CROI 2018 Abstract eBook

Abstract eBook

Poster Abstracts

analysis was performed (WinNonlin). Geometric mean ratios (GMR; 90% CI) for antimalarials +/- DTG for Cmax, Tmax and AUC to last measurable time point (AUClast) were computed in Study A, and Mann Whitney U tests compared these parameters in Study B. Results: PK parameters are presented in the Table. Study A: For ARM, GMR of Cmax without (N=7) and with DTG (N=7) was 0.87 (0.67-1.14), of Tmax was 1.06 (0.84-1.34) and of AUClast was 1.05 (0.84-1.32). For DHA, GMR of Cmax was 0.92 (0.79-1.07), for Tmax was 1.17 (0.92-1.49) and for AUClast was 0.92 (0.79-1.07). For LF, GMR of Cmax was 1.12 (0.97-1.29), for Tmax was 1.65 (1.02-2.69) and for AUClast was 1.10 (0.96-1.27). For DLF, GMR of Cmax was 0.96 (0.80-1.15), Tmax was 3.00 (2.06-4.36) and for AUClast was 0.96 (0.80-1.15). Study B: There were no statistically significant differences in AUClast for ARS (p=0.77), DHA (p=0.28), AQ (p=0.17) and DEAQ (p=0.69) between subjects administered AS-AQ alone (N=13) and those receiving DTG (N=12). No AEs ≥ grade 3 were observed in either study, and all drugs were well-tolerated. Conclusion: Standard doses of the antimalarials AL and AS-AQ can be used in patients receiving DTG 50mg once daily.

confidence interval, 16-31ng/mL). This further translates into target trough TFV level of 45.4ng/mL (95% confidence interval, 30.8-59.9ng/mL) associated with 90% decrease in HIV-1 infection. Patient time-dependent adherence patterns were estimated from PK data. Population PK parameters were in agreement with previously reported values, with overall clearance related significantly to creatinine clearance (CrCl). For every 10mL/min decrease in CrCl, TFV clearance will decrease 5.4%. Overall drug intake probability was 63.1% (RSE=3%), with large between-/within- patient variability. Conclusion: We estimated preventive TFV plasma concentration from the largest database to date. Compliance to TDF daily dosing of 300mg maintains proposed target TFV plasma concentration. In our analyses, 97% of seroconversions were observed in patients whose daily TFV concentrations were less than proposed target at least at one occasion. 461 PERSISTENT LOW-LEVEL VIREMIA IS ASSOCIATED WITH LOW PROTEASE INHIBITOR LEVELS IN HAIR Alfredo Aguirre 1 , Cyra Christina Mehta 1 , Sophia A. Hussen 1 , Igho Ofotokun 1 , Ruth Greenblatt 2 , Daniel Merenstein 3 , Angela Kashuba 4 , Kathryn Anastos 5 , Mirjam-Colette Kempf 6 , Elizabeth T. Golub 7 , Jack DeHovitz 8 , Mardge H. Cohen 9 , Sheri Weiser 2 , Anandi N. Sheth 1 1 Emory University, Atlanta, GA, USA, 2 University of California San Francisco, San Francisco, CA, USA, 3 Georgetown University, Washington, DC, USA, 4 University of North Carolina Chapel Hill, Chapel Hill, NC, USA, 5 Albert Einstein College of Medicine, Bronx, NY, USA, 6 University of Alabama at Birmingham, Birmingham, AL, USA, 7 Johns Hopkins Hospital, Baltimore, MD, USA, 8 SUNY Downstate Medical Center, Brooklyn, NY, USA, 9 Rush University Medical Center, Chicago, IL, USA Background: HIV-infected patients on combination antiretroviral therapy (ART) may experience episodes of low-level viremia (LLV). Persistent LLV is associated with antiretroviral (ARV) drug resistance and regimen failure, but its etiology and optimal management are unclear. We evaluated the association between LLV and ARV concentration in hair, a measure of long-term ARV exposure. Methods: HIV-infected women in the Women’s Interagency HIV Study receiving protease-inhibitor (PI)-containing ART for ≥1 year with plasma viral load (VL) <500 copies/mL were evaluated during semiannual visits from 2002-2014 for persistent LLV (≥2 consecutive detectable VL <500 copies/ml), transient LLV (detectable VL <500 copies/mL on non-consecutive visits), or sustained viral suppression (VS, all VL below limit of detection). Participants with virologic failure (any VL ≥500 copies/ml) were excluded. Concentrations of lopinavir, atazanavir, and darunavir were measured from hair samples using liquid chromatography/tandemmass spectrometry and divided into quartiles by drug. Multivariable logistic regression and generalized linear mixed models examined factors associated with persistent or transient LLV (versus VS) including age, race, enrollment site, year of first ART, pre-regimen VL, self- reported adherence, and hair ARV quartile. Results: Among 730 participants contributing 6266 person-visits of follow-up, 90 (12%) had persistent LLV and 167 (23%) experienced transient LLV. Maximum VL during follow-up was similar for women with persistent and transient LLV (median 132 [IQR 78, 240] and 119 [IQR 119, 210] copies/mL, p=0.12). In models including the above factors except hair ARV quartile, only non-Hispanic African American race was associated with persistent LLV (OR 1.9, 95%CI 1.2–3.0) and transient LLV (OR 1.8, 95%CI 1.0–3.3). Among 440 participants with hair PI levels, mean hair ARV concentration was lowest in the persistent LLV group for all 3 drugs (Figure 1). After adjusting for self-reported adherence, race, and the above factors, hair ARV quartile was significantly associated with persistent LLV (OR 2.5, 95%CI 1.1–5.8) but not transient LLV (OR 1.5, 95%CI 0.8–2.9). Conclusion: In this cohort of HIV-infected women receiving PI-containing ART, one-third experienced either transient or persistent LLV during >4 years follow-up. Persistent LLV was more likely to occur among women with lower hair PI levels, suggesting that improving ARV exposure could prevent persistent LLV and its adverse consequences.

