scholarly journals Phase I Safety and Pharmacokinetic Trials of 1263W94, a Novel Oral Anti-Human Cytomegalovirus Agent, in Healthy and Human Immunodeficiency Virus-Infected Subjects

2003 ◽  
Vol 47 (4) ◽  
pp. 1334-1342 ◽  
Author(s):  
Laurene H. Wang ◽  
Richard W. Peck ◽  
Yin Yin ◽  
Jane Allanson ◽  
Rebecca Wiggs ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Adverse Events ◽  
Phase I ◽  
Human Cytomegalovirus ◽  
Half Life ◽  
Clinical Laboratory ◽  
Dose Range ◽  
Taste Disturbance ◽  
Time Curve ◽  
Immunodeficiency Virus

ABSTRACT 1263W94 [maribavir; 5,6-dichloro-2-(isopropylamino)-1, β-l-ribofuranosyl-1-H-benzimidazole], a novel benzimidazole compound, has been demonstrated to potently and selectively inhibit human cytomegalovirus replication in vitro and to have favorable safety profiles in animal species. Two phase I trials evaluated the safety and pharmacokinetics of escalating single doses of 1263W94 in 13 healthy subjects (dose, 50 to 1,600 mg) and 17 human immunodeficiency virus (HIV)-infected subjects (dose, 100 to 1,600 mg). No severe safety concerns were observed in the evaluation of adverse events, vital signs, electrocardiograms, and clinical laboratory tests following administration of a single dose of 1263W94. The most frequently reported adverse events in both populations were taste disturbance (80%) and headache (53%). 1263W94 was rapidly absorbed following oral administration, with peak concentrations in plasma (C max) occurring 1 to 3 h after dosing. The increases in the C max of 1263W94 and the area under the concentration-time curve from time zero to infinity (AUC0-∞) for 1263W94 were dose dependent; C max increased slightly less than proportionally to the dose, and AUC0-∞ increased slightly more than proportionally to the dose. 1263W94 was rapidly eliminated, with a mean half-life in plasma of 3 to 5 h; the half-life was independent of the dose level. Less than 2% of the 1263W94 dose administered was eliminated unchanged in urine. The principal metabolite of 1263W94 was 4469W94 (which is derived by N-dealkylation of 1263W94 via CYP3A4), which accounted for 30 to 40% of the dose in urine. Greater than 98% of the 1263W94 in plasma is bound to proteins, and the extent of binding appears to be constant over the dose range of 200 to 1,600 mg. In the trial with HIV-infected subjects, consumption of a high-fat meal decreased the 1263W94 AUC0-∞ and C max in plasma by ∼30%.

scholarly journals Phase I Dose Escalation Trial Evaluating the Pharmacokinetics, Anti-Human Cytomegalovirus (HCMV) Activity, and Safety of 1263W94 in Human Immunodeficiency Virus-Infected Men with Asymptomatic HCMV Shedding

2002 ◽  
Vol 46 (9) ◽  
pp. 2969-2976 ◽  
Author(s):  
Jacob P. Lalezari ◽  
Judith A. Aberg ◽  
Laurene H. Wang ◽  
Mary Beth Wire ◽  
Richard Miner ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Phase I ◽  
Human Cytomegalovirus ◽  
Taste Disturbance ◽  
Time Curve ◽  
Dosage Regimens ◽  
Immunodeficiency Virus ◽  
Infected Adult

