CROI 2020 Abstract eBook

Abstract eBook

Poster Abstracts

Methods: Participants enrolled in the EPIC-NSW study with baseline eGFR≥60 ml/min/1.73m 2 , more than one PrEP dispensing visit between 1 March 2016 and 30 April 2018, and no recorded history of prior PrEP were included. Patients without eGFR monitoring during this period were excluded. Risk of renal impairment (defined as average eGFR of two consecutive tests <60) was estimated using the Kaplan-Meier method. Cox proportional hazards models stratified by study site were used to compare risk factors including baseline eGFR (60-90, ≥90), age (<40, 40-49, ≥50), sex, recreational drug use, and HBV and HCV infection status. Time-updated PrEP medication possession ratio (MPR) was included as a binary independent covariate (<0.95, ≥0.95). Significant covariates (p<0.05) were included in a multivariate model. Results: Of 9,596 participants dispensed PrEP, 4,514 met the inclusion criteria for this analysis. Most were aged <50 (88%), male (99%), and had baseline eGFR ≥90 (76%). Baseline eGFR<90 was observed in 55% of participants aged ≥50 compared to 20% aged <50 (p<0.001). The observed rate of renal impairment was 8.0/1,000 person-years (95%CI: 5.86-10.99) over 4,859 person-years follow-up, with two-year cumulative risk of 1.7% (95%CI: 1.11-2.70) (Figure 1). Renal impairment was highest in patients aged ≥50 at 44.7/1,000 person-years (95%CI: 30.65-65.16) and two-year cumulative risk of 8.3% (95%CI: 5.35-12.69). The rate of renal impairment was also increased in participants with baseline eGFR<90 (32.0/1,000 person-years [95%CI: 23.20-44.20]) and with MPR≥0.95 (11.2/1,000 person-years, [95%CI: 7.95-15.72]). A multivariate model showed increased risk associated with age ≥50 compared to <40 (HR: 12.9 [95%CI: 4.31-38.58], p<0.001) and baseline eGFR <90 (HR: 25.6 [95%CI: 5.99-109.18], p<0.001) after adjustment for MPR (HR: 2.3 [95%CI: 0.96-5.68], p=0.060). Conclusion: In a large real-world PrEP cohort, risk of renal impairment increased over two years of PrEP, with older patients and those with pre-existing renal dysfunction at significantly higher risk.

1 Southern California Men's Medical Group, Los Angeles, CA, USA, 2 University of California San Francisco, San Francisco, CA, USA, 3 Tarrant County Infectious Disease Associates, Fort Worth, TX, USA, 4 University of Colorado, Aurora, CO, USA Background: Failure on PrEP with emtricitabine (FTC)/tenofovir (TFV) disoproxil fumarate (TDF) can occur from poor adherence or acquisition of resistant virus. Here, we describe a case of seroconversion on PrEP with resistant virus but 100% self-reported adherence, with objective adherence metrics providing clues to the timing of viral resistance. Methods: History was obtained from patient and records. PrEP adherence was assessed via self-report, TFV-diphosphate (TFV-DP) levels in dried blood spots (DBS) collected at seroconversion, and measuring TFV/FTC levels with segmental hair analysis. Genotypic resistance was evaluated. Results: A 44 year-old Latino MSM started daily FTC/TDF on 12/15/17 after a non-reactive HIV antibody (Ab) and confirmatory test on 12/14/17. He reported 100% adherence to FTC/TDF since PrEP initiation with zero missed doses. HIV antigen (Ag)/Ab test was negative x 4 in 2018, 1/15/19, 4/9/19, but indeterminate on 6/10/19. HIV RNA level was 146,000 cps/ml on 6/17/2019 and 2-drug PrEP was switched to 3-drug ART (BIC/TAF/FTC) that day. Viral genotyping 6/17/19 showed an M184V and a TAM (K70N) mutation in the reverse transcriptase (RT) gene, with no TDF-associated mutations or significant mutations in the protease or integrase genes. DBS collected on 6/17/2019 showed a TFV-DP level of 1683 fmol/punch, consistent with high (7 doses/wk) adherence over the past ~6 weeks. A hair sample (~4 cm) was collected that day and, to evaluate adherence over preceding months, segmental analysis of TFV/FTC levels was performed in 1 cm segments from the scalp. Hair drug levels were consistent with high PrEP adherence over the preceding 2 months, but lower PrEP adherence (<4 doses/wk) from~mid-Feb to ~mid April 2019 when he reported 4 new partners (Figure). Conclusion: Seroconversion on PrEP can result from poor adherence or the acquisition of drug-resistant virus. However, since continuing two-drug PrEP in the face of HIV infection can lead to the emergence of new RT mutations, determining whether resistance was acquired or emerged requires timed objective adherence metrics. This patient had good adherence 6 weeks prior to seroconversion per DBS and proximal hair data, but segmental hair analysis revealed inadequate adherence 3 months prior to seroconversion, making subsequent development of M184V from consistent FTC/TDF use with active HIV infection epidemiologically most likely. Objective adherence metrics that look back over time can help unravel the etiology of PrEP failures.

