Second-Line Combination ART More Likely to Fail if Viral Load >400

SAN DIEGO, CA— Virologic failure of second-line combination antiretroviral therapy was less likely if patients were switched with an HIV RNA viral load (VL) <400c/mL, according to results of a study presented at IDWeek 2012.

However, risk of virologic failure early after the switch was similar to those with (VL) ≥400c/mL, said Joseph J. Eron, MD, of the University of North Carolina, Chapel Hill, NC.

Noting that in the United States, 20% of patients with HIV discontinue first-line combination antiretroviral therapy by six months and 50% by two years, Dr. Eron and colleagues evaluated virologic outcomes of second-line combination antiretroviral therapy among patients in three clinical cohorts. Johns Hopkins, University of North Carolina, and Vanderbilt contributed observational data on HIV patients who received first- and second-line combination antiretroviral therapy (defined as ≥2 nucleoside reverse transcriptase inhibitors [NRTI] with a protease inhibitor [PI], non-nucleoside reverse transcriptase inhibitor [NNRTI], or an integrase strand-transfer inhibitor [INSTI]).

Inclusion criteria consisted of a switch of the third agent; PI to darunavir/ritonavir or tipranavir/ritonavir; or a NNRTI to etravirine; with or without NRTI switch. The study period was from June 1996–June 2010. Virologic failure was defined as: 1) 0.5 log10 copies/mL decrease or VL ≥400c/mL at >24 weeks, if the viral load was ≥400 c/mL at initiation of second-line combination; and 2) viral load ≥400c/mL at ≥8 weeks, if VL <400c/mL at second-line combination.

Median age of the 488 study patients was 37 years; 32% were female and 67% were black. Median CD4 cell count was 135cells/mm3. Of these patients, 48.6% received an NNRTI, 32.8% received an unboosted PI, and 18.7% received a PI/ritonavir as first-line combination antiretroviral therapy.

The switch from an NNRTI to PI was observed in 47% of patients; 42% switched from PI to an NNRTI, most prior to 2004. Researchers noted that among patients on first-line combination antiretroviral therapy, switches occurred later in patients with VL <400c/mL (38%) than those with VL ≥400c/mL on first-line combination antiretroviral therapy (670 days [95% CI 280–1535]) vs. 520 days [95% CI 205–1158]; P=0.01).

Time to second-line combination antiretroviral therapy virologic failure was shorter if VL ≥400c/mL at the time of switch (P=0.001). At six months, among patients with VL <400c/mL, virologic failure was 12% and VL ≥400c/mL, it was 17%. A lower CD4 cell count at switch was associated with a greater hazard of virologic failure on second-line combination antiretroviral therapy, and this risk decreased with more recent calendar time (adjusted hazard ratio 0.40 [95% CI 0.15–1.00]; 2008–2010 relative to 1996–1998).

“Regimen sequence did not impact time to virologic failure,” Dr. Eron reported, adding that the average time from first-line to second-line combination antiretroviral therapy was 1.5 years. He noted that large multicohort collaborative studies will be required to evaluate outcomes of combination antiretroviral therapy, and that clear communication between clinicians and patients is imperative whenever treated is changed.