ABSTRACT 1263W94 [maribavir; 5,6-dichloro-2-(isopropylamino)-1,β-l-ribofuranosyl-1-H-benzimidazole] is a novel benzimidazole compound for treatment of human cytomegalovirus (HCMV) infection and disease, with potent in vitro activity against HCMV and good oral bioavailability. A phase I study was conducted to determine the pharmacokinetics (PK), anti-HCMV activity, and safety of 1263W94 administered as multiple oral doses to human immunodeficiency virus type 1-infected adult male subjects with asymptomatic HCMV shedding. Subjects received one of six dosage regimens (100, 200, or 400 mg three times a day, or 600, 900, or 1,200 mg twice a day) or a placebo for 28 days. 1263W94 demonstrated linear PK, with steady-state plasma 1263W94 profiles predictable based on single-dose data. 1263W94 was rapidly absorbed following oral dosing, and values for the maximum concentration of the drug in plasma and the area under the concentration-time curve increased in proportion to the dose. 1263W94 demonstrated in vivo anti-HCMV activity in semen at all of the dosage regimens tested, with mean reductions in semen HCMV titers of 2.9 to 3.7 log10 PFU/ml among the four regimens evaluated for anti-HCMV activity. 1263W94 was generally well tolerated; taste disturbance was the most frequently reported adverse event over the 28-day dosing period.

scholarly journals Single-Dose Pharmacokinetics and Safety of Abacavir (1592U89), Zidovudine, and Lamivudine Administered Alone and in Combination in Adults with Human Immunodeficiency Virus Infection

1999 ◽  
Vol 43 (7) ◽  
pp. 1708-1715 ◽  
Author(s):  
Laurene H. Wang ◽  
Gregory E. Chittick ◽  
James A. McDowell
Keyword(s):  
Human Immunodeficiency Virus ◽  
Adverse Events ◽  
Nucleoside Analogs ◽  
Neck Stiffness ◽  
Time Curve ◽  
Pharmacokinetic Interactions ◽  
Immunodeficiency Virus ◽  
The Mean ◽  
Clinically Significant ◽  
Hiv 1

ABSTRACT Abacavir (1592U89), a nucleoside reverse transcriptase inhibitor with in vitro activity against human immunodeficiency virus type-1 (HIV-1), has been evaluated for efficacy and safety in combination regimens with other nucleoside analogs, including zidovudine (ZDV) and lamivudine (3TC). To evaluate the potential pharmacokinetic interactions between these agents, 15 HIV-1-infected adults with a median CD4+ cell count of 347 cells/mm3 (range, 238 to 570 cells/mm3) were enrolled in a randomized, seven-period crossover study. The pharmacokinetics and safety of single doses of abacavir (600 mg), ZDV (300 mg), and 3TC (150 mg) were evaluated when each drug was given alone or when any two or three drugs were given concurrently. The concentrations of all drugs in plasma and the concentrations of ZDV and its 5′-glucuronide metabolite, GZDV, in urine were measured for up to 24 h postdosing, and pharmacokinetic parameter values were calculated by noncompartmental methods. The maximum drug concentration (C max), the area under the concentration-time curve from time zero to infinity (AUC0–∞), time to C max(T max), and apparent elimination half-life (t 1/2) of abacavir in plasma were unaffected by coadministration with ZDV and/or 3TC. Coadministration of abacavir with ZDV (with or without 3TC) decreased the meanC max of ZDV by approximately 20% (from 1.5 to 1.2 μg/ml), delayed the median T max for ZDV by 0.5 h, increased the mean AUC0–∞ for GZDV by up to 40% (from 11.8 to 16.5 μg · h/ml), and delayed the medianT max for GZDV by approximately 0.5 h. Coadministration of abacavir with 3TC (with or without ZDV) decreased the mean AUC0–∞ for 3TC by approximately 15% (from 5.1 to 4.3 μg · h/ml), decreased the meanC max by approximately 35% (from 1.4 to 0.9 μg/ml), and delayed the median T max by approximately 1 h. While these changes were statistically significant, they are similar to the effect of food intake (for ZDV) or affect an inactive metabolite (for GZDV) or are relatively minor (for 3TC) and are therefore not considered to be clinically significant. No significant differences were found in the urinary recoveries of ZDV or GZDV when ZDV was coadministered with abacavir. There was no pharmacokinetic interaction between ZDV and 3TC. Mild to moderate headache, nausea, lymphadenopathy, hematuria, musculoskeletal chest pain, neck stiffness, and fever were the most common adverse events reported by those who received abacavir. Coadministration of ZDV or 3TC with abacavir did not alter this adverse event profile. The three-drug regimen was primarily associated with gastrointestinal events. In conclusion, no clinically significant pharmacokinetic interactions occurred between abacavir, ZDV, and 3TC in HIV-1-infected adults. Coadministration of abacavir with ZDV or 3TC produced mild changes in the absorption and possibly the urinary excretion characteristics of ZDV-GZDV and 3TC that were not considered to be clinically significant. Coadministration of abacavir with ZDV and/or 3TC was generally well tolerated and did not produce unexpected adverse events.

