Browsing by Author "Bakanda, Celestin"
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Item 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.Item 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.Item Community‑based ART distribution system can effectively facilitate long‑term program retention and low‑rates of death and virologic failure in rural Uganda(AIDS research and therapy, 2015) Okoboi, Stephen; Ding, Erin; Persuad, Steven; Wangisi, Jonathan; Birungi, Josephine; Shurgold, Susan; Kato, Darius; Nyonyintono, Maureen; Egessa, Aggrey; Bakanda, Celestin; Munderi, Paula; Kaleebu, Pontiano; Moore, David M.Community-drug distribution point is a care model for stable patients in the community designed to make ART delivery more efficient for the health system and provide appropriate support to encourage long-term retention of patients. We examined program retention among ART program participants in rural Uganda, which has used a community-based distribution model of ART delivery since 2004. Methods: We analyzed data of all patients >18 years who initiated ART in Jinja, Ugandan site of The AIDS Support Organization between January 1, 2004 and July 31, 2009. Participants attended clinic or outreach visits every 2–3 months and had CD4 cell counts measured every 6 months. Retention to care was defined as any patient with at least one visit in the 6 months before June 1, 2013. We then identified participants with at least one visit in the 6 months before June 1, 2013 and examined associations with mortality and lost-to-follow-up (LTFU). Participants with >4 years of follow up during August, 2012 to May, 2013 had viral load conducted, since no routine viral load testing was available. Results: A total of 3345 participants began ART during 2004–2009. The median time on ART in June 2013 was 5.69 years. A total of 1335 (40 %) were residents of Jinja district and 2005 (60 %) resided in outlying districts. Of these, 2322 (69 %) were retained in care, 577 (17 %) died, 161 (5 %) transferred out and 285 (9 %) were LTFU. Factors associated with mortality or LTFU included male gender, [Adjusted Hazard Ratio (AHR) = 1.56; 95 % CI 1.28–1.9], CD4 cell count <50 cells/μL (AHR = 4.09; 95 % CI 3.13–5.36) or 50–199 cells/μL (AHR = 1.86; 95 % CI 1.46–2.37); ART initiation and WHO stages 3 (AHR = 1.35; 95 % CI 1.1–1.66) or 4 (AHR = 1.74; 95 % CI 1.23–2.45). Residence outside of Jinja district was not associated with mortality/LTFU (p value = 0.562). Of 870 participants who had VL tests, 756 (87 %) had VLs <50 copies/mL. Conclusion: Community-based ART distribution systems can effectively mitigate the barriers to program retention and result in good rates of virologic suppression.Item 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.Item Factors associated with long-term antiretroviral therapy attrition among adolescents in rural Uganda: a retrospective study(Journal of the International AIDS Society, 2016) Okoboi, Stephen; Ssali, Livingstone; Yansaneh, Aisha I.; Bakanda, Celestin; Birungi, Josephine; Nantume, Sophie; Lyavala Okullu, Joanne; Sharp, Alana R.; Moore, David M.; Kalibala, SamuelAs access to antiretroviral therapy (ART) increases, the success of treatment programmes depends on ensuring high patient retention in HIV care. We examined retention and attrition among adolescents in ART programmes across clinics operated by The AIDS Support Organization (TASO) in Uganda, which has operated both facility- and community-based distribution models of ART delivery since 2004. Methods: Using a retrospective cohort analysis of patient-level clinical data, we examined attrition and retention in HIV care and factors associated with attrition among HIV-positive adolescents aged 10 19 years who initiated ART at 10 TASO clinics between January 2006 and December 2011. Retention in care was defined as the proportion of adolescents who had had at least one facility visit within the six months prior to 1 June 2013, and attrition was defined as the proportion of adolescents who died, were lost to follow-up, or stopped treatment. Descriptive statistics and Cox proportional hazards regression models were used to determine the levels of retention in HIV care and the factors associated with attrition following ART initiation. Results: A total of 1228 adolescents began ART between 2006 and 2011, of whom 57% were female. The median duration in HIV care was four years (IQR 3 6 years). A total of 792 (65%) adolescents were retained in care over the five-year period; 36 (3%) had died or transferred out and 400 (32%) were classified as loss to follow-up. Factors associated with attrition included being older (adjusted hazard ratio (AHR) 1.38, 95% confidence interval (CI) 1.02 1.86), having a higher CD4 count (250 cells/mm3) at treatment initiation (AHR 0.49, 95% CI 0.34 0.69) and HIV care site with a higher risk of attrition among adolescents in Gulu (AHR 2.26; 95% CI 1.27 4.02) and Masindi (AHR 3.30, 95% CI 1.87 5.84) and a lower risk of attrition in Jinja (AHR 0.24, 95% CI 0.08 0.70). Having an advanced WHO clinical stage at initiation was not associated with attrition. Conclusions: We found an overall retention rate of 65%, which is comparable to rates achieved by TASO’s adult patients and adolescents in other studies in Africa. Variations in the risk of attrition by TASO treatment site and by clinical and demographic characteristics suggest the need for early diagnosis of HIV infection, use of innovative approaches to reach and retain adolescents living with HIV in treatment and identifying specific groups, such as older adolescents, that are at high risk of dropping out of treatment for targeted care and support.Item 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, LehanaTuberculosis (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.Item 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.Item 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.Item 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, CurtisEvaluations 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.Item No differences in clinical outcomes with the addition of viral load testing to CD4 cell count monitoring among HIV infected participants receiving ART in rural Uganda: Long-term results from the Home Based AIDS Care Project(BMC Public Health, 2015) Okoboi, Stephen; Ekwaru, Paul John; Campbell, James D.; Egessa, Aggrey; King, Racheal; Bakanda, Celestin; Muramuzi, Emmy; Kaharuza, Frank; Malamba, Samuel; Moore, David M.We compared clinical outcomes among HIV-infected participants receiving ART who were randomized to viral load (VL) and CD4 cell count monitoring in comparison to CD4 cell count monitoring alone in Tororo, Uganda. Methods: Beginning in May 2003, participants with CD4 cell counts <250 cells/μL or WHO stage 3 or 4 disease were randomized to clinical monitoring alone, clinical monitoring plus quarterly CD4 cell counts (CD4-only); or clinical monitoring, quarterly CD4 cell counts and quarterly VL testing (CD4-VL). In 2007, individuals in clinical monitoring arm were re-randomized to the other two arms and all participants were followed until March 31, 2009. We used Cox Proportional Hazard models to determine if study arm was independently associated with the development of opportunistic infections (OIs) or death. Results: We randomized 1211 participants to the three original study arms and 331 surviving participants in the clinical monitoring arm were re-randomized to the CD4-VL and CD4 only arms. At enrolment the median age was 38 years and the median CD4 cell count was 134 cells/μL. Over a median of 5.2 years of follow-up, 37 deaths and 35 new OIs occurred in the VL-CD4 arm patients, 39 deaths and 42 new OIs occurred in CD4-only patients. We did not observe an association between monitoring arm and new OIs or death (AHR =1.19 for CD4-only vs. CD4-VL; 95 % CI 0.82–1.73). Conclusion: We found no differences in clinical outcomes associated with the addition of quarterly VL monitoring to quarterly CD4 cell count monitoring.Item 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.Item 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, NathanThe 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.Item 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).