John Paul Ekwaru

Risk Factors for Recent HIV Infection in Uganda

CONTEXT Studies of factors associated with acquiring human immunodeficiency virus (HIV) are often based on prevalence data that might not reflect recent infections. OBJECTIVE To determine demographic, biological, and behavioral factors for recent HIV infection in Uganda. DESIGN AND SETTING Nationally representative household survey of cross-sectional design conducted in Uganda from August 2004 through January 2005; data were analyzed until November 2007. PARTICIPANTS There were 11,454 women and 9905 men aged 15 to 59 years who were eligible. Questionnaires were completed for 10,826 women (95%) and 8830 men (89%); of those interviewed, blood specimens were collected for 10,227 women (94%) and 8298 men (94%). MAIN OUTCOME MEASURE Specimens seropositive for HIV were tested with the BED IgG capture-based enzyme immunosorbent assay to identify recent seroconversions (median, 155 days) using normalized optical density of 0.8 and adjustments. RESULTS Of the 1023 HIV infections with BED results, 172 (17%) tested as recent. In multivariate analysis, risk factors associated with recent HIV infection included female sex (adjusted odds ratio [aOR], 2.4; 95% confidence interval [CI], 1.1-5.2); current marital status (widowed vs never married, aOR, 6.1; 95% CI, 2.8-13.3; divorced vs never married, aOR, 3.0; 95% CI, 1.5-6.1); geographic region (north central Uganda vs central Uganda/Kampala, aOR, 2.6; 95% CI, 1.7-4.1); number of sex partners in past year (> or = 2 compared with none; aOR, 2.9; 95% CI, 1.6-5.5); herpes simplex virus type 2 infection (aOR, 3.9; 95% CI, 2.6-5.8); report of a sexually transmitted disease in the past year (aOR, 1.7; 95% CI, 1.2-2.4); and being an uncircumcised man (aOR, 2.5; 95% CI, 1.1-5.3). Among married participants, recent HIV infection was associated with never using condoms with partners outside of marriage (aOR, 3.2; 95% CI, 1.7-6.1) compared with individuals having no outside partners. The risk of incident HIV infection for married individuals who used condoms with at least 1 outside partner was similar to that of those who did not have any partners outside of marriage (aOR, 1.0; 95% CI, 0.3-2.7). CONCLUSION A survey of individuals in Uganda who were tested with an HIV assay used to establish recent infection identified risk factors, which offers opportunities for prevention initiatives.

Utility of routine viral load, CD4 cell count, and clinical monitoring among adults with HIV receiving antiretroviral therapy in Uganda: randomised trial

Objective To evaluate the use of routine laboratory monitoring in terms of clinical outcomes among patients receiving antiretroviral therapy (ART) in Uganda. Design Randomised clinical trial Setting A home based ART programme in rural Uganda. Participants All participants were people with HIV who were members of the AIDS Support Organisation. Participants had CD4 cell counts <250 cells × 106/L or World Health Organization stage 3 or 4 disease. Interventions Participants were randomised to one of three different monitoring arms: a viral load arm (clinical monitoring, quarterly CD4 counts, and viral load measurements), CD4 arm (clinical monitoring and CD4 counts), or clinical arm (clinical monitoring alone). Main outcome measures Serious morbidity (newly diagnosed AIDS defining illness) and mortality. Results 1094 participants started ART; median CD4 count at baseline was 129 cells × 106/L. Median follow-up was three years. In total, 126 participants died (12%), 148 (14%) experienced new AIDS defining illnesses, and 61(6%) experienced virological failure, defined as two consecutive viral loads >500 copies/mL occurring more than three months after the start of ART. After adjustment for age, sex, baseline CD4 count, viral load, and body mass index, the rate of new AIDS defining events or death was higher in the clinical arm than the viral load arm (adjusted hazard ratio 1.83, P=0.002) or the CD4 arm (1.49, P=0.032). There was no significant difference between the CD4 arm and the viral load arm (1.23, P=0.31). Conclusion In patients receiving ART for HIV infection in Uganda, routine laboratory monitoring is associated with improved health and survival compared with clinical monitoring alone. Trial registration Clinical Trials NCT00119093.

