Our search identified 632 papers and abstracts after removing duplicates. Of these, 491 were excluded on the basis of title or abstract, and an additional 108 were excluded after a full text screen and removal of overlapping cohorts and reports that contained insufficient information. Thirty-three sources remained that met our eligibility criteria (), including 22 full text journal articles and 11 abstracts. These described outcomes for a total of 39 cohorts and 226 307 patients.
Literature Search and Application of Eligibility Criteria in a Systematic Review of Retention in Antiretroviral Therapy Programs in Sub-Saharan Africa.
Several exclusions from the review and censoring of data should be noted. First, we omitted reports from the International epidemiological Databases to Evaluate AIDS (IeDEA) group that pools data from HIV/AIDS treatment programs. We excluded these reports because many of the cohorts included in IeDEA’s analyses are described in more detail in the individual papers and abstracts in our review. Second, two studies, SA 1 and SA 2, reported outcomes to 48 months, and two studies, Botswana 2 and Cameroon 1, reported outcomes to 60 months. As these were the only cohorts reporting to time periods beyond 36 months, we censored data from these cohorts at the last time period reported to before 60 months (12 months for Cameroon 1 and 36 months for the remaining 3). And finally, we excluded several publications reporting data for cohorts from Malawi because the most recent report for Malawi, a conference abstract from July 2009 (Malawi 1), included data for the entire Malawian national ART program, thus encompassing the cohorts described in the other papers.
describes the characteristics of the cohorts. Nearly half the cohorts (49%, 19/39), representing 81% of the patients (183,486/226,307), were in southern Africa. The majority of treatment sites were either public sector (53%) or NGO (41%) facilities. About 35% of the 25 cohorts that provided information on payment reported that patients had to pay to receive care. The median years in which cohorts were enrolled for observation and in which observation ended were 2004 (range 1998–2005) and 2006 (range 2002–2007).
also reports median patient characteristics for each cohort. Patients were more likely to be female (median 65%, range 44%–100%) and had a median age at initiation of ART of 37 (range 34–40). All cohorts that reported starting CD4 count except one (Kenya 1) had a median below 200 cells/mm3 (median 113, range 60–203). For the studies that reported it, the median of the reported follow-up times was 12 months.
The proportion of patients lost from each cohort at the end of that cohort’s follow-up stratified by the cause of attrition, as well as the total proportion retained at each site, is shown in . After weighting for cohort size, loss to follow-up (LTFU) was the most common cause of attrition, followed by death (59% and 41% of total attrition respectively).
Rates of Patient Attrition and Retention from Antiretroviral Treatment Programs in Sub-Saharan Africa, as reported
Total retention rates at each time point reported are presented in . For the 39 cohorts, attrition rates were reported at only one time point for 24 (61%); the median time point for these cohorts was 18 months (IQR 12–24 months). Total attrition at 12 months was quite variable, with a median of 22.6% and a range from 7 to 45% (Rwanda 1 and SA 10b respectively). There was little change in median attrition (27%) by 24 months, but the range narrowed slightly, from 11% to 35% in Rwanda 1 and Kenya 1 respectively. By 36 months median attrition increased to 29.6%, with estimates ranging from 13.0% to 36.1% (in SA 4b and Botswana 2 respectively).
Retention of Patients at 6, 12, 18, 24 and 36 months after initiation of antiretroviral therapy in sub-Saharan Africa
To account for the variable times reported to, in all analyses presented below we interpolated retention rates at any time point where an estimate of retention was missing but a later time point was reported. Fifty estimates of attrition were interpolated, most at 6, 12, or 18 months (n = 25, 9, and 11, respectively).
show the variation in retention rates at 6, 12, 24 and 36 months using forest plots. Using random effects meta-analysis to pool the data including the interpolated time points, we estimated the retention at 6 months to be 86.1% (95% CI: 84.6%–87.4%), at 12 months to be 80.2% (95% CI: 78.0%–82.4%), at 24 months to be 76.1% (95% CI: 72.4%–79.7%) and at 36 months to be 72.3% (95% CI: 67.4%–76.9%).
Figure 2 a–d Forest Plots of Reported Retention at 6, 12, 24 and 36 Months after Initiation of Antiretroviral Therapy in Sub-Saharan Africa*. *Pooled estimates were created using random-effects meta-analysis. Data include both actual reported rates for (more ...)
We were concerned that studies reporting only to shorter time points would have higher attrition at those time points than would studies that reported longer follow-up. shows retention rates stratified by last reported time point. Each time point shows variation in retention rates, but there is no clear picture of studies reporting at later time points having higher overall retention at earlier time points compared to studies reporting only to earlier time points. While the cohorts reporting only to 6 and 12 months show lower attrition with duration of time reported to, suggesting some bias may exist, the 8 cohorts reporting to 36 months show sharper declines in the first 6–12 months than cohorts reporting to 24 months.
Figure 3 Weighted Average Retention Rates Over Time in Antiretroviral Therapy Programs in Sub-Saharan Africa*. *Studies reporting later time points and not earlier ones had the earlier attrition rates interpolated as described in the methods section and then weighted (more ...)
Using linear regression we found that median starting CD4 count <100 (−5.8%; 95% CI: −8.9% to −2.7%), median age <36 (5.7%; 95% CI: −9.2% to −2.2%), and having <60% females (−9.4%; 95% CI: −13.9% to −4.9%) were predictive of lower retention rates at 6 months when also adjusting for median follow-up and year of initiating cohort. For 12 month attrition rates, only median age <36 (−12.8%; 95% CI: −19.9% to −5.6%), median CD4 < 100 (−8.8%; 95% CI: −14.5% to −3.1%) and cohort follow-up ≤12 months (−8.6%; 95% CI: −16.9% to −0.4%) were predictive of lower retention rates. The finding that median cohort follow-up of ≤12 months is associated with lower 12 month retention rates again suggests that while we did not observe a strong trend towards studies with longer duration reporting higher retention rates at comparable time points, some bias may exist.
To project the potential paths of retention over time, we conducted three analyses to extrapolate what would have happened to retention rates at later time points for cohorts reporting only to earlier time points (). The first set of bars shows the best case scenario, in which the latest observation is carried forward with no further attrition, while the last set of bars shows a worst case scenario which assumes that retention continued at a linear rate. There was little variation in the estimates through 24 months as the retention midpoint between the two cases is 70.0% (best-case–worst-case range: 66.7%–73.3%). By 36 months, the retention midpoint between the two cases is 64.8% (best case-worst case range: 57.5%–72.1%).
Figure 4 Projected Retention Rates Over Time in Antiretroviral Therapy Programs in Sub-Saharan Africa Using Varying Assumptions*. *Best-case scenario uses last observation carried forward and assumes no additional attrition after the last time point reported to. (more ...)