Dolutegravir 50mg / Rilpivirine 25mg tablets

Long-acting antiretroviral therapy (ART) has emerged as an innovative strategy to address limitations associated with daily oral regimens in people living with human immunodeficiency virus type 1 (HIV-1), including adherence barriers, treatment fatigue, and social stigma. This systematic review, conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines and registered in International Prospective Register of Systematic Reviews (PROSPERO, CRD420251155009), identified randomized clinical trials comparing long-acting injectable cabotegravir and rilpivirine (CAB/RPV-LA) with standard daily oral ART through searches of PubMed, ScienceDirect, the Cochrane Library, and Google Scholar. Ten randomized trials involving 5,619 adults with HIV-1 were included. CAB/RPV-LA, administered intramuscularly every four or eight weeks, achieved durable virological suppression exceeding 90% across follow-up periods of 48 to 240 weeks, demonstrating non-inferiority to daily oral ART. Patient-reported outcomes consistently favored the injectable regimen, with higher treatment satisfaction scores and excellent adherence within the dosing window, while adverse events were mainly mild-to-moderate injection-site reactions (ISRs), resulting in treatment discontinuation in fewer than 1% of participants. Overall, the certainty of evidence was high for virological efficacy and moderate for safety and satisfaction outcomes, supporting long-acting CAB/RPV-LA as an effective and well-tolerated alternative that improves adherence, convenience, and quality of life in long-term HIV management.

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ImportancePediatric human immunodeficiency virus (HIV) infection continues to pose a significant global health burden, especially in low- and middle-income countries. Despite advances in antiretroviral therapy (ART), children living with HIV face unique clinical, developmental, and systemic challenges.ObjectiveTo systematically review recent developments in pediatric HIV care, with a focus on treatment innovations, complications, and the transition from pediatric to adult care.MethodsA comprehensive literature review was conducted across PubMed, Scopus, EMBASE, and the World Health Organization databases, covering studies published between 2012 and 2025. Inclusion criteria focused on original research, clinical trials, and guidelines addressing pediatric ART, long-acting therapies, prevention strategies, treatment complications, and transitional care.ResultsEarly ART initiation was associated with improved neurodevelopment and reduced disease progression. Current pediatric ART regimens favor simplified combinations and weight-based dosing, but pharmacokinetic variability, toxicity, and adherence remain concerns. Long-acting injectable therapies, such as cabotegravir/rilpivirine and investigational agents like lenacapavir and islatravir, show promise for adolescents. Prevention of mother-to-child transmission has significantly reduced pediatric HIV incidence, largely through maternal ART and pre-exposure prophylaxis. However, stigma, poor awareness, and healthcare disparities hinder broader impact. Children on lifelong ART face increased risks of metabolic, cardiovascular, renal, and neurocognitive complications. Transitioning to adult care remains a vulnerable period with high rates of treatment disengagement.InterpretationAdvances in pediatric HIV care are substantial but uneven. Continued investment in age-appropriate therapies, psychosocial support, and implementation research is essential to close persistent gaps and ensure equitable, lifelong care for children and adolescents living with HIV.

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Pharmacogenetics is a concept designed to tailor medication based on genetic profile to improve efficacy and reduce adverse effects. This personalized strategy shows considerable potential for populations facing complicated therapeutic challenges, such as the coinfected Tuberculosis (TB)-HIV population. This systematic review analyses pharmacogenes related to antiretroviral and anti-tuberculosis medications in the TB-HIV population. An analysis of 39 included studies indicated that efavirenz and CYP2B6*6 are the most extensively researched antiretroviral therapy (ART) and gene, respectively. Isoniazid and N-acetyltransferase 2 (NAT2) are the most extensively researched anti-TB drug and gene, respectively. Nevertheless, many studies relied solely on observational research and the investigation of pharmacokinetic characteristics. Research evaluated both the drug concentration of individual gene-drug interactions and the interactions between medications based on their genotypes. The NAT2 slow acetylator genotype is associated with elevated isoniazid levels, consequently increasing efavirenz plasma concentrations. Arylacetamide deacetylase (AADAC) polymorphisms that increased rifapentine plasma levels could also reduce dolutegravir plasma concentrations. Specific genes linked to significant outcomes in TB-HIV populations, such as pregnane X receptor (PXR) g.24087C>T, which increased the mortality rate. Consequently, a holistic approach to pharmacogenetics in TB-HIV populations is essential, considering all drug-gene-disease interactions. High-quality research, including randomized controlled trials (RCTs), is necessary for the implementation of pharmacogenetic testing in TB-HIV populations before it can be widely adopted in clinical practice, which is currently lacking.

Abstract licence: CC BY-NC

BackgroundThe long-acting injectable regimen of cabotegravir plus rilpivirine (CAB/RPV) emerged as an alternative to oral standard-of-care integrase strand transfer inhibitor (INSTI)-based regimens for individuals with adherence challenges or preference for reduced dosing schedules. Although oral INSTI regimens have a high barrier to emergent resistance, less is known about the potency and durability of CAB/RPV.MethodsWe reviewed clinical trial registries, PubMed, EMBASE, and conference abstract databases to identify reports of CAB/RPV for HIV therapy. We abstracted data on virologic failure (VF) and treatment-emergent INSTI resistance at 48 weeks (range: 24-52). We used single-proportion meta-analysis to summarize outcomes in 3 populations: antiretroviral therapy (ART)-naive individuals initiating CAB/RPV following suppression on oral ART, ART-experienced individuals switched to CAB/RPV with virologic suppression, and ART-experienced individuals switched to CAB/RPV with detectable viremia. Cochrane's RoB 2.0 and ROBINS-1 tools assessed risk of bias.ResultsThirty-three studies (N = 9224) reported VF prevalence. Nineteen studies (N = 5662) reported resistance data. VF prevalence was 1% (95% CI: 1%-3%) in induction-maintenance studies, 1% (1%-2%) in switch-suppressed studies, and 5% (3%-10%) in switch-viremic studies. INSTI resistance prevalence among successfully genotyped participants at failure was 71% (25%-95%), 61% (44%-75%), and 41% (20%-65%) respectively. Dolutegravir cross-resistance was common (64% of those with emergent resistance).ConclusionsAlthough VF rates with CAB/RPV were low, INSTI resistance emerged in approximately 40%-70% of individuals experiencing VF. These rates are significantly higher than those for oral INSTI-based regimens. Both individual-level and broader resistance surveillance may be warranted in populations with expanding CAB/RPV use. Clinical Trials Registration. PROSPERO registration CRD42024543919.

Abstract licence: CC BY-NC-ND