Report Back: HIV Prevention Matt Spinelli Division of HIV, ID, and Global Medicine ZSFG and UCSF

Transcription

1 Report Back: HIV Prevention Matt Spinelli Division of HIV, ID, and Global Medicine ZSFG and UCSF

2 Outline 1. Additional Undetectable=Untransmittable Data for MSM 2. Intermittent PrEP in the real-world 3. PrEP + Hormone Therapy in transgender women Break STIs/HCV with PrEP 5. Promising vaccine safety/immunologic results 6. Population-level impact of prevention strategies

3 U=U real world studies before PARTNER2 at AIDS 2018 PARTNER Study: Sero-different couples in 14 European countries, 1/3 MSM, no condoms (337 MSM couples vs. 551 non-msm) Opposites Attract: Sero-different, all MSM, in Australia, Bangkok, in Rio de Janeiro, no condoms (338 couples; PrEP allowed but not widely available) Rodgers et al. JAMA 2016; 316: Bavinton et al, Lancet HIV 2018; 5e

4 PARTNER2: Extension of PARTNER only for MSM Phase 1: (HT+MSM) Upper bound of confidence interval in MSM: 0.84 /100 couple-years (compared to 0.46/100 CY in heterosexual couples) Phase 2: (MSM only) Obtain a more precise estimate of upper bound of confidence interval in MSM Rodgers et al. AIDS 2018 WEAX0104LB

5 PARTNER2: Study Procedures Only examined intervals: PLWH VL<200 HIV- partner not using PrEP or PEP Not using condoms 783 couples contributed 1596 eligible couple years Had sex 77,000 times without a condom Rodgers et al. AIDS 2018 WEAX0104LB

6 Results: U still equals U 27% developed an STI over median 1 year FU 15 seroconversions Using phylogenetic analysis, viruses were not from the partner living with HIV, i.e. unlinked 0 Linked Transmissions Partners Partner Controls Transmission Controls Rodgers et al. AIDS 2018 WEAX0104LB

7 Now >150,000 sex acts without a linked transmission Study Population Condomless Sex Acts Transmissions within Partnership PARTNER Opposites Attract PARTNER2 888 couples, 38% MSM 343 couples, 100% MSM 783 couples 100% MSM 58, , ,000 0 Rodgers et al. JAMA 2016; 316: Bavinton et al, Lancet HIV 2018; 5e

8 Improved precision of risk estimate for MSM following PARTNER Rodgers et al. AIDS 2018 WEAX0104LB

9 First real-world cohort examining HIV incidence with intermittent PrEP Study Design Open-Label Prospective Cohort Study in the Paris Region n = 3,000 May 3 rd 2017 May 31 st 2020 HIV-negative high risk MSM Inconsistent Condom use Creat. Clearance > 50 Hep B neg. if On Demand TDF/FTC Daily Choose, may switch TDF/FTC On Demand Show 15% reduction in new HIV diagnoses among MSM in the Paris Region Molina et al. AIDS 2018 WEAE0406LB

10 >50% chose On-Demand Of 1628 MSM, 55% choose intermittent PrEP in Paris Both groups used correctly ~95% of the time at the last sexual encounter based on report Did not present data on frequency of use in on demand group Daily On Demand Molina et al. AIDS 2018 WEAE0406LB

11 No HIV infections in either group Treatment Follow-Up Pts-years HIV Incidence per 100 Pts-years (95% CI) TDF/FTC (Daily) (0-0.8) TDF/FTC (On Demand) (0-0.7) Mean follow-up: 7 months (SD: 4) 85 HIV-infections averted* * assuming an incidence of 9.17/100 PY as observed in the ANRS Ipergay study in Paris Molina et al. AIDS 2018 WEAE0406LB

12 PrEP does not affect estrogen levels, but estrogen may affect PrEP levels modestly 20 transgender women in Thailand FHT = estradiol valerate 2mg/day + cyproterone acetate 25 mg/day No change in E2 13% plasma TFV Unclear clinical relevance Already need to take daily for vaginal/fronthole exposure 300/2499 transwomen in iprex, 20% on FHT Hiransuthikul et al. AIDS 2018 TUPDX0107LB

13 E2 5 -nucleotidases Spach and Kinney. National HIV Curriculum o/antiretroviral-therapy/

14 TFV has altered pharmacology in rectal tissue of TGW, correlates with E2 level Ratio is lower, but absolute rectal TFVdp:dATP was the Median same (Min, (datp may still compete with TFVdp) Max) Unclear if clinically meaningful, no change in plasma TFV, viral load or HIV DNA in rectal tissue Concentration (fm ol/g) TFVdp datp FTCtp dctp CGW TGW CGM TFVdp:dATP p< (14.3, 30.2) 18.5 (7.8, 29.2) CGW (N=4) TGW (N=4) CGM (N=2) 2.5 (0.08, 3.8) EC90 10 PLWH on TFV-containing regimens TFVdp:dATP Cottrell et al. AIDS 2018 TUPDX0106 ρ= -0.71, p= Serum estradiol (pg/ml)

