Reversal of Integrase Inhibitor- and Tenofovir Alafenamide-Related Weight Gain after Switching Back to Tenofovir DF/Emtricitabine/Efavirenz

We report a case of substantial weight gain in a virologically suppressed patient with HIV after changing his antiretroviral therapy from efavirenz/emtricitabine/tenofovir DF to elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide with subsequent rapid weight loss upon switching back. The role of antiretrovirals in weight gain and loss and patient- and HIV-specific factors are discussed.

Tenofovir-DF versus Hydroxychloroquine in the Treatment of Hospitalized Patients with COVID-19: An Observational Study (THEDICOV)

Background: Although several therapeutic agents have been suggested for the treatment of the disease caused by the Coronavirus of the year 2019 (COVID-19), no antiviral has yet demonstrated consistent efficacy. Methods: The results of an observational study comparing Tenofovir-DF (TDF) with Hydroxychloroquine (HCQ) in the treatment of hospitalized patients with COVID-19 with evidence of pulmonary compromise and the vast majority with supplemental oxygen requirement are presented. Patients received HCQ consecutively at the dose of 400 mg. 12 hourly for 01 day and then 200 mg. every 8 to 12 hours PO for 5 to10 days; or TDF 300 mg. per day PO for 7 to 10 days. The primary outcomes of the study were the differences between the two groups regarding: hospital stay, the need for intensive care or mechanical ventilation (ICU / MV) and mortality. Results: 104 patients were included: 36 in the HCQ group and 68 in the TDF group. The unadjusted primary outcomes were: LOS (length of stay) 16.6 for HCQ versus 12.2 days for TDF (p = o.o102); need for admission to ICU / mechanical ventilation (MV): 61.1% for HCQ versus 11.8% for TDF (p = o.ooo); and mortality: 50.0% for HCQ and 8.8% for TDF (p = o.ooo). The patients in the HCQ group had significant differences at admission compared to those in the TDF group regarding: male sex, cardiovascular risk factor, greater respiratory involvement and higher glucose and creatinine levels, lower albumin levels and higher. Inflammatory markers. When the outcomes were adjusted for these baseline differences, in the multiple regression model for LOS, it was found that TDF decreased the hospital stay by 6.10 days (C.I.: -11.97 to -2.40, p = o.o42); In the logistic regression model for the need for ICU / MV, it was found that the use of TDF had an O.R. of 0.15 (C.I.: 0.03-0.76, p = o.o22); and for the Cox proportional hazards model for mortality, the H.R. was 0.16 for TDF (C.I.: 0.03-0.96, p = o.o41). In the estimation model of the treatment effects by regression adjustment, it was found that TDF decreased the stay by -6.38 days (C.I.: -12.34 to -0.42, p = o.o36); the need for ICU / MV at -41.74% (C.I.: -63.72 to -19.7, p = o.ooo); and mortality by -35.22% (C.I.: -56.47 to -13.96, p = o.oo1). Conclusion: TDF may be an effective antiviral in the treatment of COVID-19. Some of its advantages include: its wide availability, cost and oral presentation. Randomized clinical trials are imperatively required to confirm this possibility.

Effects of Highly Active Antiretroviral Therapy on Albuminuria in HIV-infected Persons

Background: Highly active antiretroviral therapy (HAART), especially tenofovir DFcontaining regimens, has been implicated in albuminuria. Objective: We prospectively evaluated the effects of HAART on albumin-to-creatinine ratios (ACRs) in antiretroviral-naïve HIV-infected individuals. Methods: One hundred and two (102) newly diagnosed, antiretroviral-naïve, human immunodeficiency virus (HIV)-infected persons were treated with Tenofovir disoproxil fumarate/ Emtricitabine/Efavirenz (TDF/FTC/EFV), n=33; Zidovudine/Lamivudine/Nevirapine (ZDV/3TC/NVP), n=53; and Zidovudine/Lamivudine/Efavirenz (ZDV/3TC/EFV), n=16. Diabetes mellitus and hypertension were excluded. ACRs and glomerular filtration rates (eGFR) were estimated at baseline, and at 1, 3, 6 and 9 months post-therapy; the prevalence of albuminuria (ACR ≥ 300mg/g), and microalbuminuria (ACR 30-300mg/g) were similarly estimated. HAART effects on normal ACR (0-30mg/g) were also monitored. Results: At baseline, one patient (0.9%) had nephrotic-range albuminuria with ACR of 2450mg/g. Overall, 8 (7.8%) patients had albuminuria; 53 (51.9%) had microalbuminuria; while 41 (40.2%) had normal ACRs, 28 (27.5% of 102) of which had nonalbuminuric renal insufficiency. eGFR and ACRs improved concurrently on HAART (ACR, Wilks’ lambda 0.439, power 0.763, p=0.032); albuminuria improved significantly on all the 3 regimens at 9 months (p=0.006, 0.012 and <0.001 respectively). Microalbuminuria resolved earlier (1 month) with ZDV/3TC/NVP than with TDF/FTC/EFV and ZDV/3TC/EFV (24.31mg/g versus 76.51mg/g and 63.59mg/g; p=0.028, 0.016 respectively). Microalbuminuria relapsed on TDF/FTC/EFV and ZDV/3TC/EFV at 6 months but resolved again at 9 months (66.7 versus 29 mg/g, p=0.006; and 51.2 versus 9.5mg/g, p=0.001 respectively); no relapse on ZDV/3TC/NVP. At 9 months, ZDV/3TC/EFV caused the greatest resolution of microalbuminuria (85.7% decline in ACR from baseline) compared with ZDV/3TC/NVP (72.5% decline) and TDF/FTC/EFV (63.9% decline). In multivariate analyses, predictors of ACR include older age (Odds ratio OR 2.8, p= 0.025); female gender (OR, 3.4, p =0.014); CD4+ (OR 0.99, p=0.002). Conclusions: HIV induces renal impairment. Thus, albuminuria, microalbuminuria and nonalbuminuric renal insufficiency are highly prevalent in antiretroviral-naïve HIV-infected persons but nephrotic-range albuminuria is uncommon. Albuminuria and/microalbuminuria and eGFR improve concurrently on HAART (with/without tenofovir DF). Zidovudine-based HAART (ZDV/3TC/NVP) resolves microalbuminuria earlier, and without relapse, unlike Tenovofir-based regimen and zidovudine with efavirenz (ZDV/3TC/EFV).

