Distance from Home to Study Clinic and Risk of Follow-Up Interruption in a Cohort of HIV-1-Discordant Couples in Nairobi, Kenya

Background: Longitudinal studies of HIV-1-infected individuals or those at risk of infection are subject to missed study visits that may have negative consequences on the care of participants and can jeopardize study validity due to bias and loss of statistical power. Distance between participant residence and study clinic, as well as other socioeconomic and demographic factors, may contribute to interruptions in patient follow-up. Methods: HIV-1-serodiscordant couples were enrolled between May 2007 and October 2009 and followed for two years in Nairobi, Kenya. At baseline, demographic and home location information was collected and linear distance from each participant’s home to the study clinic was determined. Participants were asked to return to the study clinic for quarterly visits, with follow-up interruptions (FUI) defined as missing two consecutive visits. Cox proportional hazards regression was used to assess crude and adjusted associations between FUI and home-to-clinic distance, and other baseline characteristics. Results: Of 469 enrolled couples, 64% had a female HIV-1-infected partner. Overall incidence of FUI was 13.4 per 100 person-years (PY), with lower incidence of FUI in HIV-1-infected (10.8 per 100 PY) versus -uninfected individuals (16.1 per 100 PY) (hazard ratio [HR] = 0.66; 95% confidence interval [CI]: 0.50, 0.88). Among HIV-1-infected participants, those living between 5 and 10 kilometers (km) from the study clinic had a two-fold increased rate of FUI compared to those living <5 km away (HR = 2.17; 95% CI: 1.09, 4.34). Other factors associated with FUI included paying higher rent (HR = 1.67; 95% CI: 1.05, 2.65), having at least primary school education (HR = 1.96; 95% CI: 1.02, 3.70), and increased HIV-1 viral load (HR = 1.23 per log10 increase; 95% CI: 1.01, 1.51). Conclusions: Home-to-clinic distance, indicators of socioeconomic status, and markers of disease progression may affect compliance with study follow-up schedules. Retention strategies should focus on participants at greatest risk of FUI to ensure study validity

Genome-wide association meta-analysis in 269,867 individuals identifies new genetic and functional links to intelligence

Intelligence is highly heritable(1) and a major determinant of human health and well-being(2). Recent genome-wide meta-analyses have identified 24 genomic loci linked to variation in intelligence3-7, but much about its genetic underpinnings remains to be discovered. Here, we present a large-scale genetic association study of intelligence (n = 269,867), identifying 205 associated genomic loci (190 new) and 1,016 genes (939 new) via positional mapping, expression quantitative trait locus (eQTL) mapping, chromatin interaction mapping, and gene-based association analysis. We find enrichment of genetic effects in conserved and coding regions and associations with 146 nonsynonymous exonic variants. Associated genes are strongly expressed in the brain, specifically in striatal medium spiny neurons and hippocampal pyramidal neurons. Gene set analyses implicate pathways related to nervous system development and synaptic structure. We confirm previous strong genetic correlations with multiple health-related outcomes, and Mendelian randomization analysis results suggest protective effects of intelligence for Alzheimer's disease and ADHD and bidirectional causation with pleiotropic effects for schizophrenia. These results are a major step forward in understanding the neurobiology of cognitive function as well as genetically related neurological and psychiatric disorders.Peer reviewe

Cumulative incidence of follow-up interruptions.

<p>HIV-1-discordant couples were enrolled and followed quarterly for 2 years. A follow-up interruption (FUI) was defined as missing ≥2 consecutive study visits. The Kaplan Meier curves show the cumulative incidence of FUI separately for (<b>—</b>) HIV-1-uninfected females, (<b>———</b>), -infected females, (<b>—</b>) -uninfected males, and (– – –) -infected males.</p

Baseline characteristics of study participants.

<p>NOTE. IQR  =  interquartile range; KSh  =  Kenyan Shillings. Monthly household income is the sum of the income for both study partners.</p>a<p>Linear distance, based on location of residence at enrollment. Data missing for 6 participants.</p>b<p>Based on the median rent (2,000 KSh ≈ 26 USD).</p>c<p>Based on the median monthly income (8,000 KSh ≈ 104 USD).</p

Association between home-to-clinic distance and follow-up interruption, by gender and HIV status.

<p>NOTE. HR  =  hazard ratio; CI  =  confidence interval.</p>a<p>Adjusted for housing status (own home, renting for less than the median, or renting for greater than or equal to the median).</p>*<p>p<0.05.</p

Map of distances from the study clinic.

<p>The map of Nairobi shows the location of the study clinic, with linear distances to the study clinic indicated by concentric white circles at 5 km increments. The percentage of participants living within each section is shown in yellow.</p