PrEP Trial Research Articles

P2.04A.06 A Multilevel Approach to Address Disparities in Lung Cancer Screening: The PREP Trial

P2.04A.06 A Multilevel Approach to Address Disparities in Lung Cancer Screening: The PREP Trial

Pharmacologic Drug Detection and Self-Reported Adherence in the HPTN069/ACTG5305 Phase II PrEP Trial

Adherence drives efficacy in PrEP clinical trials. We compared drug concentrations and self-reported adherence in HPTN069/ACTG5305, a double-blinded, randomized trial of the safety and tolerability of candidate PrEP regimens that included maraviroc (MVC), tenofovir (TDF), and emtricitabine (FTC). Plasma drug concentrations and self-reported adherence by computer-assisted self-interview (CASI) were assessed at study weeks 24 and 48. Descriptive statistics and a generalized linear model were used to assess the association between selected demographic factors, self-report of daily medication adherence and plasma drug concentrations consistent with daily adherence. Among 718 paired observations from 370 participants, 43% (306/718) reported daily adherence by CASI, 65% (467/718) had drug concentrations consistent with daily adherence and 11% (81/718) had CASI responses that reported daily adherence despite having drug concentrations consistent with less-than-daily adherence. In adjusted analyses, participants who were assigned male at birth (aOR 1.42 [95% CI 1.02, 1.97]), older (5-year increments aOR 1.10 [95% CI 1.09, 1.11]), White (aOR 2.2 [95% CI 1.88, 2.56]), had advanced education (aOR 3.89 [95% CI 2.97, 5.09]), were employed (aOR 1.89 [95% CI 1.50, 2.40]), or partnered/married (aOR 2 [95% CI 1.72, 2.32]) were more likely to have drug concentrations consistent with daily adherence. Participants who were not employed (aOR 2.7 [95% CI 1.31, 5.55]) or who were single/not partnered (aOR 2.33 [CI 95% 1.25, 4.34]) were more likely to have drug concentrations that did not reflect daily adherence despite self-reported PrEP adherence. These findings support the need for ongoing adherence counseling in clinical trials of new PrEP regimens.

Optimal antiseptic skin preparation agents for minimizing surgical site infection following surgery: cost and cost-effectiveness analysis.

The application of antiseptic skin agents prior to incision minimizes the rate of surgical site infection. Despite their ubiquity, the optimal skin preparation agent remains uncertain. A retrospective economic analysis was conducted to complement the results from the NEWSkin Prep trial which prospectively compared three preparation agents. A cost and cost-effectiveness analysis was performed from a healthcare service perspective to compare chlorhexidine with 70% ethanol, and aqueous povidone-iodine, against povidone-iodine with 70% ethanol. Resource use estimates accounted for hospital admissions, readmissions associated with surgical site infection, outpatient and general practitioner attendances, visits from community nurses and therapeutic consumables. The measure of effectiveness comprised the net difference in number of patients with surgical site infections per 1000 patients. Costs were compared using a two-sample Welch's t-test. Deterministic and probabilistic sensitivity analyses were performed to evaluate the incremental cost-effectiveness ratio. The null hypothesis that the mean costs for the trial arms were significantly different was not rejected (Welch's t-test P value: 0.771 for chlorhexidine with 70% ethanol against povidone-iodine with 70% ethanol; and 0.955 for aqueous povidone-iodine against povidone-iodine with 70% ethanol). Based on bootstrap averages, the chlorhexidine with 70% ethanol intervention generated 8.0 fewer surgical site infections per 1000 patients and net cost savings of €151,698 (Euros) per 1000 patients compared with povidone-iodine with 70% ethanol, and aqueous povidone-iodine produced a net cost saving of €37,494 per 1000 patients but generated an additional 11.6 surgical site infections per 1000 patients compared with povidone-iodine with 70% ethanol. The comparison of chlorhexidine with 70% ethanol to povidone-iodine with 70% ethanol was sensitive to the inclusion of cost outliers, while the comparison of aqueous povidone-iodine to povidone-iodine with 70% ethanol was sensitive to the estimated cost per surgical site infection. Based on the outcomes from the NEWSkin Prep study, this economic analysis found no definitive evidence in favour of any one of the study comparators. Future model-based economic analyses of alternative skin preparations should critically address the quality of evidence and integrate the results from the NEWSkin Prep study.

