Background: Because data are limited on 2nd line cART efficacy in clinical practice, we evaluated virologic outcomes of 2nd cART among patients in three HIV clinical cohorts.
Methods: Johns Hopkins, UNC, and Vanderbilt contributed observational data on HIV patients who received 1st and 2nd cART defined as ≥2 NRTI with a PI, NNRTI, or INSTI. 2nd cART inclusion criteria were: switch of 3rd agent; PI to darunavir/r or tipranavir/r; or NNRTI to etravirine; with or without NRTI switch. Study period was June 1996 through June 2010. Virologic failure (VF): 1) <0.5 log10 c/mL decrease or VL >400 at >24 wk, if VL>400 at 2nd cART start; and 2) VL>400 at ≥8 wk, if VL≤400 at 2nd cART start.
Results: Of the 488 HIV patients (67% black, 32% women, 34% prior AIDS) 48.6% received an NNRTI, 32.8% an unboosted PI and 18.7% a PI/r as 1st cART. 47% switched from NNRTI to PI and 42% PI to NNRTI (most prior to 2004). Median (Interquartile range [IQR]) VL at switch was 9,565 c/mL (123–94,108). Switches in those with VL≤400 (38% of total) occurred later on 1st cART than those with VL>400 (670 [280-1535]) v 520 days [205-1158]; p = 0.01). Figure shows that time to 2nd cART VF was shorter if VL>400 at switch (p = 0.001), though 14% with VL < 400 had VF within 6 mo. Regimen sequence did not impact time to VF. A lower CD4 cell count at switch was associated with a greater hazard of VF on 2nd cART and risk of VF decreased with more recent calendar time (aHR 0.40 [0.15-1.00]; 2008-2010 relative to 1996-98).
Conclusion: Virologic failure of 2nd cART was less likely if patients switched with VL<400, though the risk of VF early after switch was similar (Figure). The success of 2nd line therapy improved over time.
J. J. Eron,
Bristol-Myers Squibb: Grant Investigator, Research grant
S. Napravnik, Bristol-Myers Squibb: Grant Investigator, Research grant
T. R. Juday, Bristol-Myers Squibb: Employee and Shareholder, Salary
J. Uy, Bristol-Myers Squibb: Employee and Shareholder, Salary
R. Moore, Bristol-Myers Squibb: Grant Investigator, Research grant