Shannon A Green:RANDOMIZED TRIAL OF LEEP VS CRYOTHERAPY TO TREAT CIN2/3 IN HIV-INFECTED WOMEN

Transcription

1 WOMEN S HEALTH

2 Shannon A Green:RANDOMIZED TRIAL OF LEEP VS CRYOTHERAPY TO TREAT CIN2/3 IN HIV-INFECTED WOMEN

3 Shannon A Green:RANDOMIZED TRIAL OF LEEP VS CRYOTHERAPY TO TREAT CIN2/3 IN HIV-INFECTED WOMEN

4 Shannon A Green:RANDOMIZED TRIAL OF LEEP VS CRYOTHERAPY TO TREAT CIN2/3 IN HIV-INFECTED WOMEN

5 Shannon A Green: RANDOMIZED TRIAL OF LEEP VS CRYOTHERAPY TO TREAT CIN2/3 IN HIV-INFECTED WOMEN

6 Shannon A Green: RANDOMIZED TRIAL OF LEEP VS CRYOTHERAPY TO TREAT CIN2/3 IN HIV-INFECTED WOMEN

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9 Shannon A Green: RANDOMIZED TRIAL OF LEEP VS CRYOTHERAPY TO TREAT CIN2/3 IN HIV-INFECTED WOMEN

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11 Conclusions Disease recurrence was high after 24 months in HIV infected women Cryotherapy is more likely to result in disease recurrence in HIV infected women HIV testing prior to treatment may improve effectiveness LEEP is expensive procedure but cost effective than treatment of cervical cancer Shannon A Green: RANDOMIZED TRIAL OF LEEP VS CRYOTHERAPY TO TREAT CIN2/3 IN HIV-INFECTED WOMEN

12 HIV Cure or Remission HIV life cycle ART new developments CD8 and HLA Latency and ART Broadly neutralizing antibodies

13 Paul Bieniasz; Advances in the understanding of HIV-1

14 Paul Bieniasz; Advances in the understanding of HIV-1

15 Paul Bieniasz; Advances in the understanding of HIV-1

16 Paul Bieniasz; Advances in the understanding of HIV-1

17 Paul Bieniasz; Advances in the understanding of HIV-1

18 Winston Tse :Gilead Science CROI 2017

19 Winston Tse ; Gilead Sciences CROI 2017

20 Winston Tse: Gilead Sciences, CROI 2017

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22 Paul Bieniasz; Advances in the understanding of HIV-1

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25 Nicolas Chomont Université de Montréal, Montreal, QC, Canada

26 Nicolas Chomont Université de Montréal, Montreal, QC, Canada

27 CD32a Recent publication points towards CD32a T- Cells as source of latent reservoir

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29 Questions 1)How the capsid negotiates transition from cytoplasm to nucleopore, how it effects subsequent steps of integration? 2)Viral Latency in natural setting?

30 Richard A Koup: Advances in Antibodies

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32 Richard A Koup: Advances in Antibodies

33 Richard A Koup: Advances in Antibodies

34 Richard A Koup: Advances in Antibodies

35 Richard A Koup: Advances in Antibodies

36 Richard A Koup: Advances in Antibodies

37 Richard A Koup: Advances in Antibodies

38 Richard A Koup: Advances in Antibodies, CROI 2017

39 VRCO1 INFUSION Sharon Riddler et al; Themed discussion and poster abstrac# 330 LB; CROI 2017

40 VRCO1 Infusion In individuals with chronic ART-suppressed HIV infection, VRC01 infusions were safe and well tolerated but did not affect plasma viremia, cellular HIV RNA/DNA levels, or stimulated virus production from CD4+Tcells. Sharon Riddler et al; Themed discussion and poster abstrac# 330 LB; CROI 2017

41 Richard A Koup: Advances in Antibodies

42 Viral load by HIVCONSERV Vaccine After 3 years under viral suppression, all participants were immunized with MVA.HIVconsv (2x10E8 pfu), followed by three weekly-doses of romidepsin (RMD, 5 mg/m2 BSA), and by a second MVA.HIVconsv vaccination. Participants underwent a monitored antiretroviral pause (MAP) and treatment was resumed if plasma viral load (pvl) increased >2,000 copies/ml. Therapeutic vaccination targeting conserved regions of HIV-1 combined with HIV latency reactivation strategies may facilitate clearance of the viral reservoir in early- treated individuals. Beatriz Mothe et al. Oral Abstract 119LB 2017

43 VIRAL CONTROL INDUCED BY HIVCONSV VACCINES & ROMIDEPSIN IN EARLY TREATED INDIVIDUALS Beatriz Mothe et al. Oral Abstract 119LB 2017

44 Rich Koup; Advances in antibodies; CROI 2017

45 CD8 Previously established CD8 cytolytic activity and HLA B 27/57 responsible for HIV control in Elite Controller Together these findings redefine previous concepts of CD8+ T cell mediated control of HIV disease progression. During established infection, HIV replication appears to be controlled in lymphoid tissues by non-cytolytic rather than cytolytic mechanisms. Knowledge regarding how HIV is controlled in this setting should be used to inform the identification and development of potentially curative intervention Son Nguyn et al. Oral abstract 65

46 Syphilis and Post Exposure Prophylaxis on demand

47 Antibiotic Prophylaxis for STI Every day more than 1 million of STIs are acquired worldwide Each year 146 million of new infections with chlamydia, 78 million of gonorrhea and 6 million of syphilis. In the US, 2015 was the second year in a row with an increase in STIs, with syphilis increasing at an alarming rate among MSM.

