NRU :: Browsing by Author "Mills, Edward J."

Browsing by Author "Mills, Edward J."

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Association of aging and survival in a large HIV-infected cohort on antiretroviral therapy
(Aids, 2011) Bakanda, Celestin; Birungi, Josephine; Mwesigwa, Robert; Ford, Nathan; Cooper, Curtis L.; Au-Yeung, Christopher; Chan, Keith; Nachega, Jean B.; Woode, Evan; Hogg, Robert S.; Dybulg, Mark; Mills, Edward J.
To examine if there is a significant difference in survival between elderly (>50 years) and nonelderly adult patients receiving combination antiretroviral therapy in Uganda between 2004 and 2010. Design: Prospective observational study. Methods: Patients 18–49 years of age (nonelderly) and 50 years of age and older enrolled in the AIDS Support Organization Uganda HIV/AIDS national programme were assessed for time to all-cause mortality. We applied a Weibull multivariable regression. Results: Among the 22 087 patients eligible for analyses, 19 657 (89.0%) were aged between 18 and 49 years and 2430 (11.0%) were aged 50 years or older. These populations differed in terms of the distributions of sex, baseline CD4 cell count and death. The age group 40–44 displayed the lowest crude mortality rate [31.4 deaths per 1000 person-years; 95% confidence interval (CI) 28.1, 34.7) and the age group 60–64 displayed the highest crude mortality rate (58.9 deaths per 1000 person-years; 95% CI 42.2, 75.5).Kaplan–Meier survival estimates indicated that nonelderly patients had better survival than elderly patients (P<0.001). AdjustedWeibull analysis indicated that elderly age status was importantly associated (adjusted hazard ratio 1.23, 95% CI 1.08–1.42) with mortality, when controlling for sex, baseline CD4 cell count and year of therapy initiation. Conclusion: As antiretroviral treatment cohorts mature, the proportion of patients who are elderly will inevitably increase. Elderly patients may require focused clinical care that extends beyond HIV treatment.
Can we increase male involvement in AIDS treatment?
(2010) Birungi, Josephine; Mills, Edward J.
In Uganda, men and boys are diffi cult to enrol in testing and treatment, and have increased mortality compared with women and girls. 5 Ad hoc HIV- positive men’s groups reach out to other men to increase testing and acceptance of results. However, in our experience, funders are unsupportive or unwilling to provide assistance to male-targeted interventions. Thus, male groups lack the sophistication of the female- focused eff orts and are unsustainable. Men, whether we blame them for their behaviours or not, represent a necessary population to engage with.
Clinical And Immunological Outcomes Of A National Paediatric Cohort Receiving Combination Antiretroviral Therapy In Uganda
(Aids, 2008) Kiboneka, Andrew; Wangisi, Jonathan; Nabiryo, Christine; Tembe, Juliet; Kusemererwa, Sylvia; Olupot, Peter Olupot; Joffres, Michel; Anema, Aranka; Cooper, Curtis L.; Montaner, Julio S.; Mills, Edward J.
