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O333 Treatment discontinuation and virological failure amongst HIV-positive individuals starting second-line combination antiretroviral therapy (cART)

Background

Although much research has investigated treatment discontinuation and virologic failure (VF) to first-line ART regimens, less is known about second-line responses.

Methods

We included patients at the Royal Free Hospital, London, who were ARV-naïve when starting their first ART regimen (>=3 ARVs) and who: (i) experienced VF to their first ART regimen (at least one viral load >400 cps/ml after >4 months continuous exposure to an ARV); (ii) started second-line ART (defined by the first date on which at least one PI/NNRTI and/or at least two new NRTIs were started after VF to the first-line regimen occurred) with a latest viral load >400 cps/ml. Time to VF (the first of two consecutive viral loads >400 cps/ml more than 4 months after starting their second-line regimen; ARV changes/discontinuations ignored) was calculated using survival analysis.

Summary of results

166 patients started second-line ART with a median (IQR) CD4 count and viral load of 256 (120–358) cells/mm3 and 4.3 (3.3–5.0) log cps/ml. Twenty-five (15%), 48 (29%) and 93 (56%) patients second-line regimen included one, two and >=3 antiretrovirals they had not previously received. The median (95% CI) time to discontinuing at least one ARV was 15 (12–19) months, and 24 (17–41) months for discontinuing a PI/NNRTI. Few factors were associated with time to first discontinuation of any ARV: compared to those starting a second-line regimen containing one new ARV, the adjusted hazard ratios were 0.56 (0.33–0.95) and 0.50 (0.30,0.83; p = 0.001) for those receiving two and >=3 new ARVs. Each additional year in time from first VF to start of second-line regimen was associated with a 19% reduced hazard of discontinuing (0.66–0.99; p = 0.04). 29% (22–36%) and 44% (36–52%) experienced VF by 12 and 36 months after starting second-line cART. This compares to 14% and 27% amongst those on first-line cART. The only factors associated with VF in multivariable analysis were the inclusion of fewer new ARVs in the second-line regimen (compared to one: HR = 0.1; 0.13–0.75 for two, and 0.26; 0.12–0.60; p = 0.01 for >=3 new ARVs), lower CD4 count (HR = 0.73 per 100 cells/mm3; 0.59–0.96; p = 0.03), and higher viral load at the start of the second-line regimen (HR = 2.56 per 1 log cps/ml; 1.33–4.94; p = 0.005).

Conclusion

The median time to making at least one ARV switch on a second-line regimen was comparable to that seen on first-line regimens. Although VF appeared more common on second-line than on first-line regimens, perhaps because this is a group who are more predisposed to VF, response rates were still excellent.

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Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution 2.0 International License (https://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Smith, C., Lampe, F., Youle, M. et al. O333 Treatment discontinuation and virological failure amongst HIV-positive individuals starting second-line combination antiretroviral therapy (cART). JIAS 11, O37 (2008). https://doi.org/10.1186/1758-2652-11-S1-O37

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  • DOI: https://doi.org/10.1186/1758-2652-11-S1-O37

Keywords

  • Viral Load
  • Treatment Discontinuation
  • Virologic Failure
  • Adjusted Hazard Ratio
  • High Viral Load