We report the safety and pharmacokinetic properties of the HIV-1 maturation inhibitor GSK3739937 (GSK'937) in healthy participants. This was a phase I, first-in-human, double-blind, randomized, placebo-controlled, single- (part 1) and multiple- (part 2) dose escalation study with an additional open-label relative bioavailability and food effect study (part 3). Participants received oral ascending single doses (10-800 mg) in part 1, up to 18 once-daily 25- to 100-mg or 3 once-weekly 500-mg doses in part 2, and single 100-mg doses as powder-in-bottle or tablet (in fed and fasted states) formulations in part 3.
View Article and Find Full Text PDFLancet HIV
November 2021
Background: Long-acting cabotegravir and rilpivirine administered monthly or every 2 months might address the challenges associated with daily oral antiretroviral therapy. The ATLAS-2M week 48 results showed non-inferiority of long-acting cabotegravir and rilpivirine administered every 8 weeks compared with that of every 4 weeks. In this study, we report the efficacy, safety, and tolerability results from the week 96 analysis.
View Article and Find Full Text PDFBackground: ATLAS (NCT02951052), a phase 3, multicenter, open-label study, demonstrated that switching to injectable cabotegravir (CAB) with rilpivirine (RPV) long-acting dosed every 4 weeks was noninferior at week (W) 48 to continuing three-drug daily oral current antiretroviral therapy (CAR). Results from the W 96 analysis are presented.
Methods And Design: Participants completing W 52 of ATLAS were given the option to withdraw, transition to ATLAS-2M (NCT03299049), or enter an Extension Phase to continue long-acting therapy (Long-acting arm) or switch from CAR to long-acting therapy (Switch arm).
Objectives: The objective of this study was to describe the real-world use and effectiveness of dolutegravir-based regimens (DBRs) in routine clinical practice in the United Kingdom.
Methods: Retrospective analysis was conducted using data from four National Health Service trusts using Climate-HIV, an electronic case record system. Eligible patients were aged ≥18 years with HIV-1 infection who were prescribed a DBR from December 2012 to March 2018.
Background: Advances in HIV-1 therapeutics have led to the development of a range of daily oral treatment regimens, which share similar high efficacy rates. Consequently, more emphasis is being placed upon the individual's experience of treatment and impact on quality of life. The first long-acting injectable antiretroviral therapy for HIV-1 (long-acting cabotegravir + rilpivirine [CAB + RPV LA]) may address challenges associated with oral treatment for HIV-1, such as stigma, pill burden/fatigue, drug-food interactions, and adherence.
View Article and Find Full Text PDFBackground: Phase 3 clinical studies showed non-inferiority of long-acting intramuscular cabotegravir and rilpivirine dosed every 4 weeks to oral antiretroviral therapy. Important phase 2 results of every 8 weeks dosing, and supportive modelling, underpin further evaluation of every 8 weeks dosing in this trial, which has the potential to offer greater convenience. Our objective was to compare the week 48 antiviral efficacy of cabotegravir plus rilpivirine long-acting dosed every 8 weeks with that of every 4 weeks dosing.
View Article and Find Full Text PDFObjectives: Test of cure (TOC) for (NG) and (CT) infection is an important tool in the public health management of STIs. However, there are limited data about the optimal time to perform TOC using nucleic acid amplification tests (NAATs) for NG and CT infections. A study was performed to assess the feasibility of a larger study to determine the optimal time to TOC using NAATS.
View Article and Find Full Text PDFObjectives: Post-exposure prophylaxis (PEP) for HIV is often poorly tolerated and not completed. Alternative PEP regimens may improve adherence and completion, aiding HIV prevention. We conducted a randomized controlled trial of a maraviroc-based PEP regimen compared with a standard-of-care regimen using ritonavir-boosted lopinavir.
View Article and Find Full Text PDFThe incidence of human immunodeficiency virus (HIV) infection continues to rise among core groups and efforts to reduce the numbers of new infections are being redoubled. Post-exposure prophylaxis (PEP) is the use of short-term antiretroviral therapy (ART) to reduce the risk of acquisition of HIV infection following exposure. Current guidelines recommend a 28-day course of ART within 36-72 hours of exposure to HIV.
View Article and Find Full Text PDFObjectives: To evaluate the performance and patient acceptability of the PIMA point-of-care (POCT) CD4 test.
Methods: Parallel POCT and laboratory CD4 testing were performed in newly diagnosed HIV patients and those with chronic infection attending routine or emergency clinics. Demographics, clinical status and time taken for CD4 results to be available were recorded.
Background: Post-exposure prophylaxis (PEP) following sexual exposure to HIV has been recommended as a method of preventing HIV infection in the UK. Men who have sex with men (MSM) are the group most affected by HIV in the UK and their sexual risk taking behaviour is reported to be increasing. One-to-one behavioural interventions, such as motivational interviewing (MI) have been recommended to reduce HIV in high risk groups.
View Article and Find Full Text PDFObjectives: To assess the feasibility and outcomes of recalling men who have sex with men (MSM) diagnosed as having a bacterial sexually transmitted infection (STI) for re-screening.
Methods: This evaluation was conducted from December 2008 for a 9-month period. MSM diagnosed as having a bacterial STI in that period were offered recall for re-screening 3 months after their diagnosis.
Purpose Of Review: Postexposure prophylaxis (PEP) has become an important part of combined approaches to the prevention of onward HIV transmission. As PEP becomes more widely available after sexual as well as occupational exposure, there are ongoing debates about cost-effectiveness and utility. Different regions have adopted different PEP strategies and the availability of new antiretroviral drugs and classes means that options for PEP regimens are increasing.
View Article and Find Full Text PDFThere is an ongoing need for potent antiretroviral therapies to deal with the increasing pool of treatment-experienced patients with multiple drug resistance. The last few years have seen the arrival of 2 new and very potent protease inhibitors - darunavir and tipranavir - alongside 2 whole new classes of anti-HIV agents - the integrase inhibitors and chemokine receptor CCR5 antagonists. This review focuses on the role of darunavir in managing HIV infection, with an emphasis on darunavir's exceptional resistance profile and related clinical effectiveness, pharmacokinetics, tolerability and toxicity data.
View Article and Find Full Text PDFThis audit compared sexual histories taken by self-completed questionnaires (SQ) versus the 'gold-standard' of 'traditional' face-to-face interviews by health-care professionals (HP). It compared reporting of symptoms and sexual behaviour and looked at outcomes in terms of diagnoses of sexually transmitted infections. SQ were at least equal to HP and might therefore be a valuable tool in streamlining services.
View Article and Find Full Text PDFWe present the British Association for Sexual Health and HIV (BASHH) guidelines for post-exposure prophylaxis after sexual exposure (PEPSE) to HIV. This document includes a review of the current data to support the use of PEPSE, considers how to calculate the risks of HIV infection after a potential exposure, and provides recommendations on when PEPSE would and would not be considered. Other areas included are the possible impact on sexual behaviour, cost-effectiveness, and issues relating to service provision.
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