Changes in functional connectivity in people with HIV switching antiretroviral therapy

We assessed changes in functional connectivity by fMRI (functional magnetic resonance imaging) and cognitive measures in otherwise neurologically asymptomatic people with HIV (PWH) switching combination antiretroviral therapy (cART). In a prospective study (baseline and follow-up after at least 4 months), virologically suppressed PWH switched non-nuclease reverse-transcriptase inhibitors (NNRTI; tenofovir-DF/emtricitabine with efavirenz to rilpivirine) and integrase-strand-transfer inhibitors (INSTI; tenofovir-DF/emtricitabine with raltegravir to dolutegravir). PWH were assessed by resting-state fMRI and stop-signal reaction time (SSRT) task fMRI as well as with a cognitive battery (CogState™) at baseline and follow-up. Switching from efavirenz to rilpivirine (n = 10) was associated with increased functional connectivity in the dorsal attention network (DAN) and a reduction in SSRTs (p = 0.025) that positively correlated with the time previously on efavirenz (mean = 4.8 years, p = 0.02). Switching from raltegravir to dolutegravir (n = 12) was associated with increased connectivity in the left DAN and bilateral sensory-motor and associative visual networks. In the NNRTI study, significant improvements in the cognitive domains of executive function, working memory and speed of visual processing were observed, whereas no significant changes in cognitive function were observed in the INSTI study. Changes in fMRI are evident in PWH without perceived neuropsychiatric complaints switching cART. fMRI may be a useful tool in assisting to elucidate the underlying pathogenic mechanisms of cART-related neuropsychiatric effects.

LB1. Doravirine/Lamivudine/Tenofovir DF Continues to Be NonInferior to Efavirenz/Emtricitabine/Tenofovir DF in Treatment-Naïve Adults With HIV-1 Infection: Week 96 Results of the DRIVE-AHEAD Trial

