IAS 215 Report Back Carina Marquez, MD, MPH Assistant Professor Division of HIV, Infectious Diseases, and Global Medicine San Francisco General Hospital University of California, San Francisco Disclosures None Some slides adapted from Clinical Care Options (CCO) Highlights of IAS 215 Slide Deck: clinicaloptions.com/hiv Original slide sets can be downloaded from pag.ias215.org 1
Outline Antiretroviral Therapeutics HCV HIV Prevention Treatment as Prevention (TasP) PrEP The Global HIV Epidemic Getting to 9-9-9 Antiretroviral Therapeutics TAF GS19 Switch Study GS 112 Switch Study in Adults with Renal Impairment TAF in Patients with HIV/HBV Coinfection Doravarine Efficacy and Safety Study 2 nd Generation Maturation Inhibitor, BMS 176 Dose Ranging study with Atazanavir 2
Tenofovir Alafenamide (TAF): Novel Prodrug of Tenofovir GI TRACT PLASMA Tenofovir (TFV) Parent Nucleotide DIANION TFV TFV HIV TARGET CELL Tenofovir disoproxil fumarate (TDF) Tenofovir alafenamide (TAF) ESTER TDF 3 mg TAF 25 mg T 1/2 =.4 min T 1/2 = 9 min TFV HIV TFV AMIDATE 91% lower plasma TFV levels minimize renal and bone effects while maintaining high potency for suppressing HIV T 1/2 based on in vitro plasma data. 1. Lee W et. Antimicr Agents Chemo 25;49(5):1898-196. 2. Birkus G et al. Antimicr Agents Chemo 27;51(2):543-55. 3. Babusis D, et al. Mol Pharm 213;1(2):459-66. 4. Ruane P, et al. J Acquir Immune Defic Syndr 213; 63:449-5. 5. Sax P, et al. JAIDS 214. 214;67(1):52-8. 6. Sax P, et al. Lancet 215;385:266-15. 215 Snapshot of the Current TAF Landscape Treatment Naïve GS 14 & 111 Wohl and Sax CROI 21, Sax Lancet 215 Results: E/C/F/TAF non-inferior to E/C/F/TDF Less decline in BMD, egfr, and less alteration in tubular function Switch to E/C/F TAF Renal Impairment GS 112 48 week data Pozniack CROI 215 Results: 92% retained virologic suppression, no change in egfr, improvement in markers of tubular function and BMD. IAS 215 TAF Switch Study GS 19 Efficacy and Comorbidities in Subpopulations: GS 112 Renal Impairment- stratified by pre switch TDF use HBV/HIV Coinfected 3
Study 19: Switch from a TDF-containing regimen to E/C/F/TAF Phase 3, 96-week, multi-centered, randomized, open label, active-controlled HIV Suppressed Treatment FTC/TDF Naïve + 3rd Agent Patients HIV-1 Study RNA 12 <5 and c/ml 13 egfr 5 ml/min Key inclusion criteria HIV-1 RNA <5 c/ml for 6 months No HBV or HCV infection 2:1 N=959 N=477 Switch to E/C/F/TAF QD Continue FTC/TDF + 3 rd Agent Week 48 Week 96 Primary Endpoint Secondary Endpoints TDF-containing regimens Stribild (32%), Atripla (26%), RTV or boosted (cobi or ritonaivr) ATV+FTC/TDF (42%) Primary Endpoint : Non-inferiority (12% margin) of switch to E/C/F/TAF vs continuation of baseline regimen by FDA Snapshot analysis (HIV-1 RNA <5 copies/ml at week 48) Secondary Endpoints: Efficacy through Week 96 Safety and tolerability through Week 48 and Week 96" E/C/F/TAF: single-tablet regimen elvitegravir 15mg/ cobicistat 15mg/ emtricitabine 2mg/ tenofovir alafenamide 1mg STB = Stribild = single-tablet regimen elvitegravir 15mg/ cobicistat 15mg/ emtricitabine 2mg/ tenofovir DF 3mg ATR = Atripla = single-tablet regimen efavirenz 6mg/ emtricitabine 2mg/ tenofovir DF 3mg ATV = atazanavir, COBI = cobicistat, RTV = ritonavir Mills A, et al. IAS 215, Vancouver, Canada. Oral # TUAB12 ClinicalTrials.gov Identifier: NCT1815736 7 Primary Outcome HIV-1 RNA <5 Copies/mL at Week 48 Virologic Outcome Treatment Difference (95% CI) HIV-1 RNA <5 c/ml, % 1 8 6 4 2 n= 97 93 E/C/F/TAF n=959 TDF-Based Regimen n=477 1 1 2 Success Failure No Virologic Data 932 444 1 6 17 27 6 TDF Based E/C/F/TAF 4.1 1.6 6.7 12% +12% Mills A, et al. IAS 215, Vancouver, Canada. Oral # TUAB12 4
