Changes to inflammatory markers during 5 years of viral suppression and during viral blips in people with HIV initiating different integrase inhibitor based regimens.

Background: Heightened levels of inflammatory markers are linked to increased morbidity/mortality in people with HIV (PWH) and often remain elevated after virologic suppression by antiretroviral therapy (ART). As new combinations of ART become available, an evaluation of their effects on immune activation and inflammation is warranted. Additionally, it remains unknown whether transient increases in viral load ("blips") during ART are associated with increases in inflammation.

A pseudo-response approach to constructing confidence intervals for the subset of patients expected to benefit from a new treatment.

In precision medicine, there is much interest in estimating the expected-to-benefit (EB) subset, i.e. the subset of patients who are expected to benefit from a new treatment based on a collection of baseline characteristics.

Antiretrovirals and Weight Change: Weighing the Evidence.

Body weight is influenced by an interplay of individual and environmental factors. In people with human immunodeficiency virus (HIV), weight is also influenced by disease status with loss accompanying disease progression that is reversed with effective antiretroviral therapy. Weight changes in comparative antiretroviral therapy trials differ by regimen, with greater gains observed with the integrase strand transfer inhibitors dolutegravir and bictegravir, particularly when coadministered with tenofovir alafenamide fumarate, compared with regimens that include agents such as tenofovir disoproxil fumarate that attenuate weight gain.

Corrigendum: Translating the observed differences in interleukin-6 levels between some antiretroviral regimens into potential long-term risk of serious non-AIDS events: A modeling study.

[This corrects the article DOI: 10.3389/fimmu.2022.

Translating the observed differences in interleukin-6 levels between some antiretroviral regimens into potential long-term risk of serious non-AIDS events: A modeling study.

Introduction: Variable levels of systemic inflammation are observed in people with HIV (PWH), but the clinical significance of differences among antiretroviral therapy (ART) regimens on associated levels of inflammatory markers is unclear. Based on data from previous epidemiologic studies that defined the predicted change in risk of serious non-AIDS events (SNAEs)/death by changes in interleukin-6 (IL-6) and D-dimer, we modeled the effects of differences in these markers between specific ART regimens on the long-term risk of clinical outcomes.

Methods: We used a Markov model to compare the risk of SNAEs/death with differences in IL-6 and D-dimer levels associated with remaining on specific three-drug regimens versus switching to specific two-drug ART regimens over 5 years of treatment.

Relevance of Interleukin-6 and D-Dimer for Serious Non-AIDS Morbidity and Death among HIV-Positive Adults on Suppressive Antiretroviral Therapy.

Background: Despite effective antiretroviral treatment (ART), HIV-positive individuals are at increased risk of serious non-AIDS conditions (cardiovascular, liver and renal disease, and cancers), perhaps due in part to ongoing inflammation and/or coagulation. To estimate the potential risk reduction in serious non-AIDS conditions or death from any cause that might be achieved with treatments that reduce inflammation and/or coagulation, we examined associations of interleukin-6 (IL-6), D-dimer, and high-sensitivity C-reactive protein (hsCRP) levels with serious non-AIDS conditions or death in 3 large cohorts.

Methods: In HIV-positive adults on suppressive ART, associations of IL-6, D-dimer, and hsCRP levels at study entry with serious non-AIDS conditions or death were studied using Cox regression.

Cost-Effectiveness of Single- Versus Generic Multiple-Tablet Regimens for Treatment of HIV-1 Infection in the United States.

Background: The possibility of incorporating generics into combination antiretroviral therapy and breaking apart once-daily single-tablet regimens (STRs), may result in less efficacious medications and/or more complex regimens with the expectation of marked monetary savings. A modeling approach that assesses the merits of such policies in terms of lifelong costs and health outcomes using adherence and effectiveness data from real-world U.S.

Rilpivirine vs. efavirenz-based single-tablet regimens in treatment-naive adults: week 96 efficacy and safety from a randomized phase 3b study.

Objectives: To compare efficacy, safety, tolerability, and patient-reported outcomes between two single-tablet regimens, rilpivirine/emtricitabine/tenofovir disoproxil fumarate (RPV/FTC/TDF) and efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF), in HIV-1-infected, treatment-naive adults.

Design: This was a phase 3b, 96-week, randomized, open-label, international, noninferiority trial.

Methods: A total of 799 participants were randomized (1 : 1) to receive RPV/FTC/TDF or EFV/FTC/TDF.