48 Abx prophylaxis for STI New strategies need to be developed to contain the spread of STIs. Antibiotic prophylaxis for bacterial STIs in high risk populations should be carefully evaluated. Jean Michael Molina Abstract #55 ;CROI2017

49 Challenges for Clinicians The rise of syphilis poses challenges for clinicians as they confront increasing numbers of cases of neuro-, ocular- and oto-syphilis, and dilemmas related to performing lumbar punctures and interpreting syphilis serologies in patients tested at increasing frequency

50 Matthew R Golden; CROI 2017 University of Washington, Seattle, WA, USA

51 Matthew R Golden; CROI 2017

52 Matthew R Golden; CROI 2017

53 Matthew R Golden; CROI 2017 University of Washington, Seattle, WA, USA

54 Matthew R Golden; CROI 2017

55 Matthew R Golden; CROI 2017 University of Washington, Seattle, WA, USA

56 SYPHILIS IN THE ERA OF TREATMENT AS PREVENTION AND PRE- EXPOSURE PROPHYLAXIS Jean-Michel Molinaet al; oral abstract 91LB

57 ON DEMAND POST EXPOSURE PROPHYLAXIS WITH DOXYCYCLINE FOR MSM ENROLLED IN A PREP TRIAL On demand post-exposure prophylaxis (PEP) with doxycycline could reduce STIs incidence in this high risk group. High risk adult MSM being followed in the open-label phase of the ANRS IPERGAY trial with on demand TDF/FTC for HIV prevention, were enrolled in a prospective randomized openlabel sub-study. Participants (pts) were randomized 1:1 to take either two pills of doxycycline (100mg per pill) within 72h after condomless sexual intercourse (without exceeding 6 pills per week) or no PEP. All subjects received risk-reduction counseling and condoms, and were tested every 8 weeks for HIV and STIs with serologic assays for HIV and syphilis and PCR assays for Chlamydia trachomatis and Neisseria gonorrhoea in urine samples, oral and anal swabs. Jean-Michel Molinaet al; oral abstract 91LB

58 ON DEMAND POST EXPOSURE PROPHYLAXIS WITH DOXYCYCLINE FOR MSM ENROLLED IN A PREP TRIAL No of patients acquired STIs PEP Arm N=73 N=28 24% Events per 100 patientyears No PEP arm N= % HR for STIs 0.53 (95% CI: ,P=0. 008). Overall 71% infections were asymptomatic HR for CT 0.30 (95% CI: p=0.006) HR for GC 0.83 (95% CI: , p=0.52) HR for Syphilis 0.27 (95% CI: , p<0.05) From July 2015 to January 2016, 232 pts were randomized, 116 in each arm. Median follow-up was 8.7 months (IQR: ) Jean-Michel Molinaet al; oral abstract 91LB

59 Conclusion On demand PEP with doxycycline reduced the incidence of chlamydia infection and syphilis in high risk MSM and has an acceptable safety profile Jean-Michel Molinaet al; oral abstract 91LB

60 XDR TB AND NIX TRIAL

61 Definition: Drug Resistant TB XDR TB; Since 2007, extensively drug-resistant tuberculosis (XDR-TB) has been defined as resistance to both isoniazid and rifampin with additional resistance to at least one fluoroquinolone and one injectable agent (amikacin, kanamycin, or capreomycin)

62 Prevalence Among patients with known pulmonary TB in 2013, approximately 480,000 were estimated by the World Health Organization (WHO) to have MDR-TB Out of which 9 percent were estimated to have extensively drug-resistant tuberculosis (XDR-TB) Data taken from uptodate

63 USA In a descriptive analysis of United States TB cases reported from 1993 to 2007, a total of 83 XDR-TB cases were reported. The majority of cases were United States born (n = 45) and 33 of the patients (40 percent) were Hispanic Data taken from uptodate

64 Observations Compared with MDR-TB cases, XDR-TB cases were more likely to have disseminated TB disease and had a prolonged time to culture conversion when treated (183 days versus 93 days for MDR-TB). Twenty-six XDR-TB cases (35 percent) died during treatment, of whom 21 (81 percent) were known to be HIV infected. Mortality was higher among XDR-TB cases than among MDR-TB cases (prevalence ratio [PR] 1.82; 95% CI ) or drug-susceptible TB cases (PR 6.10; 95% CI ). Data taken from uptodate

