Switching from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF) lowers alanine transaminase (ALT) and aspartate transaminase (AST) in patients with HIV infection with or without viral hepatitis coinfection
N Squillace1, E Ricci2, B Menzaghi3, G Migliorino1, GV De Socio4, S Rusconi5, C Martinelli6, G Madeddu7, P Maggi8, K Falasca9, L Cordier10, BM Celesia11, F Vichi12, A Di Biagio13, GF Pellicanò14, G Orofino15, P Bonfanti16, the CISAI Study Group
1Infectious Diseases Unit ASST-MONZA, San Gerardo Hospital-University of Milano-Bicocca, Monza; 2Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milano; 3Unit of Infectious Diseases, ASST della Valle Olona – Busto Arsizio (VA); 4Unit of Infectious Diseases, Santa Maria Hospital, Perugia; 5Infectious Diseases Unit, DIBIC ‘Luigi Sacco’, Università degli Studi di Milano; 6SOD Malattie Infettive e Tropicali AOU Careggi, Florence; 7Unit of Infectious Diseases, Department of Medical, Surgical and Experimental Sciences, University of Sassari, Italy; 8Infectious Diseases Clinic, University of Campania ‘Luigi Vanvitelli’, Naples; 9Clinic of Infectious Diseases, Department of Medicine and Science of Aging, University ‘G. d'Annunzio’ Chieti-Pescara, Chieti; 10UO I Malattie Infettive, ASST-FBF-Sacco - PO L. Sacco, Milan; 11 Unit of Infectious Diseases, Garibaldi Hospital, Catania; 12Unit of Infectious Diseases, Santa Maria Annunziata Hospital, Florence; 13Infectious Diseases, San Martino Hospital Genoa, University of Genoa, Genoa; 14Infectious Diseases, G Martino Hospital -University of Messina, Messina; 15Divisione A Malattie I, Amedeo di Savoia Hospital, Torino; 16Unit of Infectious Diseases, A Manzoni Hospital, Lecco
Objectives: Our aim was to investigate the effect of switching TDF to TAF on liver enzymes and renal and lipid profile.
Methods: Consecutive HIV patients enrolled in Surveillance Cohort Long-term Toxicity Antiretrovirals/Antivirals (SCOLTA) project switching from TDF to TAF for any reasons were included. Changes from baseline (T0) to 6-month follow-up (T1) were evaluated using paired t-test if differences were normally distributed and using signed rank test if not.
Results: 291 patients switched from TDF to TAF, 163 had at least one follow-up visit. They were mostly males (131, 80.4%) and Caucasian (151, 92.6%). Twenty-seven (16.6%) had been intravenous drug users, 43 (26.4%) were in CDC stage C, 48 (29.4%) on second-line antiretroviral therapy (ART), and 154 (94.5%) had HIV RNA <50 copies/ml at switch. 35 (21.5%) were HCV-Ab-positive (8 with detectable HCV RNA), and 14 (8.6%) HBsAg-positive. Median time on TDF was 669 days (IQR 417-911). At baseline, mean age was 46.3 (standard deviation [sd] 10.7), body mass index 24.9 kg/m2 (SD 3.7), total cholesterol 196 mg/dl (SD 40), HDL cholesterol (HDL) 49 mg/dl (SD 16), glucose 91.7 mg/dl (SD 21.5), creatinine 1.0 mg/dl (SD 0.2), estimated glomerular filtration rate 85.7 ml/min (SD 18.6). Median CD4+ was 637 cells/ml (interquartile range [IQR] 440-898), triglycerides (TG) 109 mg/dl (IQR 81-154), aspartate aminotransferase (AST) 23 IU/l (IQR 18-30), alanine aminotransferase (ALT) 24 IU/l (IQR 17-34), 12 (7.4%) patients had AST >40 IU/l and 24 (14.7%) ALT >40 IU/l at T0.
At T1, both ALT (median −2, IQR −7-3 IU/l; P=0.0008) and AST (median −1, IQR −5-2 IU/l; P=0.003) were significantly reduced. AST and ALT reduction remained significant in patients negative for HCV-Ab and HBsAg (P<0.05 for both). Among 24 patients with ALT >40 IU/l, a significant proportion reduced this parameter (median change −20, −34 to −4; P<0.0001). Total cholesterol (TC) and HDL cholesterol increased significantly (mean change 14.8 ±4.3 mg/dl; P<<0.0001) and 3.0 ±1.3 mg/dl [P<0.05], respectively) and eGFR decreased significantly (3.3 ±1.0 ml/min; P=0.002) with no impact on TC/HDL ratio and on triglycerides.