Patient-reported outcomes in the single-tablet regimen (STaR) trial of rilpivirine/emtricitabine/tenofovir disoproxil fumarate versus efavirenz/emtricitabine/tenofovir disoproxil fumarate in antiretroviral treatment-naive adults infected with HIV-1 through 48 weeks of treatment.

This 96-week, randomized, open-label study was designed to assess the efficacy and safety of two single-tablet regimens in treatment naïve HIV-1-infected adults: rilpivirine (RPV) + emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) and efavirenz (EFV) + FTC/TDF. Assessments included patient-reported Medication Adherence Self-Report Inventory, SF-12v2 Quality of Life assessment, HIV Treatment Satisfaction Questionnaire, and HIV Symptom Index Questionnaire through Week 48. Additional evaluations included study drug discontinuations due to treatment-emergent adverse events (TEAEs).

Rilpivirine versus efavirenz with emtricitabine/tenofovir disoproxil fumarate in treatment-naïve HIV-1-infected patients with HIV-1 RNA ≤100,000 copies/mL: week 96 pooled ECHO/THRIVE subanalysis.

The once daily, single-tablet regimen (STR) combining rilpivirine (RPV), emtricitabine (FTC), and tenofovir disoproxil fumarate (TDF) provides a simplified treatment option for antiretroviral therapy (ART)-naïve patients with baseline HIV-1 RNA (BLVL) of ≤100,000 copies/mL. The aim of this analysis is to compare long-term efficacy, safety, and tolerability of RPV+FTC/TDF vs. efavirenz (EFV)+FTC/TDF as individual components in subjects with BLVL ≤100,000 copies/mL.

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.

Efficacy and safety 48 weeks after switching from efavirenz to rilpivirine using emtricitabine/tenofovir disoproxil fumarate-based single-tablet regimens.

Background: Due to ongoing neuropsychiatric adverse events in some efavirenz (EFV)-treated patients, a switch to an alternative non-nucleoside reverse transcriptase inhibitor may be considered. Rilpivirine (RPV) has been coformulated as a single-tablet regimen (STR) with emtricitabine/tenofovir disoproxil fumarate (FTC/TDF), and the components have demonstrated noninferior efficacy to EFV+FTC/TDF, good tolerability profile, and high adherence. After discontinuation, EFV has an extended inductive effect on cytochrome P450 (CYP) 3A4 that, after switching, may reduce RPV exposures and adversely impact clinical outcomes.

Association between daily antiretroviral pill burden and treatment adherence, hospitalisation risk, and other healthcare utilisation and costs in a US medicaid population with HIV.

Objectives: Lower pill burden leads to improved antiretroviral therapy (ART) adherence among HIV patients. Simpler dosing regimens have not been widely explored in real-world populations. We retrospectively assessed ART adherence, all-cause hospitalisation risk and costs, and other healthcare utilisation and costs in Medicaid enrollees with HIV treated with ART as a once-daily single-tablet regimen (STR) or two or more pills per day (2+PPD).

A randomized double-blind comparison of coformulated elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate versus efavirenz/emtricitabine/tenofovir disoproxil fumarate for initial treatment of HIV-1 infection: analysis of week 96 results.

We report week 96 results from a phase 3 trial of elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (EVG/COBI/FTC/TDF, n = 348) vs efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF, n = 352). At week 48, EVG/COBI/FTC/TDF was noninferior to EFV/FTC/TDF (88% vs 84%, difference +3.6%, 95% confidence interval: -1.

Week 96 efficacy and safety of rilpivirine in treatment-naive, HIV-1 patients in two Phase III randomized trials.

Background: In the week 48 primary analysis of ECHO and THRIVE, rilpivirine demonstrated noninferior efficacy and more favourable tolerability versus efavirenz in treatment-naive, HIV-1-infected adults. Pooled 96-week results are presented.

Methods: Patients (N = 1368) received rilpivirine 25 mg once-daily (q.

Cost-Effectiveness of Antiretroviral Therapy for Multidrug-Resistant HIV: Past, Present, and Future.

In the early years of the highly active antiretroviral therapy (HAART) era, HIV with resistance to two or more agents in different antiretroviral classes posed a significant clinical challenge. Multidrug-resistant (MDR) HIV was an important cause of treatment failure, morbidity, and mortality. Treatment options at the time were limited; multiple drug regimens with or without enfuvirtide were used with some success but proved to be difficult to sustain for reasons of tolerability, toxicity, and cost.

