HIV-positive women have higher risk of acquiring HPV, with risk inversely associated with CD4 cell count. ART lowered HPV acquisition, increased clearance, and reduced precancer progression, likely via immune reconstitution. Although some of our results are limited by small number of studies, our study can inform screening guidelines and mathematical modeling for cervical cancer prevention.
Polymers with advanced architectures can now be readily and reproducibly synthesized using controlled living polymerization. These materials are attractive as potential drug carriers due to their tunable size, versatile methods of drug incorporation and release, and ease of functionalization with targeting ligands. In this work, we report the design and development of macrocyclic brush, or “sunflower,” polymers, synthesized by controlled radical polymerization of hydrophilic “petals” from a cyclic multimacroinitiator “core.” These nanostructures can be synthesized with low polydispersity and controlled sizes depending on polymerization time. We further demonstrate that folate-functionalized sunflower polymers facilitate receptor-mediated uptake into cancer cells. These materials therefore show potential as drug carriers for anti-cancer therapies.
Polymeric delivery vehicles can improve the safety and efficacy of chemotherapy drugs by facilitating preferential tumor delivery. Polymer-drug conjugates are especially attractive carriers because additional formulation steps are not required during manufacturing, and drug release profiles can be altered based on linker choice. For clinical translation, these vehicles should also be reproducibly and controllably synthesized. Recently, we reported the development of a class of materials called “sunflower polymers,” synthesized by controlled radical polymerization of hydrophilic “petals” from a cyclic multimacroinitiator “core.” This synthesis strategy afforded control over the size of the polymer nanostructures based on their petal polymerization time. In this work, we demonstrate that particle size can be further tuned by varying the degree of polymerization of the cyclic core in addition to that of the petals. Additionally, we investigate the application of these materials for tumor-targeted drug delivery. We demonstrate that folate-targeted, doxorubicin-conjugated sunflower polymers undergo receptor-mediated uptake into cancer cells and pH-triggered drug release leading to cytotoxicity. These materials are attractive as drug carriers due to their discrete and small size, shielded drug cargo that can be triggered for release, and relative ease of synthesis.
Single dose 9vHPV vaccination is projected to avert substantial CC burden in South Africa and similar high HIV prevalence settings. Health benefits were comparable across all female subpopulations stratified by HIV status, CD4 count, and ART status.
This Minireview details the current state‐of‐the‐art relating to (co)polymerizations mediated by well‐defined RhI‐ethynyl, vinyl, and aryl complexes. In particular, we focus on RhI species suitable for the (co)polymerization of phenylacetylenes, arylisocyanides, as well as propargyl esters and amides.
IntroductionRoutine viral load monitoring for HIV‐1 management of persons on antiretroviral therapy (ART) has been recommended by the World Health Organization (WHO) to identify treatment failure. However, viral load testing represents a substantial cost in resource constrained health care systems. The central challenge is whether and how viral load monitoring may be delivered such that it maximizes health gains across the population for the costs incurred. We hypothesized that key features of program design and delivery costs drive the cost‐effectiveness of viral load monitoring within programs.MethodsWe conducted a systematic review of studies on the cost‐effectiveness of viral load monitoring in low‐ and middle‐income countries (LMICs). We followed the Cochrane Collaboration guidelines and the PRISMA reporting guidelines.Results and DiscussionWe identified 18 studies that evaluated the cost‐effectiveness of viral load monitoring in HIV treatment programs. Overall, we identified three key factors that make it more likely for viral load monitoring to be cost‐effective: 1) Use of effective, lower cost approaches to viral load monitoring (e.g. use of dried blood spots); 2) Ensuring the pathway to health improvement is established and that viral load results are acted upon; and 3) Viral load results are used to simplify HIV care in patients with viral suppression (i.e. differentiated care, with fewer clinic visits and longer prescriptions). Within the context of differentiated care, viral load monitoring has the potential to double the health gains and be cost saving compared to the current standard (CD4 monitoring).ConclusionsThe cost‐effectiveness of viral load monitoring critically depends on how it is delivered and the program context. Viral load monitoring as part of differentiated HIV care is likely to be cost‐effective. Viral load monitoring in differentiated care programs provides evidence that reduced clinical engagement, where appropriate, is not impacting health outcomes. Introducing viral load monitoring without differentiated care is unlikely to be cost‐effective in most settings and results in lost opportunity for health gains through alternative uses of limited resources. As countries scale up differentiated care programs, data on viral suppression outcomes and costs should be collected to evaluate the on‐going cost‐effectiveness of viral load monitoring as utilized in practice.
Background:
Efficient and scalable models for HIV treatment are needed to maximize health outcomes with available resources. By adapting services to client needs, differentiated antiretroviral therapy (DART) has the potential to use resources more efficiently. We conducted a systematic review assessing the cost of DART in sub-Saharan Africa compared with the standard of care.
Methods:
We searched PubMed, Embase, Global Health, EconLit, and the grey literature for studies published between 2005 and 2019 that assessed the cost of DART. Models were classified as facility-vs. community-based and individual- vs group-based. We extracted the annual per-patient service delivery cost and incremental cost of DART compared with standard of care in 2018 USD.
Results:
We identified 12 articles that reported costs for 16 DART models in 7 countries. The majority of models were facility-based (n = 12) and located in Uganda (n = 7). The annual cost per patient within DART models (excluding drugs) ranged from $27 to $889 (2018 USD). Of the 11 models reporting incremental costs, 7 found DART to be cost saving. The median incremental saving per patient per year among cost-saving models was $67. Personnel was the most common driver of reduced costs, but savings were sometimes offset by higher overheads or utilization.
Conclusions:
DART models can save personnel costs by task shifting and reducing visit frequency. Additional economic evidence from community-based and group models is needed to better understand the scalability of DART. To decrease costs, programs will need to match DART models to client needs without incurring substantial overheads.
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