turning the tide together - plus
TRANSCRIPT
Turning the Tide Together
report dallaXIX International AIDS Conference
Washington, DC22-27 luglio 2012
Giulio Maria CorbelliEuropean AIDS Treatment Group
Le conferenze AIDS
1985 Atlanta 1986 Parigi 1987 Washington 1988 Stoccolma 1989 Montreal The Scientifc and Social
Challenge of AIDS1990 S.Francisco AIDS in the 90s: from
Science to Policy 1991 Firenze Science Challenging AIDS1992 Amsterdam A World United
Against AIDS1993 Berlino
1994 Yokohama The Global Challenge of AIDS: Together for the Future
1996 Vancouver OneWorld One Hope
1998 Ginevra Bridging the Gap
2000 Durban Breaking the Silence
2002 Barcellona Knowledge and Commitment for Action
2004 Bangkok Access for All,
2006 Toronto Time to Deliver
2008 Mexico City Universal Action Now, 2010Vienna Rights here,Right now
L'attivismo
265 attività nel Global Village
La marcia
La politicaBill ClintonHillary Rodham ClintonKathleen SebeliusKgalema MotlantheLaura BushMette-MaritJim Yong KimMichel SidibèFrançoise Barré-SinoussiAnthony FauciBill GatesElton JohnWhoopi Goldberg
La scienza
12,433 abstracts submitted, 3,837 abstracts accepted 194 sessions 60 workshops, 19 plenary speeches 14 special sessions
Track A: Basic ScienceTrack B: Clinical ScienceTrack C: Epidemiology and Prevention ScienceTrack D: Social Science, Human Rights and Political ScienceTrack E: Implementation Science, Health Systems and Economics
Towards an HIV cure
La “cura” - Timothy R. Brown
1995 – diagnosi HIV+2006 – diagnosi di Leucemia mieloide• inizia la chemioterapia• sviluppa una polmonite• interrompe la chiemioterapia• gli viene proposto il trapianto di midollo e rifiuta2007 – ricompare le Leucemia• la chemioterapia non ha successo• gli viene riproposto il trapianto• viene trovato un donatore con mutazione CCR5• irradiazione totale per abbattere il sistema immunitario• no HIV2008 – ricompare la Leucemia• nuovo trapianto dalla stesso donor• problemi neurologici con biopsia2012 – nessuna traccia di HIV• Leucemia in remissione
Basic science
• cure research
• inflammation
Basic science: cure reasearchPersistent low-level HIV-1 RNA between 20 and 50 copies/ml in antiretroviral treated patients: associated
factors and virological outcomeC. Charpentier
Hopital Bichat - Claude-Bernard, Paris, France
Strategies for depleting the latent HIV reservoir• Nanoparticle targeting of CD4+ T cells (Jerome Zack)• Allogeneic bone marrow transplantation (Timothy Henrich)
Session “immune function and dysfunction”: HIV-specific NK cells responses were observed in samples from highly exposed, yet uninfected individuals (R. Fecek); an isotype switched IgG antibody response to HIV core antigens was found to be associated with better control of HIV infection in patients without known protective HLA-B alleles (M. French); it was also shown that HIV controllers maintain highly efcient Th1 efectors directed against Gag in spite of a persistently low antigenemia, while patients under long-term treatment lose CD4 efector functions (L.A. Chakrabarti).
the protective efect related to the induction of V1/V2-specific IgG antibodies in the RV144 trial, and the identification of new broadly neutralizing antibodies that provide clues regarding HIV vulnerabilities
Large amount of data (F. Bushman)Predict non HIV-related complications (P. Tarr)Human genome of highly exposed, yet uninfected individuals (J. Fellay)
Basic science: inflammationT cell “actvaton” is lower in treated than untreated
adults, but consistently higher than “normal”
Hunt et al JID 2003, PLoS ONE 2011 and unpublished
% C
D38
+H
LA
DR
+C
D8+
T C
ells
0
20
40
60
80
HIVNegative(n=82)
Non-Controller
(n=65)
HAART(n=132)
P < 0.001
P < 0.001
HIV –(n=132)
HIV +ART
(n=65)
HIV +Untreated
(n=82)
Basic science: inflammationEffect on inflammation in predicting mortality higher in
HIV disease than the general population (SOCA/SCOPE)
Hunt et al CROI 12
Lymph Node Fibrosis (Timothy Schacker)
• Inflammation loss of FRC network in T cell zone of lymph nodes decrease in IL-7 production CD4 T cell apoptosis collagen deposition
Zeng et al., PLoS Pathog. 2012
Clinical science
• early start
• when to start
• what to start
• how to switch
VISCONTI cohortVirological and Immunological Studies in CONtrollers after Treatment Interruption
Report12 patients who started HAART within 10 weeks of HIV infection (average 40 days)
HIV RNA < 50 cp/ml for a median 76 months [IQR: 67.5-84.5]
HPTN-052
Grinsztejn. THLBB05
Clinical science: when to start
HPTN-052
Grinsztejn. THLBB05
Clinical science: when to start
STARTING > 350 vs <250 (229). AIDS + Non-AIDS: No differenceAIDS: better (TB) >500 better than < 350 ?