Conclusions: Switching from TDF to TAF demonstrated a significant reduction of ALT and AST and was associated with an improvement in eGFR and increased TC and HDL. A possible mild hepatotoxicity of TDF were described. We can argue that TAF could have a better liver toxicity profile that TDF. Further studies are needed to confirm this hypothesis.
Abstract P33
Antiviral Therapy 2019; 24 Suppl 1:A84
Non-Hispanic White individuals with HIV–HBV are at increased risk for developing cirrhosis
MK Jain1,2, G Go3, P Parisot1, TT Vu4, L Hansen1, BS Taylor3, KJ Vigil4
1University of Texas Southwestern Medical Center, Dallas, Texas; 2Parkland Health and Hospital Systems, Dallas, Texas; 3University of Texas at Houston, Houston Texas; 4University of Texas at San Antonio, San Antonio, Texas
Introduction: Given the widespread use of hepatitis B virus (HBV)-specific ART which leads to HBV viral suppression, it remains unknown if progression to cirrhosis occurs while on ART in HIV–HBV patients.
Methods: We conducted a retrospective longitudinal analysis of HIV–HBV with chronic HBV (CHB) from three sites in Texas and obtained incidence of cirrhosis. Those with cirrhosis prior to or within 182 days of HBV diagnosis or study entry were excluded. We examined risk for developing cirrhosis by race, gender, age, HBV viral suppression by months, having AIDS at baseline, hepatitis C coinfection, alcohol use and diabetes (DM) by Cox proportional hazards analysis.
Results: Among the 765 patients, 501 had CHB (87% male, 23% non-Hispanic White [NHW], 62% Black, 15% Hispanic) and 3,767 person-years of follow-up data. Incident cirrhosis developed in 70 patients at a median of 7.89 years with an incidence rate of 18.2 (overall) and 28.6, 19.2 and 14.6 per 1,000 person-years in NHW, Hispanic and Black individuals, respectively. Hepatitis C (HCV) coinfection (hazard ratio [HR] 2.40, 95% CI: 1.38, 4.16), age at baseline (HR 1.04, 95% CI: 1.01, 1.07) and Black versus NHW (HR 0.49, 95% CI 0.28, 0.85) were associated with incident cirrhosis. Diabetes had a trend towards increased risk (HR 1.77, 95% CI: 0.97, 3.23). No differences were seen by gender, HBV viral suppression, AIDS and alcohol use. After adjusting for HCV, age, HBV viral suppression and AIDS, Black versus NHW individuals (adjusted HR 0.42, 95% CI: 0.22, 0.84) was associated with incident cirrhosis. See Figure 1.
(Abstract P33)
Conclusions: The incidence of developing cirrhosis in HIV–HBV patients on HBV-specific ART is 18.2 per 1,000 person-years. Non-Hispanic White individuals are at increased risk for developing cirrhosis after adjusting for HCV, age, AIDS and months of HBV suppression. Careful monitoring for development of cirrhosis is needed in HIV–HBV on HIV treatment.
Abstract P34
Antiviral Therapy 2019; 24 Suppl 1:A86
Targeting liver fibrosis in chronic treated HIV with oral ApoA-I mimetics
R Heymans1, W Mu1, E Ritou1, P Hamid1, A Kossyvakis1, S Sen Roy1, V Grijalva1, A Chattopadhyay1, A Fogelman1, S Reddy1, T Kelesidis1
1David Geffen School of Medicine at University of California – Los Angeles
Objectives/aim: Novel therapies are needed to attenuate liver fibrosis in chronic treated HIV infection. ApoA-I peptides (such as 6F) mimic HDL and attenuate pro-inflammatory mechanisms. The 6F was expressed as a transgene in tomatoes (Tg6F) and can be translated to human diet. Given that gut dysfunction and inflammation may contribute to liver fibrosis in chronic treated HIV, we used a humanized mouse model of chronic treated HIV to study whether Tg6F attenuates in vivo HIV- and/or ART-driven impact on liver fibrosis.