Cotrimoxazole prophylaxis by HIV-infected persons in Uganda reduces morbidity and mortality among HIV-uninfected family members.

Background:The effect of cotrimoxazole prophylaxis taken by persons with HIV on community health and antimicrobial resistance is unknown. Objective:To assess the effect of cotrimoxazole prophylaxis taken by persons with HIV on morbidity, mortality, and antimicrobial resistance of diarrheal pathogens infecting their HIV-negative family members. Design:Prospective cohort in rural Uganda. Methods:A total of 879 persons with HIV and 2771 HIV-negative family members received weekly home-visits. After 5 months, persons with HIV received daily cotrimoxazole prophylaxis and households were followed for an average of 17 additional months. Findings:During the study, 224 participants with HIV (25%) and 29 household members (1%) died. Mortality among HIV-negative family members < 10 years old was 63% less during the cotrimoxazole period than before [hazard ratio, 0.37; 95% confidence interval (CI), 0.14–0.95; P = 0.04]. Malaria among family members was less common during cotrimoxazole treatment [incidence rate ratio (IRR), 0.62; CI, 0.53–0.74; P < 0.0001], as were diarrhea (IRR, 0.59; CI, 0.45–0.76; P = 0.0001), and hospitalizations (IRR, 0.57; CI, 0.36–0.92; P = 0.02). Death of a parent with HIV was associated with a threefold increase in mortality among HIV-negative children < 10 years old (hazard ratio, 2.9; CI, 1.1–8.1; P = 0.04). Of 134 bacterial isolates from family members before cotrimoxazole treatment, 89 (66%) were resistant to cotrimoxazole; of 75 recovered during cotrimoxazole treatment, 54 (72%) were resistant (P = 0.41). Interpretation:Cotrimoxazole prophylaxis taken by persons with HIV was associated with decreased morbidity and mortality among family members. Antimicrobial resistance among diarrheal pathogens infecting family members did not increase. Concerns regarding the spread of bacterial resistance should not impede implementation of cotrimoxazole programs.

The Importance of Body Weight for the Dose Response Relationship of Oral Vitamin D Supplementation and Serum 25-Hydroxyvitamin D in Healthy Volunteers

Unlike vitamin D recommendations by the Institute of Medicine, the Clinical Practice Guidelines by the Endocrine Society acknowledge body weight differentials and recommend obese subjects be given two to three times more vitamin D to satisfy their bodys vitamin D requirement. However, the Endocrine Society also acknowledges that there are no good studies that clearly justify this. In this study we examined the combined effect of vitamin D supplementation and body weight on serum 25-hydroxyvitamin (25(OH)D) and serum calcium in healthy volunteers. We analyzed 22,214 recordings of vitamin D supplement use and serum 25(OH)D from 17,614 healthy adult volunteers participating in a preventive health program. This program encourages the use of vitamin D supplementation and monitors its use and serum 25(OH)D and serum calcium levels. Participants reported vitamin D supplementation ranging from 0 to 55,000 IU per day and had serum 25(OH)D levels ranging from 10.1 to 394 nmol/L. The dose response relationship between vitamin D supplementation and serum 25(OH)D followed an exponential curve. On average, serum 25(OH)D increased by 12.0 nmol/L per 1,000 IU in the supplementation interval of 0 to 1,000 IU per day and by 1.1 nmol/L per 1,000 IU in the supplementation interval of 15,000 to 20,000 IU per day. BMI, relative to absolute body weight, was found to be the better determinant of 25(OH)D. Relative to normal weight subjects, obese and overweight participants had serum 25(OH)D that were on average 19.8 nmol/L and 8.0 nmol/L lower, respectively (P<0.001). We did not observe any increase in the risk for hypercalcemia with increasing vitamin D supplementation. We recommend vitamin D supplementation be 2 to 3 times higher for obese subjects and 1.5 times higher for overweight subjects relative to normal weight subjects. This observational study provides body weight specific recommendations to achieve 25(OH)D targets.

