Estimating Loss to Follow-Up in HIV-Infected Patients on Antiretroviral Therapy: The Effect of the Competing Risk of Death in Zambia and Switzerland (original) (raw)
Related papers
Background Antiretroviral therapy (ART) initiation is now recommended irrespective of CD4 count. However data on the relationship between CD4 count at ART initiation and loss to follow-up (LTFU) are limited and conflicting. Methods We conducted a cohort analysis including all adults initiating ART (2008–2012) at three public sector sites in South Africa. LTFU was defined as no visit in the 6 months before database closure. The Kaplan-Meier estimator and Cox’s proportional hazards models examined the relationship between CD4 count at ART initiation and 24-month LTFU. Final models were adjusted for demographics, year of ART initiation, programme expansion and corrected for unascertained mortality. Results Among 17 038 patients, the median CD4 at initiation increased from 119 (IQR 54–180) in 2008 to 257 (IQR 175–318) in 2012. In unadjusted models, observed LTFU was associated with both CD4 counts <100 cells/μL and CD4 counts ≥300 cells/μL. After adjustment, patients with CD4 counts ≥300 cells/μL were 1.35 (95% CI 1.12 to 1.63) times as likely to be LTFU after 24 months compared to those with a CD4 150–199 cells/μL. This increased risk for patients with CD4 counts ≥300 cells/μL was largest in the first 3 months on treatment. Correction for unascertained deaths attenuated the association between CD4 counts <100 cells/μL and LTFU while the association between CD4 counts ≥300 cells/μL and LTFU persisted. Conclusions Patients initiating ART at higher CD4 counts may be at increased risk for LTFU. With programmes initiating patients at higher CD4 counts, models of ART delivery need to be reoriented to support long-term retention.
PLOS ONE, 2018
Setting Myanmar National AIDS Program has had significant scale-up of services and changes in CD4 eligibility criterion for ART initiation from 2013 to 2016. This study assessed early death within 6 months and attrition (death and loss to follow-up, LTFU) after ART initiation and their associated factors. Design A retrospective cohort study on people living with HIV (PLHIV >15 year of age) enrolled at three specialist hospitals in Yangon from 1 st June 2013 to 30 th June 2016. Cox regression was used to calculate hazard ratios (HRs) of early death and attrition. Results Of 11,727 adults enrolled, 11,186 (95%) were initiated on ART, providing 15,964 personyears of follow-up. At baseline, median age was 36 years [IQR: 30-43], 58% were men and median CD4 count was 151 cells/mm3 (IQR: 54-310). There were 733(6%) early deaths, 961(9%) total deaths and 1371 (12%) LTFU during the study period. Independent risk factors for early death were older age (41-50 and !51 years) [aHR 1.38, 1.07-1.78 and 1.68, 1.21-2.34], male (1.84, 1.44-2.35), low weight (2.06, 1.64-2.59), bedridden, (3.81, 2.57-5.66) and CD4 count 50 cells/mm3 (6.83, 2.52-18.57). In addition to above factors, high attrition was associated with an abacavir-based regimen.
Aids Research and Therapy, 2022
Background: People living with HIV (PLWHIV) commencing antiretroviral therapy (ART) in sub-Saharan Africa experience significant mortality within the first year. Previously, identified risk factors for mortality may be biased towards these patients, as compared to those who experience late mortality. Aim: To compare risk factors for early and late mortality in PLWHIV commencing ART. Methods: A retrospective cohort study of ART-naïve patients aged ≥ 18 years from an outpatient HIV clinic in Zimbabwe. Data were collected between January 2010 and January 2019. Predictors for early (≤ 1 year) and late mortality (> 1 year) were determined by multivariable cox proportional hazards analyses, with patients censored at 1 year and landmark analysis after 1 year, respectively. Results: Three thousand and thirty-nine PLWHIV were included in the analysis. Over a median follow-up of 4.6 years (IQR 2.5-6.9), there was a mortality rate of 8.8%, with 50.4% of deaths occurring within 1 year. Predictors of early mortality included CD4 count < 50 cells/µL (HR 1.84, 95% CI 1.24-2.72, p < 0.01), WHO Stage III (HR 2.05, 95% CI 1.28-3.27, p < 0.01) or IV (HR 2.83, 95% CI 1.67-4.81, p < 0.01), and eGFR < 90 mL/min/1.73 m 2 (HR 2.48, 95% CI 1.56-3.96, p < 0.01). Other than age (p < 0.01), only proteinuria (HR 2.12, 95% CI 1.12-4.01, p = 0.02) and diabetes mellitus (HR 3.51, 95% CI 1.32-9.32, p = 0.01) were associated with increased risk of late mortality. Conclusions: Traditional markers of mortality risk in patients commencing ART appear to be limited to early mortality. Proteinuria and diabetes are some of the few predictors of late mortality, and should be incorporated into routine screening of patients commencing ART.
