Progress towards Elimination of HIV Mother-to-Child Transmission in the Dominican Republic from 1999 to 2011

In 1999, prevention of mother-to-child transmission (pMTCT) using antiretrovirals was introduced in the Dominican Republic (DR). Highly active antiretroviral therapy (HAART) was introduced for immunosuppressed persons in 2004 and for pMTCT in 2008. To assess progress towards MTCT elimination, data from requisitions for HIV nucleic acid amplification tests for diagnosis of HIV infection in perinatally exposed infants born in the DR from 1999 to 2011 were analyzed. The MTCT rate was 142/1,274 (11.1%) in 1999–2008 and 12/302 (4.0%) in 2009–2011 (), with a rate of 154/1,576 (9.8%) for both periods combined. This decline was associated with significant increases in the proportions of women who received prenatal HAART (from 12.3% to 67.9%) and infants who received exclusive formula feeding (from 76.3% to 86.1%) and declines in proportions of women who received no prenatal antiretrovirals (from 31.9% to 12.2%) or received only single-dose nevirapine (from 39.5% to 19.5%). In 2007, over 95% of DR pregnant women received prenatal care, HIV testing, and professionally attended delivery. However, only 58% of women in underserved sugarcane plantation communities (2007) and 76% in HIV sentinel surveillance hospitals (2003–2005) received their HIV test results. HIV-MTCT elimination is feasible but persistent lack of access to critical pMTCT measures must be addressed.

Synthesis and Biological Evaluation of Novel Folic Acid Receptor-Targeted, β-Cyclodextrin-Based Drug Complexes for Cancer Treatment

Drug targeting is an active area of research and nano-scaled drug delivery systems hold tremendous potential for the treatment of neoplasms. In this study, a novel cyclodextrin (CD)-based nanoparticle drug delivery system has been assembled and characterized for the therapy of folate receptor-positive [FR(+)] cancer. Water-soluble folic acid (FA)-conjugated CD carriers (FACDs) were successfully synthesized and their structures were confirmed by 1D/2D nuclear magnetic resonance (NMR), matrix-assisted laser desorption ionization time-of-flight mass spectrometer (MALDI-TOF-MS), high performance liquid chromatography (HPLC), Fourier transform infrared spectroscopy (FTIR), and circular dichroism. Drug complexes of adamatane (Ada) and cytotoxic doxorubicin (Dox) with FACD were readily obtained by mixed solvent precipitation. The average size of FACD-Ada-Dox was 1.5–2.5 nm. The host-guest association constant Ka was 1,639 M−1 as determined by induced circular dichroism and the hydrophilicity of the FACDs was greatly enhanced compared to unmodified CD. Cellular uptake and FR binding competitive experiments demonstrated an efficient and preferentially targeted delivery of Dox into FR-positive tumor cells and a sustained drug release profile was seen in vitro. The delivery of Dox into FR(+) cancer cells via endocytosis was observed by confocal microscopy and drug uptake of the targeted nanoparticles was 8-fold greater than that of non-targeted drug complexes. Our docking results suggest that FA, FACD and FACD-Ada-Dox could bind human hedgehog interacting protein that contains a FR domain. Mouse cardiomyocytes as well as fibroblast treated with FACD-Ada-Dox had significantly lower levels of reactive oxygen species, with increased content of glutathione and glutathione peroxidase activity, indicating a reduced potential for Dox-induced cardiotoxicity. These results indicate that the targeted drug complex possesses high drug association and sustained drug release properties with good biocompatibility and physiological stability. The novel FA-conjugated β-CD based drug complex might be promising as an anti-tumor treatment for FR(+) cancer.