Albert Mwango

Universal Definition of Loss to Follow-Up in HIV Treatment Programs: A Statistical Analysis of 111 Facilities in Africa, Asia, and Latin America

Based on a statistical analysis of 111 facilities in Africa, Asia, and Latin America, Benjamin Chi and colleagues develop a standard loss-to-follow-up (LTFU) definition that can be used by HIV antiretroviral programs worldwide.

Adherence Support Workers: A Way to Address Human Resource Constraints in Antiretroviral Treatment Programs in the Public Health Setting in Zambia

Background In order to address staff shortages and improve adherence counseling for people on antiretroviral therapy (ART), the Zambia Prevention, Care and Treatment Partnership (ZPCT) developed an innovative strategy of training community volunteers to provide adherence support at the health facility and community levels. The objective of this study was to assess the effectiveness of these ‘adherence support workers’ (ASWs) in adherence counseling, treatment retention and addressing inadequate human resources at health facilities. Methodology/Principal Findings The study used quantitative and qualitative research techniques at five selected ART sites in four provinces in Zambia. Five hundred patients on ART were interviewed using a structured questionnaire to compare the quality of adherence counseling before and after the ASW scheme was introduced at the selected sites and between ASWs and HCWs after the introduction of ASWs. In addition, 3,903 and 4,972 electronic records of all new patients accessing antiretroviral therapy for the time period of 12 months before and 12 months after the introduction of ASWs respectively, were analyzed to assess loss to follow-up rates. Two focus group discussions with ASWs and health care workers (HCWs) were conducted in each clinic. Key informant interviews in the ART clinics were also conducted. There was a marked shift of workload from HCWs to ASWs without any compromise in the quality of counseling. Quality of adherence counseling by ASWs was comparable to HCWs after their introduction. The findings suggest that the deployment of ASWs helped reduce waiting times for adherence counseling. Loss to follow-up rates of new clients declined from 15% to 0% after the deployment of ASWs. Conclusion Adherence counseling tasks can be shifted to lay cadres like ASWs without compromising the quality of counseling. Follow-up of clients by ASWs within the community is necessary to improve retention of clients on ART.

Adherence to first-line antiretroviral therapy affects non-virologic outcomes among patients on treatment for more than 12 months in Lusaka, Zambia

Background High-level adherence to antiretroviral therapy (ART) is associated with favourable patient outcomes. In resource-constrained settings, however, there are few validated measures. We examined the correlation between clinical outcomes and the medication possession ratio (MPR), a pharmacy-based measure of adherence. Methods We analysed data from a large programmatic cohort across 18 primary care centres providing ART in Lusaka, Zambia. Patients were stratified into three categories based on MPR-calculated adherence over the first 12 months: optimal (≥95%), suboptimal (80–94%) and poor (<80%). Results Overall, 27 115 treatment-naïve adults initiated and continued ART for ≥12 months: 17 060 (62.9%) demonstrated optimal adherence, 7682 (28.3%) had suboptimal adherence and 2373 (8.8%) had poor adherence. When compared with those with optimal adherence, post-12-month mortality risk was similar among patients with sub-optimal adherence [adjusted hazard ratio (AHR) = 1.0; 95% CI: 0.9–1.2] but higher in patients with poor adherence (AHR = 1.7; 95% CI: 1.4–2.2). Those <80% MPR also appeared to have an attenuated CD4 response at 18 months (185 cells/µl vs 217 cells/µl; P < 0.001), 24 months (213 cells/µl vs 246 cells/µl; P < 0.001), 30 months (226 cells/µl vs 261 cells/µl; P < 0.001) and 36 months (245 cells/µl vs 275 cells/µl; P < 0.01) when compared with those above this threshold. Conclusions MPR was predictive of clinical outcomes and immunologic response in this large public sector antiretroviral treatment program. This marker may have a role in guiding programmatic monitoring and clinical care in resource-constrained settings.

