Emtricitabine 200mg / Rilpivirine 25mg / Tenofovir disoproxil 245mg tablets

BackgroundIn 2023, there were 39.9 million people living with HIV (PLWH) worldwide and 630 000 deaths related to HIV. New strategies are needed, and long-acting antiretrovirals (LAAs) are now widely considered to have great potential to help end the HIV epidemic. This systematic review and meta-analysis compare the safety and efficacy of LAA versus standard oral treatment (SOT) for HIV.MethodsPubMed and Embase databases, supplemented by ClinicalTrials.gov and grey literature, were searched. Randomized controlled trials (RCTs) reporting efficacy and/or safety of LAA versus SOT for PLWH until June 2024 were included. Efficacy (HIV RNA ResultsSix RCTs were eligible for inclusion, involving 2829 participants. LAA was non-inferior to SOT in suppressing HIV RNA ConclusionsLAA has non-inferior efficacy compared to SOT. However, participants receiving LAA were at a higher risk of developing drug resistance, cross-resistance and AEs.

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BackgroundNew HIV infections occur annually in Canada, highlighting the need for pre- and postexposure prophylaxis (PrEP and PEP). Through the Canadian Institutes of Health Research (CIHR) Pan-Canadian Network for HIV/AIDS and STBBI (sexually transmitted and blood-borne infections) Clinical Trials Research, we have updated the 2017 guideline on clinical indications and drug regimens for PrEP and PEP in Canada.MethodsDrawing on meetings with community-based organizations representing key populations affected by HIV in Canada, along with evidence from 3 systematic reviews on PrEP, PEP, and HIV risk assessment tools (searches to June 2024), our diverse panel of 19 experts formulated recommendations on PrEP and PEP. We used a formal evidence-to-decision-making framework and the Grading of Recommendations, Assessment, Development, and Evaluation system. We followed the Guidelines International Network principles for managing competing interests. Our guideline development and reporting adhere with Appraisal of Guidelines for Research and Evaluation II.RecommendationsThis guideline contains 31 recommendations and 10 good practice statements. Although it is appropriate to prescribe PrEP to adults and adolescents who request it, clinicians are also encouraged to assess HIV risk during routine health visits to identify people who would benefit from PrEP. Clinicians should elicit information about patients' anatomy and sexual partners in a culturally sensitive and affirming manner to determine which PrEP regimens - daily oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC), on-demand TDF/FTC, daily oral tenofovir alafenamide/emtricitabine, or long-acting injectable cabotegravir - are suitable options. When assessing whether PEP is needed, clinicians should consider the likelihood that the source person has transmissible HIV, as well as the biological risk of HIV transmission based on exposure type. Preferred PEP regimens are dolutegravir plus TDF/FTC, or bictegravir/tenofovir alafenamide/emtricitabine.InterpretationMultiple safe, effective PrEP and PEP regimens are now available in Canada, making it increasingly possible to find suitable options for all who could benefit. Implementation of this guideline should expand access to biomedical HIV prevention interventions for those at risk and decrease the incidence of HIV in Canada.

