analysis) 100 94.3 93.0

88.6 89.1 80 100 5.0 99 5.2 60 45 47 20 40 0 48 wk

96 wk Similar results when stratified by 3rd agent (boosted PI vs other) No emergent resistance except one FTC/TAF pt (M184V at wk 36) Raffi F. J Int AIDS Soc 2016;19(Suppl 7):6-7(abs.O125) oral & poster presentation Safety 96 wk follow-up Markers of renal, bone and lipid safety Safety and tolerability Pts (%) FTC/TDF FTC/TAF Raffi F. J Int AIDS Soc 2016;19(Suppl (N=330) 7):6(N=333) 7(abs.O125) - poster Discontinuations 1/12 2/11 Grade 3-4 lab abnormalities

26 29 LDL 5 10 due to AEs/total AEs (>10% of pts) URT infection Diarrhoea Nasopharyngitis Cough 20 12 8 6 15 13

12 11 Drug-related SAE 0.3 0 FTC/TDF FTC/TAF (N=330) (N=333) Median change in eGFR (mL/min) +4 +10 <0.001

Mean % change in bone mineral density Spine Hip -0.2 -0.3 +2.2 +1.9 <0.001 <0.001 Median LDL (mmol/L) 2.93 3.3 <0.001 Total cholesterol:HDL ratio 3.6

3.8 0.09 Pts (%) P Raffi F. J Int AIDS Soc 2016;19(Suppl 7):6-7(abs.O125) oral & poster presentation Is FTC/TAF non-inferior to FTC/TDF to maintain virological suppression in combination with a variety of 3rd agents on the long term? TAKE HOME MESSAGE In virologically suppressed pts switching from FTC/TDF to FTC/TAF, suppression seems to be maintained over 96 wk, while renal and bone parameters improved Co-infections Prevalence and predictors of HPV infection at oral cavity and anal site: findings in an Italian anal

cancer screening programme for HIV-positive males Garbuglia AR. J Int AIDS Soc 2016;19(Suppl 7):173(abs.P237) ? What is the prevalence and which are the associated risk factors of HPV infection in the oral cavity in HIV-positive men? HIV-infected men carry an increased risk of HPV-associated infection Information for appropriate allocation of cancer screening as well as vaccination programs is needed Cross-sectional study o Paired oral rinse and anal samples from HIV-positive males from anal screening program Tested with 2 primer sets for HPV o N=264 HPV positive samples typed by CLART2 HPV assay (Genomica) or Direct sequencing

Patient characteristics Median age (yr) Mode of HIV acquisition (%) Homo-/bi-sexual Heterosexual Other/unknown Median CD4 count (cells/mm) HIV-RNA (%) Not detectable Detectable <40 copies/mL 40 copies/mL On cART (%) Value 44.6 85.2 9.8 4.9 701 73.1 15.2 11.7 94.7 Garbuglia AR. J Int AIDS Soc 2016;19(Suppl 7):173(abs.P237) poster

Prevalence of HPV infection at oral cavity and anal site Oral P<0.001 84.8 HPV- HPV+ HPV- 13.3% 1.8% HPV+ 64.3% 20.5% P<0.001 77.2

80 Frequency (%) Oral Anal 100 Anal 60 Total: 100% 40 22.3 25.4 12.5% of pts with HPV- anal sites have HPV oral infection 24.1% of pts with HPV+ anal sites have HPV oral infection 20 0 N=59

N=224 HPV positive Multiple HPV infections in HPV+ P=0.10 Garbuglia AR. J Int AIDS Soc 2016;19(Suppl 7):173(abs.P237) poster Risk factors for oral HPV infection Multivariable regression analysis Age (<45 yr vs >45 yr) Drug use (current vs no/former) Smoking (current vs no/former) Number of lifetime partners 10-99 vs <10 >100 vs <10 HIV-RNA Detectable <40 c/mL vs neg >40 c/mL vs neg CD4 count (<200 vs >200 cells/mm) HPV at anal site (yes vs no) OR (95% CI) 1.5 (0.8-2.9) 1.1 (0.5-2.5)

