Implementation of Pediatric HIV Prevention and Care Guidelines in Routine Settings: Outcomes among HIV-Exposed Infants in DR Congo (2007-2013)

Outcomes of HIV-exposed infants remain inadequately studied, particularly in resource-deprived settings. We conducted an observational study of 1707 mother-infant pairs who received care in a comprehensive HIV program in Kinshasa, DR Congo during 2007-2013. The study resulted in two manuscripts, one which describes temporal changes in the outcomes of HIV-exposed infants and one that assesses the relationship between infant retention in care and the provision of combination antiretroviral therapy (cART) to their HIV-infected mothers. The first manuscript suggests there have been encouraging improvements over time in the outcomes of HIV-exposed infants but that continued efforts are needed. Accounting for competing risks (e.g. death), we estimated the cumulative incidences of having an initial specimen collected for HIV virologic testing, loss to follow-up (LTFU), HIV transmission, and death through age 18 months, as well as cART initiation among HIV-infected infants through age 24 months. The 18-month cumulative incidence of specimen collection increased from 73% (95% confidence limit [CL]: 68-78%) for infants enrolled in 2007-2008 to 99% (95% CL: 98-100%) for infants enrolled in 2011-2012. The 18-month cumulative incidence of HIV declined from 15% (95% CL: 11-21%) for infants enrolled in 2007-2008 to 8% (95% CL: 6-11%) for infants enrolled in 2011-2012 and death declined from 8% (95% CL: 5-11%) to 3% (95% CL: 2-5%). The 18-month cumulative incidence of LTFU did not improve, with 18-month cumulative incidences of 18% (95% CL: 14-22%) for infants enrolled in 2007-2008 and 18% (95% CL: 15-21%) for infants enrolled in 2011-2012. Among HIV-infected infants, the 24-month cumulative incidence of cART increased from 61% (95% CL: 43-75%) to 97% (95% CL: 82-100%); the median age at cART decreased from 17.9 to 9.3 months. In the second manuscript, we show that increasing access to cART for pregnant women could improve retention in care of their HIV-exposed infants. The 18-month cumulative incidence of LTFU was 9% among infants whose mothers had initiated cART by infant enrollment and 19% among infants whose mothers had not yet initiated cART (Gray's p-value <0.001). Adjusted for baseline factors, the subdistribution hazard ratio comparing LTFU between the two groups was 2.8 (95% CL: 1.8-4.3).Doctor of Philosoph

Does cytomegalovirus infection contribute to socioeconomic disparities in all-cause mortality?

The social patterning of cytomegalovirus (CMV) and its implication in aging suggest that the virus may partially contribute to socioeconomic disparities in mortality. We used Cox regression and inverse odds ratio weighting to quantify the proportion of the association between socioeconomic status (SES) and all-cause mortality that was attributable to mediation by CMV seropositivity. Data were from the National Health and Nutrition Examination Survey (NHANES) III (1988–1994), with mortality follow-up through December 2011. SES was assessed as household income (income-to-poverty ratio ≤1.30; >1.30 to ≤1.85; >1.85 to ≤3.50; >3.50) and education (high school). We found strong associations between low SES and increased mortality: hazard ratio (HR) 1.80; 95% confidence interval (CI): 1.57, 2.06 comparing the lowest versus highest income groups and HR 1.29; 95% CI: 1.13, 1.48 comparing high school education. 65% of individuals were CMV seropositive, accounting for 6–15% of the SES-mortality associations. Age modified the associations between SES, CMV, and mortality, with CMV more strongly associated with mortality in older individuals. Our findings suggest that cytomegalovirus may partially contribute to persistent socioeconomic disparities in mortality, particularly among older individuals

Population Distributions of Thymic Function in Adults: Variation by Sociodemographic Characteristics and Health Status

The thymus is critical for mounting an effective immune response and maintaining health. However, epidemiologic studies characterizing thymic function in the population setting are lacking. Using data from 263 adults in the Detroit Neighborhood Health Study, we examined thymic function as measured by the number of signal joint T-cell receptor excision circles (sjTREC) and assessed associations with established indicators of physiological health. Overall, increasing age and male gender were significantly associated with reduced thymic function. Adjusting for covariates, individuals with elevated levels of the pro-inflammatory biomarkers C-reactive protein (β: −0.50 [95% CI: −0.82, −0.18] for moderate elevation; β: −0.29 [95% CI: −0.59, 0.00] for high elevation) and interleukin-6 (β: −0.60 [95% CI: −0.92, −0.28] for moderate elevation; β: −0.43 [95% CI: −0.77, −0.08] for severe elevation) also had lower thymic function. Compared to individuals with a BMI <25, individuals who were overweight (β: 0.36 [95% CI: 0.07, 0.64]) or obese (β: 0.27 [95% CI: −0.03, 0.56]) had higher thymic function. Differences by self-rated health were not statistically significant. Our findings underscore demographic- and health-related gradients in thymic function among adult residents of Detroit, suggesting thymic function may be an important biomarker of health status in adults at the population level