Poster Abstracts

460 TENOFOVIR HIV-1 PLASMA PROPHYLACTIC CONCENTRATION: iPREX,VOICE,PARTNERS META-ANALYSIS

Katarina Vucicevic 1 , Craig W. Hendrix 2 , Robert M. Grant 1 , Connie L. Celum 3 , Jared Baeten 3 , Jeanne Marrazzo 4 , Peter L. Anderson 5 , David Glidden 1 , Radojka M. Savic 1 1 University of California San Francisco, San Francisco, CA, USA, 2 Johns Hopkins University, Baltimore, MD, USA, 3 University of Washington, Seattle, WA, USA, 4 University of Alabama at Birmingham, Birmingham, AL, USA, 5 University of Colorado Denver, Denver, CO, USA Background: The results from pre-exposure prophylaxis (PrEP) efficacy trials that evaluated tenofovir disoproxil fumarate (TDF) have hypothesized that individuals who acquired HIV-1 infection had low adherence based on lower rates of quantifiable/protective tenofovir (TFV) levels. However, prophylactic TFV plasma levels are still not fully characterized. Our aimwas to perform individual level data meta-analysis from double-blinded randomized trials, establish exposure-response model to define target plasma TFV concentration. Methods: This analysis included data and participants from iPrEX (men or transgender women who have sex with other men), VOICE (young unmarried women), and Partners PrEP trial (HIV-1 negative partner in heterosexual couples), taking 300mg of TDF daily with/without emtricitibine, with at least one plasma measurement. Longitudinal PK, adherence, HIV-1 status and sexual risk behavior data were available based on the specific protocol. TFV concentrations up to 100 hours post-dose including below lower limit of quantification (BLQ) were used in model building. Adherence-PK-outcome model was developed using NONMEM software and mixture model approach. Results: A total of 2478 individuals (204 HIV-1 seroconverters) contributed 7868 plasma measurements (43% BLQ), obtained on up to median 3 (1-16) follow-up visits. Significant sigmoidal E-max relationship was identified in all analyses: TFV average daily plasma concentration associated with 50% reduction in probability of HIV-1 infection was estimated to be 23.5ng/mL (95%

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