Patterns of PrEP continuation and coverage in the first year of use: a latent class analysis of a programmatic PrEP trial in Kenya.

Effective PrEP use is critical for impact, but data are limited on common patterns of continuation and coverage among persons using PrEP in real-world settings. Data are from the Partners Scale-Up Project, a programmatic stepped-wedge cluster-randomized trial to integrate PrEP delivery in 25 Kenyan public health facilities conducted between February 2017 and December 2021. We evaluated PrEP continuation using visit attendance and pharmacy refill records, and computed medication possession ratio to define coverage during the first year of use. Latent class mixture models were used to identify and characterize membership to different PrEP continuation patterns. Multinomial logistic regression was used to examine the association between group trajectories and demographic and behaviour characteristics. Overall, 4898 persons initiated PrEP, 54% (2640) were female, mean age was 33 years (standard deviation 11) and 84% (4092) had partners living with HIV. PrEP continuation was 57%, 44%, and 34% at 1, 3, and 6 months, respectively. Four unique trajectories of PrEP coverage were identified: (1) one-fourth (1154) exhibited consistent high coverage throughout the year with 93%, 94%, 96%, and 67% continuing PrEP at months 1, 3, 6, and 12, respectively; (2) 13% (682) showed high coverage trajectory throughout 6 months but coverage rapidly declined thereafter (94%, 93%, 63%, and 10% continued at months 1, 3, 6, and 12, respectively); (3) 18.9% (918) exhibited moderate coverage trajectory with 91% of clients refilling PrEP at month 1 but nearly all dropped-off thereafter (37%, 5%, and 4% continued at months 3, 6, and 12, respectively); and (4) 43.8% (2144) exhibited immediate discontinuation trajectory, in which nearly all did not have any subsequent PrEP refill. Overall, being female, older age, having partners living with HIV or of unknown HIV status were statistically associated with better PrEP continuation trajectories compared to the immediate discontinuation trajectory (p <0.05 for all). In this analysis of a real-world PrEP implementation programme in Kenya, we found four distinct patterns of PrEP continuation, with one-third of users exhibiting consistent high continuation throughout 12 months and two-fifths with immediate discontinuation patterns. These data may help guide tailored interventions to support PrEP continuation in this setting.

O067 Vessel prep trials – real life or alternative reality?

Abstract Introduction During the last ten years there have been two notable studies within vessel preparation for peripheral vascular disease; the DEFINITIVE AR prospective multi-centre randomised study (evaluating the use of atherectomy prior to drug-eluting balloon catheters (DCB)) and the DISRUPT PAD III randomized control trial (evaluating the use of intravascular lithotripsy (IVL)). This study aimed to analyse a true cohort of vascular patients who underwent vessel prep and whether this reflects those included in the studies. Methods Data were collected on patients with SFA disease in 14 countries across 17 centres. We applied the inclusion criteria for the DEFINITIVE AR and DISRUPT PAD III studies to our cohort. Results Data were collected on n=974 patients who received at least one form of vessel prep. Of these patients, 202 (20.7%) underwent atherectomy and 22 (2.26%) underwent lithotripsy. 50.1% (n=103) of those who underwent atherectomy would have been eligible to participate in the DEFINITVE AR study. 18% (n=4) of patients who underwent lithotripsy would have been eligible to participate in the DISRUPT PAD III trial. Conclusion Both the DEFINITIVE AR and DISRUPT PAD III trials have shown promising results however in this large multicentre study we have shown that the study participants reflect only a small percentage of the patients seen within a real vascular ward. We would advise caution when interpreting the results from these studies considering the disparity we have shown between the study cohorts and the real life vascular population.

