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

In this large cohort of human immunodeficiency virus-infected patients receiving first-line antiretroviral therapy in Zambia, individuals who started a tenofovir-containing regimen despite baseline renal dysfunction showed comparable mortality and renal function improvement to those not receiving tenofovi

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

Taking ART to Scale: Determinants of the Cost and Cost-Effectiveness of Antiretroviral Therapy in 45 Clinical Sites in Zambia

<div><h3>Background</h3><p>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).</p> <h3>Methods</h3><p>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.</p> <h3>Results</h3><p>The program cost $69.7 million for 125,436 person-years of ART, or$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 $833 compared to CTX alone. More than two-thirds of the variation in average incremental total and on-site cost per patient-year of treatment is explained by eight determinants, including the complexity of the patient-case load, the degree of adherence among the patients, and institutional characteristics including, experience, scale, scope, setting and sector.</p> <h3>Conclusions and Significance</h3><p>The 45 sites exhibited substantial variation in unit costs and cost-effectiveness and are in the mid-range of cost-effectiveness when compared to other ART programs studied in southern Africa. Early treatment initiation, large scale, and hospital setting, are associated with statistically significantly lower costs, while others (rural location, private sector) are associated with shifting cost from on- to off-site. This study shows that ART programs can be significantly less costly or more cost-effective when they exploit economies of scale and scope, and initiate patients at higher CD4 counts.</p> </div

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

Background. Although tenofovir (TDF) use has increased as part of first-line antiretroviral therapy (ART) across sub-Saharan Africa, renal outcomes among patients receiving TDF remain poorly understood. We assessed changes in renal function and mortality in patients starting TDF- or non-TDF-containing ART in Lusaka, Zambia. Methods. We included patients aged ≥16 years who started ART from 2007 onward, with documented baseline weight and serum creatinine. Renal dysfunction was categorized as mild (eGFR 60-89 mL/min), moderate (30-59 mL/min) or severe (<30 mL/min) using the CKD-EPI formula. Differences in eGFR during ART were analyzed using linear mixed-effect models, the odds of developing moderate or severe eGFR decrease with logistic regression and mortality with competing risk regression. Results. We included 62,230 adults, of which 38,716 (62%) initiated a TDF-based regimen. The proportion with moderate or severe renal dysfunction at baseline was lower in the TDF compared to the non-TDF group (1.9% vs. 4.0%). Among patients with no or mild renal dysfunction, those on TDF were more likely to develop moderate (adjusted OR: 3.11; 95%CI: 2.52-3.87) or severe eGFR decrease (adjusted OR: 2.43; 95%CI: 1.80-3.28), although the incidence of such episodes was low. Among patients with moderate or severe renal dysfunction at baseline, renal function improved independently of ART regimen and mortality was similar in both treatment groups. Conclusions. TDF use did not attenuate renal function recovery or increase mortality in patients with renal dysfunction. Further studies are needed to determine the role of routine renal function monitoring before and during ART use in Africa

Estimated costs of ART service delivery per patient year by ART facility characteristic.

<p>Figure shows total and on-site costs. Author’s estimates constructed from the semilog specification in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0051993#pone-0051993-t005" target="_blank">Table 5</a>. The “reference” facility is an urban public sector clinic with less than 91% adherence, less than 2 years’ experience, fewer than 300 patients, and late starting patients. Estimated effects of facility characteristics accumulate from left to right.</p

Estimated regressions of average total cost per DALY averted of antiretroviral therapy in 45 facilities in Zambia.

<p>Note: **p<0.05,</p>*<p>p<0.1,+p<0.2. p-values are given in parentheses to the right of the coefficients in columns (1), (2) and (4).</p>c<p>Values of p for “Early Start” are the significance level at which the joint hypothesis can be rejected that neither baseline CD4 nor proportion of patients initiating at WHO stage IV influences the dependent variable.</p

Distribution of cost sub-components between total and on-site components.

<p>Distribution of cost sub-components between total and on-site components.</p

Bivariate analysis of association between average total cost and its components and eight explanatory variables.

<p>Column definitions:</p><p>(1) Variable definitions.</p><p>(2) Specifies whether variable is continuous or discrete, and if discrete, the criterion used to define the dummy variable.</p><p>(3) Mean value of the explanatory variable over all 45 observations. For discrete versions of the variables, the mean is the proportion of observations for which D  = 1.</p><p>(4) Standard deviation of the explanatory variables.</p><p>(5) Correlation between a continuous explanatory variable and average total cost.</p><p>(6) Mean value of average total cost for values of the dummy variable equal to zero.</p><p>(7) Mean value of average total cost for values of the dummy variable equal to one.</p><p>(8) p-value of the test of the null hypothesis of no relationship between the explanatory variable and average total cost.</p><p>(9) – (12): Same definitions as (5) – (8), respectively, except for average on-site cost instead of average total cost.</p><p>(13) – (16): Same definitions as (5) – (8), respectively, except for average off-site cost instead of average total cost.</p