We aimed to evaluate clinical and immunological outcomes of paediatric patients receiving combination antiretroviral therapy (cART) enrolled in The AIDS Support Organization (TASO) Uganda national HIV/AIDS programme.Observational study of patients (age <14 years) enrolled in 10 clinics across Uganda for which TASO has data.We extracted patient demographic, immunological and clinical outcomes from the TASO databases regarding age, sex, cART regimen, CD4 cell count and WHO stage at initiation, tuberculosis, mortality and adherence. Outcomes were analysed using Pearson's rank–order correlations, Wilcoxon's rank sum tests, Cox proportional hazard model and survivor functions.Of the total 770 HIV children on cART, median age was 9 years (interquartile range, 5–13 years), and median follow-up time was 377 days (interquartile range, 173–624 days). Seven hundred and fifty-one children (97.5%) initiated nonnucleoside reverse transcriptase inhibitor-based regimens. Three hundred and sixty-five children (47.5%) initiated cART with severe immune suppression (CD4 cell percentage <15). Of the 18 (2.3%) children that died, mortality was associated with lower CD4 cell percentage at initiation (B coefficient −0.144, standard error 0.06, P = 0.02). Of the total, 229 (30%) were single or double orphans and more likely to initiate cART at an older age (mean age, 9.25 vs. 8.35 years, P = 0.02) and have a lower CD4 cell count (median, 268 vs. 422 cells/μl, P ≤ 0.0001) and CD4 cell percentage (median 12.8 vs. 15.5%, P = 0.02) at initiation. Pulmonary tuberculosis was present in 43 (5.6%) patients at initiation and 21 (2.3%) after cART. Almost all patients (94.9%) demonstrated more than 95% adherence.Children on cART in Uganda demonstrate positive clinical outcomes. However, additional support is required to ensure timely cART access among orphans and young children.
Cohort Profile: The TASO-CAN Cohort Collaboration
(International journal of epidemiology, 2012) Bakanda, Celestin; Birungi, Josephine; Nkoyooyo, Abdallah; Featherstone, Amber; Cooper, Curtis L.; Hogg, Robert S.; Mills, Edward J.
Sub-Saharan Africa has scaled-up access to combination anti-retroviral therapy (cART) at unprecedented rates, yet data on patient-related outcomes remain sparse. Representative databases that facilitate highquality collection, harmonization and analysis of HIV-related information from clinical and researchrelated sites are needed. The large sample sizes that nationally representative databases permit facilitate identification of rare outcomes and emerging problems and the elucidation of more complex relationships involving the use of cART. These efforts also allow meaningful comparisons between regional treatment programmes that differ in their operational procedures and serve diverse communities in different settings. Unique features of individual sites exist, such as language used and cultural norms, research and care capacity, infrastructure development, personnel training and experience, and collection of data elements that differ in type, number, definition or method of laboratory. Furthermore, the use of innovative databases and informatics approaches can provide a principled approach to pool national data, and improve uniformity and consistency in data management in such heterogeneous settings.
Density of Healthcare Providers and Patient Outcomes: Evidence from a Nationally Representative Multi-Site HIV Treatment Program in Uganda
(PLoS ONE, 2011) Bakanda, Celestin; Birungi, Josephine; Mwesigwa, Robert; Zhang, Wendy; Hagopian, Amy; Ford, Nathan; Mills, Edward J.
We examined the association between density of healthcare providers and patient outcomes using a large nationally representative cohort of patients receiving combination antiretroviral therapy (cART) in Uganda. Design: We obtained data from The AIDS Support Organization (TASO) in Uganda. Patients 18 years of age and older who initiated cART at TASO between 2004 and 2008 contributed to this analysis. The number of healthcare providers per 100 patients, the number of patients lost to follow-up per 100 person years and number of deaths per 100 person years were calculated. Spearman correlation was used to identify associations between patient loss to follow-up and mortality with the healthcare provider-patient ratios. Results: We found no significant associations between the number of patients lost to follow-up and physicians (p = 0.45), nurses (p = 0.93), clinical officers (p = 0.80), field officers (p = 0.56), and healthcare providers overall (p = 0.83). Similarly, no significant associations were observed between mortality and physicians (p = 0.65), nurses (p = 0.49), clinical officers (p = 0.73), field officers (p = 0.78), and healthcare providers overall (p = 0.73). Conclusions: Patient outcomes, as measured by loss to follow-up and mortality, were not significantly associated with the number of doctors, nurses, clinical officers, field officers, or healthcare providers overall. This may suggest that that other factors, such as the presence of volunteer patient supporters or broader political or socioeconomic influences, may be more closely associated with outcomes of care among patients on cART in Uganda.