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BackgroundThe World Health Organization recommends antiretroviral therapy (ART) for pregnant women living with HIV (WLHIV), the vast majority of whom reside in sub-Saharan Africa. In recent years, many systematic reviews, meta-analyses, and randomised controlled trials (RCTs) have been performed to assess the risks of adverse perinatal outcomes associated with ART among WLHIV. The aim of this umbrella review is to assess the available evidence regarding the risks of adverse perinatal outcomes for WLHIV receiving ART.MethodsWe conducted a systematic literature review by searching Medline, Global Health, and EMBASE and two clinical trial databases (ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform) for meta-analyses and RCTs published between 1 January 1980 and 12 February 2026. We included meta-analyses and RCTs reporting on the association of pregnant WLHIV receiving ART with perinatal outcomes, compared to WLHIV receiving different ART regimens, WLHIV naïve to ART, and women without HIV. We also included studies that assessed the timing of ART initiation (preconception or antenatal). Twelve predefined perinatal outcomes were assessed: preterm birth (PTB), very PTB (VPTB), spontaneous PTB (sPTB), low birthweight (LBW), very LBW (VLBW), term and preterm LBW, small for gestational age (SGA), very SGA (VSGA), stillbirth, neonatal death, and vertical HIV transmission. Heterogeneity measures (I 2 ) and Peter's test results for publication bias were extracted and assessed. The quality of meta-analyses was assessed using the AMSTAR 2 tool, risk of bias of RCTs was assessed using the Cochrane Risk of Bias tool, and overall certainty of evidence for each exposure comparison and perinatal outcome was assessed according to GRADE. The protocol is registered with PROSPERO, number CRD42021248987.FindingsOf 14,279 studies identified, we included nine meta-analyses of cohort studies, one network meta-analysis of seven RCTs, and three additional RCTs. The meta-analyses were composed of a total of 154 cohort studies and were of low or critically low quality, and RCTs had a high risk of bias. Meta-analyses of cohort studies found that WLHIV receiving ART are at increased risks of PTB (risk ratio (RR) 1.55, 95% confidence interval (CI) 1.38-1.74, I 2 87.4%), sPTB (RR 2.10, 95% CI 1.48-2.96, I 2 12.5%), LBW (RR 1.79, 95% CI 1.51-2.13, I 2 90.6%), term LBW (RR 1.88, 95% CI 1.23-2.85, I 2 0.0%), SGA (RR 1.80, 95% CI 1.34-2.40, I 2 97.6%), and VSGA (RR 1.22, 95% CI 1.10-1.34, I 2 0.0%), compared to HIV-negative women. RCTs comparing ART regimens among WLHIV found few differences in perinatal outcomes assessed. Meta-analyses of cohort studies comparing different ART regimens found that protease inhibitors are associated with an increased risk of SGA (RR 1.28, 95% CI 1.09-1.51, I 2 62.2%) and VSGA (RR 1.41, 95% CI 1.08-1.83, I 2 0.0%), compared to non-nucleoside reverse transcriptase inhibitors. Tenofovir disoproxil fumarate is associated with a lower risk of adverse perinatal outcomes and zidovudine is associated with an increased risk of perinatal outcomes. Compared to HIV-negative women, WLHIV receiving ART remain at increased risk of adverse perinatal outcomes, irrespective of the ART regimen and timing of ART initiation. Publication bias, as determined using the Peter's test, was found for two analyses. Most findings were of low or very low certainty as assessed using GRADE.InterpretationWLHIV receiving ART are associated with increased risks of adverse perinatal outcomes compared to HIV-negative women, irrespective of the ART regimen and timing of ART initiation. To strengthen the evidence base for ART guidelines for pregnant WLHIV, more and larger RCTs and high quality observational studies are needed to optimise ART regimens in pregnancy. Further efforts should be made to improve perinatal outcomes among WLHIV.FundingThis study received no funding.

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ObjectiveThis study evaluated rates of treatment-emergent resistance-associated mutations (TE-RAMs) and discontinuation due to adverse events (DC-AEs) across integrase strand transfer inhibitor (INSTI)-based single-tablet regimens and injectable cabotegravir + rilpivirine (CAB + RPV) in virologically suppressed people with HIV.MethodsA systematic literature review was conducted for phase 2-4 randomized controlled trials with ≥48 weeks of follow-up involving virologically suppressed people with HIV aged ≥12 years and published January 2003-March 2024. A random-effects network meta-analysis estimated comparative rates of TE-RAMs and DC-AEs among regimens at 48 weeks. Risk of bias and strength of evidence were assessed using Cochrane RoB and CINeMA, respectively.ResultsFourteen (7509 participants) and nine (4656 participants) studies were included in the TE-RAMs and DC-AEs analyses, respectively. No significant differences in rates of TE-RAMs were observed; risk ratios (RRs) for TE-RAMs for bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF), dolutegravir/abacavir/lamivudine (DTG/ABC/3TC) and CAB + RPV every 4 weeks (Q4W) versus CAB + RPV every 8 weeks (Q8W) were 0.22 (95% CI, 0.02-2.04), 0.22 (95% CI, 0.00-19.85) and 0.40 (95% CI, 0.14-1.09). Compared with CAB + RPV Q4W and Q8W, DC-AEs were significantly lower with B/F/TAF (RR, 0.15 [95% CI, 0.03-0.75] and RR, 0.16 [95% CI, 0.04-0.67], respectively) and DTG/ABC/3TC (RR, 0.05 [95% CI, 0.01-0.48] and RR, 0.05 [95% CI, 0.01-0.46], respectively).ConclusionsIn virologically suppressed people with HIV, switching to CAB + RPV Q8W yielded a non-significant increased risk of TE-RAMs compared with INSTI-based 2- and 3-drug regimens and CAB + RPV Q4W. Both CAB + RPV Q4W and Q8W had significantly higher risks of DC-AEs than B/F/TAF and DTG/ABC/3TC. Findings highlight the importance of considering both resistance and tolerability when switching regimens.

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