Long-acting injectable atovaquone nanomedicines for malaria prophylaxis.
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ABSTRACT:
SUBMITTER: Bakshi RP
PROVIDER: S-EPMC5778127 | biostudies-literature | 2018 Jan
REPOSITORIES: biostudies-literature
Publications
Long-acting injectable atovaquone nanomedicines for malaria prophylaxis.
Bakshi Rahul P RP Tatham Lee M LM Savage Alison C AC Tripathi Abhai K AK Mlambo Godfree G Ippolito Matthew M MM Nenortas Elizabeth E Rannard Steve P SP Owen Andrew A Shapiro Theresa A TA
Nature communications 20180122 1
Chemoprophylaxis is currently the best available prevention from malaria, but its efficacy is compromised by non-adherence to medication. Here we develop a long-acting injectable formulation of atovaquone solid drug nanoparticles that confers long-lived prophylaxis against Plasmodium berghei ANKA malaria in C57BL/6 mice. Protection is obtained at plasma concentrations above 200 ng ml<sup>-1</sup> and is causal, attributable to drug activity against liver stage parasites. Parasites that appear af ...[more]
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Project description:ObjectiveHIV remains a significant burden, despite expanding HIV prevention tools. Long-acting injectable cabotegravir (CAB-LA) is a new preexposure prophylaxis (PrEP) product. We reviewed existing evidence to determine the efficacy and safety of CAB-LA as PrEP to inform global guidelines.DesignSystematic review and meta-analysis.MethodsWe systematically reviewed electronic databases and conference abstracts for citations on CAB-LA from January 2010 to September 2021. Outcomes included HIV infection, adverse events, drug resistance, pregnancy-related adverse events, and sexual behavior. We calculated pooled effect estimates using random-effects meta-analysis and summarized other results narratively.ResultsWe identified 12 articles/abstracts representing four multisite randomized controlled trials. Study populations included cisgender men, cisgender women, and transgender women. The pooled relative risk of HIV acquisition comparing CAB-LA to oral PrEP within efficacy studies was 0.21 (95% confidence interval: 0.07-0.61), resulting in a 79% reduction in HIV risk. Rates of adverse events were similar across study groups. Of 19 HIV infections among those randomized to CAB-LA with results available, seven had integrase strand transfer inhibitor (INSTI) resistance. Data on pregnancy-related adverse events were sparse. No studies reported on sexual behavior.ConclusionsCAB-LA is highly efficacious for HIV prevention with few safety concerns. CAB-LA may lead to an increased risk of INSTI resistance among those who have acute HIV infection at initiation or become infected while taking CAB-LA. However, results are limited to controlled studies; more research is needed on real-world implementation. Additional data are needed on the safety of CAB-LA during pregnancy (for mothers and infants) and among populations not included in the trials.
| S-EPMC10090368 | biostudies-literature
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