Impact of tuberculosis on mortality among HIV-infected patients receiving antiretroviral therapy in Uganda: a prospective cohort analysis
(AIDS Research and Therapy, 2013) Chu, Rong; Mills, Edward J.; Beyene, Joseph; Pullenayegum, Eleanor; Bakanda, Celestin; Nachega, Jean B.; Devereaux, P. J.; Thabane, Lehana
Tuberculosis (TB) disease affects survival among HIV co-infected patients on antiretroviral therapy (ART). Yet, the magnitude of TB disease on mortality is poorly understood. Methods: Using a prospective cohort of 22,477 adult patients who initiated ART between August 2000 and June 2009 in Uganda, we assessed the effect of active pulmonary TB disease at the initiation of ART on all-cause mortality using a Cox proportional hazards model. Propensity score (PS) matching was used to control for potential confounding. Stratification and covariate adjustment for PS and not PS-based multivariable Cox models were also performed. Results: A total of 1,609 (7.52%) patients had active pulmonary TB at the start of ART. TB patients had higher proportions of being male, suffering from AIDS-defining illnesses, having World Health Organization (WHO) disease stage III or IV, and having lower CD4 cell counts at baseline (p < 0.001). The percentages of death during follow-up were 10.47% and 6.38% for patients with and without TB, respectively. The hazard ratio (HR) for mortality comparing TB to non-TB patients using 1,686 PS-matched pairs was 1.37 (95% confidence interval [CI]: 1.08 – 1.75), less marked than the crude estimate (HR = 1.74, 95% CI: 1.49 – 2.04). The other PS-based methods and not PS-based multivariable Cox model produced similar results. Conclusions: After controlling for important confounding variables, HIV patients who had TB at the initiation of ART in Uganda had an approximate 37% increased hazard of overall mortality relative to non-TB patients.
Life Expectancy of Persons Receiving Combination Antiretroviral Therapy in Low-Income Countries: A Cohort Analysis From Uganda
(Annals of internal medicine, 2011) Mills, Edward J.; Bakanda, Celestin; Birungi, Josephine; Chan, Keith; Ford, Nathan; Cooper, Curtis L.; Nachega, Jean B.; Dybul, Mark; Hogg, Robert S.
Little is known about the effect of combination antiretroviral therapy (cART) on life expectancy in sub-Saharan Africa. Objective: To estimate life expectancy of patients once they initiate cART in Uganda. Design: Prospective cohort study. Setting: Public sector HIV and AIDS disease-management program in Uganda. Patients: 22 315 eligible patients initiated cART during the study period, of whom 1943 were considered to have died. Measurements: All-cause mortality rates were calculated and abridged life tables were constructed and stratified by sex and baseline CD4 cell count status to estimate life expectancies for patients receiving cART. The average number of years remaining to be lived by patients who received cART at varying age categories was estimated. Results: After adjustment for loss to follow-up, crude mortality rates (deaths per 1000 person-years) ranged from 26.9 (95% CI, 25.4 to 28.5) in women to 43.9 (CI, 40.7 to 47.0) in men. For patients with a baseline CD4 cell count less than 0.050 109 cells/L, the mortality rate was 67.3 (CI, 62.1 to 72.9) deaths per 1000 person-years, whereas among persons with a baseline CD4 cell count of 0.250 109 cells/L or more, the mortality rate was 19.1 (CI, 16.0 to 22.7) deaths per 1000 person-years. Life expectancy at age 20 years for the overall cohort was 26.7 (CI, 25.0 to 28.4) additional years and at age 35 years was 27.9 (CI, 26.7 to 29.1) additional years. Life expectancy increased substantially with increasing baseline CD4 cell count. Similar trends are observed for older age groups. Limitations: A small (6.4%) proportion of patients were lost to follow-up, and it was imputed that 30% of these patients had died. Few patients with a CD4 cell count greater than 0.250 109 cells/L initiated cART. Conclusion: Ugandan patients receiving cART can expect an almost normal life expectancy, although there is considerable variability among subgroups of patients.
