PLoS Medicine articles
All articles on PLoS Medicine are open access, and often include additional comment.
Next stop, don’t block the doors: opening up access to clinical trials results
Under FDAAA, enrollment and outcomes data from trials of drugs, biologics, and devices (excluding phase I trials) must appear in an open repository associated with the trial’s registration, generally within a year of the trial’s completion, whether or not these results have been published. The new law is innovative in bridging the gap between a clinical trial’s registration at inception (now an established requirement for publication) and the public archiving of its final peer-reviewed report.
Safety outcomes must be posted as of 2009, and further information may be required in future years. These are not just recommendations; the law imposes fines of up to US$10,000 per day for noncompliance.
Minority HIV-1 drug resistance mutations are present in antiretroviral treatment-naive populations and associate with reduced treatment efficacy
Johnson JA et al.
These data suggest that a considerable proportion of transmitted HIV-1 drug resistance is undetected by conventional genotyping and that minority mutations can have clinical consequences. With no treatment history to help guide therapies for drug-naive persons, the findings suggest an important role for sensitive baseline drug resistance testing.
Transmitted Minority Drug-Resistant HIV Variants: A New Epidemic?
Steven G. Deeks
Despite high rates of viral turnover and viral evolution, HIV has proven to be surprisingly easy to suppress with combination antiretroviral therapy (ART) in the regions of the world where such treatment is available. Recent reports indicate that the vast majority of patients initiating ART should be able to achieve durable if not indefinite viral suppression. Given that there are now over 20 antiretroviral drugs from six unique classes, even if one regimen fails, others are often readily available. The emerging consensus among clinicians and clinical investigators is that fewer and fewer patients will generate highly resistant HIV during the course of their treatment.
A vaccine against nicotine for smoking cessation: a randomised controlled trial
Jacques Cornuz et al.
Whereas Nicotine-Q did not significantly increase continuous abstinence rates in the intention-to-treat population, subgroup analyses of the per-protocol population suggest that such a vaccination against nicotine can significantly increase continuous abstinence rates in smokers when sufficiently high antibody levels are achieved. Immunotherapy might open a new avenue to the treatment of nicotine addiction
Immunological outcomes of new tuberculosis vaccine trials: WHO panel recommendations
Hanekom WH et al.
Scaling up programmatic management of drug-resistant tuberculosis: a prioritised research agenda
Cobelens FGJ et al.
Evidence-based tuberculosis diagnosis
Pai M et al.
Can a topical microbicide prevent rectal HIV transmission?
Florian Hladik and Charlene S. Dezzutti
The researchers investigated whether rectal simian immunodeficiency virus (SIV) transmission in macaques could be prevented by the topical pre-exposure application of tenofovir gel. Rectal SIV or HIV challenge bears a much higher transmission probability than vaginal challenge. With some caveats, as discussed further below, successful prevention of rectal transmission is therefore likely to have a better predictive value for human trials than vaginal challenge models. Moreover, anal intercourse in heterosexual populations has been underestimated in the past, and means to prevent rectal HIV transmission are thus urgently needed for both women and men who have unprotected anal intercourse.
Prevention of SIV rectal transmission and priming of T cell responses in macaques after local pre-exposure application of tenofovir gel
Martin Cranage M et al.
These results indicate that colorectal pretreatment with ARV drugs, such as tenofovir, has potential as a clinically relevant strategy for the prevention of HIV transmission. We conclude that plasma tenofovir concentration measured 15 min after rectal administration may serve as a surrogate indicator of protective efficacy. This may prove to be useful in the design of clinical studies. Furthermore, in vitro intestinal explants served as a model for drug distribution in vivo and susceptibility to virus infection. The finding of T cell priming following exposure to virus in the absence of overt infection is provocative. Further studies would reveal if a combined modality microbicide and vaccination strategy is feasible by determining the full extent of local immune responses induced and their protective potential.