Publications

BACKGROUND

Prevention of unplanned pregnancies is a critical element in the prevention of mother-to-child transmission of HIV infection, but its potential has not been fully realized. We assessed the utilization of family planning (FP) and fertility desires among women of reproductive age by HIV status.

METHODS

We selected a nationally representative sample of households using a stratified 2-stage cluster design and surveyed women aged 15-49 years. We administered questionnaires and examined predictors of current use of FP and desire for children among sexually active women with known HIV infection and women who were HIV uninfected.

RESULTS

Of 3583 respondents, 68.2% were currently using FP, and 57.7% did not desire children in the future. Among women who did not desire children in the future, 70.9% reported that they were using FP, including 68.7% of women with known HIV infection and 71.0% of women who were HIV uninfected. Women with known HIV infection had similar odds of using FP as women with no HIV infection (odds ratio, 1.12; 95% confidence interval: 0.81 to 1.54). Women with no HIV infection had significantly higher adjusted odds of desiring future children (adjusted OR, 2.27; 95% confidence interval: 1.31 to 3.93) than women with known HIV infection.

CONCLUSIONS

There is unmet need for FP for HIV-infected women, underscoring a gap in the national prevention of mother-to-child transmission of HIV strategy. Efforts to empower HIV-infected women to prevent unintended pregnancies should lead to expanded access to contraceptive methods and take into account women's reproductive intentions.

BACKGROUND

In Kenya, mathematical models estimate that there are approximately 220,000 children aged less than 15 years infected with HIV. We analyzed data from the second Kenya AIDS Indicator Survey (KAIS 2012) to estimate the prevalence of HIV infection among children aged 18 months to 14 years.

METHODS

KAIS 2012 was a nationally representative 2-stage cluster sample household survey. We studied children aged 18 months to 14 years whose parents or guardians answered questions pertaining to their children by interview. Blood specimens were collected for HIV serology and viral load measurement.

RESULTS

We identified 5162 children who were eligible for the study. Blood was obtained for 3681 (71.3%) children. Among child participants, 16.4% had been tested for HIV infection in the past, and among children with parents or guardians who self-reported HIV-positive status, 52.9% had been tested for HIV infection. Twenty-eight (0.9%) children tested HIV-positive in the survey. Of these, 11 had been previously diagnosed with HIV infection before the survey. All 11 children were in HIV care and receiving cotrimoxazole; 8 were on antiretorivral therapy (ART). Among those on ART, 4 were virologically suppressed.

CONCLUSIONS

HIV causes a substantial burden of disease in the Kenyan pediatric population. Although most children who had been diagnosed with HIV before the survey were engaged in care and treatment, they represented less than half of HIV-infected children identified in the survey. Future efforts should focus on identifying infected children and getting them into care and on suppressive ART as early as possible.

OBJECTIVES

Public health professionals have debated the use of smokeless tobacco (SLT) over cigarettes for harm reduction. This article describes SLT and cigarette risk comparisons and other SLT "debate" messages potentially reaching the public through news stories.

METHODS

We conducted a content analysis of SLT-related 2006-10 articles from top newspapers and selected news wires.

RESULTS

About 16% of articles (N = 677) referred to SLT as less harmful than smoking, attributing these messages to public health professionals as frequently as to tobacco company representatives. About 29% of articles included an "anti" SLT message, including variously phrased warnings that SLT is not a safe smoking alternative, or other potential consequences such as youth uptake.

CONCLUSION

Professionals should begin developing and using more consistent messages about SLT's risks.

OBJECTIVE

To delineate the association between baseline socioeconomic status (SES) indicators and mortality and lost to follow-up (LTFU) in a cohort of HIV-infected individuals enrolled in antiretroviral therapy (ART) in urban Uganda.

DESIGN

Retrospective cohort study nested in an antiretroviral clinic-based cohort.

METHODS

SES indicators including education, employment status, and a standardized wealth index, and other demographic and clinical variables were assessed at baseline among ART-treated patients in a clinic-based cohort in Kampala, Uganda. Confirmed mortality (primary outcome) and LTFU (secondary outcome) were actively ascertained over a 4-year follow-up period from 2005 to 2009.

