Abstract
BackgroundTenofovir (TDF) is part of the WHO recommended first-line antiretroviral therapy (ART); however, there are limited data comparing TDF to other nucleoside reverse transcriptase inhibitors in resource-limited-settings. Using a routine workplace and community-based ART cohort in South Africa, we assessed single drug substitution, HIV RNA suppression, CD4 count increase, loss-from-care, and mortality between TDF, stavudine (d4T) 30 mg dose, and zidovudine (AZT).MethodsIn a prospective cohort study we included ART naïve patients aged ≥17 years-old who initiated ART containing TDF, d4T, or AZT between 2007 and 2009. For analysis of single drug substitutions we used a competing-risks time-to-event analysis; for loss-from-care, mixed-effect Poisson modeling; for HIV RNA suppression, competing-risks logistic regression; for CD4 count slope, mixed-effects linear regression; and for mortality, proportional hazards modeling.ResultsOf 6,196 patients, the initial drug was TDF for 665 (11%), d4T for 4,179 (68%), and AZT for 1,352 (22%). During the first 6 months of ART, the adjusted hazard ratio for a single drug substitution was 2.3 for d4T (95% confidence interval [CI]: 0.27, 19) and 5.2 for AZT (95% CI: 1.1, 23), compared to TDF; whereas, after 6 months, it was 10 (95% CI: 5.8, 18) and 4.4 (95% CI: 2.5, 7.8) for d4T and AZT, respectively. Virologic suppression was similar by agent; however, CD4 count rise was lowest for AZT. The adjusted hazard ratio for loss-from-care, when compared to TDF, was 1.5 (95% CI: 1.1, 1.9) for d4T and 1.2 (95% CI: 1.1, 1.4) for AZT. The adjusted hazard ratio for mortality, when compared to TDF, was 2.7 (95% CI: 2.0, 3.5) and 1.4 (95% CI: 1.3, 1.5) and for d4T and AZT, respectively.DiscussionIn routine care, TDF appeared to perform better than either d4T or AZT, most notably with less drug substitution and mortality than for either other agent.
Highlights
Tenofovir (TDF) is part of the World Health Organization (WHO) recommended first-line antiretroviral therapy (ART); there are limited data comparing tenofovir disoproxil fumarate (TDF) to other nucleoside reverse transcriptase inhibitors in resource-limited-settings
The WHO recommended a reduction in d4T dose for patients weighing more than 60 kg followed thereafter with guidelines recommending tenofovir disoproxil fumarate (TDF) as part of the preferred regimen, with AZT as an alternative [3,4]
Patients in the workplace program were started on ART if they had a CD4 count less than 250 cells/mm3 or a CD4 count less than 350 cells/mm3 with WHO clinical stage III or any CD4 and WHO clinical stage IV disease; whereas the community program required a CD4 count less than 250 cells/mm3 or any CD4 with WHO clinical stage IV disease
Summary
Tenofovir (TDF) is part of the WHO recommended first-line antiretroviral therapy (ART); there are limited data comparing TDF to other nucleoside reverse transcriptase inhibitors in resource-limited-settings. Decisions on first-line combination antiretroviral therapy (ART) regimens for use in resource-limited-settings are made based on trade-offs regarding cost, need for laboratory monitoring, severity and frequency of side effects, and effectiveness. The WHO recommended a reduction in d4T dose for patients weighing more than 60 kg followed thereafter with guidelines recommending tenofovir disoproxil fumarate (TDF) as part of the preferred regimen, with AZT as an alternative [3,4] Despite these changes in WHO recommendations, d4T and AZT remain widely used due to the higher cost of a month supply of TDF compared to either d4T or AZT. Outcome assessments comparing agents during routine patient care can be valuable for informing policy regarding ART agent selection
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
