The role of viral introductions in sustaining community-based HIV epidemics in rural Uganda: evidence from spatial clustering, phylogenetics, and egocentric transmission models.

BACKGROUND: It is often assumed that local sexual networks play a dominant role in HIV spread in sub-Saharan Africa. The aim of this study was to determine the extent to which continued HIV transmission in rural communities--home to two-thirds of the African population--is driven by intra-community sexual networks versus viral introductions from outside of communities. METHODS AND FINDINGS: We analyzed the spatial dynamics of HIV transmission in rural Rakai District, Uganda, using data from a cohort of 14,594 individuals within 46 communities. We applied spatial clustering statistics, viral phylogenetics, and probabilistic transmission models to quantify the relative contribution of viral introductions into communities versus community- and household-based transmission to HIV incidence. Individuals living in households with HIV-incident (n = 189) or HIV-prevalent (n = 1,597) persons were 3.2 (95% CI: 2.7-3.7) times more likely to be HIV infected themselves compared to the population in general, but spatial clustering outside of households was relatively weak and was confined to distances <500 m. Phylogenetic analyses of gag and env genes suggest that chains of transmission frequently cross community boundaries. A total of 95 phylogenetic clusters were identified, of which 44% (42/95) were two individuals sharing a household. Among the remaining clusters, 72% (38/53) crossed community boundaries. Using the locations of self-reported sexual partners, we estimate that 39% (95% CI: 34%-42%) of new viral transmissions occur within stable household partnerships, and that among those infected by extra-household sexual partners, 62% (95% CI: 55%-70%) are infected by sexual partners from outside their community. These results rely on the representativeness of the sample and the quality of self-reported partnership data and may not reflect HIV transmission patterns outside of Rakai. CONCLUSIONS: Our findings suggest that HIV introductions into communities are common and account for a significant proportion of new HIV infections acquired outside of households in rural Uganda, though the extent to which this is true elsewhere in Africa remains unknown. Our results also suggest that HIV prevention efforts should be implemented at spatial scales broader than the community and should target key populations likely responsible for introductions into communities.

Factors associated with incorrect identification of recent HIV infection using the BED capture immunoassay.

The BED capture enzyme immunoassay (BED-CEIA) was developed for estimating HIV incidence from cross-sectional data. This assay misclassifies some individuals with nonrecent HIV infection as recently infected, leading to overestimation of HIV incidence. We analyzed factors associated with misclassification by the BED-CEIA. We analyzed samples from 383 men who were diagnosed with HIV infection less than 1 year after a negative HIV test (Multicenter AIDS Cohort Study). Samples were collected 2-8 years after HIV seroconversion, which was defined as the midpoint between the last negative and first positive HIV test. Samples were analyzed using the BED-CEIA with a cutoff of OD-n ≤ 0.8 for recent infection. Logistic regression was used to identify factors associated with misclassification. Ninety-one (15.1%) of 603 samples were misclassified. In multivariate models, misclassification was independently associated with highly active antiretroviral treatment (HAART) for >2 years, HIV RNA <400 copies/ml, and CD4 cell count <50 or <200 cells/mm(3); adjusted odds ratios (OR) and 95% confidence intervals (CI) were 4.72 (1.35-16.5), 3.96 (1.53-10.3), 6.85 (2.71-17.4), and 11.5 (3.64-36.0), respectively. Among 220 men with paired samples, misclassification 2-4 years after seroconversion was significantly associated with misclassification 6-8 years after seroconversion [adjusted OR: 25.8 (95% CI: 8.17-81.5), p<0.001] after adjusting for race, CD4 cell count, HIV viral load, and HAART use. Low HIV viral load, low CD4 cell count, and >2 years of HAART were significantly associated with misclassification using the BED-CEIA. Some men were persistently misclassified as recently infected up to 8 years after HIV seroconversion.

Short communication: Colony-forming hematopoietic progenitor cells are not preferentially infected by HIV type 1 subtypes A and D in vivo.

