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Rapporteurs Session Track B (Clinical Science)

Rapporteurs Session Track B (Clinical Science). Juan Ambrosioni Htal. Clinic-IDIBAPS, Barcelona, Spain. Alexandra Calmy. Olivier Segeral ANRS (Cambodja). Sipho Dlamini Univ. Cape Town. Graeme Meintjes Univ. Cape Town. Juan. Stephanie Shiau Columbia Univ. NY, USA. Content.

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Rapporteurs Session Track B (Clinical Science)

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  1. Rapporteurs SessionTrack B (Clinical Science) Juan Ambrosioni Htal. Clinic-IDIBAPS, Barcelona, Spain

  2. Alexandra Calmy Olivier Segeral ANRS (Cambodja) Sipho Dlamini Univ. Cape Town Graeme Meintjes Univ. Cape Town Juan Stephanie Shiau Columbia Univ. NY, USA

  3. Content • Populations (Adolescents, preg. W, incarc., MSM) • ART • Co-infections (HBV, HCV, TB) • Other topics • Take-home messages

  4. Content Populations (Adolescents) ART Co-infections (HBV, HCV, TB) Other topics Take-home messages

  5. Adolescents: growing key population South Africa. Maskew et al. TUAB01 • success of mother-to-child-transmission prevention • pediatric HIV is increasingly an adolescent and young adult epidemic • only group for which mortality is increasing

  6. Adolescents: growing key population South Africa. Maskew et al. TUAB01

  7. Thailand and Europe. Judd et al. TUAB01 Adolescents: growing key population • Increase % detectable • Increase transmission? • Drug resistance? • Transition to adult care: critical period • INCREASING MORTALITY AGED ≥14

  8. Content Populations (Adolescents) ART Co-infections (HBV, HCV, TB) Other topics Take-home messages

  9. ART: Naive Efficacy and Safety comparable D1 W1 W – 8.5 W2 W48 W8 W60 W4 W84 W16 W24 W36 W96 W98 W72 14 Day Follow-Up Key entry criteria:ART naïve, ≥18 yrs old, HIV-1 RNA ≥1000 c/mL Reformulated RAL 1200 mg QD + TDF/FTC (N ~ 500) 14 Day Follow-Up RAL 400 mg BID + TDF/FTC (N ~ 250) Primary Analysis Time Point Secondary Analysis Time Point Interim Analysis Time Point Early Discontinuation and/or Virologic Failure Confirmation visits (if applicable) Cahn et al. FRAB01 ONCEMRK

  10. ART: Naive Orrell et al. THAB02 ARIA

  11. ART: Naive Superior efficacy and overall lower toxicity Orrell et al. THAB02 ARIA

  12. ART: Simplification/Switch N=275 N=278 Aboud et al. THAB02 STRIIVING: Switch to DTG-ABC-3TC from a variety of PI, INI or NNRTI Based Regimen

  13. ART: Simplification/Switch Late Switch efficacy at 48 weeks Well tolerated. Why less AE than in W24??? No Virological Failures DTG-3TC-ABC good alternative for simplification Aboud et al. THAB02 STRIIVING: Switch to DTG-ABC-3TC from a variety of PI, INI or NNRTI Based Regimen

  14. ART: Simplification/Switch Inclusion: no R to InSTI or RIL 48W, no failures Spain, Moreno et al. TUDB01 DTG-RIL in suppressed heavily pre-treated pat.

  15. ART: Perspectives Argentina, Cahn et al. FRAB01 PADDLE: DTG-3TC in naïve patients (48w)

  16. ART: Perspectives • CAB is an HIV-1 integrase inhibitor • Oral 30 mg tablet (t½, ~40 hours) • LA nanosuspension 200 mg/mL (t½, ~20-40 days) • RPV is an HIV-1 NNRTI • Oral 25 mg tablet (t½, ~50 hours) • LA nanosuspension 300 mg/mL (t½, ~30-90 days) • Oral 2-drug CAB + RPV proof of efficacy through Week 96 in LATTE-1 Margolis et al. THAB0206 LATTE‑2 (CAB-RIL) Week 48 Results

  17. LATTE-2 Study Design Maintenance perioda Induction period CAB 400 mg IM + RPV 600 mg IM Q4W (n=115) CAB loading dose at Day 1 CAB 600 mg IM + RPV 900 mg IM Q8W (n=115) CAB 30 mg + ABC/3TC PO QD for 20 weeks (N=309) CAB 30 mg + ABC/3TC for 20 weeks CAB loading doses at Day 1 and Week 4 CAB 30 mg + ABC/3TC PO QD (n=56) Add RPV PO QD 4 weeks Week 96b Week 48 Analysis Dosing regimen confirmation Week 32 Primary analysis Dosing regimen selection Day 1 Randomization 2:2:1 Margolis et al. THAB0206