65 Treatment of MDR TB Successful treatment of multidrug-resistant tuberculosis (MDR-TB) with a shorter-course regimen, sometimes referred to as the Bangladesh regimen, have been reported with nine months of gatifloxacin, ethambutol, pyrazinamide, and clofazimine, supplemented in the first four months by kanamycin, prothionamide, and higher-dose isoniazid. While the majority of MDR-TB patients were able to complete therapy in 9 to 12 months, the strongest predictor of failure was fluoroquinolone resistance, and, thus, a similar regimen would be expected to fail in XDR-TB Data from uptodate

66 Drugs used Bedaquilline; Inhibits mycobacterial ATP (adenosine 5'-triphosphate) synthase, by binding to subunit c of the enzyme that is essential for the generation of energy in Mycobacterium tuberculosis. PDR

67 Linezolid The oxazolidinones areprotein synthesis inhibitors:they stop the growth and reproduction of bacteria by disrupting translation of messenger RNA (mrna) into proteins in the ribosome. PDR

68 Pretomanid (PA 824) Pretomanid is a bicyclic nitroimidazole-like molecule with a very complex mechanism of action. It is active against both replicating and hypoxic, non-replicating Mycobacterium tuberculosis. online drug reference resources

69 Francesca Conradie Oral abstract CROI 2017

70 Francesca Conradie Oral abstract LB 80; CROI 2017

71 Francesca Conradie Oral abstract LB 80; CROI 2017

72 Francesca Conradie Oral abstract LB 80; CROI 2017

73 Francesca Conradie Oral abstract LB 80; CROI 2017

74 Francesca Conradie Oral abstract LB 80; CROI 2017

75 Francesca Conradie Oral abstract LB 80; CROI 2017

76 Francesca Conradie Oral abstract LB 80; CROI 2017

77 Francesca Conradie Oral abstract LB 80; CROI 2017

78 COMBINATION ART

79 Bictegravir plus FTC/TAF Vs Dolutegravir plus FTC/TAF Treatment-naive people living with HIV. All 98 patients received open-label emtricitabine plus tenofovir, And 65 patients were randomized to either bictegravir or dolutegravir. Paul Sax et al; CROI 2017, oral abstract 41

80 Paul Sax et al; CROI 2017, oral abstract 41

81 Bictegravir vs Dolutegravir After 24 weeks, more patients in the bictegravir group than in the dolutegravir group achieved a viral load below 50 copies/ml (97% vs 94%). The same pattern remained at 48 weeks, although the difference was not significant (97% vs 91%). Paul Sax et al; CROI 2017, oral abstract 41

82 Bic vs Dolu However, at 48 weeks, decreases in the estimated glomerular filtration rate, an indication of renal function, were less extensive in the bictegravir group than in the dolutegravir group ( 7.0 vs 11.3 ml/min). There was also no interaction between bictegravir and the HLA-B*5701 allele, a marker of extreme sensitivity to abacavir. And because it is a new drug, no drug-resistant mutations have developed yet. Paul Sax et al; CROI 2017, oral abstract 41

83 Pathways for Resistance to Dolutegravir A total of 178 ART-experienced subjects with no prior InSTI-VF changed from different ARTregimens to DTG monotherapy (DTG-M). Eleven (6.1%) had VF and 7 (3.9%) selected any InSTI- RAMs. The three different pathways by the time of VF were: 148R/H in 3 patients, 155H in 2, and 118R in 2 Jose Blanco ; Oral Abstract #42

84 SWORD 1 and 2 Of the 1024 study participants, 513 patients were switched to the two-drug regimen and the 511 in the control group stayed on their current antiretroviral regimen, which usually involved three or four drugs. Dolutegravir plus Rilpivirine was shown to be noninferior to the current antiretroviral regimens for viral suppression at 12 months in people already on treatment. In both SWORD 1 and SWORD 2, the rate of viral suppression below 50 copies/ml was around 95% in both treatment groups. Joseph M Llibre et al; oral abstract 44LB

85 SWORD 1 and 2 Treatment failure was experienced by two patients in the two-drug group and two in the control group. More patients in the two-drug group than in the control group discontinued therapy because of adverse events, but the difference was not significant (3% vs 1%). Joseph M Llibre et al; oral abstract 44LB

86 Joseph M Llibre et al; oral abstract 44LB

87 Acknowledgements Slide materials adapted from the following talks in CROI Shannon A Green:RANDOMIZED TRIAL OF LEEP VS CRYOTHERAPY TO TREAT CIN2/3 IN HIV-INFECTED WOMEN Paul Bieniasz; Advances in the understanding of HIV-1 Nicolas Chomont Université de Montréal, Montreal, QC, Canada Richard A Koup: Advances in Antibodies Matthew R Golden; CROI 2017; University of Washington Francesca Conradie; Oral abstract LB 80; CROI 2017 Paul Sax et al; CROI 2017, oral abstract 41 Joseph M Llibre et al; oral abstract 44LB Thanks to AETC Texas, Dr Henry Pacheco and Dr Arti Barnes for support to attend CROI 2017