1.5 (0.8-2.9) P NS NS NS 2.7 (0.4-17.0) 8.5 (1.4-53.6) NS <0.05 1.1 (0.5-2.6) 2.1 (0.8-5.4) 14.6 (2.1-104.4) 1.7 (0.6-4.7) NS NS <0.05 NS Garbuglia AR. J Int AIDS Soc 2016;19(Suppl 7):173(abs.P237) poster What is the prevalence and which are the

associated risk factors of HPV infection in the oral cavity in HIV-positive men? TAKE HOME MESSAGE In HIV-positive pts, prevalence of HPV infection in the oral cavity was significantly lower than observed at anal site Severe immune depression and sexual history, but not anal infection, seem to be associated with increased oral HPV infection TURQUOISE-I part 2: safety and efficacy of ombitasvir + paritaprevir/r dasabuvir with or without RBV in pts with HIV-1 and HCV GT1 or 4 co-infection Rockstroh J. J Int AIDS Soc 2016;19(Suppl 7):179-80(abs.P248) What is the efficacy and safety profile of 3D RBV in HIV/HCV GT1 pts and 2D in HIV/HCV GT4 pts, with(out) compensated cirrhosis and with HIV virological suppression?

? OBV + PTV/r + DSV = 3 direct-acting-antiviral (3D) regimen RBV approved for HCV GT 1 infection OBV +PTV/r + RBV = 2 direct-acting-antiviral (2D) approved for HCV GT4 infection Study design: Phase III, multi-centre, global, randomised study TURQUOISE-I part 2 3D HIV/HCV GT 1 or 4 pts 18-70 yr HCV tx-nave or -experienced with pegIFN/RBV or SOF + RBV pegIFN HIV-RNA <40 c/mL Stable ART: ATV/r, DRV/r, RAL, DTG No HBsAg+ Good blood/renal/liver values GT1 (N=200)

(with*)out cirrhosis 3D* 3D + RBV* 3D + RBV 3D + RBV* GT4 (N=28) No cirrhosis 2D Wk 12 Wk 24 Primary endpoint: N and % of pts achieving SVR12 (HCV-RNA < lower limit of quantitation [LLOQ]) Other endpoints: on-tx virological failure and post-tx relapse, maintenance of HIV suppression, AEs/lab abnormalities, resistance analyses for failures Rockstroh J. J Int AIDS Soc 2016;19(Suppl 7):179-80(abs.P248) poster Baseline characteristics 80

% pts 96 100 98 100 80 60 60 40 40 20 20 0

0 (N ... 29 7 25 39 96 100 mITT population** GT 4 25 47 28 ITT population* (N

... GT4 N=28 47 93 0 61 GT 1 Median age (yr) Male (% pts) Cirrhosis (%) HCV tx-nave (%) ART regimen (%) DRV/r ATV/r RAL DTG GT1 N=200 50 78

12 67 % pts Variable Efficacy: SVR12 3 pts no SVR12: 1 on-tx virological failure, 2 relapses *includes pts missing data as virological failures **excludes non-virological failures and pts missing data Rockstroh J. J Int AIDS Soc 2016;19(Suppl 7):179-80(abs.P248) poster Outcome 12 wk Maintenance of HIV suppression in HIV/GT1+4 Episodes of intermittent HIV viraemia during tx (N=228) 10 218 Virological failure No virological failure

Safety/tolerability AE (%) GT1 N=200 GT4 N=28 Any AE 85 86 AEs leading to tx discontinuation 0 0 Serious AE 5

4 Common AE (10% pts) Fatigue Nausea Diarrhoea Headache Insomnia Pruritus Hgb decrease 24 21 16 14 15 11 10 18 18 4 18 7 4

