Nurse versus doctor management of HIV-infected patients receiving antiretroviral therapy (CIPRA-SA): a randomised non-inferiority trial

Abstract

Background: Expanded access to combination antiretroviral therapy (ART) in resource-poor settings is dependent on task shifting from doctors to other health-care providers. We compared outcomes of nurse versus doctor management of ART care for HIV-infected patients.

Methods: This randomised non-inferiority trial was undertaken at two South African primary-care clinics. HIV-positive individuals with a CD4 cell count of less than 350 cells per microL or WHO stage 3 or 4 disease were randomly assigned to nurse-monitored or doctor-monitored ART care. Patients were randomly assigned by stratified permuted block randomisation, and neither the patients nor those analysing the data were masked to assignment. The primary objective was a composite endpoint of treatment-limiting events, incorporating mortality, viral failure, treatment-limiting toxic effects, and adherence to visit schedule. Analysis was by intention to treat. Non-inferiority of the nurse versus doctor group for cumulative treatment failure was prespecified as an upper 95% CI for the hazard ratio that was less than 1.40. This study is registered with ClinicalTrials.gov, number NCT00255840.

Findings: 408 patients were assigned to doctor-monitored ART care and 404 to nurse-monitored ART care; all participants were analysed. 371 (46%) patients reached an endpoint of treatment failure: 192 (48%) in the nurse group and 179 (44%) in the doctor group. The hazard ratio for composite failure was 1.09 (95% CI 0.89-1.33), which was within the limits for non-inferiority. After a median follow-up of 120 weeks (IQR 60-144), deaths (ten vs 11), virological failures (44 vs 39), toxicity failures (68 vs 66), and programme losses (70 vs 63) were similar in nurse and doctor groups, respectively.

Interpretation: Nurse-monitored ART is non-inferior to doctor-monitored therapy. Findings from this study lend support to task shifting to appropriately trained nurses for monitoring of ART.

Funding: National Institutes of Health; United States Agency for International Development; National Institute of Allergy and Infectious Diseases.

Figure 1

CONSORT study flow chart and participant disposition for the CIPRA-SA trial, a randomised trial of doctor vs. nurse monitored antiretroviral therapy in South Africa.

Figure 2

Figure 2a: Kaplan-Meier curves of time to cumulative treatment failure by study arm among 812 subjects randomised to doctor or nurse monitored antiretroviral therapy in the CIPRA-SA trial in South Africa; Figure 2b-d: Kaplan-Meier curves of time to specific reasons for treatment failure by study arm among 812 subjects randomised to doctor or nurse monitored antiretroviral therapy in the CIPRA-SA trial in South Africa* * a) a Kaplan-Meier curve demonstrating the composite end-point of cumulative treatment failure. The primary health care nurse arm of the study is non-inferior to the doctor arm (log-rank p-value 0.4238). b) shows time to virologic failure stratified by treatment ARM (log-rank p-value = 0.5340); c) shows time to toxicity failure stratified by treatment ARM (log-rank p-value = 0.4678); d) shows time to loss to follow-up stratified by treatment ARM (log-rank p-value = 0.8358);