Co-formulated elvitegravir, cobicistat, emtricitabine, and tenofovir versus co-formulated efavirenz, emtricitabine, and tenofovir for initial treatment of HIV-1 infection: a randomised, double-blind, phase 3 trial, analysis of results after 48 weeks.

Background: The integrase inhibitor elvitegravir (EVG) has been co-formulated with the CYP3A4 inhibitor cobicistat (COBI), emtricitabine (FTC), and tenofovir disoproxil fumarate (TDF) in a single tablet given once daily. We compared the efficacy and safety of EVG/COBI/FTC/TDF with standard of care-co-formulated efavirenz (EFV)/FTC/TDF-as initial treatment for HIV infection.

Methods: In this phase 3 trial, treatment-naive patients from outpatient clinics in North America were randomly assigned by computer-generated allocation sequence with a block size of four in a 1:1 ratio to receive EVG/COBI/FTC/TDF or EFV/FTC/TDF, once daily, plus matching placebo.

Efficacy and safety of rilpivirine (TMC278) versus efavirenz at 48 weeks in treatment-naive HIV-1-infected patients: pooled results from the phase 3 double-blind randomized ECHO and THRIVE Trials.

Background: Pooled analysis of phase 3, double-blind, double-dummy ECHO and THRIVE trials comparing rilpivirine (TMC278) and efavirenz.

Methods: Treatment-naive HIV-1-infected adults were randomized 1:1 to rilpivirine 25 mg once daily or efavirenz 600 mg once daily, with background tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) (ECHO) or TDF/FTC, zidovudine/lamivudine, or abacavir/lamivudine (THRIVE). The primary endpoint was confirmed response [viral load <50 copies per milliliter; intent-to-treat time-to-loss-of-virologic-response (ITT-TLOVR) algorithm] at week 48.

Impact of Tai Chi exercise on multiple fracture-related risk factors in post-menopausal osteopenic women: a pilot pragmatic, randomized trial.

Background: Tai Chi (TC) is a mind-body exercise that shows potential as an effective and safe intervention for preventing fall-related fractures in the elderly. Few randomized trials have simultaneously evaluated TC's potential to reduce bone loss and improve fall-predictive balance parameters in osteopenic women.

Methods: In a pragmatic randomized trial, 86 post-menopausal osteopenic women, aged 45-70, were recruited from community clinics.

Cost-effectiveness of nucleoside reverse transcriptase inhibitor pairs in efavirenz-based regimens for treatment-naïve adults with HIV infection in the United States.

Objective: To estimate the cost-effectiveness of once-daily tenofovir/emtricitabine compared with twice-daily zidovudine/lamivudine and once-daily abacavir/lamivudine in treatment-naïve adults with HIV-1 infection in the United States.

Methods: A Markov model with four therapy lines and six health states based on CD4(+) cell-count ranges was developed to estimate lifetime costs and health outcomes. Efficacy data (virologic response and CD4(+) cell-count changes) for first-line therapy were from 144-week results of Study 934 comparing tenofovir/emtricitabine with zidovudine/lamivudine and 48-week results of Study CNA30024 comparing abacavir/lamivudine with zidovudine/lamivudine, all in combination with efavirenz.

Rilpivirine versus efavirenz with two background nucleoside or nucleotide reverse transcriptase inhibitors in treatment-naive adults infected with HIV-1 (THRIVE): a phase 3, randomised, non-inferiority trial.

Background: The non-nucleoside reverse transcriptase inhibitor (NNRTI), rilpivirine (TMC278; Tibotec Pharmaceuticals, County Cork, Ireland), had equivalent sustained efficacy to efavirenz in a phase 2b trial in treatment-naive patients infected with HIV-1, but fewer adverse events. We aimed to assess non-inferiority of rilpivirine to efavirenz in a phase 3 trial with common background nucleoside or nucleotide reverse transcriptase inhibitors (N[t]RTIs).

Methods: We undertook a 96-week, phase 3, randomised, double-blind, double-dummy, non-inferiority trial in 98 hospitals or medical centres in 21 countries.

Similar efficacy of raltegravir when used with or without a protease inhibitor in treatment-experienced patients.

Background: Patients with multiclass-resistant HIV-1 have limited treatment options. Raltegravir, an inhibitor of integrase, has shown excellent efficacy when used with protease inhibitors (Pis) in patients with drug-resistant HIV-1. Limited data are available however about the outcomes when using raltegravir without Pis in this population.