Poster Abstracts

1005 DEVELOPMENT OF A PrEP EQUITY INDEX TO SET LOCAL TARGETS FOR PREP COVERAGE Julie Myers 1 , Sarah L. Braunstein 1 , Zoe R. Edelstein 1 , Alexis Rivera 1 , Njideka Motanya 1 , Oni J. Blackstock 1 1 New York City Department of Health and Mental Hygiene, Long Island City, NY, USA Background: Scaling up PrEP is a priority in ending the HIV epidemic plans, yet progress remains inequitable. Indicators are needed to drive PrEP programming, guide resource allocation, and quantify inequities. We developed a PrEP equity index (PEI) to support local target development for PrEP coverage among MSM, focusing on racial equity. Methods: To calculate the PEI, we first estimated PrEP coverage using a PrEP-to-need ratio, where the numerator was prevalence of PrEP use in the past 6-months (derived either from the Sexual Health Survey (SHS) among NYC MSM aged 18-40, 2018, or the National HIV Behavioral Surveillance (NHBS) study among NYC MSM, 2017) and the denominator was epidemiologic need (derived either from HIV diagnosis rate per 100,000 for men ages 13-59 from NYC HIV surveillance data and US Census data, or the number of new diagnoses among MSM, both for 2017), each stratified by race/ethnicity (Black, Latino, White). We then calculated the PEI by dividing the PrEP coverage for white MSM by that for Black and Latino MSM. To set targets for Black and Latino MSM, we then multiplied the PEI by the PrEP use prevalence for each group, effectively quantifying the improvement in PrEP coverage needed to approximate the PrEP coverage of White MSM (with a maximum of 100%).

1004 RENAL IMPAIRMENT IN A PREEXPOSURE PROPHYLAXIS IMPLEMENTATION COHORT IN AUSTRALIA

Hamish McManus 1 , Douglas Drak 2 , Jack E. Heron 2 , Tobias Vickers 1 , Stefanie Vaccher 1 , Iryna Zablotska 3 , Rebecca J.Guy 1 , Benjamin Bavinton 1 , Fengyi Jin 1 , Andrew E.Grulich 1 , Mark Bloch 4 , Catherine C.O'Connor 2 , David Gracey 2 , for the EPIC Study 1 University of New South Wales, Sydney, NSW, Australia, 2 University of Sydney, Camperdown, NSW, Australia, 3 University of Sydney, Westmead, NSW, Australia, 4 Holdsworth House Medical Practice, Sydney, NSW, Australia Background: Co-formulated tenofovir disoproxil fumarate/emtricitabine is prescribed as pre-exposure prophylaxis (PrEP) to prevent HIV infection. Prior studies have found low incidence of new renal impairment in people taking PrEP but have been restricted to clinical trial settings. We sought to quantify rates of renal impairment in a large prospective cohort of participants taking PrEP as part of a population-level implementation study in Australia.

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