Background Doravirine (DOR) is a novel non-nucleoside reverse-transcriptase inhibitor (NNRTI). In the phase 3 DRIVE-AHEAD trial in HIV-1-infected treatment-naïve adults, DOR demonstrated noninferior efficacy to efavirenz (EFV) and favorable profiles for neuropsychiatric tolerability and lipids at 48 weeks. We present data through week 96. Methods DRIVE- AHEAD (Clinical Trials Registration: NCT02403674) is a phase 3, multicenter, double-blind, noninferiority trial that compared DOR with EFV. Eligible participants were HIV-1-infected treatment-naïve adults with pre-treatment HIV-1 RNA ≥1,000 copies/mL. Participants were randomized (1:1) to a fixed-dose regimen of DOR 100 mg, lamivudine 300 mg and tenofovir disoproxil fumarate 300 mg (DOR/3TC/TDF) QD or EFV 600 mg, emtricitabine 200 mg and TDF 300 mg (EFV/FTC/TDF) QD for up to 96 weeks. Randomization was stratified by screening HIV-1 RNA (≤/&gt;100,000 copies/mL) and hepatitis B/C co-infection (yes/no). The efficacy endpoint of interest at week 96 was HIV-1 RNA &lt;50 copies/mL with predefined noninferiority margin of 10%. Safety endpoints of interest included occurrence of pre-specified neuropsychiatric adverse events and mean change from baseline in fasting lipid levels at week 96. Results Of 734 participants randomized, 728 received study drug and were included in analyses (mean age 33 years, 85% male, 48% white, 19% black, 34% Hispanic). At week 96, HIV-1 RNA &lt;50 copies/mL was achieved by 77.5% of DOR/3TC/TDF recipients vs. 73.6% of EFV/FTC/TDF recipients (difference 3.8%, 95%CI [−2.4, 10.0]). No additional phenotypic resistance to DOR was observed between weeks 48 and 96, while two additional participants in the EFV/FTC/TDF group developed resistance to EFV. Dizziness, sleep disorders/disturbances, altered sensorium, and rash were less frequent in DOR/3TC/TDF recipients than in EFV/FTC/TDF recipients. Fasting LDL-C and non-HDL-C increased in the EFV/FTC/TDF group but not in the DOR/3TC/TDF group, while change in total cholesterol/HDL-C ratio was similar. Conclusion Week 96 results support non-inferiority of DOR/3TC/TFD to EFV/FTC/TDF established at Week 48 with no additional DOR resistance between week 48 and 96. DOR/3TC/TDF was safe and well-tolerated with fewer neuropsychiatric and rash events and favorable lipid profile compared with EFV/FTC/TDF. Disclosures C. Orkin, AbbVie, Abbott, Boehringer Ingelheim, BMS, Gilead, GSK, Janssen, ViiV: Grant Investigator and Research Contractor, Research grant and Research support. K. Squires, Merck & Co., Inc.: Ad Board, Ad Board. Gilead Sciences: Grant, Ad Board. VIIV: Ad Board, Ad Board. Bristol Myers Squibb: Ad Board, Ad Board. Janssen: Ad Board, Ad Board. J. M. Molina, Gilead: Scientific Advisor, Consulting fee. Merck: Scientific Advisor, Consulting fee. ViiV: Scientific Advisor, Consulting fee. Teva: Scientific Advisor, Consulting fee. P. Sax, Gilead: Consultant and Grant Investigator, Consulting fee, Grant recipient and Research grant. ViiV Healthcare: Consultant and Grant Investigator, Consulting fee, Grant recipient and Research grant. Merck: Consultant and Grant Investigator, Consulting fee, Grant recipient and Research grant. Janssen: Consultant, Consulting fee. BMS: Grant Investigator, Grant recipient and Research grant. W. Wong, Merck & Co., Inc.: Research Contractor, Research grant. G. Lin, Merck Sharp & Dohme, a subsidiary of Merck & Co., Inc.: Employee and Shareholder, May hold stock/stock options in the company and Salary. S. Kumar, Merck & Co., Inc.: Employee and Shareholder, Salary. G. Hanna, Merck & Co., Inc.: Employee and Shareholder, Salary. C. Hwang, Merck & Co., Inc.: Employee and Shareholder, Salary. E. Martin, Merck & Co., Inc.: Employee and Shareholder, Salary. H. Teppler, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA: Employee, May hold stock/stock options in the company and Salary.

1294. Acceptability and Feasibility of a Pharmacist-led Pre-exposure Prophylaxis Program in the Midwestern United States

Background Despite evidence that HIV pre-exposure prophylaxis (PrEP) substantially reduces the risk of infection in at-risk populations, significant barriers exist to its prescription and use. Utilizing pharmacists may help increase patient access to PrEP services. We designed and implemented a novel pharmacist-led PrEP program in Omaha, Nebraska. Methods Our pharmacist-led PrEP program was developed in the fall of 2016. Six pharmacists from four sites (one community pharmacy, two community-based clinics and one HIV-specialized clinic) were selected for participation based on interest, senior management support, and availability of appropriate infrastructure. All pharmacists received training for the provision of PrEP. Through a collaborative practice agreement, pharmacists met with patients individually, obtained a medical history, performed a risk assessment and point-of-care laboratory testing (HIV screen, creatinine, and syphilis), and collected samples for gonorrhea and chlamydia. They also provided medication and adherence counseling, and prescribed emtricitabine-tenofovir DF when appropriate. Pharmacists completed a survey reporting their experience after each visit. Presented here are patient demographics, retention rates, and pharmacist-reported experience from the first 6 months of the program. Results Sixty patients enrolled in the pharmacist-led PrEP program between January and June 2017 and completed 139 visits. 95% of participants were men, 83% were white, 80% were privately insured, and 90% had completed some college or higher. The mean age of participants was 34 years (range 20–61 years) and 88% identified as men who have sex with men. 73% were retained in care at 3 months and 58% were retained in care at 6 months. To date, no patient has seroconverted. Pharmacists reported feeling comfortable performing point-of-care testing at all visits and only reported feeling uncomfortable counseling patients on three occasions (2.2%). Finally, pharmacist-reported workflow disruption only occurred on 1 occasion (0.7%). Conclusion Implementation of a pharmacist-led PrEP program is feasible, associated with high rates of pharmacist acceptability, and results in retention rates that are comparable to other real-world PrEP programs. Disclosures S. Bares, Gilead: Grant Investigator, Grant recipient. S. Swindells, Merck: Investigator, Research support. ViiV: Investigator, Research support.