scholarly journals Pharmacokinetics of Nelfinavir and Efavirenz in Antiretroviral-Naïve, Human Immunodeficiency Virus-Infected Subjects when Administered Alone or in Combination with Nucleoside Analog Reverse Transcriptase Inhibitors

2005 ◽  
Vol 49 (8) ◽  
pp. 3558-3561 ◽  
Author(s):  
Patrick F. Smith ◽  
Gregory K. Robbins ◽  
Robert W. Shafer ◽  
Hulin Wu ◽  
Song Yu ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Reverse Transcriptase ◽  
Half Life ◽  
Pharmacokinetic Studies ◽  
Reverse Transcriptase Inhibitors ◽  
Time Curve ◽  
Minimum Concentration ◽  
Concentration Time ◽  
Immunodeficiency Virus ◽  
The Mean

ABSTRACT Pharmacokinetic studies were conducted with human immunodeficiency virus-infected patients receiving efavirenz, nelfinavir, or both agents at weeks 4 and 32. Reductions of 25% and 45% were observed in the mean nelfinavir area under the concentration-time curve and minimum concentration of the drug in serum, and there was a 31% more rapid half-life for patients receiving both drugs compared to patients receiving nelfinavir alone. There were no significant differences in efavirenz pharmacokinetics.

scholarly journals Pharmacokinetics and Safety of Single Oral Doses of Emtricitabine in Human Immunodeficiency Virus-Infected Children

2004 ◽  
Vol 48 (1) ◽  
pp. 183-191 ◽  
Author(s):  
Laurene H. Wang ◽  
Andrew A. Wiznia ◽  
Mobeen H. Rathore ◽  
Gregory E. Chittick ◽  
Saroj S. Bakshi ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Dose Range ◽  
Transcriptase Inhibitor ◽  
Open Label ◽  
Capsule Formulation ◽  
Time Curve ◽  
Therapeutic Trials ◽  
Drug Concentrations ◽  
Immunodeficiency Virus ◽  
Oral Doses

ABSTRACT Emtricitabine (FTC; Emtriva), a potent deoxycytidine nucleoside reverse transcriptase inhibitor, has recently been approved by the U.S. Food and Drug Administration for the treatment of human immunodeficiency virus (HIV) infection. In adults, FTC has demonstrated linear kinetics over a wide dose range, and FTC 200 mg once a day (QD) is the recommended therapeutic dose. A phase I open-label trial was conducted in children to identify an FTC dosing regimen that would provide comparable plasma exposure to that observed in adults at 200 mg QD. Two single oral doses of FTC (60 and 120 mg/m2, up to a maximum of 200 mg, in solutions) were evaluated in HIV-infected children aged <18 years old. Children ≥6 years old also received a third dose of ∼120 mg/m2 in capsules. A total of 25 children (two <2 years old, eight 2 to 5 years old, eight 6 to 12 years old, and seven 13 to 17 years old) received at least two doses of FTC. Single escalating oral doses of FTC were well tolerated and produced dose-proportional plasma drug concentrations in children. The FTC pharmacokinetics was comparable between adults and children 22 months to 17 years of age. The capsule formulation provided ∼20% higher plasma FTC exposure than the solution formulation. Using plasma area under the concentration-time curve (AUC) data at the 120-mg/m2 dose, it is projected (based on dose proportionality) that a 6-mg/kg dose (up to a maximum of 200 mg) of FTC would produce plasma AUCs in children comparable to those in adults given a 200-mg dose (i.e., median of ∼10 h·μg/ml). This pediatric FTC dose is being evaluated in long-term phase II therapeutic trials in HIV-infected children.

