A Pooled Analysis of Eight Clinical Studies Suggests a Link Between Influenza-Like Symptoms and Pharmacodynamics of the Toll-Like Receptor-7 Agonist Vesatolimod.

Introduction: Vesatolimod is a Toll-like receptor-7 (TLR7) agonist in clinical development as part of a combination regimen for human immunodeficiency virus (HIV) cure. Influenza-like symptoms associated with TLR7-mediated immune activation have been reported in clinical trials of vesatolimod. Therefore, a broader understanding of the safety profile of vesatolimod and association with dose and mechanism of action will help inform future clinical studies.

StudySearch: a web-based application for posting and searching clinical research studies.

Participant accrual into research studies is critical to advancing clinical and translational research to clinical care. Without sufficient recruitment, the purpose of any research study cannot be realized; yet, low recruitment and enrollment of participants persist. StudySearch is a web-based application designed to provide an easily readable, publicly accessible, and searchable listing of IRB-approved protocols that are accruing study participants.

Comparison of the metabolic effects of ritonavir-boosted darunavir or atazanavir versus raltegravir, and the impact of ritonavir plasma exposure: ACTG 5257.

Background: Metabolic effects following combination antiretroviral therapy (cART) vary by regimen type. Changes in metabolic effects were assessed following cART in the AIDS Clinical Trials Group (ACTG) A5257 study, and correlated with plasma ritonavir trough concentrations (C24).

Methods: Treatment-naive adult subjects were randomized to ritonavir-boosted atazanavir or darunavir, or raltegravir-based cART.

Impact of chemotherapy for HIV-1 related lymphoma on residual viremia and cellular HIV-1 DNA in patients on suppressive antiretroviral therapy.

The first cure of HIV-1 infection was achieved through complex, multimodal therapy including myeloablative chemotherapy, total body irradiation, anti-thymocyte globulin, and allogeneic stem cell transplantation with a CCR5 delta32 homozygous donor. The contributions of each component of this therapy to HIV-1 eradication are unclear. To assess the impact of cytotoxic chemotherapy alone on HIV-1 persistence, we longitudinally evaluated low-level plasma viremia and HIV-1 DNA in PBMC from patients in the ACTG A5001/ALLRT cohort on suppressive antiretroviral therapy (ART) who underwent chemotherapy for HIV-1 related lymphoma without interrupting ART.

The design of single-arm clinical trials of combination antiretroviral regimens for treatment-naive HIV-infected patients.

Single-arm clinical trials are useful to evaluate antiretroviral regimens in certain populations of HIV-infected treatment-naive patients for whom a randomized controlled trial is not feasible or desirable. They can also be useful to establish initial estimates of efficacy and safety/tolerability of novel regimens to inform the design of large phase III trials. In this article, we discuss key design considerations for such single-arm studies.

Polymorphism in glutamate cysteine ligase catalytic subunit (GCLC) is associated with sulfamethoxazole-induced hypersensitivity in HIV/AIDS patients.

Background: Sulfamethoxazole (SMX) is a commonly used antibiotic for prevention of infectious diseases associated with HIV/AIDS and immune-compromised states. SMX-induced hypersensitivity is an idiosyncratic cutaneous drug reaction with genetic components. Here, we tested association of candidate genes involved in SMX bioactivation and antioxidant defense with SMX-induced hypersensitivity.

HIV and asthma, is there an association?

Objective: To evaluate whether asthma and airway hyper-responsiveness are associated with HIV infection.

Methods: We reviewed the literature on HIV-associated pulmonary diseases, pulmonary symptoms, and immune changes which may play a role in asthma. The information was analyzed comparing the pre-HAART era to the post-HAART era data.

Human N-acetyltransferase 1 *10 and *11 alleles increase protein expression through distinct mechanisms and associate with sulfamethoxazole-induced hypersensitivity.

Objectives: N-acetyltransferase 1 (NAT1) metabolizes drugs and environmental carcinogens. NAT1 alleles *10 and *11 have been proposed to alter protein level or enzyme activity compared with wild-type NAT1 *4 and to confer cancer risk, through uncertain pathways. This study characterizes regulatory polymorphisms and underlying mechanisms of NAT1 expression.

Phase I/II trial of the anti-HIV activity of mifepristone in HIV-infected subjects ACTG 5200.

Background: Mifepristone is a glucocorticoid receptor inhibitor shown in vitro to have anti-HIV activity and anti-simian immunodeficiency virus activity in a macaque model. A phase I/II trial was performed to assess the drug's safety and anti-HIV activity.