Virologic Outcome: By Prior FTC/TDF-Based Regimens Primary Endpoint p <.1 p=.2 E/C/F/TA F p=.2 FTC/TDF+3 rd Agent p=ns Patients With HIV-1 RNA <5 c/ml, % 1 8 6 4 2 97 932 959 93 444 477 96 241 251 All Prior Regimens EFV/FTC/TDF Boosted Stribild ATV + FTC/TDF 95% CI = 1.6-6.7.5-12.3.9-9.2-1.9-3.9 Study 19: Suppressed Adults Switched from a TDF-containing regimen to E/C/F/TAF Mills A, et al. IAS 215, Vancouver, Canada. Oral # TUAB12 9 112 125 97 39 42 92 183 199 98 97 31 36 149 153 9 GS-US-292-19 Renal Safety Results Median % Change 3 2 1-1 -2-3 -4-5 -6-21 UPCR UACR RBP: RBP:Cr Ratio B2MG: β 2 m:cr Ratio 1 9-18 -33 Each difference between treatment arms was statistically significant (p <.1). Tubular Proteinuria 18 19 Statistically significant improvements for participants who switched from either E/C/F/TDF or from boosted ATV + FTC/TDF Serum creatinine (p <.1); egfr (p <.1) Fractional excretion of phosphate, FEPO4 (p=.5); fractional excretion of uric acid, FEUA (p <.1) Changes began by Week 2 and persisted to Week 48 UPCR: urine protein: creatinine ratio; UACR: urine albumin: creatinine ratio; RBP, retinol-binding protein; β 2 m:cr, beta-2 microglobulin. -52 E/C/F/TAF TDF-Based Regimen 1 5
Study 19: Suppressed Adults Switched from a TDF-containing regimen to E/C/F/TAF AEs Leading to Discontinuation E/C/F/TAF n=959 FTC/TDF+3 rd Agent n=477 Participants, % (n).9 (9) 2.5 (12) Renal Events All Other Events Acute renal failure Interstitial nephritis ǂ Depression Leg swelling, impaired concentration Memory loss, speech disturbance, lack of motivation Nausea, vomiting, headache Panic attack Reiter syndrome Suicide attempt Chronic kidney disease Elevated serum creatinine Fanconi syndrome, mild jaundice Increased creatinine Nephretic colic (nephrolithiasis) Abnormal dreams Depression, insomnia, irritability Depression, insomnia, nightmares Elevated bilirubin Icterus (n=2) Increased forgetfulness After cancer chemotherapy, participant hospitalized with neutropenia, sepsis, and multi-system organ failure ǂ Recurrent hematuria on treatment, subsequent off-treatment diagnosis of Hodgkin s Lymphoma Mills A, et al. IAS 215, Vancouver, Canada. Oral # TUAB12 11 1 Change in Diagnosis of Osteopenia/Osteoporosis Through Week 48 (As Defined by T-Score) Normal Osteopenia Osteoporosis Spine (N=1,369) Hip (N=1,354) 5.8 4.8 7.2 7.6.7.7 1.3 2.1 8 36 32 35 37 31 26 32 32 Patients, % 6 4 2 59 64 57 56 69 73 67 66 Baseline Week 48 E/C/F/TAF n=912 Baseline Week 48 FTC/TDF+3 rd Agent n=457 Baseline Week 48 E/C/F/TAF n=92 Baseline Week 48 FTC/TDF+3 rd Agent n=452 Differences between E/C/F/TAF and TDF-based regimens were statistically significant (p <.1) Mills A, et al. IAS 215, Vancouver, Canada. Oral # TUAB12 1 2 6
How will this change practice? We know the switch is safe There are less bone and renal effects The clinical significance remains unclear. Correlation between subclinical markers and overt clinical disease. Correlation between declines in BMD and osteoporosis and fractures Are there subgroups that benefit most, older patients, vasculopaths? Will the answer be in post marketing studies? Justify the cost? GS-112: Switching to a TAF-Based Regimen in Pts With Renal Impairment Multicenter, open-label phase III trial Virologically suppressed, HIV-positive pts with mild-moderate renal impairment (stable egfr CG [3-69 ml/min]) (N = 242) TDF-Based ART (n = 158) Non-TDF Based ART (n = 84) Wk 24 Wk 48 EVG/COBI/FTC/TAF (N = 242) Wk 96 Pre-Switch ART Use PI NNRTI INSTI CCR5 Antag. TDF ABC Other NRTI ART use,% 44 42 24 3 65 22 7 5 No NRTI Gupta S, et al. IAS 215. Abstract TUAB13. Slide from CCO 7
