Browsing by Author "Chan, Keith"

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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.
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    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.
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    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.
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    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.
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    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.
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    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).