14 *All pts with HIV-RNA <200 c/mL Rockstroh J. J Int AIDS Soc 2016;19(Suppl 7):179-80(abs.P248) poster What is the efficacy and safety profile of 3D RBV in HIV/HCV GT1 pts and 2D in HIV/HCV GT4 pts, with(out) compensated cirrhosis and with HIV virological suppression? TAKE HOME MESSAGE 99% overall SVR12 rates were achieved in HIV/HCV GT1 pts following tx with 3D RBV and HIV/HCV GT4 pts on 2D, without impact on HIV control Over 12 wk, the regimen was well tolerated with no hepatic decompensation and no tx discontinuations due to AEs SOF/VEL single-tablet regimen in HCV mono-infected and HIV/HCV co-infected pts: comparison of efficacy and safety data from phase III clinical trials Wyles D. J Int AIDS Soc 2016;19(Suppl 7):187-8(abs.P259) ?

Does the SOF/VEL single-tablet regimen show a similar efficacy and safety profile in HCV vs HIV/ HCV co-infected pts? 12-wk oral SOF/VEL single-tablet regimen (400/100 mg qd) has demonstrated high SVR in HCV GT 1-6 pts Previous SOF-based combinations showed a comparable efficacy/safety profile in HCV vs HIV/HCV co-infected pts Study design: Descriptive analysis of phase III 12-wk studies ASTRAL-1 GT 1, 2, 4-6 12 wk HCV ASTRAL-2 GT 2 12 wk HCV ASTRAL-3 GT 3 12 wk SOF/VEL 24 wk SOF+RBV

HCV ASTRAL-5 GT 1-4 12 wk HIV/HCV coinfection SOF/VEL N=624 SOF/VEL N=134 SOF/VEL N=277 SOF/VEL N=106 Placebo N=116 SOF+RBV N=132 SOF+RBV N=275 *HIV: stable ART various ART regimens! mean CD4 count 598 cells/L Tx experienced (28%); cirrhosis (21%)

Tx experienced (29%); cirrhosis (18%) Primary endpoints: SVR12 Discontinuations due to AEs Wyles D. J Int AIDS Soc 2016;19(Suppl 7):187-8(abs.P259) poster SVR12 outcome of SOF/VEL: total and based on GT ASTRAL 1-2-3: HCV mono-infected pts 100 98 98 99 95 100 97 ASTRAL 5: HIV/HCV co-infected pts

100 100 60 40 N 95 100 92 100 92 80 SVR12 (% pts) SVR12 (% pts) 80 95

60 40 20 20 0 0 Total GT 1 GT 2 GT 3 GT 4 GT 5 GT 6 1,035 328 238 277 116 35 41

N Total 106 GT 1a GT 1b 66 12 GT 2 GT 3 11 12 GT 4 5 No influence of presence of baseline NS5A class RAVs on SVR12 outcome in either patient group Wyles D. J Int AIDS Soc 2016;19(Suppl 7):187-8(abs.P259) poster Safety of SOF/VEL (retrospective integrated analysis)

SOF/VEL HCV SOF/VEL HCV/HIV Placebo SOF+RBV 12-wk (N=1,035) (N=106) (N=116) (N=132) AE 79 71 77 77

Grade 3 or 4 3 8 <1 2 SAE** 2* 2* 0 2 AE leading to tx discontinuation <1 2

2 0 Death <1* 0 0 0 Pts (%) *none were assessed as related to study tx; **SAE: acute radial nerve palsy and left toe infection/sepsis/UTI No pt with confirmed on-tx HIV virologic rebound Type of most common AEs (>10%) of SOF/VEL were similar to placebo: headache, fatigue, nausea, insomnia, nasopharyngitis No impact of SOF/VEL on renal function, irrespective of TDF use Wyles D. J Int AIDS Soc 2016;19(Suppl 7):187-8(abs.P259) poster Does the SOF/VEL single-tablet regimen show a similar efficacy and safety profile in HCV vs HIV/HCV co-infected pts? TAKE HOME MESSAGE