Clinical science: what to start
Raffi. THLBB04
SPRING-2
Clinical science: what to start
Raffi. THLBB04
Clinical science: what to start
No difference by NUCs or high viral loads No INI mutatons nor NRTI mutatons were detected through 48 weeks on
DTG No withdrawals due to renal events Small increase in creatnine due to blockade of Cr secreton in DTG arm
DOLUTEGRAVIR QD NEW OPTION
NO RESISTANCE “UNPRECEDENTED”
Clinical science: what to start
Hazra. TUAB0203
Clinical science: what to start
Gallant. TUAB0103
Clinical science: what to start
Gallant. TUAB0103
Clinical science: what to start
No development of PI resistance in either group. Similar lipids Expected small increase in serum creatnine (≈0.1 mg/dL) Iin the COBI arm Low and comparable discontnuaton rates due to renal AE Similar discontnuaton rates due to bilirubin-related AEs
COBI AND RITONAVIR
CAN YOU SPOT THE DIFFERENCES?
Clinical science: how to switch
Lower rate of virologic non-suppression in FTC/RPV/TDF (17/17 with transmitted K103N suppressed)
Switching: improvement in fastng lipids and 10-year Framingham Risk Score
Palella. TUAB0104
Clinical science: new drugs
Ledgins, a novel class of integrase inhibitorsTUAA0301 - Oral Abstract
Pre-clinical evaluation of HIV replication inhibitors that target the HIV-integrase-LEDGF/p75 interaction
Conclusions: The biochemical data together with the lack of cross resistance and the observed synergistic efects of LEDGINs in combination with strand transfer inhibitors support the potential for combined use of LEDGINs with strand transfer inhibitors in HIV therapy.
Tre-recombinase, a compound that is able to excise HIV-1 proviral DNA from infected cells.
TUAA0302 - Oral Abstract
Towards HIV eradication: excision of HIV-1 proviral DNA by Tre-recombinase in HIV-positive humanized mice
Conclusions: The presented data suggest that Tre-recombinase may be a valuable component of future antiretroviral therapies of the post HAART era that aim at virus eradication, thereby providing a cure for AIDS.
Death rates in people with access to care down AIDS still leading cause of death
Non AIDS cancers leading non-AIDS cause of death
Epidemiology and Prevention Science
• epidemiology among MSMs
• where HIV+ people live
• HIV prevention combined interventions
• Harm reduction
• Treatment as prevention
• PrEP
Epidemiology and Prevention Science
(Prejean et al., 2011)
MSM
Epidemiology and Prevention ScienceMost people living with HIV will live where the wealth is concentrated
Source: McKinsey Insttute, UNAIDS 2012
2 of every 3 people living with HIV will be living in urban areas by 2030
600 big cities in the world in 2025:
25% of the population 60% of the global wealth
Schwartlander.
Behavioural Intervention
HIV Counselling and Testing
Coates T, Lancet 2000
STRUCTURAL
Male & female condoms
Treatment of STIs
Grosskurth H, Lancet 2000
Male circumcision
Auvert B, PloS Med 2005 Gray R, Lancet 2007 Bailey R, Lancet 2007
Treatment for preventionDonnell D, Lancet 2010Cohen M, NEJM 2011
Microbicidesfor women
Abdool Karim Q, Science 2010
Grant R, NEJM 2010 (MSM)Baeten J , NEJM 2012 (couples)Thigpen, NEJM, 2012 (Heterosexuals)
Oral pre-exposure prophylaxis
Post Exposure prophylaxis (PEP)
Scheckter M, 2002
HIV
PREVENTION combined
interventons
Mugo TUPL0102
PMTCT
Harm Reducton/Needle
exchange
Epidemiology and Prevention Science
Epidemiology and Prevention Science
Harm reduction
• Harm reduction is working. In Amsterdam unsafe injections down and incidence declining (Grady MOAC0401)
• In Vietnam, IDUs account for 75% of all new infections. RCT of sexual risk reduction and needle-sharing intervention, needle sharing decreased from 14% at baseline to 3% at 3 months, and exhibited a durable efect (Go THAC0404).
• Modeling results of combination IDU interventions in particular high coverage sterile syringe distribution (Marshall FRLBC05)
Epidemiology and Prevention Science
Treatment as Prevention• Mathematical models can help guide decision-making (Granich, Kessler,
Stover, Gweshe).
• Targeting all HIV-infected persons is always the most efective strategy
• The challenge will be determining which populations to target in the short-term given limited resources:
– What CD4 level? (200-350? 350-500? >500?)
– Which patients? (pregnant women? discordant couples? TB patients? IDUs? all?)
• This will depend on the epidemic context, current service delivery environment , and resources available.
Epidemiology and Prevention Science
PrEP
PrEP (like ART) works when taken
% of blood samples with tenofovir
detected
HIV protecton efcacy in
randomized comparison
Partners PrEPFTC/TDF arm
81% 75%
TDF2 79% 62%
iPrEx 51% 44%
FEM-PrEP 26% 6%
Baeten et al N Engl Med 2012Grant et al N Engl J Med 2010Van Damme et al N Engl J Med 2012Thigpen et al N Engl J Med 2012Mugo TUPL0102
Epidemiology and Prevention Science
PrEPAuthor/Populaton Year PrEP
KnowledgePrEP Acceptability
Risk compensaton?
Metsch et al653 MSM in Miami, DC
2011 15% Miami30% DC
48% Miami61% DC
--
Duffus et al89 seronegatve partners in SD couple in South Carolina(74% heterosexual)
2010-2011
-- 94% 26% would be more likely to have unprotected sex with HIV+ partner, 27% reported would be difficult to take a daily pill
Krakower et al.Internet-based survey of 5035 MSM in North America
Dec 2010-Jan 2011
19% 50% A substantal minority of MSM antcipate risk compensaton for insertve (20%) or receptve (14%) anal sex while using PrEP
Yang et al238 MSM and TG men in Northern Thailand
2012 66% 41% for MSM37% for TGs
--
Grazie per l'attenzioneGiulio Maria Corbelli - [email protected]