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Purpose of Review: Recent research on efficacy and safety of long-acting preexposure prophylaxis (PrEP) holds the promise to transform HIV prevention in high HIV burden settings. We review emerging findings regarding early end-user acceptability of long-acting PrEP modalities, feasibility of integrating long-acting PrEP into health systems, and considerations regarding drug resistance and cost., Recent Findings: Long-acting PrEP, particularly injectables, was found to be highly acceptable among individuals across key populations in high HIV burden settings. Concerns around use of long-acting PrEP highlight the importance of choice and ability to switch methods. Existing provider-level barriers to oral PrEP implementation (e.g., overburdened staff, training gaps) may impact long-acting PrEP rollout - however, utilization of PrEP implementation strategies such as task-shifting, timely PrEP training for all providers, differentiated service delivery, and integration with sexual health services, may mitigate barriers. Studies modeling injectable PrEP scale-up demonstrate substantial benefits in HIV mortality reduction, outweighing risks of increased integrase inhibitor resistance, but also highlight the urgency of pricing long-acting PrEP to ensure access and affordability., Summary: Long-acting PrEP could be a game changer in HIV prevention in high burden settings. There is an urgent need for rapid scale production and price reductions to ensure access in high HIV burden settings. Implementation strategies are needed to address individual and provider-level barriers., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: There are few data on tenofovir-diphosphate (TFV-DP) concentrations in pregnant and postpartum women on Tenofovir Disoproxil Fumarate-Emtricitabine (TDF-FTC) or Tenofovir Alafenamide-Emtricitabine (TAF-FTC)., Methods: Eligible pregnant women were randomized to TDF-FTC or TAF-FTC and followed for 16 weeks (8-weeks pregnant, 8-weeks postpartum) with weekly collection of dried blood spot (DBS) and 4-weekly peripheral blood mononuclear cells (PBMC). PrEP dosing was observed daily via asynchronous videos sent via cell phone. We report geometric means (GM) and their ratios (GMR) with 95% confidence intervals (CIs) for TFV-DP in PBMC and DBS from pregnancy and postpartum., Results: We enrolled N = 39 participants (n = 19 TDF-FTC, n = 20 TAF-FTC): median age was 28 years (IQR:25-34); median gestational age was 24-weeks (IQR:21-28). For TDF-FTC, TFV-DP DBS concentrations at 8-weeks did not differ significantly between pregnancy (GM: 675; 95%CI:537-849) and postpartum (GM: 583; 95%CI:471-722; GMR-TDF = 1.16; 95%CI:0.74-1.80). For TAF-FTC, TFV-DP DBS concentrations at 8-weeks were 44% higher in postpartum (GM: 1199; 95%CI:929-1549) versus pregnancy (GM: 832; 95%CI:751-922; GMR-TAF = 1.44; 95% CI: 1.01-2.06). In PBMC analysis of TDF-FTC, 8-week median TFV-DP (pmol/10^6 cell) was 71 (IQR 44-112) in pregnancy and 73 (IQR 50-102) in postpartum (GMR = 1.04; 95%CI:0.44-2.44). In TAF-FTC, median PBMC at 8-weeks was 580 (IQR:341-985) in pregnancy and 666 (IQR:396-1123) in postpartum (GMR = 1.15; 95%CI:0.30-2.49)., Conclusion: TFV-DP concentrations were overall lower during pregnancy than postpartum for TAF-FTC. We found high concentrations of TFV-DP in PBMC in pregnancy and postpartum on TAF-FTC, suggesting PrEP efficacy is maintained. Efficacy and safety studies are warranted to evaluate TAF-FTC for PrEP in pregnant and postpartum women., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)