Male gender predicts mortality in a large cohort of patients receiving antiretroviral therapy in Uganda
(Journal of the International AIDS Society, 2011) Mills, Edward J.; Bakanda, Celestin; Birungi, Josephine; Chan, Keith; Hogg, Robert S.; Ford, Nathan; Nachega, Jean B.; Cooper, Curtis L.
Because men in Africa are less likely to access HIV/AIDS care than women, we aimed to determine if men have differing outcomes from women across a nationally representative sample of adult patients receiving combination antiretroviral therapy in Uganda. Methods: We estimated survival distributions for adult male and female patients using Kaplan-Meier, and constructed multivariable regressions to model associations of baseline variables with mortality. We assessed person-years of life lost up to age 55 by sex. To minimize the impact of patient attrition, we assumed a weighted 30% mortality rate among those lost to follow up. Results: We included data from 22,315 adults receiving antiretroviral therapy. At baseline, men tended to be older, had lower CD4 baseline values, more advanced disease, had pulmonary tuberculosis and had received less treatment follow up (all at p < 0.001). Loss to follow up differed between men and women (7.5 versus 5.9%, p < 0.001). Over the period of study, men had a significantly increased risk of death compared with female patients (adjusted hazard ratio 1.43, 95% CI 1.31-1.57, p < 0.001). The crude mortality rate for males differed importantly from females (43.9, 95% CI 40.7-47.0/1000 person-years versus 26.9, 95% CI 25.4-28.5/1000 person years, p < 0.001). The probability of survival was 91.2% among males and 94.1% among females at 12 months. Person-years of life lost was lower for females than males (689.7 versus 995.9 per 1000 person-years, respectively). Conclusions: In order to maximize the benefits of antiretroviral therapy, treatment programmes need to be gender sensitive to the specific needs of both women and men. Particular efforts are needed to enroll men earlier into care.
Mortality by baseline CD4 cell count among HIV patients initiating antiretroviral therapy: evidence from a large cohort in Uganda
(Aids, 2011) Mills, Edward J.; Bakanda, Celestin; Birungi, Josephine; Mwesigwa, Robert; Chan, Keith; Ford, Nathan; Hogg, Robert S.; Cooper, Curtis
Evaluations of CD4 cell count and other prognostic factors on the survival of HIV patients in sub-Saharan Africa are extremely limited. Funders have been reticent to recommend earlier initiation of treatment. We aimed to examine the effect of baseline CD4 cell count on mortality using data from HIV patients receiving combination antiretroviral therapy (cART) in Uganda. Design: Observational study of patients aged at least 14 years enrolled in 10 clinics across Uganda for which The AIDS Support Organization (TASO) has data. Methods: CD4 cell count was stratified into categories (<50, 50–99, 100–149, 150– 199, 200–249, 250–299, 300 cells/ml) and Cox proportional hazards regression was used to model the associations between CD4 cell count and mortality. Results: A total of 22 315 patients were included. 1498 patients died during follow-up (6.7%) and 1433 (6.4%) of patients were lost to follow-up. Crude mortality rates (CMRs) ranged from 53.8 per 1000 patient-years [95% confidence interval (CI) 48.8–58.8] among those with CD4 cell counts of less than 50, to 15.7, (95% CI 12.1–19.3) among those with at least 300 cells/ml. Relative to a baseline CD4 cell count of less than 50 cells/ml, the risk of mortality was 0.75 (95% CI 0.65–0.88), 0.60 (95% CI 0.51–0.70), 0.43 (0.37–0.50), and 0.41 (0.33–0.51) for those with baseline CD4 cell counts of 50–99, 100–149, 150–249, and 250 cells/ml, respectively. Conclusion: Earlier initiation of cART is associated with increased survival benefits over deferred treatment.
Outcomes, Feasibility and Acceptability of a Group Support Psychotherapeutic Intervention for Depressed HIV Affected Ugandan Adults: A Pilot Study
(Journal of affective disorders, 2014) Nakimuli-Mpungu, Etheldreda; Wamala, Kizito; Okello, James; Alderman, Stephen; Odokonyero, Raymond; Musisi, Seggane; Mojtabaie, Ramin; Mills, Edward J.