A Phase I/II Evaluation of Stavudine (d4T) in Children With Human Immunodeficiency Virus Infection

PEDIATRICS ◽  
1995 ◽  
Vol 96 (2) ◽  
pp. 247-252
Author(s):  
Mark W. Kline ◽  
Lisa M. Dunkle ◽  
Joseph A. Church ◽  
Jonathan C. Goldsmith ◽  
Alice T. Harris ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Adverse Events ◽  
Phase I ◽  
Lymphocyte Count ◽  
Plasma Concentrations ◽  
Hiv Disease ◽  
Immunodeficiency Virus ◽  
Pharmacokinetic Properties ◽  
Cd4 Lymphocyte Count ◽  
Cd4 Lymphocyte

Objectives. To determine the pharmacokinetic properties, tolerance, safety, and preliminary activity of stavudine in human immunodeficiency virus (HIV)-infected children. Design. Phase I/II, open and dose-ranging (0.125 to 4 mg/kg/day in two divided doses). Patients. Thirty-seven HIV-infected children (median age, 5.5 years; range, 7 months to 15 years) with a median CD4+ lymphocyte count at baseline of 242 cells/µL (range 2 to 2290 cells/µL). Thirty children had symptomatic HIV disease at entry; seven had HIV-related immunosuppression alone. Twenty-nine subjects had a history of prior zidovudine (ZDV) therapy. Results. As compared with adults receiving the same weight-adjusted doses, the children we studied had lower maximum observed stavudine plasma concentrations (CMAX) and area under the plasma concentration versus time curves (AUC), and more rapid stavudine elimination. The absolute oral bioavailability of the drug ranged from 61% to 78%. There was no plasma accumulation of the drug between day 1 and week 12. Week 12 cerebrospinal fluid stavudine concentrations in seven subjects, obtained approximately 2 to 3 hours after oral doses, ranged from 16% to 97% of concomitant plasma concentrations. Stavudine was well-tolerated and there were no dose-related clinical or laboratory adverse events. One subject with baseline neurologic abnormalities experienced a transient episode of apparent pain or discomfort in her fingers, possibly related to stavudine. All other adverse events were attributed to underlying disease. Stavudine activity, measured indirectly by CD4+ lymphocyte count and serum p24 antigen concentration changes, was observed in some subjects. Progression of HIV disease and survival correlated with prior ZDV therapy, HIV disease classification, baseline CD4+ lymphocyte count, and weight growth velocity. Conclusions. Stavudine appears to hold promise for the treatment of HIV infection in children. Its pharmacokinetic properties are consistent and predictable, and it appears to be remarkably well-tolerated and safe. Although our study was not designed to assess the drug's efficacy, preliminary clinical and laboratory evidence of activity was observed.

scholarly journals Clinical Pharmacokinetics of 1-[((S)-2-Hydroxy-2-Oxo-1,4,2-Dioxaphosphorinan-5-yl)methyl]cytosine in Human Immunodeficiency Virus-Infected Patients

1999 ◽  
Vol 43 (2) ◽  
pp. 271-277 ◽  
Author(s):  
Kenneth C. Cundy ◽  
Patricia Barditch-Crovo ◽  
Brent G. Petty ◽  
April Ruby ◽  
Murphy Redpath ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Intravenous Administration ◽  
Half Life ◽  
Dose Range ◽  
Urine Samples ◽  
Clinical Pharmacokinetics ◽  
Immunodeficiency Virus ◽  
Methyl Cytosine ◽  
Serum And Urine ◽  
Serum And Urine Samples