Early Antiretroviral Therapy Initiation and Mortality Among Infants Diagnosed With HIV in the First 12 Weeks of Life: Experiences From Kinshasa, DR Congo and Blantyre, Malawi

AB Background: Based on clinical trial results, the WHO recommends infant HIV testing at age 4-6 weeks and immediate antiretroviral therapy (ART) initiation in all HIV-infected infants. Little is known about the outcomes of HIV infected infants diagnosed with HIV in the first weeks of life in resource-limited settings. We assessed ART initiation and mortality in the first year of life among infants diagnosed with HIV by 12 weeks of age. Methods: Cohort of HIV-infected infants in Kinshasa and Blantyre diagnosed before 12 weeks to estimate 12-month cumulative incidences of ART initiation and mortality, accounting for competing risks. Multivariate models were used to estimate associations between infant characteristics and timing of ART initiation. Results: 121 infants were diagnosed at a median age of 7 weeks (interquartile range 6-8). The cumulative incidence of ART initiation was 46% (95% CI: 36%, 55%) at 6 months and 70% (95% CI: 60%, 78%) at 12 months. Only age at HIV diagnosis was associated with ART initiation by age 6 months, with a subdistribution hazard ratio of 0.70 (95% CI: 0.52, 0.91) for each week increase in age at DNA PCR test. The 12-month cumulative incidence of mortality was 20% (95% CI: 13%, 28%). Conclusions: Despite early diagnosis of HIV, ART initiation was slow and mortality remained high, underscoring the complexity in translating clinical trial findings and WHO guidance into real-life practice. Novel and creative health system interventions will be required to ensure that all HIV infected infants achieve optimal treatment outcomes under routine care settings

Income and Markers of Immunological Cellular Aging

Socioeconomic disadvantage may contribute to poor health through immune-related biological mechanisms. We examined the associations between socioeconomic status, as measured by annual household income, and T-cell markers of aging, including the ratios of CD4 and CD8 effector cells to naïve cells (E:N ratio) and the CD4:CD8 T-cell ratio. We hypothesized that participants with a lower income would have higher E:N ratios and lower CD4:CD8 ratios compared to participants with a higher income, and that these associations would be partially mediated by elevated cytomegalovirus (CMV) IgG antibody levels, a virus implicated in aging and clonal expansion of T-cells

PTSD is associated with an increase in aged T cell phenotypes in adults living in Detroit

Psychosocial stress is thought to play a key role in the acceleration of immunological aging. This study investigated the relationship between lifetime and past-year history of post-traumatic stress disorder (PTSD) and the distribution of T cell phenotypes thought to be characteristic of immunological aging

Antenatal and delivery services in Kinshasa, Democratic Republic of Congo: care-seeking and experiences reported by women in a household-based survey

Increasing coverage of quality reproductive health services, including prevention of mother-to-child transmission services, requires understanding where and how these services are provided. To inform scale-up, we conducted a population-based survey in Kinshasa, Democratic Republic of Congo

Temporal changes in the outcomes of HIV-exposed infants in Kinshasa, Democratic Republic of Congo during a period of rapidly evolving guidelines for care (2007–2013)

Guidelines for prevention of mother-to-child transmission of HIV have developed rapidly, yet little is known about how outcomes of HIV-exposed infants have changed over time. We describe HIV-exposed infant outcomes in Kinshasa, Democratic Republic of Congo, between 2007 and 2013

Implementation and Operational Research: Maternal Combination Antiretroviral Therapy Is Associated With Improved Retention of HIV-Exposed Infants in Kinshasa, Democratic Republic of Congo

Programs to prevent mother-to-child HIV transmission (PMTCT) are plagued by loss to follow-up (LTFU) of HIV-exposed infants. We assessed if providing combination antiretroviral therapy (cART) to HIV-infected mothers was associated with reduced LTFU of their HIV-exposed infants in Kinshasa, DR Congo

Trends in Hospitalizations for Peptic Ulcer Disease, United States, 1998–20051

TOC summary: Decreased hospitalization rates suggest decline in complications from Helicobacter pylori infection