Pharmacokinetics and Safety of Twice-daily Ritonavir-boosted Atazanavir With Rifampicin.

Background: Critical drug-drug interactions (DDI) and hepatotoxicity complicate concurrent use of rifampicin and protease inhibitors. We investigated whether dose escalation of atazanavir/ritonavir could safely overcome the DDI with rifampicin.

Methods: DERIVE (NCT04121195, EDCTP) was a dose-escalation trial in people with human immunodeficiency virus (HIV) on atazanavir/ritonavir-based antiretroviral therapy (ART) in Uganda.

Ambulatory induction phase treatment of cryptococcal meningitis in HIV integrated primary care clinics, Yangon, Myanmar.

Background: Cryptococcal meningitis (CM) is a common HIV-associated opportunistic-infection worldwide. Existing literature focusses on hospital-based outcomes of induction treatment. This paper reviews outpatient management in integrated primary care clinics in Yangon.

Attitudes to disclosure of HIV-serostatus to new sexual partners and sexual behaviours among HIV-diagnosed gay, bisexual and other men who have sex with men in the UK.

We assessed attitudes to disclosure to new sexual partners and association with sexual behaviours among HIV-diagnosed gay, bisexual, and other men who have sex with men (GBMSM) in the UK Antiretrovirals, Sexual Transmission Risk and Attitudes (ASTRA) study in 2011-12. Among 1373 GBMSM diagnosed with HIV for ≥3 months and reporting sex in the past three months (84% on antiretroviral therapy (ART), 75% viral load (VL) ≤50c/mL), 56.3% reported higher sexual disclosure ("agree" or "tend to agree" with "I'd expect to tell a new partner I'm HIV-positive before we have sex").

Factors associated with virological rebound in HIV-infected patients receiving protease inhibitor monotherapy.

Objective: The Protease Inhibitor Monotherapy Versus Ongoing Triple Therapy (PIVOT) trial found that protease inhibitor monotherapy as a simplification strategy is well tolerated in terms of drug resistance but less effective than combination therapy in suppressing HIV viral load. We sought to identify factors associated with the risk of viral load rebound in this trial.

Methods: PIVOT was a randomized controlled trial in HIV-positive adults with suppressed viral load for at least 24 weeks on combination therapy comparing a strategy of physician-selected ritonavir-boosted protease inhibitor monotherapy versus ongoing triple therapy.

A randomized comparative trial of continued abacavir/lamivudine plus efavirenz or replacement with efavirenz/emtricitabine/tenofovir DF in hypercholesterolemic HIV-1 infected individuals.

Background: Drug choice and metabolic changes with antiretroviral therapy contribute to cardiovascular risk in persons with HIV-1 infection.

Methods: A randomized, 12 week, open-label, comparative study of the impact on lipids of continuation of abacavir/lamivudine (ABC/3TC) plus efavirenz (EFV) or replacement with the single tablet regimen of EFV/emtricitabine/tenofovir DF (EFV/FTC/TDF) in hypercholesterolaemic subjects on successful antiretroviral therapy, with a 12-week extension with all subjects on EFV/FTC/TDF.

Results: 157 subjects received study drug, 79 switched to EFV/FTC/TDF and 78 subjects continued ABC/3TC+EFV.

Week 48 results from a randomized clinical trial of rilpivirine/emtricitabine/tenofovir disoproxil fumarate vs. efavirenz/emtricitabine/tenofovir disoproxil fumarate in treatment-naive HIV-1-infected adults.

Objectives: To compare the safety and efficacy of the two single-tablet regimens (STRs), rilpivirine/emtricitabine/tenofovir disoproxil fumarate (RPV/FTC/TDF) and efavirenz/emtricitabine/tenofovir DF (EFV/FTC/TDF), in HIV-1-infected, treatment-naive adults.

Design: This is a phase 3b, randomized, open-label, multicenter, international, 96-week study.

Methods: Participants were randomized 1:1 to receive either RPV/FTC/TDF or EFV/FTC/TDF.

In vivo mitochondrial function in HIV-infected persons treated with contemporary anti-retroviral therapy: a magnetic resonance spectroscopy study.

Modern anti-retroviral therapy is highly effective at suppressing viral replication and restoring immune function in HIV-infected persons. However, such individuals show reduced physiological performance and increased frailty compared with age-matched uninfected persons. Contemporary anti-retroviral therapy is thought to be largely free from neuromuscular complications, whereas several anti-retroviral drugs previously in common usage have been associated with mitochondrial toxicity.