ABSTRACT The pharmacokinetics and bioavailability of 1-[((S)-2-hydroxy-2-oxo-1,4,2-dioxaphosphorinan-5-yl)methyl]cytosine (cyclic HPMPC) were examined at four doses in 22 patients with human immunodeficiency virus infection. Two groups of six patients received a single dose of cyclic HPMPC at 1.5 or 3.0 mg/kg of body weight by each of the oral and intravenous routes in a random order with a 2-week washout period between administrations. Additional patients received single intravenous doses of cyclic HPMPC at 5.0 mg/kg (n = 6) or 7.5 mg/kg (n = 4). Serial serum and urine samples were collected at intervals over 24 h after dosing. The concentrations of cyclic HPMPC and cidofovir in serum and urine samples were determined by validated reverse-phase ion-pairing high-performance liquid chromatography methods with derivatization and fluorescence detection. After intravenous administration of cyclic HPMPC, concentrations of cyclic HPMPC declined in a biexponential manner, with a mean ± standard deviation half-life of 1.09 ± 0.12 h (n = 22). The pharmacokinetics of cyclic HPMPC were independent of dose over the dose range of 1.5 to 7.5 mg/kg. The total clearance of cyclic HPMPC from serum and the volume of distribution of intravenous cyclic HPMPC were 198 ± 39.6 ml/h/kg and 338 ± 65.1 ml/kg, respectively (n = 22). The renal clearance of cyclic HPMPC (132 ± 27.3 ml/h/kg; n = 22) exceeded the creatinine clearance (86.2 ± 16.3 ml/h/kg), indicating active tubular secretion. The cyclic HPMPC excreted in urine in 24 h accounted for 71.3% ± 16.0% of the administered dose. Cidofovir was formed from cyclic HPMPC in vivo with a time to the maximum concentration in serum of 1.64 ± 0.23 h (n= 22). Cidofovir levels declined in an apparent monoexponential manner, with a mean terminal half-life of 3.98 ± 1.26 h (n = 22). The cidofovir excreted in urine in 24 h accounted for 9.40% ± 2.33% of the administered cyclic HPMPC dose. Exposure to cidofovir after intravenous administration of cyclic HPMPC was dose proportional and was 14.9% of that from an equivalent dose of cidofovir. The present study suggests that intravenous cyclic HPMPC also has a lower potential for nephrotoxicity in humans compared to that of intravenous cidofovir. The oral bioavailabilities of cyclic HPMPC were 1.76% ± 1.48% and 3.10% ± 1.16% with the administration of doses of 1.5 and 3.0 mg/kg, respectively (n = 6 per dose). The maximum concentrations of cyclic HPMPC in serum were 0.036 ± 0.021 and 0.082 ± 0.038 μg/ml after the oral administration of doses of 1.5 and 3.0 mg/kg, respectively. Cidofovir reached quantifiable levels in the serum of only one patient for each of the 1.5- and 3.0-mg/kg oral cyclic HPMPC doses.

scholarly journals Pharmacokinetics, Safety, and Tolerability of Oral Posaconazole Administered in Single and Multiple Doses in Healthy Adults

2003 ◽  
Vol 47 (9) ◽  
pp. 2788-2795 ◽  
Author(s):  
Rachel Courtney ◽  
Sudhakar Pai ◽  
Mark Laughlin ◽  
Josephine Lim ◽  
Vijay Batra
Keyword(s):  
Half Life ◽  
Clinical Laboratory ◽  
Dose Range ◽  
Apparent Volume ◽  
Dose Proportionality ◽  
Healthy Adults ◽  
Terminal Phase ◽  
Two Phase ◽  
Double Blind ◽  
Time Curve

