Characteristics of the 3628 HIV-infected adults newly initiating ART between January 1, 2004 and September 30, 2007 have been previously reported In short, the median age was 35 years (interquartile range (IQR) 30 to 42), and 61% were women. The median CD4+ T cell count prior to therapy in 1674 patients in whom it was available was 95/mm3 (IQR 36 to 172). The median time between last pre-therapy CD4+ T cell determination and ART initiation was 41 days (IQR 15 to 83).
As previously reported, over a maximum of 3.75 years of follow-up, 829 patients became lost to follow-up as defined by six months of absence from clinic for a cumulative incidence at 1, 2 and 3 years of 16% (95% confidence interval, 15 to 17%), 30% (95% CI, 28 to 32%), and 39% (37 to 42%), respectively. Of the 829 patients lost to follow-up, a sample of 128 (15%) was sought after in the community. Of the 128 lost patients in this sample, 111 (87%) had ascertainment of vital status. Of these 111, 32 had died. As previously reported, in 48 cases (43%), the patient was directly found, and in 63 cases (57%) an informant was found. Informants included parents (15%), children (9%), friends (5%), neighbors (8%), siblings (5%), spouse (4%), and others (11%).
The cumulative incidence of death in the lost patients at 1, 3, 6 and 12 months was 9.1% (95% CI, 5.0–16%), 15% (95% CI, 9.3 to 23%), 23% (95% CI, 16 to 33%) and 36% (95% CI, 24 to 44%), respectively. Patients who were lost and subsequently had their vital status ascertained by tracking (n=111) were similar in age (median 35 vs. 36 years), gender (59% vs. 58% women), pre-therapy CD4+ T cell count (median 74.5 vs. 72.0 cells/mm3), to those who were lost and did not have ultimate vital status ascertained (n=718).
Naïve analyses (), where only deaths known passively to the clinic were considered, found statistically significant associations between death and male sex and pre-ART CD4+ T-cell count. In multivariable analyses, men had a 1.86-fold higher rate of death (95% CI, 1.06–3.26) compared to women and those with higher pre-ART CD4+ T cell counts had lower rates of death. Compared to a reference group of those with < 50 cells/mm3, the hazard ratio (HR) was 0.56 (95% CI, 0.25–1.24) for those with a CD4+ T cell count 51–100 cells/mm3, 0.24 (95% CI, 0.08–0.68) for those with 101–200 cells/mm3, and 0.15 (95% CI, 0.03–0.67) for those with > 200 cells/mm3. Age, weight, distance, WHO clinical stage and calendar year of ART initiation were not statistically significantly associated with death.
Naïve analysis of factors associated with mortality among ART initiators in Mbarara, Uganda. Results of unadjusted and multivariable proportional hazards regression models using only deaths passively ascertained in routine clinical care.
In the sample-corrected analysis (), deaths found through patient tracking were incorporated to represent outcomes in all lost patients. In multivariable analyses, pre-ART CD4+ T cell count remained a significant predictor of death and the magnitude of association was similar to the naïve analysis. Male sex, however, which was found to be significantly associated with mortality in the naïve analysis, was not significantly associated with mortality in the sample-corrected analysis with a change in the magnitude of association from 1.86 to 1.02 (95% CI: 0.57–1.83). In contrast, age, which was not significantly associated with death in the naïve analysis, was found to be significantly associated with death in the corrected analysis with each additional 10 years of age conferring a 37% increase in the rate of death (HR=1.37, 95% CI: 1.04–1.81). Weight less than 40 kg at ART initiation (HR=3.04, 95% CI: 1.58–5.85) and calendar year of ART initiation were also found to be significantly associated with mortality in this analysis whereas in the naïve analysis they were not. In the sample-corrected analysis, there was a significant increase in the risk of death for subjects initiating ART in 2005 versus 2004 (the reference year) and a significant decrease in risk among those starting ART in 2007 compared to 2004.
Table 2 Sample-corrected analysis of factors associated with mortality among ART initiators in Mbarara, Uganda. Results of unadjusted and multivariable proportional hazards regression models that incorporated deaths identified through tracking a representative (more ...)
A sensitivity analysis to explore the effect of residual bias from the 13% of patients in the tracked sample whose outcomes were not ascertained found no substantial differences. Neither a pessimistic model (which assumed all patients without vital status ascertainment had died) nor an optimistic model (which assumed they were all alive) changed the findings of multivariable model – all hazard ratios were similar and no p-values crossed the significance threshold.