2079. Comparison of Recency Assays to Estimate HIV Incidence in the SIENA (eStimating hIv incidEnce amoNg Agyw) Study in Uganda

Abstract Background HIV-1 recent infection testing algorithms (RITAs) use recency assays to estimate population level HIV incidence rates (IRs), and are currently being employed in PrEP trials to estimate background HIV incidence rates (bHIV-IR). The SIENA study was conducted to determine the HIV incidence rate among young women in and around central and mid-western Uganda, and to assess the suitability of different recency assay platforms for use in determining bHIV-IR in future PrEP trials. Methods Diagnosis of HIV was confirmed by positive results on both the Alere Determine HIV-1/2 and Oraquick HIV-1/2 rapid tests. Positive samples were analyzed for recent infection using the Sedia HIV-1 Limiting Antigen Avidity Enzyme ImmunoAssay (LAg-EIA; Sedia Biosciences, Beaverton, OR) and the Sedia Asante HIV-1 Rapid Recency Assay (Asante; Sedia Biosciences). The Asante assay was performed by electronic reader (Asante-Reader) or visual read (Asante-Visual). VL was determined by COBAS TaqMan HIV-1 Test (LabCorp, Indianapolis, IN). HIV incidence was calculated based on previously determined MDRI and FRRs that were specific for the study population. Results Of 743 women screened, 191 were diagnosed with HIV, of whom 44 (23%) had a viral load of &amp;lt; 75 copies/mL. The 3 recency assays identified between 43 and 57 samples as recent and between 35 and 37 samples when the VL cutoff of &amp;lt; 75 copies/mL was used (Table). When no VL cutoff was used the calculated bHIV-IR was 17.9/100 person-years (PY) for the LAg-EIA, 12.8/100PY for the Asante-Reader and 20.3/100PY for the Asante-Visual. Using the VL cutoff, the calculated bHIV-IR was 11.4/100 PY with the LAg-EIA assay and 10.9/100 PY with the Asante-Reader. No MDRI or FRR for the Asante-Visual with a VL cutoff was available for calculation of the Asante-Visual HIV incidence. Conclusion When the RITA included a VL cutoff of 75 cp/mL, the LAg-EIA and Asante assays classified the number of recent and long-term infections similarly, resulting in comparable bHIV-IR results. Overall, these analyses support the use of these recency assays in the RITA to estimate the bHIV-IR in future PrEP trials. Our results demonstrate extremely high prevalence and incidence of HIV in young women in central and mid-western Uganda, highlighting the need for expanded HIV prevention options in these areas. Disclosures Stephanie Cox, BS, Gilead Sciences: Paid employee|Gilead Sciences: Stocks/Bonds Shelley N. Facente, PhD, MPH, CDC-funded TRACE program: Grant/Research Support|Gilead Sciences: Advisor/Consultant|Sedia Biosciences Corporation: Grant/Research Support Eduard Grebe, PhD, CDC-funded TRACE program: Grant/Research Support|Gilead Sciences: Advisor/Consultant|Sedia Biosciences Corp: Grant/Research Support Ramin Ebrahimi, MS, Gilead Sciences: Paid employee|Gilead Sciences: Stocks/Bonds Christoph C. Carter, MD, PhD, Gilead Sciences: Employee|Gilead Sciences: Employee|Gilead Sciences: Stocks/Bonds|Gilead Sciences: Stocks/Bonds Christian Callebaut, PhD, Gilead Sciences: Paid employee|Gilead Sciences: Stocks/Bonds Jared Baeten, MD, PhD, Gilead Sciences: Employee|Gilead Sciences: Stocks/Bonds Moupali Das, MD, Gilead Sciences: Employee|Gilead Sciences: Employee|Gilead Sciences: Stocks/Bonds|Gilead Sciences: Stocks/Bonds.

Is tenofovir disoproxil fumarate associated with weight loss?

