Using viral sequence diversity to estimate time of HIV infection in infants.

Age at HIV acquisition may influence viral pathogenesis in infants, and yet infection timing (i.e. date of infection) is not always known. Adult studies have estimated infection timing using rates of HIV RNA diversification, however, it is unknown whether adult-trained models can provide accurate predictions when used for infants due to possible differences in viral dynamics. While rates of viral diversification have been well defined for adults, there are limited data characterizing these dynamics for infants. Here, we performed Illumina sequencing of gag and pol using longitudinal plasma samples from 22 Kenyan infants with well-characterized infection timing. We used these data to characterize viral diversity changes over time by designing an infant-trained Bayesian hierarchical regression model that predicts time since infection using viral diversity. We show that diversity accumulates with time for most infants (median rate within pol = 0.00079 diversity/month), and diversity accumulates much faster than in adults (compare previously-reported adult rate within pol = 0.00024 diversity/month [1]). We find that the infant rate of viral diversification varies by individual, gene region, and relative timing of infection, but not by set-point viral load or rate of CD4+ T cell decline. We compare the predictive performance of this infant-trained Bayesian hierarchical regression model with simple linear regression models trained using the same infant data, as well as existing adult-trained models [1]. Using an independent dataset from an additional 15 infants with frequent HIV testing to define infection timing, we demonstrate that infant-trained models more accurately estimate time since infection than existing adult-trained models. This work will be useful for timing HIV acquisition for infants with unknown infection timing and for refining our understanding of how viral diversity accumulates in infants, both of which may have broad implications for the future development of infant-specific therapeutic and preventive interventions.

Head Impact Exposure During a Weekend Youth Soccer Tournament.

Concussion is a known risk in youth soccer, but little is known about subconcussive head impacts. The authors provided a prospective cohort study measuring frequency and magnitude of subconcussive head impacts using accelerometry in a middle school-age soccer tournament, and association between head impacts and changes in (1) symptoms, (2) cognitive testing, and (3) advanced neuroimaging. A total of 17 youth completed the study (41% female, mean 12.6 years). There were 73 head impacts >15g measured (45% headers) and only 2 had a maximum peak linear acceleration >50g No youth reported symptoms consistent with concussion. After correction for multiple comparisons and a sensitivity analysis excluding clear outliers, no significant associations were found between head impact exposure and neuropsychological testing or advanced neuroimaging. The authors conclude that head impacts were relatively uncommon and low in acceleration in youth playing a weekend soccer tournament. This study adds to the limited data regarding head impacts in youth soccer.

Agreement between High School Athletes and Their Parents on Reporting Athletic Events and Concussion Symptoms.

An enhanced understanding of agreement levels between adolescents and parents for reporting athletic events and symptoms can help inform surveillance systems as well as clinical and epidemiological investigations of sports-related concussions. We sought to quantify agreement levels between high school athletes and parents for reporting: (1) number of games; (2) number of practices; (3) occurrence of an injury resulting in any concussion symptoms; and (4) presence of each specific symptom on the date of that injury among high school boys' football and girls' soccer athletes playing in Autumn 2012 in Washington State. There was substantial agreement on reporting the number of athletic events. Agreement levels were greater for games (kappa = 0.82; 95% confidence interval [CI]: 0.79-0.85 in boys' football; kappa = 0.75; 95% CI: 0.72-0.79 in girls' soccer) than for practices (kappa = 0.64; 95% CI: 0.62-0.67 in boys' football; kappa = 0.65; 95% CI: 0.62-0.67 in girls' soccer). There was moderate to substantial agreement on the occurrence of injury resulting in any concussion symptoms; however, agreement on the presence and severity of each symptom varied from poor to almost perfect. Overall, athletes reported greater severity of symptoms than parents did; notably, no difference in mean symptom scores was found when the athlete had a history of concussion. Agreement levels were greater when information was ascertained within 1 week of injury than when it was obtained later than 1 week. Including both athletes' and parents' reports of sports-related events and ascertaining information as soon as possible after injury are important considerations in designing injury surveillance systems.

Treatment-naive individuals are the major source of transmitted HIV-1 drug resistance in men who have sex with men in the Swiss HIV Cohort Study.

BACKGROUND: Human immunodeficiency virus type 1 (HIV-1) transmitted drug resistance (TDR) can compromise antiretroviral therapy (ART) and thus represents an important public health concern. Typically, sources of TDR remain unknown, but they can be characterized with molecular epidemiologic approaches. We used the highly representative Swiss HIV Cohort Study (SHCS) and linked drug resistance database (SHCS-DRDB) to analyze sources of TDR. METHODS: ART-naive men who have sex with men with infection date estimates between 1996 and 2009 were chosen for surveillance of TDR in HIV-1 subtype B (N = 1674), as the SHCS-DRDB contains pre-ART genotypic resistance tests for >69% of this surveillance population. A phylogeny was inferred using pol sequences from surveillance patients and all subtype B sequences from the SHCS-DRDB (6934 additional patients). Potential sources of TDR were identified based on phylogenetic clustering, shared resistance mutations, genetic distance, and estimated infection dates. RESULTS: One hundred forty of 1674 (8.4%) surveillance patients carried virus with TDR; 86 of 140 (61.4%) were assigned to clusters. Potential sources of TDR were found for 50 of 86 (58.1%) of these patients. ART-naive patients constitute 56 of 66 (84.8%) potential sources and were significantly overrepresented among sources (odds ratio, 6.43 [95% confidence interval, 3.22-12.82]; P < .001). Particularly large transmission clusters were observed for the L90M mutation, and the spread of L90M continued even after the near cessation of antiretroviral use selecting for that mutation. Three clusters showed evidence of reversion of K103N or T215Y/F. CONCLUSIONS: Many individuals harboring viral TDR belonged to transmission clusters with other Swiss patients, indicating substantial domestic transmission of TDR in Switzerland. Most TDR in clusters could be linked to sources, indicating good surveillance of TDR in the SHCS-DRDB. Most TDR sources were ART naive. This, and the presence of long TDR transmission chains, suggests that resistance mutations are frequently transmitted among untreated individuals, highlighting the importance of early diagnosis and treatment.