Actual GFR by Iohexol Clearance through Week 24 Total TDF Non-TDF 8 agfr (ml/min) 6 4 2 59 57 58 63 62 63 5 48 49 BL W2/4/8 W24 BL W2/4/8 W24 BL W2/4/8 W24 GLSM Ratio, % (9% CI)* Week 2, 4, or 8 vs baseline 98 (94, 12) TDF (n=21) Week 24 vs baseline 1 (96, 15) Week 2, 4, or 8 vs baseline 96 (86, 18) Non-TDF (n=1) Week 24 vs baseline 98 (87, 111) *Lack of alteration boundary: 8 125% (GLSM). Actual GFR unaffected by E/C/F/TAF switch, regardless of previous regimen 15 Conclusions No change in actual GFR, regardless of whether TDF in prior regimen Improvement in mean BMD if TDF in prior regimen, but not if on a non-tdf regimen pre-switch Safe Promising for a single tablet regimen Significance of improvement in renal markers unclear among those previously on TDF unclear. Caution: Big difference between CrCL of 3 & 69. More analyses for those between 3-5? 8
Is TAF effective with HIV/HBV Coinfection? Switching Patients With HIV/HBV Coinfection to a TAF-Based Regimen International, multicenter, single-arm, open-label phase IIIb trial (N = 72) Pts with virologically suppressed HIV infection on any regimen, chronic HBV coinfection, and egfr > 5 ml/min switched to EVG/COBI/FTC/TAF for 48 Wks HIV-1 RNA < 5 c/ml 1 94 92 8 HBV DNA < 29 IU/mL 1 8 86 92 Pts (%) 6 4 6 4 Wk 24 Wk 48 2 2 By Wk 48, 2/7 (3%) pts lost HBsAg/gained HBsAb; 2/3 (7%) pts had lost HBeAg; 1/3 (3%) pts gained HBeAb Significant improvement in median Wk 48 FibroTest score with switch (-.4; P =.18) Gallant J, et al. IAS 215. Abstract WELBPE13. Slide from CCO. Phase 2b Efficacy and Safety of Doravirine vs. Efavarinz Why is Doravirine of Interest? Excellent potency for suppressing K13N and Y181C mutants NNRTI, unique resistance pathway Fewer DDI: not an inducer or an inhibitor of CYP34A Daily Dosing Phase 2B Results: Primary outcome: No difference in VL <4 at 24 weeks: 73% DOR vs. 72% EFZ, N=25 24 week virologic response similar between arms, regardless of baseline HIV RNA Doravirine plus TDF/FTC was well tolerated and associated with fewer AEs and discontinuations. Week 24 Virologic Response Rates by Baseline HIV-RNA Level, N=216 Gatell JM, et al. IAS 215. Abstract TUAB14. Adapted from from CCO 9
Maximum median change in HIV-1 RNA (log 1 copies/ml) Activity and Safety of 2 nd Generation Maturation Inhibitor plus ATV/r Why is BMS 176 of Interest? Novel Mechanism: Inhibits the last protease cleavage event (between capsid protein p24 and spacer peptide 1 in Gag), resulting in the release of immature non-infectious virions. Long half life allows for once daily dosing NRTI sparing regimen? Methods and Results : 28 Day Dosing Ranging Study N=26, Treatment naïve (<1 week of ART) or experienced (but PI and MI naïve) ATV/r + 4mg & unboosted ATV+ 8 mg of BMS-176 comparable to control. No As leading to discontinuation Two drug combination studies in vitro demonstrated that BMS-955176 + ATV had an additive effect. Due to the proximity of their sites of inhibition in the virus life cycle and the 3/2 potential for mg synergy, we