Recent clinical trials have shown weight gain associated with newer antiretrovirals. It is unclear how the nucleoside reverse transcriptase inhibitor backbone affects weight. Recent evidence suggests greater weight gain with tenofovir alafenamide (TAF) compared with tenofovir disoproxil fumarate (TDF). However, it is not fully understood whether TDF contributes to weight suppression. A systematic search of PubMed, Embase and clinicaltrials.gov was conducted to identify all randomized control trials comparing TDF/FTC or TDF to control in HIV-negative individuals. The primary endpoint included the number of events of 5% weight loss. Mantel-Haenszel test with random-effects modelling was used to calculate the odds ratio (OR) and 95% confidence intervals (95% CI). Further analyses of gastrointestinal (GI) adverse events were also undertaken. Seven PrEP trials: PARTNERS, VOICE, TDF-2, Bangkok PrEP, iPrEX, FEM-PrEP and HPTN 084 were included in the analysis of weight loss, with a total sample size of 19 359. One study (HPTN 084) compared TDF/FTC to cabotegravir (CAB). HIV-negative individuals taking TDF were more likely to experience weight loss compared with control [odds ratio (OR) 1.44; 95% CI 1.12-1.85; P = 0.005). Exposure to TDF was also linked to greater odds of vomiting (OR 1.81; 95% CI 1.20-2.73; P < 0.005). There were no increased odds of nausea, diarrhoea or loss of appetite. There is evidence in HIV-negative individuals that TDF may be associated with weight loss. Further research should be carried out in HIV-positive individuals, and clinical trials of TDF/FTC should publish weight data to widen the evidence base.

882. Use of Tenofovir Disoproxil Fumarate Shows Weight Loss vs Placebo: A Meta-Analysis of 7 Clinical Trials in 19,359 HIV-negative Individuals

Abstract Background Recent clinical trials have shown weight gain associated with newer antiretrovirals. It is unclear how the nucleoside reverse transcriptase inhibitor backbone affects weight. Recent evidence suggests greater weight gain with tenofovir alafenamide (TAF) compared to tenofovir disoproxil fumarate (TDF). However, it is not fully understood whether TDF contributes to weight suppression or weight loss. Methods A systematic search of PubMed, Embase and clinicaltrials.gov was conducted to identify all randomised control trials comparing TDF/FTC or TDF to control in HIV-negative individuals. The primary endpoint included the number of events of ‘5% weight loss’ or ‘abnormal loss of weight’. The Mantel-Haenszel test with random-effects modelling was used to calculate the odds ratio (OR) and 95% confidence intervals (95% CI). Further analyses of gastrointestinal (GI) adverse events (AEs) were undertaken, including the number of reported adverse events of nausea, vomiting, loss of appetite and diarrhoea. Results Seven PrEP trials: PARTNERS, VOICE, TDF-2, Bangkok PrEP, iPrEX, FEM-PrEP and HPTN 084 were included in the analysis of weight loss, with a total sample size of 19,359. One study (HPTN 084) compared TDF/FTC to cabotegravir (CAB). The remaining compared either TDF or TDF/FTC or placebo. HIV-negative individuals taking TDF were more likely to experience weight loss compared to control (OR 1.44 95% CI 1.12 – 1.85 p = 0.005 (table 1)). In a separate analysis of GI AEs, exposure to TDF was also linked to greater odds of vomiting (OR 1.81 95% CI (1.20, 2.73) p &amp;lt; 0.005). There were no increased odds of nausea, diarrhoea, or loss of appetite. Weight loss events in PrEP trials. Conclusion There is evidence in HIV-negative individuals that TDF may be associated weight loss when compared to placebo. Further research should be carried out in HIV positive individuals, and clinical trials of TDF/FTC should publish weight data to widen the evidence base Disclosures All Authors: No reported disclosures

Barriers and Facilitators to Participation in Long-Acting Injectable PrEP Research Trials for MSM, Transgender Women, and Gender-Nonconforming People of Color.

We collected 216 responses from sexually active MSM, transgender women, and gender-nonconforming (GNC) people of color through a web-based survey to understand the facilitators and barriers to research participation in a hypothetical LAI PrEP trial. In adjusted models, these items were found to be significantly associated with research participation likelihood: ever participated in HIV research study; comfort with taking daily pill; comfort with providing urine sample; and concerns over potential side effects of shot. Asian participants were more concerned about others knowing they were being recruited than were Black and Latinx respondents F(2, 216) = 3.98; p < .05. Asian respondents were also less comfortable with being recruited at organizations serving communities of color than Black and Latinx respondents, F(2, 216) = 5.10; p < .05. Cisgender respondents were more comfortable with being recruited by a friend or colleague than were transgender/GNC respondents, F(1, 215) = 4.8; p < .05.

