Objective To compare the immunogenicity of one vs. two doses of meningococcal conjugate vaccine (MCV4) in youth infected with HIV. Study design P1065 was a Phase I/II immunogenicity and safety trial of MCV4 in 324 youth infected with HIV performed at 27 sites of the IMPAACT network in the U.S. At entry subjects received one dose of MCV4. At 24 weeks, those with screening CD4% ≥15 were randomized to receive a second dose or not, and all with screening CD4% <15 received a second dose. Immunogenicity was evaluated as the proportion of subjects with a ≥4-fold rise from entry in serum bactericidal antibody against each meningococcal serogroup at weeks 28 and 72. Logistic regression models adjusting for HIV disease severity were used to evaluate the effect of one vs. two MCV4 doses among those with screening CD4% ≥15. Results Subjects randomized to receive two vs. one MCV4 dose had significantly higher response rates to all serogroups at week 28 and to all except N meningitidis serogroupY at week 72, with adjusted ORs of 2.5–5.6. In 31 subjects with screening CD4% <15 who received two MCV4 doses, response rates ranged from 22–55% at week 28 and 6–28% at week 72. Conclusion In youth infected with HIV with a CD4% ≥15, a second dose of MCV4 given six months after the initial dose significantly improves response rates at 28 and 72 weeks. Subjects with CD4% <15 at entry had lower response rates despite 2 doses of MCV4.
Background Alternatives to the available stavudine-containing paediatric fixed-dose combination (FDC) tablets are rapidly needed due to concerns regarding the cumulative toxicity of long-term stavudine exposure. We report the bioavailability and short-term safety of a novel paediatric FDC tablet of zidovudine (ZDV)/lamivudine (3TC)/nevirapine (NVP; 30/15/28 mg) in HIV-infected children. Methods In this Phase I/II open-label pharmacokinetic study, 42 children weighing 6–30 kg treated with NVP-based HAART for ≥4 weeks were randomized to receive the FDC tablets (GPO-VIR Z30) or the liquid formulations. Dosing was weight-based. Intensive 12-h blood sampling was performed after 2 weeks; subjects then crossed-over to the alternate formulation at equal doses and sampling repeated 2 weeks later. Pharmacokinetic parameters were determined by non-compartmental analysis. Buccal-swab samples were collected for cytochrome P450 (CYP)2B6 polymorphism analysis. Results With the FDC tablet, the geometric mean (90% CI) area under the curve (AUC) for ZDV, 3TC and NVP was 1.58 (1.49–1.68), 7.78 (7.38–8.19) and 68.88 (62.13–76.36) μg•h/ml, respectively. Rules for NVP therapeutic inadequacy were defined a priori, and despite lower NVP exposure with the tablet (P<0.001), the levels remained therapeutically adequate. ZDV AUC was similar between formulations. 3TC exposure was significantly higher with the tablet but comparable to historical data in adults and children taking branded tablets. While receiving the tablet, NVP AUC in children with CYP2B 516 GG (45%), GT (45%) and TT (10%) genotypes were 67.0, 74.5 and 106.4 μg•h/ml, respectively (P=0.04). Conclusions Disparities in drug exposure between formulations were observed; however, the FDC tablet delivered therapeutically adequate exposures of each drug and could well play an important role in simplifying antiretroviral treatment for children.
The interaction between the human host micro biome and over the counter products has recently been investigated, with surprising results. Some over the counter items may negatively affect the health of the host, supporting the concept of the “hygiene hypothesis”, that is, that disease may be actually caused by the lack of beneficial commensal bacteria. Recent reports on the gluten metabolizing genus, Rothia, and a possible association with Celiac Disease beg the question, what happened to the Rothia? In this study inhibitory factors, such as, Over The Counter oral hygiene products and antagonistic bacteria were investigated and, in vitro, significantly inhibited the gluten metabolizing bacteria, possibly affecting human digestion and contributing to gluten sensitivity.
This pilot study of Streptococcus mutans ATCC 35668 grown in media with and without polyols (erythritol) measured the resultant metabolites, including the short chain fatty acids by using head space analysis. Brain Heart Infusion Broth (BHI2 or BHI10) supplemented with 2% or 10% sucrose containing no polyols or either erythritol or xylitol and Streptococcus mutans (ATCC 35668) was grown aerobically. After 48 hours of growth the supernatant were harvested and centrifuged to pellet bacteria. Supernatants were removed from bacterial pellets then submitted for Short Chain Fatty Acid (SCFA) analysis with an Agilent Technologies (Santa Clara, CA 95051) system configured from three components, a 5973 mass selective detector, a 6890N gas chromatographer, and a 7697A headspace sampler. Streptococcus mutans growing in Brain Heart Infusion Broth (BHI2 or BHI10) supplemented with 2% or 10% sucrose but containing no polyols produced the following short chain fatty acids: methyl isovalerate, acetic acid, propionic acid, butanoic acid, pentanoic acid, ethyl butaric acid, 4-methylvaleric acid, hexanoic acid. When the Brain Heart Infusion Broth (BHI2 or BHI10) supplemented with 2% or 10% sucrose containing erythritol was used as media for this Streptococcus mutans strain, the following were produced: ethanol, acetoin, and acetic acid. Our results would suggest that constituents of the media may affect the bacterial metabolite production.
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