Methods: The C57BL/6 Rag2-/-γc-/-CD47-/- bone marrow/liver/thymus mice do not develop early graft versus host disease. After 4 weeks of infection with the 89.6 HIV-1 virus, mice were treated with daily emtricitabine, tenofovir, raltegravir for up to 12 weeks. Oral ApoA-I mimetics were given as Tg6F (at 0.06% by weight of diet) to HIV+/ART-treated mice (n=20) after suppression of viraemia with ART. The groups were: A (n=10): uninfected (HIV-); B (n=10): HIV+; C (n=20): HIV+, ART; D (n=20): HIV+/ART/Tg6F. Human and murine plasma levels of matrix metalloproteinases (MMPs) MMP-1, MMP-2, MMP-9, MMP-12 and tissue inhibitors of metalloproteinase (TIMP)-1 were determined by Luminex Assays. Liver murine mRNA levels of collagen I, III and TIMP-1, MMP-2, MMP-9 were determined by real-time PCR. Results are described as mean + sem and t-test was used for statistical analysis.
Results: Potent ART induced a mean >20% increase in human plasma biomarkers of fibrosis (Table 1) compared with HIV viraemic and uninfected mice. ART induced a mean >15% increase in mRNA levels of collagen I, III, TIMP-1, MMP-2, MMP-9 in HIV+/ART+ compared with HIV+ and uninfected mice (P<0.05). Tg6F attenuated all ART-induced increases in plasma biomarkers of fibrosis and in mRNA levels of mediators of liver fibrosis (P<0.05).
(Abstract P34)
Uninfected
HIV
HIV/ART
HIV/ART/TgF
P values
Pg/ml (mean ± SEM)
Fold to uninfected group (mean ± SEM)
^: HIV+/ART+ vs HIV+, ^^^: HIV+/ART+/Tg6F vs HIV+/ART
MMP-1
87.44 ± 28.90
0.860 ± 0.038
1.174 ± 0.065
0.874 ± 0.061
0.001^, 0.002^^^
hMMP-2
946.08 ± 294.71
1.714 ± 0.876
1.018 ± 0.030
0.903 ± 0.024
0.454^; 0.006^^^
hMMP-9
250.44 ± 86.47
0.587 ± 0.059
1.564 ± 0.250
0.892 ± 0.075
0.002^, 0.021^^^
hMMP-12
6.06 ± 2.05
0.908 ± 0.116
1.578 ± 0.198
0.774 ± 0.087
0.009^, 0.002^^^
hTIMP-1
32.50 ± 10.62
0.804 ± 0.047
1.343 ± 0.120
0.940 ± 0.058
0.001^, 0.007^^^
mMMP-2
4648.20 ± 1444.00
1.007 ± 0.019
1.105 ± 0.027
0.992 ± 0.017
0.007^; 0.002^^^
mMMP-9
129.01 ± 44.43
0.889 ± 0.083
1.380 ± 0.203
0.847 ± 0.098
0.039^, 0.029^^^
mTIMP-1
59.62 ± 20.21
0.377 ± 0.027
1.824 ± 0.266
0.821 ± 0.102
0.000^, 0.003^^^
Conclusions/discussion: Tg6F attenuated ART-induced increase in mediators of liver fibrosis. Given that Tg6F is not absorbed systemically, gut dysfunction may contribute to liver fibrosis in chronic treated HIV. Further studies are needed to determine whether oral ApoA-I mimetics can be a novel strategy to attenuate liver fibrosis in chronic treated HIV.
Abstract P35
Antiviral Therapy 2019; 24 Suppl 1:A88
Targeting liver fibrosis in chronic treated HIV with MitoQ
S Sen Roy1, A Kossyvakis1, R Heymans1, P Hamid1, S Beaven1, T Kelesidis1
1David Geffen School of Medicine at University of California – Los Angeles
Objectives/aim: Elucidating mechanisms of HIV-related liver fibrosis will set the basis for therapies that can lessen its impact including cirrhosis, morbidity and mortality. As mitochondria are the main source of intracellular reactive oxygen species (ROS; mito-ROS), therapies that target oxidative stress and mitochondrial dysfunction such as the mitochondria-targeted antioxidant MitoQ, may target HIV-related liver fibrosis. MitoQ has been used in clinical trials in humans for diseases like Parkinson and liver disease. We used a physiologically relevant humanized mouse model of chronic treated HIV to study whether MitoQ attenuates in vivo HIV- and/or ART-driven liver fibrosis.