ABSTRACT The pharmacokinetics, safety, and tolerability of posaconazole, an investigational triazole antifungal, were evaluated following the administration of rising single and multiple oral doses. A total of 103 healthy adults were enrolled in two phase I trials. Each study had a double-blind, placebo-controlled, parallel-group design with a rising single-dose (RSD) or rising multiple-dose (RMD) scheme. In the RSD study, subjects received single doses of posaconazole oral tablets (50 to 1,200 mg) or placebo. In the RMD study, subjects received posaconazole oral tablets (50 to 400 mg) or placebo twice daily for 14 days. By using model-independent methods, the area under the plasma concentration-time curve and the maximum concentration in plasma were determined and used to assess dose proportionality. In the RSD study, the levels of posaconazole in plasma increased proportionally between the 50- and 800-mg dose range, with saturation of absorption occurring above 800 mg. Dose proportionality was also observed in the RMD study. In both studies, the apparent volume of distribution was large (range, 343 to 1,341 liters) and the terminal-phase half-life was long (range, 25 to 31 h). Posaconazole was well tolerated at all dose levels, and the adverse events were not dose dependent. No clinically significant changes in clinical laboratory test values or electrocardiograms were observed. Following the administration of single and twice-daily rising doses, the level of posaconazole exposure increased in a dose-proportional manner. The long elimination-phase half-life of posaconazole supports once- or twice-daily dosing in clinical trials; however, additional studies are required to determine if further division of the dose will enhance exposure.

scholarly journals A Randomized Controlled Trial of Isoniazid to Prevent Mycobacterium tuberculosis Infection in Kenyan Human Immunodeficiency Virus–Exposed Uninfected Infants

2020 ◽  
Author(s):  
Sylvia M LaCourse ◽  
Barbra A Richardson ◽  
John Kinuthia ◽  
A J Warr ◽  
Elizabeth Maleche-Obimbo ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Mycobacterium Tuberculosis ◽  
High Risk ◽  
Adverse Events ◽  
Controlled Trial ◽  
Preventive Therapy ◽  
Infection Prevalence ◽  
Mycobacterium Tuberculosis Infection ◽  
Immunodeficiency Virus ◽  
Exposed Uninfected

Abstract Background Human immunodeficiency virus (HIV)–exposed uninfected (HEU) infants in endemic settings are at high risk of tuberculosis (TB). For infants, progression from primary Mycobacterium tuberculosis (Mtb) infection to TB disease can be rapid. We assessed whether isoniazid (INH) prevents primary Mtb infection. Methods We conducted a randomized nonblinded controlled trial enrolling HEU infants 6 weeks of age without known TB exposure in Kenya. Participants were randomized (1:1) to 12 months of daily INH (10 mg/kg) vs no INH. Primary endpoint was Mtb infection at end of 12 months, assessed by interferon-γ release assay (QuantiFERON-TB Gold Plus) and/or tuberculin skin test (TST, added 6 months after first participant exit). Results Between 15 August 2016 and 6 June 2018, 416 infants were screened, with 300 (72%) randomized to INH or no INH (150 per arm); 2 were excluded due to HIV infection. Among 298 randomized HEU infants, 12-month retention was 96.3% (287/298), and 88.9% (265/298) had primary outcome data. Mtb infection prevalence at 12-month follow-up was 10.6% (28/265); 7.6% (10/132) in the INH arm and 13.5% (18/133) in the no INH arm (7.0 vs 13.4 per 100 person-years; hazard ratio, 0.53 [95% confidence interval {CI}, .24–1.14]; P = .11]), and driven primarily by TST positivity (8.6% [8/93] in INH and 18.1% [17/94] in no INH; relative risk, 0.48 [95% CI, .22–1.05]; P = .07). Frequency of severe adverse events was similar between arms (INH, 14.0% [21/150] vs no INH, 10.7% [16/150]; P = .38), with no INH-related adverse events. Conclusions Further studies evaluating TB preventive therapy to prevent or delay primary Mtb infection in HEU and other high-risk infants are warranted. Clinical Trials Registration NCT02613169.

scholarly journals SAT0078 SAFETY OF LOW DOSE METHOTREXATE (MTX) IN HUMAN IMMUNODEFICIENCY VIRUS (HIV) INFECTION

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 974.2-974
Author(s):  
A. Gunay ◽  
A. Davidson ◽  
I. Colmegna ◽  
D. Lacaille ◽  
H. Loewen ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Adverse Events ◽  
Low Dose ◽  
Opportunistic Infections ◽  
Case Reports ◽  
Cross Sectional Study ◽  
Study Quality ◽  
Sectional Study ◽  
Cross Sectional ◽  
Immunodeficiency Virus