A Statistical Error in the Estimation of the Recommended Dietary Allowance for Vitamin D

The Institute of Medicine (IOM) issues dietary recommendations on the request of the U.S. and Canadian governments. [...]

Using HIV voluntary counseling and testing data for monitoring the Uganda HIV epidemic, 1992-2000.

ObjectiveTo assess trends in the prevalence of HIV infection among voluntary counseling and testing (VCT) clients in Uganda and to describe the utility of VCT data for monitoring the HIV epidemic in 1992–2000. MethodsWe analyzed routinely collected data from first-time VCT clients not reporting illness as a reason for testing. We developed a model adjusting for test site, couple testing, and premarital testing, assessed trends in adjusted prevalence of HIV infection and shifts in age-specific peak prevalence, and compared antenatal clinic (ANC) surveillance data and VCT prevalence trends. ResultsAmong 201,741 clients, adjusted prevalence of HIV infection declined from 23% in 1992 to 13% in 2000 (P < 0.001) (men, 17%–9% [P < 0.001]; women, 31%–18% [P < 0.001]). The prevalence declined for all age groups except men older than 39 years and women older than 34 years. The prevalence increased for women older than 39 years (P < 0.003). Between 1992 and 2000, peak prevalence declined for both men (31% to 24%) and women (44% to 41%), whereas the age at which the peak occurred increased for both men (36 to 41 years) and women (31 to 36 years). VCT and ANC prevalence trends were similar. ConclusionIn Uganda, the prevalence of HIV infection among male and female VCT clients declined from 1992 to 2000, similar to ANC surveillance data, but did not decline in older age groups. In regions with well-established VCT programs, VCT data may provide a useful and convenient tool for monitoring the HIV epidemic.

Optimal Vitamin D Supplementation Doses that Minimize the Risk for Both Low and High Serum 25-Hydroxyvitamin D Concentrations in the General Population

The Recommended Dietary Allowance (RDA) is the nutrient intake considered to be sufficient to meet the requirements of 97.5% of the population. Recent reports revealed a statistical error in the calculation of the RDA for vitamin D opening the question of what the recommendation should be. We took a dual approach to answer this question: (1) we aggregated 108 published estimates on vitamin D supplementation and vitamin D status; and (2) we analyzed 13,987 observations of program participants. The aggregation of published data revealed that 2909 IU of vitamin D per day is needed to achieve serum 25-hydroxyvitamin D (25(OH)D) concentrations of 50 nmol/L or more in 97.5% of healthy individuals. For normal weight, overweight and obese program participants this was 3094, 4450 and 7248 IU respectively. These supplementation doses would also result in 2.5% of normal weight, overweight and obese participants having 25(OH)D concentrations above 210, 200 and 214 nmol/L respectively. As these concentrations are high, an approach that minimizes the risk for both low and high concentrations seems desirable. With this approach we estimated, for example, that doses of 1885, 2802 and 6235 IU per day are required for normal weight, overweight and obese individuals respectively to achieve natural 25(OH)D concentrations (defined as 58 to 171 nmol/L). In conclusion, the large extent of variability in 25(OH)D concentrations makes a RDA for vitamin D neither desirable nor feasible. We therefore propose recommendations be articulated in the form of an optimal intake that minimizes the risk for both low and high serum 25(OH)D concentrations. This contribution includes body weight specific recommendations for optimal intakes for various combinations of lower and upper 25(OH)D concentration targets.

The Effect of Changing Serum 25-Hydroxyvitamin D Concentrations on Metabolic Syndrome: A Longitudinal Analysis of Participants of a Preventive Health Program.