999. Using the F/TDF Adherence-Efficacy Relationship to Calculate Background HIV incidence: Results from the DISCOVER trial

BackgroundRRandomized trials of new PrEP agents compare to oral emtricitabine+tenofovir disoproxil fumarate (F/TDF) and do not have a placebo arm. We used the well-characterized adherence-efficacy relationship for F/TDF from iPrEX OLE, to back-calculate the (non-PrEP) background HIV incidence (bHIV) in the F/TDF arm of DISCOVER and estimate comparative efficacy (to bHIV).MethodsTDISCOVER is an ongoing randomized active-controlled trial in 5,387 men who have sex with men and transgender women that demonstrated non-inferiority of F+tenofovir alafenamide (F/TAF) to F/TDF (IRR 0.47 (95% CI 0.19, 1.15). TFV-DP levels in DBS were assessed for all diagnosed with HIV and in a randomized subset of 10%. We used a Bayesian model with a prior distribution, derived from iPrEx OLE, relating TFV-DP levels to HIV prevention efficacy: eg TFV-DP levels of < 350 (low), 350 to < 700 (medium) and ≥700 (high) fmol/punch were assumed to provide 0%, 86% and 98% HIV protection, respectively. This prior, combined with F/TDF seroconversion rate and TFV-DP levels, yields Bayesian inferences on the bHIV. In R, STAN was used to sample 10,000 realizations from the posterior distribution.ResultsThere were 6 vs. 11 post-baseline HIV infections (0.14 v. 0.25 per 100 person-years [PY]) on F/TAF and F/TDF. Of the 11 on F/TDF, 10 had low, 0 had medium, and 1 had high TFV-DP levels; among HIV-negative controls, 5% of the person-time had low, 9% had medium, and 86% had high TFV-DP levels. A non-informative prior distribution for bHIV, combined with the prior for TFV-DP level-efficacy relationship, yielded a posterior bHIV incidence [0.80 Bayesian credible interval (CrI)] of 3.4/100 [1.9, 6.0/100] PY; which suggests a median F/TAF efficacy [0.95 CrI] of 96% [88%,99%] and 93% [87%,96%] for F/TDF compared to bHIV. If we chose a conservative prior distribution for bHIV of 1.0/100 PY, the model yields a median posterior bHIV [0.80 CrI] of 2.8/100 [1.7, 4.7/100] PY; which suggests a median efficacy [0.95 Cr] of 95% [86%, 99%] for F/TAF and 92% [86%, 67%] for F/TDF compared to bHIV with corresponding number of HIV infections averted of 117 and 114, respectively (Figure).Figure. ConclusionThe F/TDF adherence-efficacy relationship can be used to back-calculate bHIV incidence in MSM/TW PrEP trials and assess the efficacy of new PrEP agents compared to bHIV.Disclosures David V. Glidden, MD, Gilead Sciences Inc. (Other Financial or Material Support, Personal fees) David T. Dunn, MD, Gilead Sciences Inc. (Other Financial or Material Support, Personal fees)Viiv Healthcare (Other Financial or Material Support, Personal fees) Moupali Das, MD, Gilead Sciences Inc. (Employee, Shareholder) Ramin Ebrahimi, MSc, Gilead Sciences Inc. (Employee, Shareholder) Lijie Zhong, PhD, Gilead Sciences Inc. (Employee, Shareholder) Oliver T. Stirrup, MD, Gilead Sciences Inc. (Other Financial or Material Support, Personal fees) Peter L. Anderson, PharmD, Gilead Sciences Inc. (Other Financial or Material Support, Personal fees)

Early diagnosis and risk factors of acute hepatitis C in high-risk MSM on preexposure prophylaxis