  18. Results: HIV-1 RNA <50 c/mL by Snapshot (ITT-ME) Maintenance period Induction period Proportion of patients with virological suppression, % W-4 W36 W44 W48 BL W-16 W-12 W-8 D1 W4 W8 W12 W16 W20 W24 W28 W32 W40 Study visit Oral CAB induction (ME population) Oral CAB (n=56) Q4W IM (n=115) Q8W IM (n=115) Margolis et al. THAB0206

  19. Snapshot Outcomes:HIV-1 RNA <50 c/mL at Week 48 (ITT-ME) aWeek 48 HIV-1 RNA Q8W: 50 c/mL, 57 c/mL, 97 c/mL, 110 c/mL, 135 c/mL, 463/205 c/mL; Q4W: 59 c/mL; Q8W: 5 of 6 remain in the study, 4 of 6 have HIV-1 RNA <50 c/mL at all subsequent visits through W80. bWithdrew consent: intolerability of injections. cQ4W: hepatitis C, rash, depression, psychosis, epilepsy, and Churg-Strauss vasculitis; oral CAB: hepatitis C, DILI. dQ8W: ISR; Q4W: pregnancy, prohibited medication, relocation; oral CAB: lost to follow-up, relocation, withdrew consent (wanted injections rather than oral tablets). Margolis et al. THAB0206

  20. Conclusions • LATTE-2 results successfully demonstrate ability to maintain HIV-1 VL <50 c/mL with IM CAB + RPV LA, dosed every 4 or 8 weeks • Three subjects met PDVF criteria during maintenance • Q8W (n=2), oral CAB (n=1); one Q8W subject with emergent RPV and CAB resistance • Injection tolerability • Majority of ISRs were Grade 1 to 2 pain, with a median duration of 3 days • Few subjects had an ISR that led to discontinuation • High overall reported satisfaction • Dose selection • Q4W dosing resulted in lower rates of virologic non-response with similar safety to Q8W • Q4W dosing was selected for pivotal phase III studies

  21. ART: GAPS WHO, 2016 InSTI: Preferred regimens in the North, alternative in the South (and limited use)

  22. Content Populations (Adolescents) ART Co-infections (HBV, HCV, TB) Other topics Take-home messages

  23. Co-infections • ASTRAL 5: SOF-VEL in HIV-HCV (pan-GTP)

  24. Co-infections • ASTRAL 5: SOF-VEL in HIV-HCV (pan-GTP) Safe, well tolerated, no DDI

  25. Co-infections • TURQUOISE-I, PART 2 : OMBITASVIR/PARITAPREVIR/RITONAVIR ± DASABUVIR WITH OR WITHOUT RIBAVIRIN IN PATIENTS WITH HIV-1 AND HCV GT1 OR GT4 CO-INFECTION

  26. TURQUOISE-I Part 2 Study Design *Arm G was omitted from this analysis as the recommended regimen for GT1b patients is 3D without RBV = randomized treatment arms R

  27. Efficacy: ITT & mITT Analyses by Genotype • 3 patients with GT1 infection did not achieve SVR12: • 1 on-treatment virologic failure • 2 relapses ART RESTRICTIONS *5 out of 200 patients have not yet reached the SVR12 time point and are excluded from the analysis mITT: modified ITT population, which excludes non-virologic failures and patients missing data ITT: intent-to-treat population

  28. Co-infections • HIV-HBV: -3TC vs. 3TC-TDF for HBV MTCT -HCC in HIV-HBV at younger age than HIV (-) • HIV-TB, always present: Need to improve Diagnosis and Therapy (new drugs, new administration of old drugs) -RAFA trial: High R dose, reduce mortality

  29. Content Populations (Adolescents) ART Co-infections (HBV, HCV, TB) Other topics Take-home messages

  30. Other topics: Non-AIDS co-morbidities Session TUSY05, WEPDB01 Several studies on non-AIDS co-morbidities and non-AIDS tumors in Africa (increase ART coverage) Confirmation of the increasing co-morbidities and accelerated aging in European studies

  31. Other Topics: Lab Sessions TUDB01, THPDB02 Optimizing laboratory diagnosis and monitoring (Point-of-Care test for diagnosis and monitoring of HIV, TB and other opportunistic infections) Heterogeneity of resistance studies

  32. Content Populations (Adolescents) ART Co-infections (HBV, HCV, TB) Other topics Take-home messages

  33. Take-Home Messages (for non-clinicians) Adolescents becoming a key population: special programs needed ART: strong differences in initial therapy North-South (InSTI) Dual therapies (Ex: DTG-3TC, DTG-RIL) may be a line to explore, even in experienced patients Long-lasting action injecting drugs? HCV-HIV do not seem longer a different population among HCV patients TB always there: need to improve D and T

  34. Take-Home Messages (for non-clinicians) Non-AIDS conditions and aging, increasing problem in the North, emerging problem in the South Continue working to translate all this science into action… For EVERYONE

  35. Thank you very much for your attention Barcelona Durban (this morning) ambrosioni@clinic.cat jambrosioni@intramed.net

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