Several studies have shown that a poor vitamin D status may increase the risk of developing metabolic syndrome, which leaves the question whether improving one’s vitamin D status may reduce the risk for the syndrome. Here we investigate the effect of temporal changes in serum 25-hydroxyvitamin D (25(OH)D) concentrations on metabolic syndrome among Canadians enrolled in a preventive health program that promotes vitamin D supplementation. We accessed and analyzed data of 6682 volunteer participants with repeated observations on serum 25(OH)D concentrations and metabolic syndrome. We applied logistic regression to quantify the independent contribution of baseline serum 25(OH)D and temporal increases in serum 25(OH)D to the development of metabolic syndrome. In the first year in the program, participants, on average, increased their serum 25(OH)D concentrations by 37 nmol/L. We observed a statistical significant inverse relationship of increases in serum 25(OH)D with risk for metabolic syndrome. Relative to those without improvements, those who improved their serum 25(OH)D concentrations with less 25 nmol/L, 25 to 50 nmol/L, 50 to 75 nmol/L, and more 75 nmol/L had respectively 0.76, 0.64, 0.59, 0.56 times the risk for metabolic syndrome at follow up. These estimates were independent of the effect of baseline serum 25(OH)D concentrations on metabolic syndrome. Improvement of vitamin D status may help reduce the public health burden of metabolic syndrome, and potential subsequent health conditions including type 2 diabetes and cardiovascular disease.

The Relationship of Serum 25-Hydroxyvitamin D and Insulin Resistance among Nondiabetic Canadians: A Longitudinal Analysis of Participants of a Preventive Health Program.

Observational and intervention studies have revealed inconsistent findings with respect to the relationship between vitamin D and insulin resistance. No intervention studies have been conducted in community samples whereas this may be particularly relevant to the primary prevention of type 2 diabetes (T2D) and cardiovascular disease (CVD). In the present study we examined whether temporal improvements in vitamin D status, measured as serum 25-hydroxyvitamin D [25(OH)D], reduce the risk of insulin resistance among individuals without T2D. We accessed and analyzed data from 5730 nondiabetic participants with repeated measures of serum 25(OH)D who enrolled in a preventive health program. We used the homeostatic model assessment for insulin resistance (HOMA-IR) and applied logistic regression to quantify the independent contribution of baseline serum 25(OH)D and temporal increases in 25(OH)D on HOMA-IR. The median time between baseline and follow up was 1.1 year. On average serum 25(OH)D concentrations increased from 89 nanomoles per liter (nmol/L) at baseline to 122 nmol/L at follow up. Univariate analyses showed that relative to participants with baseline serum 25(OH)D less than 50 nmol/L, participants with baseline concentrations of “50-<75”, “75-<100”, “100-<125”, and ≥125 nmol/L were 0.76 (95% confidence intervals: 0.61–0.95), 0.54 (0.43–0.69), 0.48 (0.36–0.64) and 0.36 (0.27–0.49) times as likely to have insulin resistance at follow up, respectively. More importantly, relative to participants without temporal increases in 25(OH)D, those with increases in serum 25(OH)D of “<25”, “25-<50”, “50-<75”, “≥75” nmol/L were 0.92 (0.72–1.17), 0.86 (0.65–1.13), 0.66 (0.47–0.93), and 0.74 (0.55–0.99) times as likely to have insulin resistance at follow up, respectively. In the subgroup of participants without insulin resistance at baseline, this was 0.96 (0.72–1.27), 0.78 (0.56–1.10), 0.66 (0.44–0.99), and 0.67 (0.48–0.94), respectively. These observations suggest that improvements in vitamin D status reduce the risk for insulin resistance and herewith may contribute to the primary prevention of T2D and CVD.

The economic burden of inadequate consumption of vegetables and fruit in Canada.

Objective Public health decision makers not only consider health benefits but also economic implications when articulating and issuing lifestyle recommendations. Whereas various estimates exist for the economic burden of physical inactivity, excess body weight and smoking, estimates of the economic burden associated with our diet are rare. In the present study, we estimated the economic burden attributable to the inadequate consumption of vegetables and fruit in Canada. Design We accessed the Canadian Community Health Survey to assess the inadequacy in the consumption of vegetables and fruit and published meta-analyses to assemble risk estimates for chronic diseases. Based on these inadequacy and risk estimates, we calculated the population-attributable fraction and avoidable direct and indirect costs to society. Direct costs include those for hospital care, physician services and drugs in 2015. Results About 80 % of women and 89 % of men consume inadequate amounts of vegetables and fruit. We estimated this to result in an economic burden of