A high incidence of acute hepatitis C virus (HCV) (AHCV) infection has been reported among at-risk HIV-negative MSM. The optimal strategy for early diagnosis of AHCV in this population is not clearly defined. In the ANRS IPERGAY PrEP trial, among high-risk HIV-negative MSM, HCV serology and serum alanine aminotransferase (ALT) were used for screening at enrollment and during follow-up. Behavioral risk factors were compared at baseline between participants who were diagnosed with AHCV during the study compared with those who did not. In participants with a positive HCV serology, we used stored sera to perform the following tests at diagnosis and on previous visits: HCV-antibodies rapid tests, plasma HCV viral load and HCV antigen immunoassay. We evaluated the sensitivity of each test for AHCV diagnosis. Among 429 enrolled participants, 14 were diagnosed with AHCV infection, with a median follow-up of 2.1 (interquartile range, 1.5-2.8) years. AHCV incidence was 1.40 per 100 person-years (95% confidence interval, 0.74-2.39). Patients with AHCV reported a significantly higher number of sexual acts and/or partners, and more frequent recreational drug use at baseline. At the prior visit before AHCV diagnosis (median of 2 months earlier), sensitivities of HCV RNA and HCV antigen tests were, respectively, 100 and 89%, whereas none of the patients had a positive serology, and only 25% had elevated ALT. HCV antigen and RNA tests were positive within a median of 2 months before the detection of antibodies and ALT elevation. These tests could be considered for HCV screening in high-risk MSM.

HIV prevention clinical trials’ community engagement guidelines: inequality, and ethical conflicts

ABSTRACT In 2004 and 2005, the first clinical trials were launched to investigate the use of tenofovir for HIV prevention in Cambodia, Cameroon, Nigeria and Thailand. Controversies erupted over the ethical integrity of the research protocol. We reflect on the events that led to the controversies and identified that scientific and ethical concerns raised by members of local communities at each of these sites were erased by trialists, causing crisis that led to premature shut down the early PrEP trials. In the aftermath of these trials, the World Health Organisation, UNAIDS, and AVAC developed ethics guidelines intended to recognize the concerns as authentic, and developed guidelines to improve researchers’ engagement of communities in biomedical HIV prevention trial design and implementation. Our findings suggest that the ethics guidelines are limited in its ability to address power inequalities that leads to voice erasures and non-recognition of local competencies. Rather the ethical documents enabled trialists to gain a new sense of authority through the interpretations of ethical research conduct enabling trialists regain power that can further entrench inequality and voice erasures. To address concerns with what seems an intractable problem, we suggested models of engagement for off-shored research may be the option.

1288. Bone Safety Outcomes with F/TAF vs. F/TDF for PrEP in the DISCOVER Trial

BackgroundIn the DISCOVER PrEP trial, emtricitabine/tenofovir alafenamide (F/TAF) was noninferior to emtricitabine/tenofovir disoproxil fumarate (F/TDF) for HIV prevention. Here we report the bone safety outcomes of F/TAF and F/TDF.MethodsMen who have sex with men (MSM) and transgender women (TGW) at risk of HIV were randomized 1:1 to receive blinded F/TDF or F/TAF, taken once daily. Those on PrEP with F/TDF were eligible to enroll. Bone densitometry (DXA) of the hip and spine were performed in a subset of participants (BMD subset). Fracture events were compared in all study participants. Week 48 data are presented.Results5387 participants were enrolled in the main study, with 383 included in the BMD subset. In the BMD subset, the median age was 37 (IQR 29, 46); 0.8% were TGW, 9.4% were black, and 20.6% were Hispanic or Latinx. Fifty-three BMD subset participants were on baseline F/TDF PrEP at enrollment, 26 of whom were randomized to F/TAF. F/TAF was associated with more favorable changes in hip and spine BMD compared with F/TDF (Table 1); these differences were similar when participants on baseline PrEP were excluded. Participants age <35 on F/TAF gained BMD, whereas those on F/TDF lost BMD (Table 1). BMD decreases of ≥3% were less frequent in the F/TAF group than the F/TDF group at the hip (3.8% vs. 18.4%, P < 0.001) and spine (10.1% vs. 26.9%, P < 0.001). Osteopenia was more frequently diagnosed in the spine in participants on F/TDF compared with F/TAF (Figure 1, P = 0.007); but not in the hip. Fracture event frequency was the same (53 [2.0%] per group, P = 1.00). One pathological fracture was reported in the F/TAF group compared with two in the F/TDF group (P = 0.57). In participants on baseline F/TDF PrEP, those randomized to F/TAF had significantly improved hip BMD compared with baseline (median percent change 1.13 [IQR −0.86, 3.47], P = 0.027), while spine BMD was unchanged.ConclusionThrough 48 weeks, DXA subset participants taking F/TAF for PrEP had significantly less change in BMD than those taking F/TDF, and were less likely to develop spine osteopenia. The incidence of fracture was similar, and pathological fractures were rare. F/TAF for PrEP is effective and has a superior bone safety profile compared with F/TDF. Disclosures All authors: No reported disclosures.

