Darunavir 800mg / Cobicistat 150mg / Emtricitabine 200mg / Tenofovir alafenamide 10mg tablets

The introduction of antiretroviral therapy (ART) has significantly prolonged the lifespan of people living with human immunodeficiency virus (PLWH). However, the sustained use of this drug regimen has also been associated with a cluster of metabolic anomalies, including renal toxicity, which can lead to the development of kidney diseases. In this study, we reviewed studies examining kidney disease in PLWH sourced from electronic databases such as PubMed/MEDLINE, Scopus, and Google Scholar, as well as gray literature. The narrative synthesis of data from these clinical studies demonstrated that the serum levels of cystatin C remained unchanged or were not affected in PLWH on ART, while the creatinine-based glomerular filtration rate (GFR) fluctuated. In fact, some of the included studies showed that the creatinine-based GFR was increased in PLWH taking tenofovir disoproxil fumarate-containing ART, perhaps indicating that the use of both cystatin C- and creatinine-based GFRs is vital to monitor the development of kidney disease in PLWH. Clinical data summarized within this study indicate the potential detrimental effects of tenofovir-based ART regimens in causing renal tubular injury, while highlighting the possible beneficial effects of dolutegravir-based ART on improving the kidney function in PLWH. However, the summarized literature remains limited, while further clinical studies are required to provide insights into the potential use of cystatin C as a biomarker for kidney disease in PLWH.

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BackgroundTreatment guidelines recommend rapid antiretroviral therapy (ART) initiation among eligible people with HIV to improve treatment outcomes and reduce HIV transmission. Bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF), an integrase strand transfer inhibitor-based single-tablet regimen, is recommended for rapid start in US and European guidelines. This systematic literature review synthesized evidence on the efficacy, safety and effect on patient-reported outcomes (PROs) of B/F/TAF rapid start among newly diagnosed people with HIV.MethodsMEDLINE, Embase, Cochrane Database of Systematic Reviews and Cochrane Central Register of Controlled Trials databases were searched in January 2024, supplemented by searches of conference proceedings and clinical trial records. English-language interventional studies of B/F/TAF rapid start among ART-naïve people with HIV reporting efficacy, safety or PROs were eligible. Study quality was assessed using York Centre for Reviews and Dissemination or Risk Of Bias In Non-randomized Studies of Interventions checklists. Results were synthesized narratively.ResultsAcross eight included studies, 745 people with HIV received B/F/TAF rapid start, 171 received rapid start comparators and 255 received non-rapid start comparators. At Weeks 24 and 48, 80%-94% and 74%-96% of people with HIV treated with B/F/TAF rapid start achieved viral load ConclusionsB/F/TAF rapid start was efficacious, safe and associated with high engagement in care and improved PROs.

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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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