assessed the 4 antiviral mg activity and safety of BMS-955176 with ATV±RTV BMS-955176 Two drug combination studies in vitro demonstrated that BMS-955176 + ATV had an additive effect. Due to the proximity of their sites of inhibition in the + ATV 3 mg + ATV 3 mg 4 mg 8 mg + virus life cycle and the potential for synergy, we assessed the antiviral activity and safety of BMS-955176 with ATV±.5 1 1.5 2 2.5 TDF/FTC + RTV 1 mg* (n=4) 2.39 BMS-955176 + RTV 1 mg (n=8) 2.2 BMS-955176 + ATV 4 mg (n=8) 1.86 Hwang C TUAB16LB ATV 4 mg (n=8) 2.23 Hepatitis C Treatment: The Good News Continues ION-4 LDV/SOF in genotype 1/4 HIV/HCV-coinfected patients C-EDGE Coinfection Study Grazoprevir/Elbasvir for patients coinfected with HIV/HCV, genotypes 1/4/6 1
SVR12 by Prior Treatment Experience and Cirrhosis Status HIV-HCV (ION-4) Overall Naïve vs Experienced Cirrhosis Status 1 96 95 97 96 94 8 SVR12 (%) 6 4 2 321/335 142/15 179/185 258/268 63/67 LDV/SOF 12 Weeks Naïve Experienced No Cirrhosis Cirrhosis Error bars represent 95% confidence intervals. 21 ION-4 LDV/SOF in HIV/HCV SVR12 by ARV Regimen and Race Non-Black Black 1 8 99 1 98 1 95 9 85 9 % SVR12 6 4 2 215/217 13/115 97/97 52/61 13/13 1/12 42/44 49/5 18/18 9/1 Overall EFV/FTC/TDF RAL+FTC/TDF RPV/FTC/TDF 11
C-EDGE Coinfection: Grazoprevir/Elbasvir for Patients Coinfected With HIV/HCV Methods Multicenter, single-arm, open-label phase III trial HCV treatment-naive pts coinfected with HIV and GT1, 4, or 6 HCV; stable on ART 8 wks (N = 218) Grazoprevir/Elbasvir HCV PI (NS3/4A inhibitor)/hcv NS5A inhibitor Wk 12 Coformulation dosed orally 1/5 mg QD 66% GT1a HCV, 6% had HCV RNA > 8, IU/mL, 16% cirrhotic Baseline ART Characteristic, % Grazoprevir/Elbasvir (N = 218) Undetectable HIV-1 RNA on ART 96.8 ART regimen Abacavir containing 21.6 TDF containing 75.2 Raltegravir 51.8 Dolutegravir 27.1 Rilpivirine 17.4 Rockstroh JK, et al. IAS 215. Abstract TUAB26LB. Rockstroh JK, et al. Lancet HIV. 215;2:e319-e327. C-EDGE Coinfection: Key Findings SVR12 With 12 Wks GZR/EBV According to Genotype High rates of SVR. No subgroup provided efficacy advantage or disadvantage, including ART regimen 1% of cirrhotics with SVR 12 SVR12 (%) 1 8 6 4 2 n/n = 96.3 96.5 95.5 96.4 21/ 218 139/ 144 42/ 44 27/ 28 All Pts GT1a GT1b GT4 Discontinued* 1 1 Relapse 5 4 1 New NS3, NS5A RAVs detected at failure in 4 of 5 pts who relapsed Short-lived HIV-1 RNA increases in 2 pts on ART during GZR/EBV treatment Both suppressed HIV-1 RNA without change of ART During GZR/EBV Tx, no significant changes in CD4+ cell count Reinfection 2 1 1 GZR/EBV well tolerated: no pt *Unrelated to virologic failure. discontinued for AEs and no serious treatment-related AEs Rockstroh JK, et al. IAS 215. Abstract TUAB26LB. Rockstroh JK, et al. Lancet HIV. 215;2:e319-e327. Slide from CCO 12
TaSP Combination HIV Prevention Final Results from HPTN 52 PrEP Final HPTN 52 Results: ART for Prevention of HIV Transmission in Serodiscordant Couples Partner Infections, n (rate/1 PY) Overall (April 25 - May 215) Early (4314 PY F/U) Delayed (418 PY F/U) All 19 (.44) 59 (1.41) Linked 3 (.7) 43 (1.3) Risk Reduction With Early ART, % All infections 69 -- Linked infections 93 -- No linked HIV transmissions observed when index participant stably suppressed on ART, N=1763 couples 8 linked HIV infections diagnosed after seropositive pt started ART 4 infections likely occurred before, or soon after, ART initiation, and 4 infections occurred after ART failure in seropositive patient Unlinked partner infection rates similar between study arms Cohen MS, et al. IAS 215. Abstract MOAC11LB. 13