1962. Renal Outcomes for Participants Taking F/TAF vs. F/TDF for HIV PrEP in the DISCOVER Trial

BackgroundIn the DISCOVER PrEP trial, emtricitabine/tenofovir alafenamide (F/TAF) was noninferior to emtricitabine/tenofovir disoproxil fumarate (F/TDF) for HIV prevention. Here, we report on the renal outcomes of F/TAF and F/TDF among all DISCOVER participants and in those on baseline F/TDF PrEP who were randomized to F/TAF.MethodsIn total, 5387 men who have sex with men (MSM) and transgender women (TGW) at risk for HIV were randomized 1:1 to receive blinded F/TDF or F/TAF taken once daily (full cohort). Of these, 905 were on F/TDF PrEP at enrollment; of whom, 465 were randomized to F/TAF. Renal function and safety assessments included urinalysis (UA), estimated glomerular filtration rate (eGFRCG), urine protein:creatinine (Cr) ratio (UPCR), markers of proximal tubular function (β2-microglobulin:Cr ratio [β2M:Cr] and retinol-binding protein:Cr ratio [RBP:Cr]) and investigator-reported renal adverse events (AEs). Week 48 data are presented.ResultsIn the full cohort, F/TAF was associated with more favorable changes in eGFRCG, β2M:Cr, and RBP:Cr compared with F/TDF (Table 1). Treatment-emergent proteinuria by UA was more common with F/TDF than F/TAF (24.3% vs. 21.3% P = 0.009), as were treatment-emergent elevations in UPCR >200 mg/g (35 [1.5%] vs. 16 [0.7%], P = 0.005). Compared with F/TDF, participants taking F/TAF had numerically fewer study drug-related renal AEs, severe study drug-related renal AEs, and discontinuations due to renal AEs (Table 2). Proximal renal tubulopathy (Fanconi syndrome) was reported in one participant in the F/TDF arm and none in the F/TAF arm. In participants on F/TDF PrEP at enrollment who were randomized to F/TAF, statistically significant increases in eGFRCG were apparent as early as week 4 (Table 1 and Figure 1), as were decreases in tubular proteinuria (Table 1). Renal biomarker changes in PrEP-naïve participants mirrored those in the full cohort.ConclusionThrough 48 weeks, MSM and TGW taking F/TAF for PrEP had significantly better measures of renal function and fewer study-drug-related renal AEs compared with those taking F/TDF; switching from F/TDF to F/TAF was associated with improvements in eGFRCG and tubular function biomarkers. F/TAF for PrEP is effective and has a superior renal safety profile compared with F/TDF. Disclosures All Authors: No reported Disclosures.

BHIVA/BASHH guidelines on the use of HIV pre-exposure prophylaxis (PrEP) 2018.