Methods: The C57BL/6 Rag2-/-γc-/-CD47-/- bone marrow/liver/thymus mice do not develop early graft versus host disease and thus HIV- and/or ART-driven changes on liver fibrosis can be dissected in vivo. After 4 weeks of infection with the dual-tropic 89.6 HIV-1 virus, mice (n=20) were treated with daily emtricitabine (200 mg/kg), tenofovir (208 mg/kg), raltegravir (80 mg/kg) for up to 12 weeks. MitoQ was given in water at 250 μM daily. The groups were: A (n=5): uninfected (HIV-); B (n=10): HIV+, ART; C (n=10): HIV+/ART/MitoQ. Liver fibrosis was assessed histopathologically by Picrosirius red staining of fibrotic mouse liver and a digital imaging expert system. Quantified Digital Fibrosis % (QDF%) was calculated as the percentage of the total section or biopsy that is masked as fibrosis relative to the entire tissue area. Real-time PCR was also used to determinate mRNA levels of key mediators of liver fibrosis (TIMP-1, TGF-beta, MMP-9). Results are described as mean +sem and t-test was used for statistical analysis.
Results: Liver fibrosis was not detected in uninfected mice (Figure 1). Potent ART for 12 weeks suppressed viraemia within 4 weeks. Humanized HIV mice exposed to HIV/ART for 12 weeks demonstrated a moderate lobular and sinusoidal fibrotic pattern and had an approximately 12-fold increase in fibrosis. In the liver of HIV+/ART+ mice there was a mean 22%, 16%, 18% and 12.3% increase in Picrosirius Red signal, TGF-b, TIMP-1 and MMP-9 compared with uninfected mice (P<0.05). MitoQ attenuated HIV/ART-induced increase in Picrosirius Red signal, TGF-b, TIMP-1 and MMP-9 (P<0.05).
(Abstract P35)
Conclusions/discussion: Our in vivo model provided preclinical data that support the use of MitoQ as therapeutic strategy for liver fibrosis in chronic treated HIV. MitoQ attenuated HIV/ART-driven increase in collagen content and molecular mediators of fibrosis in the liver. Further studies are needed to determine whether MitoQ can be a novel therapeutic strategy for liver fibrosis in chronic treated HIV.
Abstract P36
Antiviral Therapy 2019; 24 Suppl 1:A89
Evolutive NAFLD predicts frailty in people living with HIV
J Milic1, 2, V Menozzi3, A Malagoli1, F Schepis4, G Besutti2, 5, I Franconi1, F Carli1, S Zona1, G Ciusa1, C Mussini1, G Sebastiani6, G Guaraldi1
1Modena HIV Metabolic Clinic, University of Modena and Reggio Emilia, Italy; 2Clinical and Experimental Medicine PhD Program, University of Modena and Reggio Emilia, Modena, Italy; 3University of Modena and Reggio Emilia, Modena, Italy; 4Department of Gastroenterology, University of Modena and Reggio Emilia, Italy; 5Radiology Unit, University of Modena and Reggio Emilia, Italy; 6Department of Medicine, Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal, Canada
Objective: The objective of the study was to investigate the contribution of liver steatosis and significant fibrosis alone and in association (evolutive NAFLD) with frailty in PLWH in order to optimize the estimation of biological age.
Methods: This was a cross-sectional study of consecutive patients attending Modena HIV Metabolic Clinic in 2018-2019. Patients with hazardous alcohol intake and HBV or HCV coinfection were excluded. Controlled attenuation parameter (CAP) and liver stiffness measurement (LSM) were evaluated by transient elastography. Liver steatosis was diagnosed by CAP as follows: S0 (no steatosis; CAP<248 dB/m), S1 (mild steatosis; 248≥CAP<268), S2 (moderate steatosis; 269≥CAP<280), S3 (severe steatosis; CAP≥280) dB/m. Liver fibrosis was diagnosed by LSM as follows: stage F0-F1 (mild fibrosis, LSM<7.1 kPa), F2-F3 (significant fibrosis, 7.1>LSM<13), F4 (cirrhosis, LSM>13 kPa). Evolutive NAFLD was defined as the contemporary presence of liver steatosis (CAP≥248) and significant liver fibrosis or cirrhosis (stage ≥F2). Frailty was assessed using 36-item frailty index (FI). FI was categorized as fit (<0.25), frail (0.25-0.4), most frail (>0.4). Logistic regression was used to explore frailty predictors using steatosis and evolutive NAFLD as covariates.