Changing mortality risk associated with CD4 cell response to antiretroviral therapy in South Africa
AIDS, 2009
Objective-To determine the relationship between mortality risk and the CD4 cell response to antiretroviral therapy (ART). Design-Observational community-based ART cohort in South Africa. Methods-CD4 cell counts were measured 4 monthly, and deaths were prospectively ascertained. Cumulative person-time accrued within a range of updated CD4 cell count strata (CD4 cell-strata) was calculated and used to derive CD4 cell-stratified mortality rates. Results-Patients (2423) (median baseline CD4 cell count of 105 cells/ml) were observed for up to 5 years of ART. One hundred and ninety-seven patients died during 3155 person years of observation. In multivariate analysis, mortality rate ratios associated with 0-49, 50-99, 100-199, 200-299, 300-399, 400-499 and at least 500 cells/ml updated CD4 cell-strata were 11.6, 4.9, 2.6, 1.7, 1.5, 1.4 and 1.0, respectively. Analysis of CD4 cell count recovery permitted calculations of person-time accrued within these CD4 cell strata. Despite rapid immune recovery, high mortality in the first year of ART was related to the large proportion of person-time accrued within CD4 cell-strata less than 200 cells/ml. Moreover, patients with baseline CD4 cell counts less than 100 cells/ml had much higher cumulative mortality estimates at 1 and 4 years (11.6 and 16.7%) compared with those of patients with baseline counts of at least 100 cells/ml (5.2 and 9.5%) largely because of greater cumulative person-time at CD4 cell counts less than 200 cells/ml. Conclusion: Updated CD4 cell counts are the variable most strongly associated with mortality risk during ART. High cumulative mortality risk is associated with person-time accrued at low CD4 cell counts. National HIV programmes in resource-limited settings should be designed to minimize the time patients spend with CD4 cell counts less than 200 cells/ml both before and during ART.
BMJ Open
ObjectiveTo determine the loss to follow-up (LTFU) rates at different healthcare levels after antiretroviral therapy (ART) services decentralisation among ART patients who initiated ART between 2004 and 2017 using the competing risk model in addition to the Kaplan-Meier and Cox regressions analysis.DesignA retrospective cohort study.SettingThe study was done in Zimbabwe using a nationwide routinely collected HIV patient-level data from various health levels of care facilities compiled through the electronic patient management system (ePMS).ParticipantsWe analysed 390 771 participants aged 15 years and above from 538 health facilities.OutcomesThe primary endpoint was LTFU defined as a failure of a patient to report for drug refill for at least 90 days from last appointment date or if the patient missed the next scheduled visit date and never showed up again. Mortality was considered a secondary outcome if a patient was reported to have died.ResultsThe total exposure time contributed ...
Adjusting mortality for loss to follow-up: analysis of five ART programmes in sub-Saharan Africa
PloS one, 2010
Evaluation of antiretroviral treatment (ART) programmes in sub-Saharan Africa is difficult because many patients are lost to follow-up. Outcomes in these patients are generally unknown but studies tracing patients have shown mortality to be high. We adjusted programme-level mortality in the first year of antiretroviral treatment (ART) for excess mortality in patients lost to follow-up. Treatment-naïve patients starting combination ART in five programmes in Côte d'Ivoire, Kenya, Malawi and South Africa were eligible. Patients whose last visit was at least nine months before the closure of the database were considered lost to follow-up. We filled missing survival times in these patients by multiple imputation, using estimates of mortality from studies that traced patients lost to follow-up. Data were analyzed using Weibull models, adjusting for age, sex, ART regimen, CD4 cell count, clinical stage and treatment programme. A total of 15,915 HIV-infected patients (median CD4 cell co...