Background:Increased awareness of the efficacy of MTX in rheumatic disease is leading to more MTX use in patients from HIV endemic areas. While HIV related immunosuppression may contribute to improvement of some rheumatic diseases, immune reconstitution from highly active antiretroviral therapy (HAART) may lead to exacerbation or presentation of autoimmune disorders for which MTX therapy may be warranted. Most management guidelines for rheumatic disease do not address MTX use in the context of HIV.Objectives:To systematically review the published literature on the safety of using MTX ≤30 mg per week in HIV.Methods:We searched CINAHL, Embase, Global, MEDLINE and World of Science databases (Jan 1990 to May 2018) for terms including ‘methotrexate’ and ‘human immunodeficiency virus’. We also searched citations from review articles. Titles, abstracts or full manuscripts were screened independently by 2 reviewers to identify studies reporting HIV in patients taking MTX. Study quality was assessed using the McGill Mixed Methods Appraisal Tool (MMAT). Data was extracted on MTX and HIV adverse events (MTX toxicity, HIV viral load, CD4 count). Descriptive summaries are presented for studies providing outcomes in patients taking MTX ≤30 mg per week.Results:After removing duplicates and studies not meeting criteria or not providing sufficient information, 42 of the 2714 identified reports were included (1 clinical trial, 2 cohort, 1 cross-sectional study, 38 case reports/case series). Most reports (81%) originated from USA or Europe. Study quality was generally good with most studies fulfilling 50-100% of MMAT criteria. The randomized controlled trial (USA) assessing MTX on atherosclerotic disease in HIV showed that adverse events were more common in MTX versus placebo (12.8% vs 5.6%, p non-inferiority <0.05) and included infection, transient CD4 and CD8 drop, pulmonary toxicity, and death (1 attributed to MTX/HIV, 1 unrelated). One cohort study (South Africa) reported 43 RA patients on MTX who acquired HIV. In this cohort, RA generally improved despite only 5 individuals continuing MTX. No data on MTX adverse event rates was reported. One cohort study (USA) reported 13 HIV patients with myositis. One received MTX (with other immunosuppression) without MTX adverse effects but died due to AIDS. A cross-sectional study (France) of 43 HIV pts with autoimmune disease reported one patient on MTX (and other immunosuppression) developed an adverse event (cytopenia) compared to 5/33 patients not on MTX (cytopenia). The 38 case reports/series described 54 individuals with HIV receiving MTX. Of these studies, 27 (describing 42 subjects) reported on MTX adverse events and 35 (describing 46 subjects) reported on HIV adverse events. MTX adverse events developed in 29 subjects (hematologic 13, renal/hepatic 1, opportunistic infections 10, other events 2). HIV adverse events were noted in 23 subjects (Kaposi’s sarcoma 4, CD4 decrease 16, HIV viral titer increase 4). Five deaths were reported (2 infection, 1 infection and wasting, 2 HIV related deaths). Most subjects also received corticosteroids or other immunosuppressants including biologics.Conclusion:There remains limited data on the safety of low dose MTX in HIV. Surveillance for HIV is warranted for individuals on MTX who are at risk for acquiring HIV. Caution and careful monitoring for MTX toxicity, opportunistic infections and HIV state is suggested if MTX is used in the setting of HIV particularly if combined with other immunosuppression.References:[1] Clin Infectious Disease 2019:68[2] J Rheumatology 2014:41[3] Arthritis and Rheumatism 2003:49[4] Medicine 2017:96Acknowledgments :Funding from International League Against RheumatismMcGill University Global Health Scholar AwardsDisclosure of Interests:Alize Gunay: None declared, Anna Davidson: None declared, Ines Colmegna: None declared, Diane Lacaille: None declared, Hal Loewen: None declared, Michele Meltzer: None declared, Yewondwossen Mengistu: None declared, Rosie Scuccimarri: None declared, Zenebe Yirsaw: None declared, Sasha Bernatsky: None declared, Carol Hitchon Grant/research support from: UCB Canada; Pfizer Canada

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