Results: We analysed 707 PLWH. Mean age was 53.5 (±8.2) years, 76.2% males, current median was CD4=700 μl (IQR=539-889), HIV viral load undetectable in 98.7%. Evolutive NAFLD was present in 10.2%; frail and most-frail in 18.9% and 3.9%, respectively. Evolutive NAFLD group had a higher prevalence of obesity, elevated waist circumference and BMI, lower HDL cholesterol levels, higher total and LDL cholesterol levels, longer HIV duration and lower CD4 nadir, current use of NNRTI (P<0.001). Univariate analysis demonstrated that neurocognitive impairment (OR=5.1, 1.6–15), vitamin D insufficiency (OR=1.94, 1.2–3.2), obesity (OR=8.1, 4.4–14.6), diabetes (OR=3.2, 1.9–5.6) and osteoporosis (OR=0.4, 0.2–0.8) were statistically significantly related to evolutive NAFLD. Predictors for FI were: age (OR=0.6, 0.4–0.9), steatosis (OR=2.1, 1.3–3.5) and fibrosis (OR=2, 1–3.7), evolutive NAFLD (OR=9.2, 5.2–16.8), diabetes (OR=1.7, 1–2.7), multi-morbidity (OR=2.5, 1.5–4).
Conclusions: Evolutive NAFLD increases the risk of frailty in PLWH by 9.2-fold and we may suggest it as an indicator of metabolic age. Liver steatosis alone was associated with frailty, implying that health-care interventions such as lifestyle changes, should be promoted in PLWH.
Abstract P37
Antiviral Therapy 2019; 24 Suppl 1:A90
Combined kidney–liver transplant in HIV-positive patients: Modena experience
G Dolci1, E Franceschini1, E Bacca1, I Franconi1, P Magistri2, M Codeluppi1, F Di Benedetto2, C Mussini1, G Guaraldi1
1Infectious Disease Clinic, University of Modena and Reggio Emilia; 2Liver and Multivisceral Transplant Centre, University of Modena and Reggio Emilia
Objective: To describe indication, survival and clinical outcomes of a case series of five combined liver–kidney transplants in HIV-infected patients.
Results: Since 2001 in the Liver and Multivisceral Transplant Centre of the Policlinico Modena Hospital, Italy, five combined liver–kidney transplants were performed in people living with HIV (PLWH).
Table 1 describes patients characteristics at transplantation and clinical outcomes at follow-up.
All patients were male, Caucasian and had an HIV-VL undetectable at LT.
Four patients had HCV-related cirrhosis and one of them had hepatocarcinoma. The other one had HBV and HDV-related cirrhosis.
Every patient had undetectable HIV viral load at transplant. HCV median viral load at transplant was 464,327 copies/mmc and all three alive patients with HCV obtained a sustained virological response (SVR) to HCV therapy after transplant.
Kidney transplant indication was HIV-associated nephropathy in three out of five patients, whereas the other two had focal glomerulosclerosis and mesangial proliferative glomerulonephritis, respectively. All the patients were on haemo-dialysis at the time of transplantation.
Four out of five patients are still alive with a median follow-up of 3,407 days. Patient number 2 died on post-transplant day 41 for a disseminated candidiasis with cerebral involvement.
Discussion: Contrary to previously published data, this case series describes a favourable clinical outcome in PLWH who received combined liver and kidney transplant.
Dedicated immunosuppression strategies, infection screening and prophylaxis were used in our case series. Infectious disease specialists, nephrologists, liver transplant surgeons, clinical pharmacologists and intensive care physicians need to work together in an interdisciplinary team to find shared strategies to manage the unique aspects of the combined kidney–liver transplant needs including fluids management in the immediate post-transplant period, induction immunosuppression and HCV therapy after transplant.
Our results could lead other transplant programmes to consider combined kidney–liver transplants as a reliable clinical option in PLWH with liver and kidney insufficiency.
