Publications

INTRODUCTION

Infection with HIV subtype A has been associated with poorer neurocognitive outcomes compared to HIV subtype D in Ugandan children not eligible for antiretroviral therapy (ART). In this study, we sought to determine whether subtype-specific differences are also observed among children receiving ART.

MATERIALS AND METHODS

Children were recruited from a clinical trial in which they were randomized to receive either lopinavir (LPV)- or non-nucleoside reverse transcriptase inhibitor (NNRTI)- based ART (NCT00978068). Age at initiation of ART ranged from six months to six years. HIV subtype was determined by PCR amplification and population sequencing of the pol region derived from peripheral blood mononuclear cell DNA, followed by application of the REGA and Recombinant Identification Programme algorithms. General cognition was assessed using the Kaufman Assessment Battery for Children (Second Edition), attention using the Test of Variables of Attention, and motor skills using the Bruininks-Oseretsky Test of Motor Proficiency (Second Edition). Home environment was assessed using the Home Observation for the Measurement of the Environment (HOME). Age-adjusted test z-scores were entered into a regression model that adjusted for sex, socio-economic status score, HOME score, years of schooling, and ART treatment type.

RESULTS

One hundred and five children were tested; median (interquartile range) age was 7.05 years (6.30 to 8.44), CD4 count was 867.7 cells/mm (416.0 to 1203.5), and duration on ART was 4.03 years (3.55 to 4.23). Seventy-eight children had HIV subtype A and 27 had subtype D; the groups had comparable home and socio-economic status, except that there were more males among children infected with subtype A than D (64.7% vs. 35.3%, p = 0.02). There were no differences between the subtypes in general cognition (estimated mean difference: 0.20; 95% CI: -0.11 to 0.50); p = 0.21), attention (-0.18, 95% CI: -0.60 to 0.24, p = 0.41) and motor skills (1.60, 95% CI: -0.84 to 4.04, p = 0.20).

CONCLUSIONS

Our results imply that ART may diminish the neurocognitive disadvantage seen in treatment-naïve HIV-infected children with subtype A.

Despite a poor toxicity profile, zidovudine supersedes abacavir (ABC) as an alternative first-line agent in most international treatment guidelines because of concerns about HLA-B*57:01-related ABC-hypersensitivity. We detected one case of HLA-B*57:01 carriage among 513 HIV-infected individuals in Uganda, which, in combination with previous reports, supports the safety of ABC in the region.

BACKGROUND

The World Health Organization defines HIV virologic failure as 2 consecutive viral loads >1000 copies/mL, measured 3-6 months apart, with interval adherence support. We sought to empirically evaluate these guidelines using data from an observational cohort.

SETTING

The Uganda AIDS Rural Treatment Outcomes study observed adults with HIV in southwestern Uganda from the time of antiretroviral therapy (ART) initiation and monitored adherence with electronic pill bottles.

METHODS

We included participants on ART with a detectable HIV RNA viral load and who remained on the same regimen until the subsequent measurement. We fit logistic regression models with viral resuppression as the outcome of interest and both initial viral load level and average adherence as predictors of interest.

RESULTS

We analyzed 139 events. Median ART duration was 0.92 years, and 100% were on a nonnucleoside reverse-transcriptase inhibitor-based regimen. Viral resuppression occurred in 88% of those with initial HIV RNA <1000 copies/mL and 42% if HIV RNA was >1000 copies/mL (P <0.001). Adherence after detectable viremia predicted viral resuppression for those with HIV RNA <1000 copies/mL (P = 0.011) but was not associated with resuppression for those with HIV RNA >1000 copies/mL (P = 0.894; interaction term P = 0.077).

CONCLUSIONS

Among patients on ART with detectable HIV RNA >1000 copies/mL who remain on the same regimen, only 42% resuppressed at next measurement, and there was no association between interval adherence and viral resuppression. These data support consideration of resistance testing to help guide management of virologic failure in resource-limited settings.

BACKGROUND

Ambient air pollution and tuberculosis (TB) have an impact on public health worldwide, yet associations between the two remain uncertain.

OBJECTIVE

We determined the impact of residential traffic on mortality during treatment of active TB.

METHODS

From 2000-2012, we enrolled 32,875 patients in California with active TB and followed them throughout treatment. We obtained patient data from the California Tuberculosis Registry and calculated traffic volumes and traffic densities in 100- to 400-m radius buffers around residential addresses. We used Cox models to determine mortality hazard ratios, controlling for demographic, socioeconomic, and clinical potential confounders. We categorized traffic exposures as quintiles and determined trends using Wald tests.

RESULTS

Participants contributed 22,576 person-years at risk. There were 2,305 deaths during treatment for a crude mortality rate of 1,021 deaths per 10,000 person-years. Traffic volumes and traffic densities in all buffers around patient residences were associated with increased mortality during TB treatment, although the findings were not statistically significant in all buffers. As the buffer size decreased, fifth-quintile mortality hazards increased, and trends across quintiles of traffic exposure became more statistically significant. Increasing quintiles of nearest-road traffic volumes in the 100-m buffer were associated with 3%, 14%, 19%, and 28% increased risk of death during TB treatment [first quintile, referent; second quintile hazard ratio (HR)=1.03 [95% confidence interval (CI): 0.86, 1.25]; third quintile HR=1.14 (95% CI: 0.95, 1.37); fourth quintile HR=1.19 (95% CI: 0.99, 1.43); fifth quintile HR=1.28 (95% CI: 1.07, 1.53), respectively; p-trend=0.002].

CONCLUSIONS

Residential proximity to road traffic volumes and traffic density were associated with increased all-cause mortality in patients undergoing treatment for active tuberculosis even after adjusting for multiple demographic, socioeconomic, and clinical factors, suggesting that TB patients are susceptible to the adverse health effects of traffic-related air pollution. https://doi.org/10.1289/EHP1699.

Patient-centered medical home models are fundamental to the advanced alternative payment models defined in the Medicare Access and Children's Health Insurance Plan Reauthorization Act (MACRA). The patient-centered medical home is a model of healthcare delivery supported by alternative payment mechanisms and designed to promote coordinated medical care that is simultaneously patient-centric and population-oriented. This transformative care model requires shifting reimbursement to include a per-patient payment intended to cover services not previously reimbursed such as disease management over time. Payment is linked to quality measures, including proportion of care delivered according to predefined pathways and demonstrated impact on outcomes. Some medical homes also include opportunities for shared savings by reducing overall costs of care. Recent proposals have suggested expanding the medical home model to specialized populations with complex needs because primary care teams may not have the facilities or the requisite expertise for their unique needs. An example of a successful care model that may provide valuable lessons for those creating specialty medical home models already exists in many hematopoietic cell transplantation (HCT) centers that deliver multidisciplinary, coordinated, and highly specialized care. The integration of care delivery in HCT centers has been driven by the specialty care their patients require and by the payment methodology preferred by the commercial payers, which has included bundling of both inpatient and outpatient care in the peritransplant interval. Commercial payers identify qualified HCT centers based on accreditation status and comparative performance, enabled in part by center-level comparative performance data available within a national outcomes database mandated by the Stem Cell Therapeutic and Research Act of 2005. Standardization across centers has been facilitated via voluntary accreditation implemented by Foundation for the Accreditation of Cell Therapy. Payers have built on these community-established programs and use public outcomes and program accreditation as standards necessary for inclusion in specialty care networks and contracts. Although HCT centers have not been described as medical homes, most HCT providers have already developed the structures that address critical requirements of MACRA for medical homes.