Immunodeficiency at the start of combination antiretroviral therapy in low-, middle- and high-income countries

Objective:To describe the CD4 cell count at the start of combination antiretroviral therapy (cART) in low-income (LIC), lower middle-income (LMIC), upper middle-income (UMIC), and high-income (HIC) countries. Methods:Patients aged 16 years or older starting cART in a clinic participating in a multicohort collaboration spanning 6 continents (International epidemiological Databases to Evaluate AIDS and ART Cohort Collaboration) were eligible. Multilevel linear regression models were adjusted for age, gender, and calendar year; missing CD4 counts were imputed. Results:In total, 379,865 patients from 9 LIC, 4 LMIC, 4 UMIC, and 6 HIC were included. In LIC, the median CD4 cell count at cART initiation increased by 83% from 80 to 145 cells/&mgr;L between 2002 and 2009. Corresponding increases in LMIC, UMIC, and HIC were from 87 to 155 cells/&mgr;L (76% increase), 88 to 135 cells/&mgr;L (53%), and 209 to 274 cells/&mgr;L (31%). In 2009, compared with LIC, median counts were 13 cells/&mgr;L [95% confidence interval (CI): −56 to +30] lower in LMIC, 22 cells/&mgr;L (−62 to +18) lower in UMIC, and 112 cells/&mgr;L (+75 to +149) higher in HIC. They were 23 cells/&mgr;L (95% CI: +18 to +28 cells/&mgr;L) higher in women than men. Median counts were 88 cells/&mgr;L (95% CI: +35 to +141 cells/&mgr;L) higher in countries with an estimated national cART coverage >80%, compared with countries with <40% coverage. Conclusions:Median CD4 cell counts at the start of cART increased 2000–2009 but remained below 200 cells/&mgr;L in LIC and MIC and below 300 cells/&mgr;L in HIC. Earlier start of cART will require substantial efforts and resources globally.

Early clinical and programmatic outcomes with tenofovir-based antiretroviral therapy in Zambia.

Background:In July 2007, amid some controversy over cost, Zambia was the first African country to introduce tenofovir (TDF) as a component of first-line antiretroviral therapy (ART) on a wide scale. Methods:We compared drug substitutions, mortality, and “programmatic failure” among adults starting TDF-, zidovudine (ZDV)-, and stavudine (d4T)-containing ART. Programmatic failure was defined as death, withdrawal, or loss to follow-up. Results:Between July 2007 and January 2009, 10,485 adults initiated ART (66% on TDF, 23% on ZDV, 11% on d4T), with a median follow-up time of 239 (interquartile range 98, 385) days. Those starting TDF were more likely to be male and more likely to have indicators of severe disease at baseline. In adjusted Cox proportional hazards models, ZDV- (adjusted hazard ratio [AHR] = 2.74, 95% confidence interval [CI] = 2.30-3.28) and d4T-based regimens (AHR = 1.92, 95% CI = 1.55-2.38) were associated with higher risk for drug substitution when compared with TDF-based regimens. Similar hazards were noted for overall mortality (ZDV: AHR = 0 .81, 95% CI = 0.62-1.06; d4T: AHR = 1.03, 95% CI = 0.74-1.43) and programmatic failure (ZDV: AHR = 0.99, 95% CI = 0.88-1.11; d4T: AHR = 1.11, 95% CI = 0.96-1.28) when compared with TDF. Conclusions:TDF is associated with similar clinical and programmatic outcomes as ZDV and d4T but appears to be better tolerated. Although further evaluation is needed, these results are encouraging and support Zambias policy decision.

