Efficacy and safety of long‐acting cabotegravir versus oral tenofovir disoproxil fumarate‐emtricitabine as HIV pre‐exposure prophylaxis: A systematic review and meta‐analysis

Abstract

WHO guidelines recommend daily oral tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) for pre-exposure prophylaxis (PrEP) of HIV in people at high risk of HIV infection. However, due to social, psychological and other reasons, the compliance with daily oral TDF-FTC in real life is low. Long-acting cabotegravir is currently the only long-acting drug approved by the U.S. Food and Drug Administration (FDA) for HIV PrEP. Due to the long dosing interval (8 weeks), long-acting cabotegravir has low compliance requirements for people at high risk of HIV infection. We aimed to discuss the feasibility of long-acting cabotegravir to replace TDF-FTC as HIV PrEP based on efficacy and safety analyses. Randomized controlled trials were retrieved, and R software was used for meta-analysis after data extraction. and discussion: Results of the meta-analysis showed that compared with TDF-FTC, long-acting cabotegravir was associated with a lower risk of HIV infection (HR = 0.22, 95% CI: 0.08-0.59, p < 0.01), less decreased creatinine clearance (RR = 0.96, 95% CI: 0.93-0.99, p < 0.01), but more tolerated injection sites adverse events (p < 0.01). No statistically significant differences were found between longacting cabotegravir and oral placebo in non-injection-related adverse events (creatine phosphokinase, headache, nasopharyngitis, upper respiratory tract infection and gastroenteritis) (p > 0.05). Long-acting cabotegravir has a manageable safety profile and is more effective than TDF-FTC in preventing HIV infection. Interestingly, decreased creatinine clearance occurred less frequently with long-acting cabotegravir than with TDF-FTC. Long-acting cabotegravir is very promising to replace TDF-TFC in the future, which requires more large-sample, high-quality RCTs to verify.

Changes in inflammatory biomarkers and lipid profiles after switching to long-acting cabotegravir plus rilpivirine

“…In this study, serum creatinine decreased after switching to CAB plus RPV LA, regardless of the preswitching regimen. Unlike DTG, bictegravir, ritonavir or cobicistat, CAB does not inhibit the renal organic cation transporter (OCT) 2 or the multidrug and toxin extrusion transporter (MATE) 1 and therefore is unlikely to inhibit tubular secretion of creatinine [24]. Although the detailed analysis will be left for future studies due to the different objectives of the study, it is important to examine the effect of CAB on renal function.…”