Safety, immunogenicity and efficacy assessment of HIV immunotherapy in a multi-centre, double-blind, randomised, Placebo-controlled Phase Ib human trial.

Background: Combination antiretroviral therapy (cART) is the main therapeutic management tool for HIV/AIDS. Despite its success in controlling viral load and disease progression, cART is expensive, associated with a range of significant side effects and depends for its efficacy on the patient's life-long commitment to high levels of treatment adherence. Immunotherapeutic agents can provide potential solutions to these shortcomings.

A randomized phase 3 study comparing once-daily elvitegravir with twice-daily raltegravir in treatment-experienced subjects with HIV-1 infection: 96-week results.

: This 96-week, double-blind, active-controlled, phase 3 study, randomized subjects to elvitegravir once daily or raltegravir twice daily with a fully active, ritonavir-boosted protease inhibitor plus a third agent. The proportion of subjects randomized to elvitegravir that achieved and maintained HIV-1 RNA < 50 copies/mL through week 96 was 47.6% (167/351) compared with 45.

Real-life outcomes of maraviroc-based regimens in HIV-1-infected individuals.

Purpose: The use of maraviroc in our unit was reviewed with regard to efficacy and safety and also reviewed with regard to how our experience reflects the data presented in clinical trials.

Methods: We utilized the pharmacy dispensary system to identify any patient dispensed maraviroc and conducted a case note review.

Results: We identified 27 patients who have been prescribed maraviroc as part of their antiretroviral treatment.

Does interferon-sparing tenofovir disoproxil fumarate-based therapy have a role in the management of severe acute hepatitis delta superinfection?

Infection with hepatitis delta virus (HDV) always occurs in association with hepatitis B virus (HBV) and is a cause of significant morbidity and mortality. We present a case of severe acute HDV infection superimposed on a previously unrecognized HBV infection, in which an interferon-sparing antiviral therapy consisting of tenofovir disoproxil fumarate (TDF) and lamivudine was initiated and subsequently maintained. Evidence of successful suppression of HDV ribonucleic acid (RNA) was obtained after 65 weeks of TDF-based treatment.

British HIV Association guidelines for the treatment of HIV-1-positive adults with antiretroviral therapy 2012.

The overall purpose of these guidelines is to provide guidance on best clinical practice in the treatment and management of adults with HIV infection with antiretroviral therapy (ART). The scope includes: (i) guidance on the initiation of ART in those previously naïve to therapy; (ii)support of patients on treatment; (iii) management of patients experiencing virological failure; and (iv) recommendations in specific patient populations where other factors need to be taken into consideration. The guidelines are aimed at clinical professionals directly involved with and responsible for the care of adults with HIV infection and at community advocates responsible for promoting the best interests and care of HIV-positive adults.

A randomized comparative trial of continued zidovudine/lamivudine or replacement with tenofovir disoproxil fumarate/emtricitabine in efavirenz-treated HIV-1-infected individuals.

Background: Long-term antiretroviral therapy dramatically reduces HIV-related morbidity and mortality but is also associated with metabolic and morphological changes and requires high levels of adherence.

Methods: A randomized, 48-week, open-label, comparative study of continuation of twice-daily zidovudine/lamivudine or replacement with once-daily tenofovir disoproxil fumarate/emtricitabine in individuals on successful efavirenz-based antiretroviral therapy. Limb fat mass was assessed by dual x-ray absorptiometry in a subset of participants through week 48.

Audit of the management of antiretroviral treatment-naïve HIV patients in Greater Manchester, UK.

We evaluated the management of antiretroviral treatment (ART)-naïve HIV-positive patients in Greater Manchester against the 2005 British HIV association (BHIVA) guidelines. Fifty-seven HIV patients (median age 36 years, 61% males, 53% black Africans) commenced their first ART regimen between 1 October and 31 December 2005. Most of them presented with advanced HIV disease (74% had CD4 lymphocytes <200 and 33% were Centers for Disease Control and Prevention stage C) and 51% commenced ART within three months of their HIV diagnosis.

HIV-associated lipodystrophy: a review of underlying mechanisms and therapeutic options.