(Abstract P37)
Patient 1
Patient 2
Patient 3
Patient 4
Patient 5
Age at SOT
50
54
48
38
49
LTx indication
HCC in HCV-related cirrhosis (genotype 4)
HCV-related cirrhosis (genotype 4a)
HCV-related cirrhosis (genotype 4)
HCV-related cirrhosis (genotype lb)
HBV/HDV-related cirrhosis
KTx indication
Focal glomerulosclerosis
Mesangial proliferative glomerulonephritis
HIVAN
HIVAN
First dialysis date
21/03/2008
24/09/2013
17/11/2009
13/05/2007
01/02/2011
SOT date
11/12/2009
25/10/2014
12/06/2010
20/10/2007
04/10/2013
MELD at SOT
21
24
21
28
22
Childpugh at SOT
B9
C10
B7
B9
B7
CD4 nadir
218
73
96
90
1
CD4 at SOT
601
329
135
308
110
ART at SOT
LPV+RTV
RAL+DRV+RTV
ABC+3TC+LPVr
3TC + ABC + ATV
3TC+fosAPV+RAL
Days in waiting list
331
121
88
135
288
Days of follow-up
1858
41
1675
2641
465
Hospital stay (days)
41
18
41
Induction IS
steroids+fk
steroids
Abstract P38
Antiviral Therapy 2019; 24 Suppl 1:A91
Incidence and prevalence of hepatitis C in two prospective studies of HIV pre-exposure prophylaxis adherence interventions in men who have sex with men in southern California
A Hassan1, G San Agustin2, R Kofron3, K Corado4, R Bolan5, W Jordan6, R Landovitz3, MP Dubé2, S Morris1
1University of California at San Diego, CA, USA; 2University of Southern California Keck School of Medicine, Los Angeles, CA, USA; 3University of California at Los Angeles, CA, USA; 4Harbor-UCLA Medical Center, Torrance, CA, USA; 5LA LGBT Center, Los Angeles, CA, USA; 6OASIS Clinic, Charles R. Drew University of Medicine and Science, Los Angeles CA, USA
Objectives: There is concern that increased risk behaviour during HIV pre-exposure prophylaxis (PrEP) will be associated with increased incidence of hepatitis C virus (HCV) infection in men who have sex with men (MSM). We sought to establish the prevalence of HCV prior to PrEP in a high-risk cohort of MSM and transgender women (TGW) to determine the incidence of HCV seroconversion during PrEP.
Methods: Participants were 603 MSM and 2 TGW at high risk of acquiring HIV infection who all received daily PrEP with tenofovir disoproxil fumarate-emtricitabine (TDF-FTC) and had available paired specimens from two parallel, prospective, 48-week studies conducted in southern California. These were a randomized trial of text messaging for PrEP adherence (CCTG 595) with 395 participants enrolled from February 2013 to February 2015, and a longitudinal strategy study of real-time plasma tenofovir levels to support PrEP adherence (PATH-PrEP) with 301 participants enrolled from April 2014 to July 2016. Routine screening for rectal, urethral, and pharyngeal gonorrhea and chlamydia as well as syphilis was done at regular intervals in both studies. Paired specimens were obtained at entry and week 48. HCV antibodies were assayed at week 48 in all participants. For those with positive week 48 antibodies, the entry specimen was also assayed.
Results: Four participants (prevalence 0.66%) had HCV antibodies detected at week 48. All four were also seropositive at entry. Thus, zero incident HCV cases were detected during the study period. Risk factors for HCV seropositivity at entry included greater age (median 53 years HCV+ versus 37 years HCV-; P=0.001, two sample t-test), lower education level (P<0.001, Fisher's exact test), and lower PrEP adherence estimated by dried blood spot tenofovir levels (P=0.029, Fisher's exact test). Incident sexually transmitted infections (STI) were common among participants in both studies: 47.5% were diagnosed with a new bacterial STI in CCTG 595 and 46.4% in PATH-PrEP.
Conclusions: Among early PrEP adopters engaged in clinical trials, the prevalence of HCV antibodies was modest. Incident HCV did not occur during the study period, despite ongoing risk behaviour and a high incidence of STI. These results suggest that daily TDF-FTC PrEP in MSM/TGW is not associated with increased risk of acquiring HCV in this setting.