RESULTS

Among 1763 adults [70.5% female; mean age, 36.2 years (SD = 8.4)] enrolled in ART, 14.4% (n = 253) were confirmed dead and 19.7% (n = 346) were LTFU at 4-year follow-up. No formal education [adjusted odds ratio (AOR) 1.76; 95% confidence interval (CI): 1.19 to 2.59], having fewer than 6 dependents (AOR 1.39; 95% CI: 1.04 to 1.86), unemployment (AOR 1.98; 95% CI: 1.48 to 2.66), and housing tenure index score (a component of the wealth index) (AOR 1.11; 95% CI: 1.00 to 1.23) were significantly associated with confirmed mortality at 4 years. SES indicators were not associated with LTFU at 4 years.

CONCLUSIONS

Baseline SES indicators, including education, number of dependents, employment status, and components of a standard wealth index may indicate long-term vulnerability to mortality in patients with HIV/AIDS, despite uniform access to ART. Future studies delineating the pathways through which poverty and limited assets affect clinical outcomes may lead to more effective HIV interventions in low-resource settings.

BACKGROUND

Current recommendations for limits on metalworking fluids may provide insufficient protection from workplace-related illness. Chronic obstructive pulmonary disease (COPD) is a challenging outcome in occupational cohorts because its long period of worsening pulmonary function allows sicker workers to reduce exposure, causing a healthy worker survivor bias. G-estimation is a statistical method that reduces this bias. We introduce a public health approach using g-estimation to compare a series of potential exposure-reducing interventions.

METHODS

Autoworkers at three General Motors plants in Michigan were followed for COPD mortality from 1 January 1941 to 31 December 1994. For each of the three fluid types (straight, soluble, synthetic), a series of binary variables indicated whether exposure exceeded a series of potential limits. Separate g-estimation analyses for each limit yielded results expressed as the total number of years of life that could have been saved among those who died from COPD had that exposure limit been enforced.

RESULTS

Lower limits would have had greater effect than higher limits. A ban on soluble fluids (the most common type) would have had the greatest effect, saving an estimated 1550 years of life. Corresponding estimates were 737 and 260 years for straight and synthetic fluids, respectively. Few workers were exposed to synthetic fluids, limiting analytic power.

CONCLUSIONS

This application of g-estimation suggests that limiting exposure to metalworking fluids could have saved many years of life lost to COPD in this cohort. The approach permits comparison of different interventions. Separate limits should be considered for different types of fluids.

OBJECTIVE

To compare educational and vocational outcomes among adults with childhood-onset systemic lupus erythematosus (SLE) and adult-onset SLE.

METHODS

We used data derived from the 2002–2010 cycles of the Lupus Outcomes Study, a longitudinal cohort of 1,204 adult subjects with SLE. Subjects ages 18–60 years living in the US (n = 929) were included in the analysis and were classified as childhood-onset SLE if age at diagnosis was <18 years (n = 115). Logistic regression was used to assess the unadjusted and adjusted effect of childhood-onset SLE, sex, race/ethnicity, baseline age, urban or rural location, and US region on the likelihood of completing a bachelor's degree. Generalized estimating equations were used to assess the effect of childhood-onset SLE, demographics, education, and disease-related factors on the odds of employment, accounting for multiple observations over the study period.

RESULTS

Subjects with childhood-onset SLE were on average younger (mean ± SD 29 ± 10 years versus 44 ± 9 years), with longer disease duration (mean ± SD 15 ± 10 years versus 11 ± 8 years). Subjects with adult-onset SLE and childhood-onset SLE subjects were equally likely to complete a bachelor's degree. However, subjects with childhood-onset SLE were significantly less likely to be employed, independent of demographic and disease characteristics (odds ratio 0.62, 95% confidence interval 0.42–0.91).

CONCLUSION

While subjects with SLE are just as likely as those with adult-onset SLE to complete college education, childhood-onset SLE significantly increases the risk of not working in adulthood, even when controlling for disease and demographic factors. Exploring reasons for low rates of employment and providing vocational support may be important to maximize long-term functional outcomes in patients with childhood-onset SLE.