Psychotherapy is the recommended first line treatment for mild to moderate depression. However, its availability in low resource settings is limited. We developed a manualized culturally sensitive group support psychotherapeutic intervention for depressed HIV affected Ugandan adults. In this study, we aimed to assess its feasibility, acceptability and impact on depression, functioning, social support and self-esteem. A total of 77 depressed individuals were assigned to the group intervention (n=48) and a wait-list control group (n=29), and assessed before, during and at the end of the intervention. The self-reporting questionnaire, a locally relevant function assessment instrument, the Rosenberg self-esteem scale, and the multiple dimensions perceived social support scale were administered to assess depression symptoms, functioning, self-esteem and social support at three assessment periods. Multivariate longitudinal regression models were used to determine change in outcomes over time between the two groups. Participants were asked to evaluate the intervention. Post –intervention assessments indicate that, in comparison to the wait-list control group, the intervention group had a faster reduction in depression symptom scores [OR=0.00,95% CI, 0.00–0.003] and faster increase in functioning scores [OR=4.82, 95% CI, 2.39 to 9.75], social support scores [OR=2.68, 95% CI, 1.50–4.78] and self-esteem [OR=1.90, 95% CI 1.48–2.44]. Sixty-three percent of participants strongly agreed that the intervention had reduced their depression and would recommend it to other depressed individuals. Inadequate study power due to small sample sizes may result in imprecise confidence intervals even when there are significant differences. The use of non-random samples could have resulted in selection bias. This intervention appears feasible, acceptable and promising in treating depression and restoring function, enhancing social support and self-esteem. Larger and randomized evaluations are warranted.
Predictive value of CD4 cell count nadir on long-term mortality in HIV-positive patients in Uganda
(HIV/AIDS – Research and Palliative Care, 2012) Bray, Sarah; Gedeon, Jillian; Hadi, Ahsan ard J Mills; Kotb, Ahmed; Rahman, Tarun; Sarwar, Elaha; Savelyeva, Anna; Sévigny, Marika; Bakanda, Celestin; Birungi, Josephine; Chan, Keith; Yaya, Sanni; Deonandan, Raywat; Mills, Edward J.
Although international guidelines recommend initiating antiretroviral therapy (ART) when a patient’s CD4 cell count is #350 cells/μL, most patients in resource-limited settings present with much lower CD4 cell counts. The lowest level that their CD4 cell count reaches, the nadir, may have long-term consequences in terms of mortality. We examined this health state in a large cohort of HIV+ patients in Uganda. Design: This was an observational study of HIV patients in Uganda aged 14 years or older, who were enrolled in 10 major clinics across Uganda. Methods: We assessed the CD4 nadir of patients, using their CD4 cell count at initiation of ART, stratified into categories (,50, 50–99, 100–149, 150–249, 250+ cells/μL). We constructed Kaplan–Meier curves to assess the differences in survivorship for patients left-censored at 1 year and 2 years after treatment initiation. We used Cox proportional hazards regression to model the associations between CD4 nadir and mortality. We adjusted mortality for loss-to-follow-up. Results: Of 22,315 patients, 20,129 patients had greater than 1 year of treatment follow-up. Among these patients, 327 (1.6%) died and 444 (2.2%) were lost to follow-up. After left-censoring at one year, relative to lowest CD4 strata, patients with higher CD4 counts had significantly lower rates of mortality (CD4 150–249, hazard ratio [HR] 0.60, 95% confidence interval [CI]: 0.45–0.82, P = 0.001; 250+, HR 0.66, 95% CI, 0.44–1.00, P = −0.05). Male sex, older age, and duration of time on ART were independently associated with mortality. When left-censoring at 2 years, CD4 nadir was no longer statistically significantly associated with mortality. Conclusion: After surviving for 1 year on ART, a CD4 nadir was strongly predictive of longer-term mortality among patients in Uganda. This should argue for efforts to increase engagement with patients to ensure a higher CD4 nadir at initiation of treatment.