15 Break: Any Questions?

16 Outline 1. Additional Undetectable=Untransmittable Data for MSM 2. Intermittent PrEP in the real-world 3. PrEP + Hormone Therapy in transgender women Break STIs/HCV with PrEP 5. Promising vaccine safety/immunologic results 6. Population-level impact of prevention strategies

17 High incidence of HCV reinfection in Amsterdam AMPrEP: PrEP Demo with 376 MSM and TGW Tested every 6 months for HCV Overall incidence rate of HCV: 1.9/100 py (95%CI ) (n=12) Incidence of primary infection: 1.0/100 py (95%CI ) (n=6) Incidence of re-infection: 25.5/100 py (95%CI ) (n=6) Hoornenborg et al. AIDS 2018 TUPDX0104

18 STI Incidence pre/post PrEP in Australia Region of Victoria, included 10 clinics offering PrEP services 1,378 individuals accessing clinics pre and post PrEP initiation STI incidence increased, but only in PrEP naive participants 1 year before PrEPX Incidence rate (per 100 person-years) During PrEPX IRR (95% CI) P- value Any STI ( ) <0.001 Chlamydia ( ) <0.001 Gonorrhea ( ) Syphilis ( ) Rectal Infections ( ) <0.001 Pharyngeal Infections ( ) <0.001 Urethral Infections ( ) <0.001 Previous PrEP users ( ) PrEP naïve participants ( ) <0.001 Traeger et al. AIDS 2018 THAC0502

19 Increased screening explains some but not all of STIs PrEP naïve participants Any STI Chlamydia Gonorrhea Syphilis Unadjusted Adjusted* IRR (95% CI) p-value airr (95% CI) 1.71 ( ) 1.84 ( ) 1.69 ( ) 1.24 ( ) <0.001 < ( ) 1.38 ( ) 1.11 ( ) 0.93 ( ) p- value *Adjusted for differential testing frequency Traeger et al. AIDS 2018 THAC0502

20 Group sex and partners, not condoms drove STIs p ( ) ( ) < ( ) <0.001 more than ( ) <0.001 Group sex in last 6 months None Adjusted hazard ratio (95% CI) Number of anal sex partners in last 6 months 2-5 -reference- -reference- Once / a few times 1.28 ( ) At least monthly 1.47 ( ) At least weekly 1.67 ( ) Condom use with casual partners in last 6 months Always -reference- Usually (>50%) 1.38 ( ) Sometimes (<50%) 1.38 ( ) Never 1.31 ( ) Traeger et al. AIDS 2018 THAC0502

21 We need to screen or STIs may increase Male gonococcus cases in SF Model of national GC/CT incidence per proportion screened over 6 month intervals Number of cases SFDPH SF HIV Epi. 2017; ; Spinelli et al. OFID 2018 Jenness et al. CROI 2017 #1034

22 Phase 1/2a data on Ad26/Ad26 + gp140 (Clade C) HIV Vaccine (APPROACH) Recombinant adenovirus serotype 26 vector expressing mosaic Gag, Pol, Env antigens and a clade C soluble trimeric envelope protein (s) gp140 67% full protection in primates after 6 challenges Percent uninfected Presenting Phase 1/2a data (Double-Blind/Placebo- Controlled) Number of IR challenges Barouch, et al., Lancet 2018; 392:

23 Safety; Breadth, and Durability of Immune Response No vaccine related serious adverse events (SAEs) reported No vaccine related grade 3/4 adverse events reported 80% response to all antigens at one year (Durability + Breadth) Currently in phase 2b testing in Southern Africa % Vaccine Responders Cross-clade gp140 panel: Clade A (1) Clade B (3) Clade C (3) CRF AE (1) Consensus M (1) Antigen count Study week 9 Tomaka et al. AIDS 2018 TUAA 0104

24 States with largest PrEP uptake have fewest HIV diagnoses regardless of viral suppression 4 HIV Diagnoses by Quintiles of PrEP Uptake PrEP uptake at the state level significantly associated with decline in HIV diagnoses (- 4.7% vs % comparing highest to lowest quintile) *adjusting for viral suppression at state level (38 jurisdictions) HIV Dx Annual Percent Change, % Low 1.53 Medium Low Medium Medium High High Sullivan et al. AIDS 2018 LBPEC036