We aim to provide evidence-based guidance on best clinical practice in the provision, monitoring and support of pre-exposure prophylaxis (PrEP) for the prevention of HIV acquisition. The guidelines include: (i) Guidance on risk assessment prior to PrEP; (ii) Baseline assessment; (iii) Dosing schedules; (iv) Monitoring; (v) Supporting adherence; (vi) Buying generic PrEP; and (vii) Cost-effectiveness. The guidelines are aimed at clinical professionals directly involved in, and responsible for, HIV prevention, and at community advocates and organisations responsible for supporting HIV prevention strategies in those at risk of HIV acquisition. A detailed review of the evidence base is included in Section 4. Sections 5 to 7 are intended to offer practical guidance in risk assessment, starting PrEP, ongoing management while on PrEP and stopping PrEP.

More than a quarter of sexual health clinics closed to new PrEP trial places

More than a quarter of sexual health clinics closed to new PrEP trial places

NHS England offers to fund doubling of PrEP trial

NHS England offers to fund doubling of PrEP trial

Expanded PrEP trial places to be opened soon, NHS England confirms

Expanded PrEP trial places to be opened soon, NHS England confirms

Ethics and HIV prevention research: An analysis of the early tenofovir PrEP trial in Nigeria.

In 2004, the first ever multi-sited clinical trials studied the prospect of HIV biomedical prevention (referred to as pre-exposure prophylaxis-'PrEP'). The trials were implemented at several international sites, but many officially closed down before they completed. At most sites, both scientists and community AIDS advocates raised concerns over the ethics and scientific rationales of the trial. Focusing on the Nigerian trial site, we detail the controversy that emerged among mostly Nigerian research scientists who scrutinized the research design and protocol. While some of the disputes, especially those pertaining to community engagement mechanisms, were ultimately resolved in international fora and implemented in later PrEP trials, concerns over science rationales and assumptions were never addressed. We argue that scientific rationales should be treated as ethical concerns and suggest that such concerns should be deliberated at host sites before the trial protocol is finalized.

Development and Validation of an Immunoassay for Tenofovir in Urine as a Real-Time Metric of Antiretroviral Adherence

BackgroundPharmacologic adherence measures were critical to the interpretation of the tenofovir (TFV)-disoproxil-fumarate/emtricitabine (TDF/FTC) PrEP trials. These measures are being incorporated into PrEP demonstration projects, but currently-available metrics in plasma, cells, hair or urine involve expensive and time-intensive mass-spectrometry (MS)-based methods. No point-of-care method to assess PrEP adherence in real-time has yet been implemented. Antibody-based tests allow for low-cost, easy-to-perform, point-of-care drug detection. In this study, we developed an antibody-based TFV immunoassay and evaluated its test characteristics among individuals taking TDF/FTC. MethodsWe synthesized possible immunogens based on TFV's molecular structure, injected rabbits with the conjugated derivatives, and bled them monthly for subsequent ELISA-testing for TFV-specific antibodies. We purified an antibody with specific TFV binding and created dose–response curves for ELISA-quantification. We then quantified TFV in urine from human participants not taking TDF/FTC and from individuals taking daily TDF/FTC 300 mg/200 mg for 7 days with a 7-day washout period using ELISA with this TFV-specific antibody. ELISA results were compared with the gold-standard test for TFV detection/quantification using liquid-chromatography-tandem-MS (LC–MS/MS). FindingsNone of the urine samples from 115 participants not taking TDF/FTC showed ELISA- reactivity, indicating 100% specificity (95% CI 97–100%) of the immunoassay. Among participants taking TDF/FTC, 67 of 70 samples positive by LC–MS/MS were positive by the ELISA-immunoassay for an estimated diagnostic sensitivity of 96% (95% CI 88–99%). The precision of the assay was high (coefficient of variation<15%). The rank correlation between ELISA and LC–MS/MS values in the 70 quantitative urine TFV levels positive by LC–MS/MS across a wide range of concentrations among participants on TDF/FTC was high (r = 0.96). InterpretationOur antibody-based immunoassay for measuring TFV in urine performed well compared to the gold-standard of LC–MS/MS among individuals taking TDF/FTC. A sensitive and specific immunoassay paves the way for real-time monitoring/feedback on recent adherence to TFV-based regimens, which should optimize interpretation and outcomes during PrEP and ART roll-out. FundingNIAID/NIH 2R01AI098472.