Browsing by Author "Brinkhof, Martin W G"

Now showing 1 - 5 of 5
  • Thumbnail Image
    Item
    Open Access
    Adjusting mortality for loss to follow-up: analysis of five ART programmes in sub-Saharan Africa
    (Public Library of Science, 2010) Brinkhof, Martin W G; Spycher, Ben D; Yiannoutsos, Constantin; Weigel, Ralf; Wood, Robin; Messou, Eugène; Boulle, Andrew; Egger, Matthias; Sterne, Jonathan A C; (IeDEA), for the International epidemiological Database to Evaluate AIDS
    BACKGROUND: 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. Methods and FINDINGS: 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 count 110 cells/µL, median age 35 years, 68% female) were included; 1,001 (6.3%) were known to have died and 1,285 (14.3%) were lost to follow-up in the first year of ART. Crude estimates of mortality at one year ranged from 5.7% (95% CI 4.9-6.5%) to 10.9% (9.6-12.4%) across the five programmes. Estimated mortality hazard ratios comparing patients lost to follow-up with those remaining in care ranged from 6 to 23. Adjusted estimates based on these hazard ratios ranged from 10.2% (8.9-11.6%) to 16.9% (15.0-19.1%), with relative increases in mortality ranging from 27% to 73% across programmes. CONCLUSIONS: Naïve survival analysis ignoring excess mortality in patients lost to follow-up may greatly underestimate overall mortality, and bias ART programme evaluations. Adjusted mortality estimates can be obtained based on excess mortality rates in patients lost to follow-up.
  • Thumbnail Image
    Item
    Restricted
    Long-term immunologic response to antiretroviral therapy in low-income countries: a collaborative analysis of prospective studies
    (Lippincott, Williams & Wilkins, 2008) Nash, Denis; Katyal, Monica; Brinkhof, Martin W G; Keiser, Olivia; May, Margaret; Hughes, Rachael; Dabis, Francois; Wood, Robin; Sprinz, Eduardo; Schechter, Mauro; Egger, Matthias
    Background: Few data are available on the long-term immunologic response to ART in resource-limited settings, where antiretroviral therapy (ART) is being scaled up using a public health approach, with a limited repertoire of drugs. Objectives: To describe immunologic response to ART in a network of cohorts from sub-Saharan Africa, Latin America, and Asia. Study population/methodsL: Treatment-naïve patients aged 15 and older from 27 treatment programs were eligible. Multi-level, linear mixed models were used to assess associations between predictor variables and CD4 count trajectories following ART initiation. Results: Of 29,175 patients initiating ART, 8,933 patients (31%) were excluded due to insufficient follow-up time and early lost to follow-up or death. The remaining 19,967 patients contributed 39,200 person-years on ART and 71,067 CD4 measurements. The median baseline CD4 count was 114 cells/μL, with 35%<100 cells μL and substantial inter-site variation (range: 61-181 cells/μL). Females had higher median baseline CD4 counts than males (121 vs. 104 cells/μL). The median CD4 count increased from 114 cells/μL at ART initiation to 230 (IQR:144-338) at 6 months, 263 (IQR:175-376) at 1 year, 336 (IQR:224-472) at 2 years, 372 (IQR:242-537) at 3 years, 377 (IQR:221-561) at 4 years, and 395 (IQR:240-592) at 5 years. In multivariable models, baseline CD4 count was the most important determinant of subsequent CD4 count trajectories. Conclusions: These data demonstrate robust and sustained CD4 response to ART among patients remaining on therapy. Public health and programmatic interventions leading to earlier HIV diagnosis and initiation of ART could substantially improve patient outcomes in resource-limited settings.
  • Thumbnail Image
    Item
    Open Access
    Mortality of HIV-infected patients starting antiretroviral therapy in sub-Saharan Africa: comparison with HIV-unrelated mortality
    (Public Library of Science, 2009) Brinkhof, Martin W G; Boulle, Andrew; Weigel, Ralf; Messou, Eugène; Mathers, Colin; Orrell, Catherine; Dabis, François; Pascoe, Margaret; Egger, Matthias; (IeDEA), for the International epidemiological Databases to Evaluate AIDS
    Comparing mortality rates between patients starting HIV treatment and the general population in four African countries, Matthias Egger and colleagues find the gap decreases over time, especially with early treatment.
  • Thumbnail Image
    Item
    Open Access
    Public-health and individual approaches to antiretroviral therapy: township South Africa and Switzerland compared
    (Public Library of Science, 2008) Keiser, Olivia; Orrell, Catherine; Egger, Matthias; Wood, Robin; Brinkhof, Martin W G; Furrer, Hansjakob; vCutsem, Gilles; Ledergerber, Bruno; Boulle, Andrew; (IeDEA-SA), for the Swiss HIV Cohort Study (SHCS) and the International Epidemiologic Databases
    Comparing HIV treatment in Switzerland, where drug selection is individualized, and South Africa, where a programmatic approach is used, Matthias Egger and colleagues find similar virologic outcomes over two years.
  • Thumbnail Image
    Item
    Open Access
    Universal Definition of Loss to Follow-Up in HIV Treatment Programs: A Statistical Analysis of 111 Facilities in Africa, Asia, and Latin America
    (Public Library of Science, 2011) Chi, Benjamin H; Yiannoutsos, Constantin T; Westfall, Andrew O; Newman, Jamie E; Zhou, Jialun; Cesar, Carina; Brinkhof, Martin W G; Mwango, Albert; Balestre, Eric; Carriquiry, Gabriela
    Background: Although patient attrition is recognized as a threat to the long-term success of antiretroviral therapy programs worldwide, there is no universal definition for classifying patients as lost to follow-up (LTFU). We analyzed data from health facilities across Africa, Asia, and Latin America to empirically determine a standard LTFU definition. Methods and Findings: At a set ''status classification'' date, patients were categorized as either ''active'' or ''LTFU'' according to different intervals from time of last clinic encounter. For each threshold, we looked forward 365 d to assess the performance and accuracy of this initial classification. The best-performing definition for LTFU had the lowest proportion of patients misclassified as active or LTFU. Observational data from 111 health facilities - representing 180,718 patients from 19 countries - were included in this study. In the primary analysis, for which data from all facilities were pooled, an interval of 180 d (95% confidence interval [CI]: 173–181 d) since last patient encounter resulted in the fewest misclassifications (7.7%, 95% CI: 7.6%–7.8%). A secondary analysis that gave equal weight to cohorts and to regions generated a similar result (175 d); however, an alternate approach that used inverse weighting for cohorts based on variance and equal weighting for regions produced a slightly lower summary measure (150 d). When examined at the facility level, the best-performing definition varied from 58 to 383 d (mean = 150 d), but when a standard definition of 180 d was applied to each facility, only slight increases in misclassification (mean = 1.2%, 95% CI: 1.0%–1.5%) were observed. Using this definition, the proportion of patients classified as LTFU by facility ranged from 3.1% to 45.1% (mean = 19.9%, 95% CI: 19.1%–21.7%). Conclusions: Based on this evaluation, we recommend the adoption of $180 d since the last clinic visit as a standard LTFU definition. Such standardization is an important step to understanding the reasons that underlie patient attrition and establishing more reliable and comparable program evaluation worldwide.