Methods: A 28-day double-blind, placebo-controlled trial of mifepristone at doses of 75 mg, 150 mg, and 225 mg given daily was conducted in HIV+ persons with CD4+ lymphocyte counts >or=350 cells per cubic millimeter who had no recent antiretroviral therapy.

Pharmacokinetic interaction between efavirenz and dual protease inhibitors in healthy volunteers.

The combination of efavirenz with HIV-1 protease inhibitors (PI) results in complex interactions secondary to mixed induction and inhibition of oxidative metabolism. ACTG A5043 was a prospective, open-label, controlled, two-period, multiple-dose study with 55 healthy volunteers. The objective of the present study was to evaluate the potential pharmacokinetic interaction between efavirenz and dual PIs.

Antiretroviral Drug Levels and Interactions Affect Lipid, Lipoprotein, and Glucose Metabolism in HIV-1 Seronegative Subjects: A Pharmacokinetic-Pharmacodynamic Analysis.

Background: HIV-infected patients treated with antiretroviral medications (ARVs) develop undesirable changes in lipid and glucose metabolism that mimic the metabolic syndrome and may be proatherogenic. Antiretroviral drug levels and their interactions may contribute to these metabolic alterations.

Methods: Fifty six HIV-seronegative adults were enrolled in an open-label, randomized, pharmacokinetic interaction study, and received a nonnucleoside reverse transcriptase inhibitor (efavirenz on days 1-21) plus a protease inhibitor (PI; amprenavir on days 11-21), with a second PI on days 15-21 (saquinavir, nelfinavir, indinavir, or ritonavir).

Compartmental pharmacokinetic analysis of oral amprenavir with secondary peaks.

Amprenavir is a protease inhibitor that has been shown to have secondary peaks postulated to be due to enterohepatic recycling. We propose a model to describe the pharmacokinetics of amprenavir which accommodates the secondary peak(s). A total of 82 healthy human immunodeficiency virus (HIV)-seronegative subjects were administered a single 600-mg dose of amprenavir as part of adult AIDS Clinical Trials Group protocol A5043.

Partner-specific sexual behavioral differences between phase 3 HIV vaccine efficacy trial participants and controls: Project VISION.

Objective: To assess and compare sexual behaviors using partner-specific data between HIV-negative men who have sex with men (MSM) recruited for an HIV vaccine efficacy trial and a control group.

Methods: HIV-negative MSM from an HIV vaccine trial (n = 525) and controls (n = 732) were recruited by similar strategies and interviewed about behaviors with the 3 most recent partners in the past 6 months, obtained by audio computer-assisted self-interview (A-CASI).

Results: Vaccine trial participants were more likely than controls to report an HIV-positive partner (24.

Third-trimester maternal toxicity with nevirapine use in pregnancy.

Objective: Nevirapine-based therapy is associated with increased frequency of adverse events among women with CD4+ cell count of 250 cells/microL or greater. We evaluated the safety of nevirapine-based antiretroviral therapy in human immunodeficiency virus (HIV)-1-infected pregnant women.

Methods: We retrospectively evaluated 23 pregnancies managed with nevirapine-based regimens from July 2001 to April 2005.

Amprenavir and efavirenz pharmacokinetics before and after the addition of nelfinavir, indinavir, ritonavir, or saquinavir in seronegative individuals.

Adult AIDS Clinical Trials Group 5043 examined pharmacokinetic (PK) interactions between amprenavir (APV) and efavirenz (EFV) both by themselves and when nelfinavir (NFV), indinavir (IDV), ritonavir (RTV), or saquinavir (SQV) is added. A PK study was conducted after the administration of single doses of APV (day 0). Subjects (n = 56) received 600 mg of EFV every 24 h (q24h) for 10 days and restarted APV with EFV for days 11 to 13 with a PK study on day 14.

Placebo-controlled phase 3 trial of a recombinant glycoprotein 120 vaccine to prevent HIV-1 infection.

Background: A vaccine is needed to prevent human immunodeficiency virus type 1 (HIV-1) infection.

Methods: A double-blind, randomized trial of a recombinant HIV-1 envelope glycoprotein subunit (rgp120) vaccine was conducted among men who have sex with men and among women at high risk for heterosexual transmission of HIV-1. Volunteers received 7 injections of either vaccine or placebo (ratio, 2 : 1) over 30 months.