Research Article: Predictors of switch to and early outcomes on third-line antiretroviral therapy at a large public-sector clinic in Johannesburg, South Africa

Date Published: April 10, 2018

Publisher: BioMed Central

Author(s): Denise Evans, Kamban Hirasen, Rebecca Berhanu, Given Malete, Prudence Ive, David Spencer, Sharlaa Badal-Faesen, Ian M. Sanne, Matthew P. Fox.

http://doi.org/10.1186/s12981-018-0196-9

Abstract

While efficacy data exist, there are limited data on the outcomes of patients on third-line antiretroviral therapy (ART) in sub-Saharan Africa in actual practice. Being able to identify predictors of switch to third-line ART will be essential for planning for future need. We identify predictors of switch to third-line ART among patients with significant viraemia on a protease inhibitor (PI)-based second-line ART regimen. Additionally, we describe characteristics of all patients on third-line at a large public sector HIV clinic and present their early outcomes.

Retrospective analysis of adults (≥ 18 years) on a PI-based second-line ART regimen at Themba Lethu Clinic, Johannesburg, South Africa as of 01 August 2012, when third-line treatment became available in South Africa, with significant viraemia on second-line ART (defined as at least one viral load ≥ 1000 copies/mL on second-line ART after 01 August 2012) to identify predictors of switch to third-line (determined by genotype resistance testing). Third-line ART was defined as a regimen containing etravirine, raltegravir or ritonavir boosted darunavir, between August 2012 and January 2016. To assess predictors of switch to third-line ART we used Cox proportional hazards regression among those with significant viraemia on second-line ART after 01 August 2012. Then among all patients on third-line ART we describe viral load suppression, defined as a viral load < 400 copies/mL, after starting third-line ART. Among 719 patients in care and on second-line ART as of August 2012 (with at least one viral load ≥ 1000 copies/mL after 01 August 2012), 36 (5.0% over a median time of 54 months) switched to third-line. Time on second-line therapy (≥ 96 vs. < 96 weeks) (adjusted Hazard Ratio (aHR): 2.53 95% CI 1.03–6.22) and never reaching virologic suppression while on second-line ART (aHR: 3.37 95% CI 1.47–7.73) were identified as predictors of switch. In a separate cohort of patients on third-line ART, 78.3% (47/60) and 83.3% (35/42) of those in care and with a viral load suppressed their viral load at 6 and 12 months, respectively. Our results show that the need for third-line is low (5%), but that patients’ who switch to third-line ART have good early treatment outcomes and are able to suppress their viral load. Adherence counselling and resistance testing should be prioritized for patients that are at risk of failure, in particular those who never suppress on second-line and those who have been on PI-based regimen for extended periods. The online version of this article (10.1186/s12981-018-0196-9) contains supplementary material, which is available to authorized users.

Partial Text

In many resource-limited settings (RLS), antiretroviral therapy (ART) treatment guidelines call for switching patients who fail non-nucleoside reverse transcriptase inhibitor (NNRTI)-based first-line regimens to protease-inhibitor (PI) based second-line regimens [1, 2]. Estimates from sub-Saharan Africa in particular suggest that 6% of all patients receiving first-line ART will require second-line treatment per year [3]. However, when looking specifically at South Africa, this is estimated to be closer to 10% [4].

As ART programmes in sub-Saharan Africa mature, increasing numbers of people will require third-line regimens. Here we report that 5% of patients with significant viraemia on second-line ART at Themba Lethu Clinic switched to third-line ART (over a median time of 54 months). The small proportion in need of third-line is consistent with what has been previously reported [6].

Our results show that the need for third-line, based on significant viraemia while on second-line ART, is low (5% over a median time of 54 months). But that patients’ who switch to third-line ART have good early treatment outcomes and are able to suppress their viral load. Adherence counselling and resistance testing should be prioritized for patients that are at risk of failure, in particular those who never suppress on second-line and those who have been on PI-based regimen for extended periods. Despite a poor response to second-line ART, we report 57.3% (47/82) of all patients on third-line ART suppressed their viral load during the first 6 months on third-line therapy. In addition, tracing initiatives confirmed that 93.9% (77/82) of patients on third-line remained alive and in care by 12 months.

 

Source:

http://doi.org/10.1186/s12981-018-0196-9

 

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