PrEP in Non-Clinical Settings and in Diverse Populations Key Topics at IAS PReP in the Real World: Implementation Success and Challenges Demo Projects from US, Brazil, Youth Open Label Extension Bostswana Feasibility of Intermittent Dosing in Diverse Patient Populations ADAPT/HPTN 67 US PrEP Demo Implementation of Daily PrEP by US MSM/TGW The first US multi-site, open-label study assessing PrEP delivery in 2 STD clinics (SF, Miami) and 1 community health clinic (Washington, DC) (N = 557) Enrolled HIV-negative MSM (98%) and TGW (1.3%) who met behavioral risk criteria; participants offered daily TDF/FTC as PrEP for up to 48 wks Retention rates declined from 93% at Mo 1 to 78% at Mo 12 Participants with prior PrEP knowledge and those who reported condomless receptive anal sex at baseline had higher retention rates 63% of participants had protective TFV DBS levels at all study visits (consistent with 4 doses/wk) Odds of protective blood levels lower in Miami (aor.32), black participants (aor.28), higher in those who had > 2 condomless sex partners in 3 months (1.8), higher for those who own or rent (aor 2), no difference by age, drug use, or education PrEP dispensation interrupted in 15% participants most commonly due to side effect concerns or low perceived risk No evidence of risk compensation, but high background rate of STIs. HIV incidence rates low at.43/1 PY (95% CI:.5-1.54) 3 acute infections at enrollment, M184V in one patient 2 during follow up, both with low or undetectable drug levels throughout the study Liu A, et al. IAS 215. Abstract TUAC22. 14
US PrEP Demo Project: Implications for Scalingup PrEP in the US These data show relatively high PrEP adherence among MSM. PrEP was safe, no major adverse events 23 creatinine elevations in 13 patients (2.3%), all grade 1, all resolved without stopping PrEP. Implementations questions moving forward Do we need as frequent lab monitoring? Who type of counseling should be provided by whom and how often? Effects of cost and insurance on adherence and uptake. High rates of sexually transmitted infections supports need for quarterly screening Interventions to address racial and geographic disparities and housing instability may increase PrEP impact in the US. We need to understand of why adherence was lower in African American participants and in Miami. -elucidate role of medical mistrust, health literacy, privacy concerns, acculturation factors, social support, and unmet medical/social-structural needs in these health disparities ATN 11: TDF/FTC PrEP for Young US MSM, N=2 Adherence decreased from baseline to Wk 48 Undetectable levels of DBS TFV occurred in < 1% of pts at Wk 4 and ~ 3% of pts at Wk 48 Black pts had decreased adherence compared with other races Sample comprised of 53% black, 17% Latio 4 seroconversions in 48 weeks, drug levels undetectable 12 Levels of TFV in DBS (fmol/spot) 1 8 6 4+ doses 4 2 4+ doses Overall White Latino Mixed Black 4 8 12 24 36 48 Wks Hosek S, et al. IAS 215. Abstract TUAC24LB. Slide from Clinical Care Options 15