SOF/VEL appears to result in a similarly high % SVR12 in mono-infected vs HIV/HCV co-infected pts (across all HCV genotypes) Tx with SOF/VEL for 12 wk seems safe and well tolerated in HIV/HCV co-infected pts on various ART regimens Liver fibrosis regression in HIVHCV co-infected individuals after sustained virologic response with HCV direct-acting antivirals Arias A. J Int AIDS Soc 2016;19(Suppl 7):197-8(abs.P276) ? How is liver fibrosis evolving after sustained virological suppression in HIV-HCV co-infected pts who were treated with HCV direct-acting antivirals? HCV eradication with peginterferon-ribavirin was shown to be associated with significant improvements in liver function and fibrosis Information on the extent of liver fibrosis regression is lacking in HIV-HCV co-infected individuals in whom hepatic fibrosis more rapidly develops

Study: Single-centre, prospective study in Spain *Defined as: Shift from advanced fibrosis (metavir F3-4, >9.5 kPa) to null-mild fibrosis (F0-2) and/or >30% reduction on kPa from any baseline value Arias A. J Int AIDS Soc 2016;19(Suppl 7):197-8(abs.P276) poster Pt characteristics (N=50) Liver fibrosis outcome o Male 79% o Mean age 52 yr Baseline F3-F4 liver fibrosis

o HCV viral count 6.2 log UI/mL o IL28B no CC 53% FibroScan value o DAA therapy: At time of SVR12 Liver fibrosis Mean reduction in FibroScan value vs baseline % pts with sign. improvements in liver fibrosis SOF-LVP N=31 3D N=8 SOF-DCV N=8 SOF-SMV N=8 o Mean tx duration 12 wk

o Pts receiving RBV 54% Results 65% (80% for IL28B-CC vs 52% IL28-CT/TT, P=0.04) 20.1 kPa Results Sign. regression in 39% vs baseline 4.8 kPa, P<0.001 47% of F3-4 pts vs 22% of F0-2 pts, P=0.08 Arias A. J Int AIDS Soc 2016;19(Suppl 7):197-8(abs.P276) poster How is liver fibrosis evolving after sustained virological suppression in HIV-HCV co-infected pts who were treated with HCV direct-acting antivirals? TAKE HOME MESSAGE HCV treatment with DAA in HIV-HCV coinfected pts seems associated with significant and rapid improvements in liver fibrosis (38% at SVR12) Hepatitis C can be cured for less than $100 per person: analysis of drug exports from India

Hill A. J Int AIDS Soc 2016;19(Suppl 7):182(abs.P251) ? Is it theoretically possible to manage hepatitis C at low cost? Novel direct-acting antivirals (DAA) for chronic hepatitis C achieve sustained virologic response rates of >90% But high drug prices limit access to DAAs Study: data analysis of online database of Indian export ledgers Hill A. J Int AIDS Soc 2016;19(Suppl 7):182(abs.P251) Results DAA SOF DCV LDV SOF+LDV VEL SOF+VEL Export volume from India (kg)

~ N of 12-wk courses Mean API price/kg ($) 10,200 ~ 303,000 courses 5,443 ~ 1,080,000 courses 240 ~ 32,000 courses 1,094 998 2,441 - 8,900-11,700 Theoretical target price per 12-wk tx ($) 62 14 34 96 119-154 181-216

US price per 12-wk tx x-fold target price 804-1,355 3,618-4,500 591-984 346-413 UK, Germany and France are in the top 3 countries (out of 7-9) with the highest price for 12-wk courses with SOF and with DCV (based on selected literature data) Hill A. J Int AIDS Soc 2016;19(Suppl 7):182(abs.P251) Is it theoretically possible to manage hepatitis C at low cost? TAKE HOME MESSAGE HCV DAAs tx costs could be very low in principle, when using APIs exported from India, and still include a 50% profit margin for generic suppliers New ARVs The integrase strand transfer inhibitor bictegravir has a long

integrase/DNA dissociation halflife White K. J Int AIDS Soc 2016;19(Suppl 7):36(abs.P025) ? Does bictegravir have longer dissociation kinetics compared to other INSTIs? Bictegravir is a HIV INSTI with a high barrier to resistance selection in vitro Potent ARV activity and a higher genetic barrier to resistance have been predicted to correlate with a longer dissociation rate constant Pharmacokinetics of bictegravir and other INSTIs Apparent association td Dissociation t1/2 35 140 34 120

