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01.12.2017 | Research article | Ausgabe 1/2017 Open Access

BMC Infectious Diseases 1/2017

The virological durability of first-line ART among HIV-positive adult patients in resource limited settings without virological monitoring: a retrospective analysis of DART trial data

Zeitschrift:
BMC Infectious Diseases > Ausgabe 1/2017
Autoren:
David I. Dolling, Ruth L. Goodall, Michael Chirara, James Hakim, Peter Nkurunziza, Paula Munderi, David Eram, Dinah Tumukunde, Moira J. Spyer, Charles F. Gilks, Pontiano Kaleebu, David T. Dunn, Deenan Pillay, on behalf of the DART Virology Group
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1186/​s12879-017-2266-3) contains supplementary material, which is available to authorized users.

Abstract

Background

Few low-income countries have virological monitoring widely available. We estimated the virological durability of first-line antiretroviral therapy (ART) after five years of follow-up among adult Ugandan and Zimbabwean patients in the DART study, in which virological assays were conducted retrospectively.

Methods

DART compared clinically driven monitoring with/without routine CD4 measurement. Annual plasma viral load was measured on 1,762 patients. Analytical weights were calculated based on the inverse probability of sampling. Time to virological failure, defined as the first viral load measurement ≥200 copies/mL after 48 weeks of ART, was analysed using Kaplan-Meier plots and Cox regression models.

Results

Overall, 65% of DART trial patients were female. Patients initiated first-line ART at a median (interquartile range; IQR) age of 37 (32–42) and with a median CD4 cell count of 86 (32–140). After 240 weeks of ART, patients initiating dual-class nucleoside reverse-transcriptase inhibitor (NRTI) -non-nucleoside reverse-transcriptase (NNRTI) regimens containing nevirapine + zidovudine + lamivudine had a lower incidence of virological failure than patients on triple-NRTI regimens containing tenofovir + zidovudine + lamivudine (21% vs 40%; hazard ratio (HR) =0.48, 95% CI:0.38–0.62; p < 0.0001). In multivariate analyses, female patients (HR = 0.79, 95% CI: 0.65–0.95; p = 0.02), older patients (HR = 0.73 per 10 years, 95% CI: 0.64–0.84; p < 0.0001) and patients with a higher pre-ART CD4 cell count (HR = 0.64 per 100 cells/mm3, 95% CI: 0.54–0.75; p < 0.0001) had a lower incidence of virological failure after adjusting for adherence to ART. No difference in failure rate between the two randomised monitoring strategies was observed (p= 0.25).

Conclusions

The long-term durability of virological suppression on dual-class NRTI-NNRTI first-line ART without virological monitoring is remarkable and is enabled by high-quality clinical management and a consistent drug supply. To achieve higher rates of virological suppression viral-load-informed differentiated care may be required.

Trial Registration

Prospectively registered on 18/10/2000 as ISRCTN13968779.
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