The prognostic value of baseline CD4R cell count beyond 6 months of antiretroviral therapy in HIV-positive patients in a resource-limited setting
(Aids, 2012) Mills, Edward J.; Bakanda, Celestin; Birungi, Josephine; Yaya, Sanni; Ford, Nathan
The risk of death is highest in the first few months after initiation of antiretroviral therapy (ART). We examined whether initial CD4þ cell count maintains a strong prognostic value among patients with at least 6 months follow-up after the initiation of ART. Design: Observational study of HIV patients in Uganda aged 14 years or older enrolled in 10 clinics across Uganda. Methods: Baseline CD4þ cell count of patients with more than 6 months of follow-up were stratified into categories (<50, 50–99, 100–149, 150–249, >250 cells/ml). A Kaplan–Meier survival analysis and Cox proportional hazards regression was used to model the associations between baseline CD4þ cell count and mortality. Results: Of 22 315 patients, 20 730 (92.8%) had more than 6 months of follow-up. Six hundred and eleven (2.9%) patients died during follow-up and 737 (3.6%) were lost to follow-up. Relative to a baseline CD4þ cell counts of less than 50 cells/ml, the adjusted hazard ratios for death were 0.83 [95% confidence interval (CI) 0.67–1.02], 0.71 (95% CI 0.57–0.88), 0.52 (95% CI 0.42–0.64), and 0.55 (95% CI 0.42–0.70) favouring those with baseline CD4þ cell counts of 50–99, 100–149, 150–249, and at least 250 cells/ml, respectively. Differing ages and male sex increased the likelihood of mortality. Conclusion: Among patients with more than 6 months of follow-up after initiation of ART, baseline CD4þ cell count at initiation still has important prognostic value. This suggests that active engagement and earlier treatment initiation is important for longterm survival.
Survival of HIV-Infected Adolescents on Antiretroviral Therapy in Uganda: Findings from a Nationally Representative Cohort in Uganda
(PLoS ONE, 2011) Bakanda, Celestin; Birungi, Josephine; Mwesigwa, Robert; Nachega, Jean B.; Chan, Keith; Palmer, Alexis; Ford, Nathan; Mills, Edward J.
Adolescents have been identified as a high-risk group for poor adherence to and defaulting from combination antiretroviral therapy (cART) care. However, data on outcomes for adolescents on cART in resource-limited settings remain scarce. Methods: We developed an observational study of patients who started cART at The AIDS Service Organization (TASO) in Uganda between 2004 and 2009. Age was stratified into three groups: children (#10 years), adolescents (11–19 years), and adults ($20 years). Kaplan-Meier survival curves were generated to describe time to mortality and loss to follow-up, and Cox regression used to model associations between age and mortality and loss to follow-up. To address loss to follow up, we applied a weighted analysis that assumes 50% of lost patients had died. Findings: A total of 23,367 patients were included in this analysis, including 810 (3.5%) children, 575 (2.5%) adolescents, and 21 982 (94.0%) adults. A lower percentage of children (5.4%) died during their cART treatment compared to adolescents (8.5%) and adults (10%). After adjusting for confounding, other features predicted mortality than age alone. Mortality was higher among males (p,0.001), patients with a low initial CD4 cell count (p,0.001), patients with advanced WHO clinical disease stage (p,0.001), and shorter duration of time receiving cART (p,0.001). The crude mortality rate was lower for children (22.8 per 1000 person-years; 95% CI: 16.1, 29.5), than adolescents (36.5 per 1000 person-years; 95% CI: 26.3, 46.8) and adults (37.5 per 1000 person-years; 95% CI: 35.9, 39.1).

Browsing by Author "Mills, Edward J."

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