Celestin Bakanda

Life Expectancy of Persons Receiving Combination Antiretroviral Therapy in Low-Income Countries: A Cohort Analysis From Uganda

BACKGROUND 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 × 10(9) 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 × 10(9) 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 × 10(9) 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. PRIMARY FUNDING SOURCE Canadian Institutes of Health Research.

Mortality by baseline CD4 cell count among HIV patients initiating antiretroviral therapy: evidence from a large cohort in Uganda

Objective: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/μl) 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/μl. Relative to a baseline CD4 cell count of less than 50 cells/μl, 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/μl, respectively. Conclusion:Earlier initiation of cART is associated with increased survival benefits over deferred treatment.

Survival of HIV-infected adolescents on antiretroviral therapy in Uganda: findings from a nationally representative cohort in Uganda.

Background 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). Interpretation This study is the largest assessment of adolescents receiving cART in Africa. Adolescents did not have cART mortality outcomes different from adults or children.

Male gender predicts mortality in a large cohort of patients receiving antiretroviral therapy in Uganda

BackgroundBecause 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.MethodsWe 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.ResultsWe 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).ConclusionsIn 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.

Association of aging and survival in a large HIV-infected cohort on antiretroviral therapy.

Objective: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). Adjusted Weibull 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.

The prognostic value of baseline CD4(+) cell count beyond 6 months of antiretroviral therapy in HIV-positive patients in a resource-limited setting.

Objective:The risk of death is highest in the first few months after initiation of antiretroviral therapy (ART). We examined whether initial CD4+ 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 CD4+ 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/&mgr;l). A Kaplan–Meier survival analysis and Cox proportional hazards regression was used to model the associations between baseline CD4+ 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 CD4+ cell counts of less than 50 cells/&mgr;l, 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 CD4+ cell counts of 50–99, 100–149, 150–249, and at least 250 cells/&mgr;l, 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 CD4+ cell count at initiation still has important prognostic value. This suggests that active engagement and earlier treatment initiation is important for long-term survival.

Impact of tuberculosis on mortality among HIV-infected patients receiving antiretroviral therapy in Uganda: a prospective cohort analysis

BackgroundTuberculosis (TB) disease affects survival among HIV co-infected patients on antiretroviral therapy (ART). Yet, the magnitude of TB disease on mortality is poorly understood.MethodsUsing 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.ResultsA 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.ConclusionsAfter 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.

Density of Healthcare Providers and Patient Outcomes: Evidence from a Nationally Representative Multi-Site HIV Treatment Program in Uganda

Objective 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.

Cohort Profile: The TASO-CAN Cohort Collaboration

This study Cohort largely 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

Factors associated with long-term antiretroviral therapy attrition among adolescents in rural Uganda: a retrospective study

As 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.