25 HIV diagnoses dropped in high PrEP PrEP Use/1000 Population use states FTC/TDF for PrEP Use and HIV Diagnosis Rates For US States in High PrEP Use Quintile* Compare to U.S. level change: 15.7 (2012) to 14.5 (2016) per 100k HIV Diagnoses/100,000 Population PrEP Use Average HIV Diagnoses HIV Diagnoses Trend Sullivan et al. AIDS 2018 LBPEC036

26 National U.S. data on PrEP in young adults and adolescents 45,000 40,000 35,000 30,000 25,000 20,000 15,000 6-YearTotal: 177, and older: 149,893 (84.6%) : 27,330 (15.4%) 20,819 38,938 35,175 39,252 PrEP Rx to need based on HIV incidence is most sub-optimal in age<24 (Siegler et al. Ann. Epi. 2018) 10,000 9,071 8,001 6,683 6,663 5,639 5,000 3,696 1,362 1, Proportion years 17.0% 17.8% 15.1% 14.6% 13.8% 16.9% Magnuson et al. AIDS 2018 TUAC0305

27 Adolescent prescribing low and the overall proportion is decreasing 9,000 8,000 7,000 6,000 5,000 6-YearTotal: 27, : 24,740 (90.5%) 12 17: 2,590 ( 9.5%) Most often prescribed by pediatricians Account for 1.5% of PrEP usage 5,845 5,417 7,691 4,000 3,000 3,150 2,000 1,544 1,093 1, Proportion years 19.8% 21.6% 14.8% 12.3% 3.9% 3.9% Magnuson et al. AIDS 2018 TUAC0305

28 Time spent viremic in SF Goal: measure time spent above transmission thresholds in the entire population of patients living with HIV in SF How are we doing in SF on a population level in the context of early linkage and rapid treatment initiation? What are the implications for U=U? Hughes et al. AIDS 2018 TUAC0104

29 Trends in time spent viremic in SF: where do thresholds come from? 200 copies: threshold in PARTNER/Opposites Attract 1500 copies: risk of sexual HIV transmission is higher above threshold of 1500 copies (Quinn et al NEJM 2000) In a sample of 6 U.S. Clinics, patients spent 23% of the time above a threshold of 1500 copies (Marks et al. AIDS 2015) Transmission Rate per 100 couples x years < k 50k >50k

30 Viral load (in copies/ml) Method for estimating time spent >10000 copies/ml VL1 VL2 Example for hypothetical individual Orange shaded area shows the time spent above copies/ml VL3 VL Days Gardner CROI 2014; Marks AIDS 2015; Buchacz CROI 2017; Hughes et al. AIDS 2018 TUAC0104

31 Time spent viremic is decreasing in SF, but still not optimal 100% Percent time spent above threshold 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% >200 copies/ml >1500 copies/ml >10,000 copies/ml 70% 68% 62% 58% 59% 59% 49% 48% 50% 46% 47% 41% 39% 39% 41% 39% 36% 35% 33% 31% 32% 28% 27% 24% 25% 22% 17% Hughes et al. AIDS 2018 TUAC0104

32 Factors associated with time VL >200 copies Characteristic Adjusted Rate Ratio (95% CI) Year of HIV diagnosis (numeric) 0.96 (0.95, 0.97) MSM-PWID (vs MSM) 1.15 (1.06, 1.24) Age years (vs 50+ years) 1.1 (1, 1.2) Homeless (vs housed) 1.12 (1.02, 1.22) CD4 count (vs 500+) 0.87 (0.81, 0.94) CD4 count (vs 500+) 0.89 (0.83, 0.96) Time from HIV diagnosis to ART days (vs 0-7 days) 1.21 (1.11, 1.32) days (vs 0-7 days) 1.7 (1.54, 1.86) No known ART use within 1 year after HIV diagnosis (vs 0-7 days) 1.78 (1.62, 1.95) *No significant differences by gender, race/ethnicity or insurance type. Hughes et al. AIDS 2018 TUAC0104

33 HIV Incidence following achievement of 90% virally suppressed in Melbourne 90% undetectable VL PrEP Scale-Up * Random Point estimate (uniform distribution) with Linear and Poisson trend Stoove et al. AIDS 2018 TUAC0105

34 Proportion undetectable at one year and time to first undetectable VL Stoove et al. AIDS 2018 TUAC0105

35 In the U.S., as of 2014, 68.2% are suppressed at one Proportion year; virally with suppressed disparities at by one state year and time race/ethnicity to first suppressed VL (Hess et al J Comm. Health). Stoove et al. AIDS 2018 TUAC0105

36 Questions?