Emtricitabine 200mg / Rilpivirine 25mg / Tenofovir alafenamide 25mg tablets

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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Objective: Integrase inhibitors, including dolutegravir (DTG), are associated with weight gain and obesity, especially when combined with tenofovir alafenamide (TAF). Obesity increases the risk of adverse pregnancy outcomes (APOs). This study aimed to predict the risk of APOs caused by treatment-associated obesity, using a hypothetical sample based on the ADVANCE trial. Design: Risk prediction. Methods: Firstly, a meta-analysis was performed to determine the relative risk (RR) for APOs in women with obese (≥30) versus normal prepregnancy BMIs (18.5–24.9). For the hypothetical sample, 3000 nonpregnant women with normal BMIs at Week 0 of treatment were evenly allocated across the following treatment arms: TAF/FTC+DTG, TDF/FTC+DTG, TDF/FTC/EFV. The treatment-associated obesity rates from ADVANCE were used to calculate the number of women with obese and normal BMIs expected at Week 96 in our sample. This was combined with the APO RRs to predict the number of women at risk of APOs, in each treatment arm, assuming they conceived at Week 96. Results: At Week 96, the percentage of women predicted to be obese was 14.1% with TAF/FTC+DTG, 7.9% with TDF/FTC+DTG and 1.5% with TDF/FTC/EFV. The RR in women with obese versus normal BMIs was significantly higher for most APOs. Therefore, the number of women at risk of APOs was higher with TAF/FTC+DTG than TDF/FTC+DTG and TDF/FTC/EFV. For example, 11/1000 additional gestational hypertension cases were predicted with TAF/FTC+DTG, 6/1000 with TDF/FTC+DTG and 1/1000 with TDF/FTC/EFV. Conclusion: Treatment-associated obesity increased the APO risk in women. This risk is likely to increase, as preliminary data from ADVANCE demonstrates ongoing weight gain beyond Week 96.

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Abstract Background Doravirine/islatravir is an investigational regimen that is being studied for human immunodeficiency virus type 1 (HIV-1) treatment. Methods In this phase 3, double-blind, double-dummy trial (ClinicalTrials.gov NCT04233879), previously untreated adults with HIV-1 were randomized (1:1) and stratified by HIV-1 RNA (≤/>100 000 copies/mL) and CD4 count (</≥200 cells/µL) to doravirine/islatravir (100/0.75 mg) or bictegravir/emtricitabine/tenofovir alafenamide (50/200/25 mg) orally once-daily (primary endpoint: percentage of participants with HIV-1 RNA <50 copies/mL at week 48; US Food and Drug Administration snapshot, 10% noninferiority margin). Results Overall, 597 participants were treated; enrollment stopped early due to decreases in CD4 and lymphocyte counts observed in other islatravir studies. Doravirine/islatravir was noninferior to bictegravir/emtricitabine/tenofovir alafenamide: 265 of 298 (88.9%) versus 264 of 299 (88.3%) had HIV-1 RNA <50 copies/mL (difference, 0.5%; 95% confidence interval [CI]: −4.7, 5.6). Mean change from baseline in CD4 count was +182 and +234 cells/µL (difference, −50; 95% CI: −79, −21) with doravirine/islatravir versus bictegravir/emtricitabine/tenofovir alafenamide. Mean change in lymphocyte count was 0.01 and 0.21 × 109/L (difference, −0.20; 95% CI: −0.30, −0.10). Adverse events (AEs) occurred in 90.6% and 87.3% of participants, with coronavirus disease 2019 being most common (14.1%, 16.4%). Treatment-related AEs were similar (28.9%, 25.8%). AEs that led to discontinuations were higher with doravirine/islatravir (8.7%, 3.7%) due to protocol-specified criteria that required discontinuation for decreased CD4 and lymphocyte counts. Conclusions Doravirine/islatravir (100/0.75 mg) once-daily was noninferior to bictegravir/emtricitabine/tenofovir alafenamide through week 48 for initial HIV-1 treatment. Due to decreases in CD4 and lymphocyte counts, development of this dose of doravirine/islatravir was stopped. Clinical Trials Registration NCT04233879.

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