31 30 25 22 20 15 10 5 0 122 P=0.0018 100 14 t1/2 (h) td (min) 40

80 71 P=0.046 60 35 40 20 0 15 3.6 Apparent 11 5.4 1.6 Actual*

Measure H-labelled INSTIs with wild-type HIV integrase/DNA complexes and scintillation proximity assay: Exponential decay: apparent association and dissociation kinetics *Equilibrium binding model: t1/2 more representative of actual t1/2 by converting initial values of the dissociation rate constants (koff) White K. J Int AIDS Soc 2016;19(Suppl 7):36(abs.P025) Does bictegravir have longer dissociation kinetics compared to other INSTIs? TAKE HOME MESSAGE Bictegravir has the longest reported dissociation half-life from wild-type HIV integrase/DNA complexes compared to dolutegravir, elvitegravir and raltegravir Efficacy and safety of long-acting HIV fusion inhibitor albuvirtide in ARV-experienced adults with HIV-1: interim 48-wk results from the randomized, controlled, phase III, non-inferiority TALENT study Wu H. J Int AIDS Soc 2016;19(Suppl 7):21-2(abs.O336) ?

What is the efficacy and safety profile of albuvirtide + LPV/r in ARV-experienced adults with HIV-1? Study design: Multi-centre, open-label, phase III, non-inferiority RCT in China TALENT Adults with HIV-1 failing 1st-line treatment: plasma viral load >1,000 c/mL >6 mo ABT* + LPV/r bid (N=210) LPV/r + TDF/ZDV+3TC (N=210) 48 wk Primary endpoint: % pts with plasma viral load <50 c/mL at wk 48 (non-inferiority margin of 12%) * Once weekly by iv infusion Wu H. J Int AIDS Soc 2016;19(Suppl 7):21-2(abs.O336) oral presentation Baseline characteristics Age (yr) Male (%)

HIV-RNA (log10 c/mL) CD4 count (cells/l) Time of 1st-line regimen (mo) ART use (%): TDF+3TC ZDV+3TC ABC+3TC TDF+ZDV+3TC ART resistance (%) ABT (N=83) 40 74 3.8 NRTI (N=92) 40 73 3.8 240 26

234 31 % p ts w ith H IV -RN A <5 0 c/m L Variable Interim analysis Primary endpoint (mITT population) Virological suppression at wk 48 100 80 14.4% difference (95% CI -3.0%, +31.9) 80.4 66 80 72 26 1 1 83

60 40 20 0 ABT (N=46) NRTI (N=50) Wu H. J Int AIDS Soc 2016;19(Suppl 7):21-2(abs.O336) oral presentation Drug-related AE (%) in 2% pts Diarrhoea Gastroenteritis Rash Headache Dizzy Haematuria Drug-related lab abnormalities (%) in 2% of pts High triglycerides High total cholesterol ABT (N=93)

7.5 0 1.1 2.2 2.2 NRTI (N=99) 14.1 3 2 0 0 0 2 32.3 12.9 29.3 2.0 Wu H. J Int AIDS Soc 2016;19(Suppl 7):21-2(abs.O336) oral presentation

What is the efficacy and safety profile of albuvirtide + LPV/r in ARV-experienced adults with HIV-1? TAKE HOME MESSAGE Once-weekly albuvirtide + daily LPV/r seems well tolerated and non-inferior to 2nd-line regimen in patients who failed 1st-line treatment

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    Figure 4A showed the distribution of DMN connectivity before and after ComBat. The first row is with wavelet coherence and Power's parcellation, and the second row is with Pearson's correlation and AAL parcellation. Left-hand-side is without ComBat, and right-hand-side is...