Estimating the individualized HIV-1 genetic barrier to resistance using a nelfinavir fitness landscape

<p>Abstract</p> <p>Background</p> <p>Failure on Highly Active Anti-Retroviral Treatment is often accompanied with development of antiviral resistance to one or more drugs included in the treatment. In general, the virus is more likely to develop resistance to drugs with a lower genetic barrier. Previously, we developed a method to reverse engineer, from clinical sequence data, a fitness landscape experienced by HIV-1 under nelfinavir (NFV) treatment. By simulation of evolution over this landscape, the individualized genetic barrier to NFV resistance may be estimated for an isolate.</p> <p>Results</p> <p>We investigated the association of estimated genetic barrier with risk of development of NFV resistance at virological failure, in 201 patients that were predicted fully susceptible to NFV at baseline, and found that a higher estimated genetic barrier was indeed associated with lower odds for development of resistance at failure (OR 0.62 (0.45 - 0.94), per additional mutation needed, p = .02).</p> <p>Conclusions</p> <p>Thus, variation in individualized genetic barrier to NFV resistance may impact effective treatment options available after treatment failure. If similar results apply for other drugs, then estimated genetic barrier may be a new clinical tool for choice of treatment regimen, which allows consideration of available treatment options after virological failure.</p

Effects of body size on estimation of mammalian area requirements

Accurately quantifying species’ area requirements is a prerequisite for effective area‐based conservation. This typically involves collecting tracking data on species of interest and then conducting home‐range analyses. Problematically, autocorrelation in tracking data can result in space needs being severely underestimated. Based on previous work, we hypothesized the magnitude of underestimation varies with body mass, a relationship that could have serious conservation implications. To evaluate this hypothesis for terrestrial mammals, we estimated home‐range areas with GPS locations from 757 individuals across 61 globally distributed mammalian species with body masses ranging from 0.4 to 4,000 kg. We then applied block cross‐validation to quantify bias in empirical home‐range estimates. Area requirements of mammals 1, meaning the scaling of the relationship changed substantially at the upper end of the mass spectrum

Association Between Use of Specific Drugs and Antiretroviral Adherence: Findings from MACH 14

To determine the association between individual substances of abuse and antiretroviral adherence, analyses require a large sample assessed using electronic data monitoring (EDM). In this analysis, EDM data from 1636 participants in 12 U.S. adherence-focused studies were analyzed to determine the associations between recent use of various substances and adherence during the preceding four weeks. In bivariate analyses comparing adherence among patients who had used a specific substance to those who had not, adherence was significantly lower among those who had recently used cocaine, other stimulants or heroin but not among those who had used cannabis or alcohol. In multivariate analyses controlling for sociodemographics, amount of alcohol use and recent use of any alcohol, cocaine, other stimulants and heroin each was significantly negatively associated with adherence. The significant associations of cocaine, other stimulants, heroin, and alcohol use with adherence suggest that these are important substances to target with adherence-focused interventions

Mortality from HIV and TB coinfections is higher in Eastern Europe than in Western Europe and Argentina

Membro del HIV/TB Study Writing Group per la ricerca collaborativa pubblicata sulla rivista: AID

Death rates in HIV-positive antiretroviral-naive patients with CD4 count greater than 350 cells per microL in Europe and North America: a pooled cohort observational study

Whether people living with HIV who have not received antiretroviral therapy (ART) and have high CD4 cell counts have higher mortality than the general population is unknown. We aimed to examine this by analysis of pooled data from industrialised countries