First PrEP Demonstration in Middle Income Country High uptake 51% (49/798) Highest among those at increased risk and awareness of PrEP 6% of participants were trans women. Targeted Trans community education activities and environment can play major role in getting Trans people to access PrEP services. Grizstejn et al., et al. IAS 215. Vancouver, Canada. Oral #TUAC25LB TDF-2 OLE Botswana % of visits with extracellular TFV detected Detectable Drug Levels- DBS 1 9 8 7 6 5 4 3 2 1 Fem Months Months Months Months 1-3 4-6 7-9 1-12 Study Months Overall, TFV was detected at ~93% of visits. TDF 2: 62% protective efficacy (Thigpen NEJM 212) TDF2 OLE 213-214 to assess safety, effectiveness, behavioral risk compensation, adherence 86% Eligible started Truvada, N=229 High adherence to daily PrEP among both heterosexual men and women at risk for HIV Mean number of condomless sex acts decreased by 39% No HIV infections observed (expected 5-6 based on TDF2 incidence rate) Supports recent findings that women and men who are at risk for HIV can adhere to daily PrEP N=12, lower limit of detection= =5ng/ml 16
A Phase II, Randomized, Open-label, Pharmacokinetic And Behavioral Study Of The Use Of Intermittent Oral Emtricitabine/Tenofovir Disoproxil Fumarate Preexposure Prophylaxis (PrEP) Alternative Dosing to Augment PrEP Pill Taking HPTN 67 ADAPT Study Primary Objective To assess whether recommending non-daily oral FTC/TDF PrEP, compared with daily, is associated with: Equivalent coverage of sex events with preand post-exposure dosing Lower number of tablets needed Decreased self-reported symptoms/side effects 17
Harlem Prevention Center 179 HIV-uninfected at risk MSM/TGW NYC (Harlem), USA Completed Dec 214 Silom Community Clinic 178 HIV-uninfected at risk MSM/TGW Bangkok, Thailand Completed March 214 Bekker IAS215, Vancouver, 215 Emavundleni Prevention Centre 179 HIV-uninfected at risk WSM Cape Town, South Africa Completed June 213 HPTN 67/ADAPT International, randomized, open-label phase II trial Wk Wk 6 Wk 3 Wk 34 Daily PrEP 1 dose daily HIV-negative MSM and Women (including TGW) Lead-in period of directly observed therapy Time-Driven PrEP 1 dose twice weekly + 1 dose after sex Event-Driven PrEP 1 dose before and 1 dose after sex Final study visit TDF/FTC PrEP given at standard dose and dispensed using an electronic monitoring device. Adherence and sexual risk behavior assessed by weekly interview conducted by phone or in person. Inclusion criteria for MSM and TGW: reported anal intercourse and 1 other risk factor for HIV infection in last 6 mos; creatinine clearance > 7 ml/min. Participants instructed to take no more than 2 doses daily or 7 doses/wk. Slide from Clinical Care Options 18
Definition: Covered sex event Coverage for all arms: >1 pill taken in the 4 days before sex >1 pill taken in the 24 hours after sex >1 tablet >1 tablet Bekker IAS215, Vancouver, 215 HPTN 67/ADAPT: Results Bangkok Cohort N=178 1% 8% 6% 4% 2% % 84% 84% 85% 74% 79% 65% Complete coverage of Sexual Intercourse* Compared to daily and time driven dosing, coverage lower in event driven arm. Drug levels similar across dosing arms Adherence 91% 95% 86% High TDF Level** Week 3 2 HIV seroconversions during pre randomization directly observed dosing phase Both associated with undetectable or low levels of FTC or TFV in plasma/pbmcs Daily Time Driven Event Driven Complete coverage taking taking 1 PrEP dose within 4 days before sex and 1 dose within 24 hrs after sex **>9.1 fmol/million PBMC, 2 tablets per week T. Holtz, IAS 215, Vancouver, # MOSY14 19
