Efavirenz 600mg / Emtricitabine 200mg / Tenofovir disoproxil 245mg tablets

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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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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IntroductionPre- and post-exposure prophylaxis (PrEP and PEP) are important pillars of the HIV prevention portfolio to reduce the risk of acquisition just before or after HIV exposure. While PrEP efficacy has been elucidated in many randomized clinical trials, corresponding data for PEP is extremely difficult to obtain in a controlled setting. Consequently, it is almost impossible to study the impact of PEP initiation delay and duration on HIV risk reduction clinically, which would inform recommendations on PEP use.MethodsWe employ pharmacokinetics, pharmacodynamics and viral dynamics models, along with individual factors, such as drug adherence to investigate the impact of initiation delay and PEP duration on HIV risk reduction. We evaluated PEP using two- and three-drug regimens with a TDF/FTC backbone. Moreover, we study PEP efficacy in the context of PrEP-to-PEP transitions.ResultsIn our simulations, early initiation of PEP emerged as a pivotal factor for HIV risk reduction. We found that 2-drug (TDF/FTC) PEP may insufficiently protect when initiated > 1 hour post-exposure. When adding a third drug, early initiation was still a critical factor; however, over 90% efficacy could be achieved when PEP was initiated 48 hours post-exposure and taken for at least 14-28 days, depending on the efficacy of the third-drug component. When investigating PrEP-PEP transitions, we observed that preceding PrEP can (1) contribute directly to prophylactic efficacy, and (2) boost subsequent PEP efficacy by delaying initial viral dynamics and building-up drug concentrations, overall facilitating self-managed transitioning between PrEP and PEP.ConclusionsOur study confirms the critical role of early (< 48 hours) PEP initiation, preferably with three drugs taken for 28 days. Self-start with TDF/FTC and later addition of a third drug is better than not self-starting. Furthermore, our study highlights the synergy between recent PrEP intake and PEP and may help to inform recommendations on PEP use.

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