An Empirical Approach to Defining Loss to Follow-up Among Patients Enrolled in Antiretroviral Treatment Programs

In many programs providing antiretroviral therapy (ART), clinicians report substantial patient attrition; however, there are no consensus criteria for defining patient loss to follow-up (LTFU). Data on a multisite human immunodeficiency virus (HIV) treatment cohort in Lusaka, Zambia, were used to determine an empirical “days-late” definition of LTFU among patients on ART. Cohort members were classified as either “in care” or LTFU as of December 31, 2007, according to a range of days-late intervals. The authors then looked forward in the database to determine which patients actually returned to care at any point over the following year. The interval that best minimized LTFU misclassification was described as “best-performing.” Overall, 33,704 HIV-infected adults on ART were included. Nearly one-third (n = 10,196) were at least 1 day late for an appointment. The best-performing LTFU definition was 56 days after a missed visit, which had a sensitivity of 84.1% (95% confidence interval (CI): 83.2, 85.0), specificity of 97.5% (95% CI: 97.3, 97.7), and misclassification of 5.1% (95% CI: 4.8, 5.3). The 60-day threshold performed similarly well, with only a marginal difference (<0.1%) in misclassification. This analysis suggests that ≥60 days since the last appointment is a reasonable definition of LTFU. Standardization to empirically derived definitions of LTFU will permit more reliable comparisons within and across programs.

Estimating Loss to Follow-Up in HIV-Infected Patients on Antiretroviral Therapy: The Effect of the Competing Risk of Death in Zambia and Switzerland

Background Loss to follow-up (LTFU) is common in antiretroviral therapy (ART) programmes. Mortality is a competing risk (CR) for LTFU; however, it is often overlooked in cohort analyses. We examined how the CR of death affected LTFU estimates in Zambia and Switzerland. Methods and Findings HIV-infected patients aged ≥18 years who started ART 2004–2008 in observational cohorts in Zambia and Switzerland were included. We compared standard Kaplan-Meier curves with CR cumulative incidence. We calculated hazard ratios for LTFU across CD4 cell count strata using cause-specific Cox models, or Fine and Gray subdistribution models, adjusting for age, gender, body mass index and clinical stage. 89,339 patients from Zambia and 1,860 patients from Switzerland were included. 12,237 patients (13.7%) in Zambia and 129 patients (6.9%) in Switzerland were LTFU and 8,498 (9.5%) and 29 patients (1.6%), respectively, died. In Zambia, the probability of LTFU was overestimated in Kaplan-Meier curves: estimates at 3.5 years were 29.3% for patients starting ART with CD4 cells <100 cells/µl and 15.4% among patients starting with ≥350 cells/µL. The estimates from CR cumulative incidence were 22.9% and 13.6%, respectively. Little difference was found between naïve and CR analyses in Switzerland since only few patients died. The results from Cox and Fine and Gray models were similar: in Zambia the risk of loss to follow-up and death increased with decreasing CD4 counts at the start of ART, whereas in Switzerland there was a trend in the opposite direction, with patients with higher CD4 cell counts more likely to be lost to follow-up. Conclusions In ART programmes in low-income settings the competing risk of death can substantially bias standard analyses of LTFU. The CD4 cell count and other prognostic factors may be differentially associated with LTFU in low-income and high-income settings.

Taking ART to scale: determinants of the cost and cost-effectiveness of antiretroviral therapy in 45 clinical sites in Zambia.

Background We estimated the unit costs and cost-effectiveness of a government ART program in 45 sites in Zambia supported by the Centre for Infectious Disease Research Zambia (CIDRZ). Methods We estimated per person-year costs at the facility level, and support costs incurred above the facility level and used multiple regression to estimate variation in these costs. To estimate ART effectiveness, we compared mortality in this Zambian population to that of a cohort of rural Ugandan HIV patients receiving co-trimoxazole (CTX) prophylaxis. We used micro-costing techniques to estimate incremental unit costs, and calculated cost-effectiveness ratios with a computer model which projected results to 10 years. Results The program cost

Impact of Baseline Renal Function on Tenofovir-containing Antiretroviral Therapy Outcomes in Zambia

69.7 million for 125,436 person-years of ART, or

Effect of Baseline Renal Function on Tenofovir-Containing Antiretroviral Therapy Outcomes in Zambia

556 per ART-year. Compared to CTX prophylaxis alone, the program averted 33.3 deaths or 244.5 disability adjusted life-years (DALYs) per 100 person-years of ART. In the base-case analysis, the net cost per DALY averted was