9% 8% 7% 66% 6% 52% 5% 47% 4% 3% Results 2% 1% % Complete coverage of Sexual Intercourse* HPTN 67/ADAPT: Harlem Cohort 8% 7% 55% Adherence 7% African American, young- one third less than 25 years Daily dosing resulted in higher coverage of sex events, higher drug concentrations, higher adherence. Suboptimal coverage and drug levels. HIV seroconversion seen in 2 pts Both pts had low or undetectable TDF in dried blood spots/plasma at study visits Complete coverage taking taking 1 PrEP dose within 4 days before sex and 1 dose within 24 hrs after sex.** S. Mannheimer, IAS 215, Vancouver, #MOSY115 **>35 fmol DBS, includes participants reportingsex in last 7 days 5% 17% 17% High TDF Level** Week 3 Daily Time Driven Event Driven 2
PrEP and Stigma ADAPT- Harlem Qualitative Study HIV-related Stigma Even if I told them it was a study, maybe some of them wouldn t believe it, and put some ideas into people s heads that I did have HIV. My partners would be like, Why are you taking those pills? [and] sometimes it would never get to the intercourse part. It would just stop the night. They would be mad and leave. Promiscuity-related stigma One of my partners was like, Whoa. What does this mean? What are you doing? Indicating that taking the pill means that I m willy-nilly having unprotected sex Stigma and Adherence, Challenges for Sex-Dependent Dosing My partners would be like, Why are you taking those pills? [and] sometimes it would never get to the intercourse part. It would just stop the night. They would be mad and leave. J. Franks, IAS 215, Vancouver, #MOSY18 HPTN 67/ADAPT: South African Women 9% 8% 7% 6% 5% 4% 3% 2% 1% % 8% 75% 7% 56% 52% 55% Complete coverage of Sexual Intercourse* Adherence 66% 46% 32% High TDF Level** Week 3 Daily Time Driven Event Driven Majority of young, predominantly single, South African women took oral PrEP when made available in an open label study Daily dosing resulted in higher coverage of sex events, higher drug concentrations, and higher adherence. 2 seroconversion in DOT phase, 5 during self-administered PrEP phase (5.4/1PY) Complete coverage taking taking 1 PrEP dose within 4 days before sex and 1 dose within 24 hrs after sex.** **>35 fmol DBS Bekker IAS 215, Vancouver, 215 21
Implications for PrEP Implementation In general daily dosing looks better for coverage, adherence, and drug levels except in Bangkok. Different strategies might wok better with different subpopulations and individuals. Would drug levels have been better if IPERGAY dosing is used. More data is needed for adherence in African American MSM and Trans women UNAIDS: 9-9-9 Global Estimated Gaps People (%) 1 8 6 4 2 36.9 million HIV Positive People 53% 41% Breakpoint 1: 13.4 million undiagnosed Breakpoint 2: 14.9 million not treated 19.8 million 32% Breakpoint 3: 15.3 million not virally suppressed 15. million 11.6 million Diagnosed On ART Viral Suppression* *HIV-1 RNA < 1 copies/ml. Levi J, et al. IAS 215. Abstract MOAD12. Slide from Clinical Care Options 22
Target 3 Percentage of HIV+ People with HIV RNA suppression -Results 1% 9% 8% UNAIDS Target 3: 73% of all HIV+ people achieving viral suppression 7% 68% 6% 5% 62% 61% 59% 58% 52% 52% 4% 4% 35% 32% 3% 3% 3% 2% 23% 2% 19% 17% 1% 9% % Switzerland Australia United Denmark Netherlands Rwanda France Brazil British Sub Saharan Cuba USA Columbia Georgia Estonia Ukraine Russia <2 <4 Kingdom <5 <2 <4 <5 <1 Columbia Africa (N/A) <2 (N/A) <4 <2 (NA) <1 <2 (Canada) <4 to <4 <5 (*SSA = Regional average From 3 countries) How do we get to 9-9-9? Highlights of Innovative Studies Image avert.org 23