Matrix metalloproteinase-9 is elevated within the acutely injured murine spinal cord and blockade of this early proteolytic activity with GM6001, a broad-spectrum matrix metalloproteinase inhibitor, results in improved recovery after spinal cord injury. As matrix metalloproteinase-9 is likewise acutely elevated in dogs with naturally occurring spinal cord injuries, we evaluated efficacy of GM6001 solubilized in dimethyl sulfoxide in this second species. Safety and pharmacokinetic studies were conducted in naïve dogs. After confirming safety, subsequent pharmacokinetic analyses demonstrated that a 100 mg/kg subcutaneous dose of GM6001 resulted in plasma concentrations that peaked shortly after administration and were sustained for at least 4 days at levels that produced robust in vitro inhibition of matrix metalloproteinase-9. A randomized, blinded, placebo-controlled study was then conducted to assess efficacy of GM6001 given within 48 hours of spinal cord injury. Dogs were enrolled in 3 groups: GM6001 dissolved in dimethyl sulfoxide (n = 35), dimethyl sulfoxide (n = 37), or saline (n = 41). Matrix metalloproteinase activity was increased in the serum of injured dogs and GM6001 reduced this serum protease activity compared to the other two groups. To assess recovery, dogs were a priori stratified into a severely injured group and a mild-to-moderate injured group, using a Modified Frankel Scale. The Texas Spinal Cord Injury Score was then used to assess long-term motor/sensory function. In dogs with severe spinal cord injuries, those treated with saline had a mean motor score of 2 (95% CI 0-4.0) that was significantly (P<0.05; generalized linear model) less than the estimated mean motor score for dogs receiving dimethyl sulfoxide (mean, 5; 95% CI 2.0-8.0) or GM6001 (mean, 5; 95% CI 2.0-8.0). As there was no independent effect of GM6001, we attribute improved neurological outcomes to dimethyl sulfoxide, a pleotropic agent that may target diverse secondary pathogenic events that emerge in the acutely injured cord.

BACKGROUND

Defining the association of non-AIDS-defining events with inflammation and immune activation among human immunodeficiency virus (HIV)-infected persons with antiretroviral therapy (ART)-associated virological suppression is critical to identifying interventions to decrease the occurrence of these events.

METHODS

We conducted a case-control study of HIV-infected subjects who had achieved virological suppression within 1 year after ART initiation. Cases were patients who experienced non-AIDS-defining events, defined as myocardial infarction, stroke, non-AIDS-defining cancer, non-AIDS-defining serious bacterial infection, or death. Controls were matched to cases on the basis of age, sex, pre-ART CD4(+) T-cell count, and ART regimen. Peripheral blood mononuclear cells and plasma specimens obtained at the visit before ART initiation (hereafter, baseline), the visit approximately 1 year after ART initiation (hereafter, year 1), and the visit immediately preceding the non-AIDS-defining event (hereafter, pre-event) were analyzed for activated CD4(+) and CD8(+) T cells, plasma interleukin 6 (IL-6) level, soluble tumor necrosis factor receptor I (sTNFR-I) level, sTNFR-II level, soluble CD14 level, kynurenine-to-tryptophan (KT) ratio, and D-dimer level. Conditional logistic regression analysis was used to study the association between biomarkers and outcomes, with adjustment for potential confounders.

RESULTS

Higher IL-6 level, sTNFR-I level, sTNFR-II level, KT ratio, and D-dimer level at year 1 were associated with the occurrence of a non-AIDS-defining event. Significant associations were also seen between non-AIDS-defining events and values of these biomarkers in specimens obtained at baseline and the pre-event time points. Effects remained significant after control for confounders. T-cell activation was not significantly related to outcomes.

CONCLUSIONS

Interventional trials to decrease the incidence of non-AIDS-defining events among HIV-infected persons with virological suppression should consider targeting the pathways represented by these soluble markers. Clinical Trials Registration. NCT00001137.