HIV subtype C has previously been shown to infect hematopoietic progenitor cells (HPCs) at a significantly higher rate than subtype B. To better understand the subtype-specific nature of HPC infection, we examined the prevalence of HPC infection in vivo by HIV-1 subtypes A and D. HIV-1 infection of HPC was examined in 40 individuals, 19 infected with subtype A and 21 with subtype D, using a single colony assay format. DNA from 1177 extracted colonies was tested for integrated viral DNA of the p24 gene. Four colonies were found to be stably infected, three of 462 colonies (0.65%) from HIV-1A-infected individuals (1/19 individuals) and one of 715 colonies (0.14%) from HIV-1D-infected individuals (1/22 individuals). These rates of colony infection were comparable to the rates observed in PBMCs from the same subjects. Additionally, no correlation was observed between cell colony density and circulating viral load or proviral load. Our findings suggest that HIV-1 subtypes A and D do not preferentially infect colony-forming HPCs over mature HIV target cells in vivo.

Responsiveness of 2 procedures for measurement of temporal and spatial gait parameters in older adults.

OBJECTIVE: To determine the responsiveness of the GAITRite system and a stopwatch-footfall count technique for measurement of walking speed, cadence, and stride length during comfortable and fast-paced walking. DESIGN: Criterion standard. SETTING: Research laboratory in a physical therapy education program. PARTICIPANTS: Twenty-four healthy volunteers (13 men, 11 women; mean age 74.5 years) without lower extremity injury or history of falls. INTERVENTIONS: Participants walked across a GAITRite mat with embedded pressure sensors at their self-selected comfortable and fast walking speeds. Simultaneously, an examiner, using a stopwatch, recorded the elapsed time necessary to cross the mat and counted the number of complete footfalls. MAIN OUTCOME MEASURE(S): Walking speed, cadence, and stride length were compared between the GAITRite system and the stopwatch-footfall count technique for both comfortable and fast walking speeds. Responsiveness values for each procedure were described by the 95% minimal detectable change (MDC). RESULTS: During comfortable self-paced walking, MDC values for the stopwatch-footfall count technique ranged from 10% to 65% greater than those obtained for the GAITRite system. During fast self-paced walking MDC values for the stopwatch-footfall count technique ranged from 26% to 65% larger than those measured by the GAITRite system for the temporal and spatial gait performance parameters. CONCLUSIONS: When measured by the GAITRite system, the 95% MDC values for temporal and spatial gait parameters of older community-dwelling adults were more responsive to change than those obtained by the stopwatch-footfall technique. Clinicians should recognize that self-selected walking speed, cadence, and stride length when obtained by an instrumented walkway must be equal to or exceed 12.6 cm/s, 8.4 steps/min, or 7 cm, respectively, for the change to be considered real change and not from measurement error.

Number of strides required for reliable measurements of pace, rhythm and variability parameters of gait during normal and dual task walking in older individuals.

The reliability with which spatiotemporal gait parameters are measured has neither been well-established for variability parameters nor during dual task walking. The purpose of this study was to examine test-retest reliability of three gait parameters representing pace, rhythm and variability in healthy older persons during normal and dual task walking and to determine the number of strides necessary to measure the parameters reliably. Twenty-four healthy adults aged 65 or older participated in the study. Subjects walked during normal and dual task (backward spelling) walking conditions at self-selected speeds and then repeated the tests. Velocity, cadence and variability in stride velocity were measured with GAITRite instrumentation. Intraclass correlation coefficients (ICCs) were calculated and the numbers of strides required to meet desired magnitudes of reliability were estimated with the Spearman-Brown prophecy formula. ICCs for velocity and cadence were high (>0.841) during normal and dual task walking, indicating strong test-retest reliability. Test-retest reliability for variability in stride velocity was moderate (ICC=0.656) in normal walking and poor (ICC=0.226) in dual task walking. While data collected from fewer than 10 to 20 strides may reliably measure velocity and cadence in either normal or dual task walking, measuring variability in stride velocity reliably may require that data be collected from hundreds of strides, particularly in dual task walking.