Lipodystrophy (LD) is a common adverse effect of HIV treatment with highly active antiretroviral therapy, which comprises morphological and metabolic changes. The underlying mechanisms for LD are thought to be due to mitochondrial toxicity and insulin resistance, which results from derangements in levels of adipose tissue-derived proteins (adipocytokines) that are actively involved in energy homeostasis. Several management strategies for combating this syndrome are available, but they all have limitations.

Thalidomide treatment for refractory HIV-associated colitis: a case series.

Thalidomide has been used as a treatment for various human immunodeficiency virus (HIV)-associated and non-HIV-associated illnesses, generally in cases in which inflammatory disease is refractory to standard therapy. Here, we discuss the successful use of thalidomide in 3 patients with severe, idiopathic HIV-associated colitis.

Predictors of renal outcome in HIV-associated nephropathy.

Background: Human immunodeficiency virus (HIV)-associated nephropathy (HIVAN) is an important cause of end-stage renal disease among African American patients. This study was performed to study the epidemiology of HIVAN in a predominantly black African population and the impact of highly active antiretroviral therapy and other factors on the development of end-stage renal disease.

Methods: We retrospectively identified all patients with HIVAN, defined by biopsy or strict clinical criteria, in 8 clinics in the United Kingdom.

A randomized comparative trial of tenofovir DF or abacavir as replacement for a thymidine analogue in persons with lipoatrophy.

Background: Long-term antiretroviral therapy, while dramatically reducing HIV-related morbidity and mortality, is associated with metabolic and morphological changes. Peripheral fat loss, lipoatrophy, appears most associated with prolonged therapy with thymidine nucleoside analogues.

Methods: A randomized, open-label, comparative study of switching from a thymidine nucleoside analogue to either tenofovir disoproxil fumarate (DF) or abacavir in 105 individuals on successful antiretroviral therapy with clinically evident moderate to severe lipoatrophy.

Pharmacologic optimization of protease inhibitors and nonnucleoside reverse transcriptase inhibitors (POPIN)--a randomized controlled trial of therapeutic drug monitoring and adherence support.

We evaluated the feasibility and effectiveness of therapeutic drug monitoring (TDM) and adherence support (collectively, AT) vs standard of care (SOC) in patients receiving HIV protease inhibitors (PIs) and nonnucleoside reverse transcriptase inhibitors (NNRTIs) within a nurse-led clinic. Primary end points were failure to achieve viral load of <50 copies/mL at 24 weeks, viral rebound, or development of treatment limiting toxicity. One hundred twenty-two patients (AT 63 and SOC 59) were followed-up every 12 weeks, for a median of 72 weeks.

Lipodystrophy in patients with HIV-1 infection: effect of stopping protease inhibitors on TNF-alpha and TNF-receptor levels, and on metabolic parameters.

Objective: To evaluate the effects of stopping treatment with protease inhibitors (PIs) on tumour necrosis factor (TNF)-alpha and TNF-receptor levels, and on the metabolic and morphological abnormalities seen in patients with lipodystrophy.

Design: Longitudinal study.

Methods: Ten HIV-positive patients with lipodystrophy (LD) were studied whilst on PIs (LD1) and 3 months after stopping PIs (LD2) together with 10 HIV-positive subjects on PIs without LD (controls).

Lesson of the week: a new cause of treatable dementia.

Case Report: A 69-year-old married British man presented with 4 months of falls and confusion. HIV antibody test, performed after exclusion of other diagnoses, was positive. Institution of triple antiretroviral therapy resulted in an almost complete recovery.

TNF-alpha promoter region gene polymorphisms in HIV-positive patients with lipodystrophy.

Objective: The pathogenic mechanisms underlying lipodystrophy in HIV-positive patients are largely unknown. TNF-alpha has many actions that are consistent with the features of lipodystrophy; therefore, an analysis was carried out to determine whether functionally active polymorphisms in the promoter region of the TNF-alpha gene are associated with the development of lipodystrophy.

Design: Genetic case-control association study.

Intracellular accumulation of human immunodeficiency virus protease inhibitors.

Intracellular accumulation of the protease inhibitors (PIs) saquinavir (SQV), ritonavir (RTV), and indinavir (IDV) was determined in 50 human immunodeficiency virus-positive patients. Following extraction, PIs were quantified by mass spectrometry. Paired plasma and intracellular samples were collected over a full dosing interval from patients (13 on SQV, 6 on RTV, 8 on IDV, 16 on SQV plus RTV, 7 on IDV plus RTV) with a plasma viral load of <400 copies/ml.