People starting therapy on a boosted protease inhibitor don't need to switch after one virological failure episode, study indicates

Subsequent viral suppression rates similar whether patients switched or not

Michael Carter
Published: 09 June 2014

Remaining on the same regimen is a “reasonable” strategy for people taking first-line antiretroviral therapy (ART) based on a ritonavir-boosted protease inhibitor who experience virologic failure, according to a study in the online edition of Clinical Infectious Diseases. Investigators from the United States retrospectively examined outcomes 24 weeks after virologic failure according to treatment strategy. Rates of HIV suppression did not differ significantly between people who remained on their first-line combination and those who switched therapy.

“This study provides important information that adds to current knowledge about management of ART after VF [virologic failure] on first-line PI/r [protease inhibitor/ritonavir] plus two NRTIs [nucleoside reverse transcriptase inhibitors],” comment the authors. “Our study suggests that a large proportion of patients failing these regimens can subsequently achieve virologic suppression without changing their ART regimen.”

HIV therapy comprising a ritonavir-boosted protease inhibitor plus two NRTIs is one of the strategies recommended for first-line ART. An advantage of this strategy is that virologic failure rarely results in the emergence of virus with resistance to protease inhibitors.

However, the best approach for people who experience virologic failure while taking first-line ART based on a ritonavir-boosted protease inhibitor is unclear.

A team of investigators therefore examined outcomes among 209 people who had at least 24 weeks of follow-up after the virologic failure of their treatment. Subsequent HIV treatment strategy and virologic suppression were assessed. "Virological failure" was defined differently by the three studies but meant broadly that HIV was either still incompletely suppressed 8-16 weeks after starting therapy, or that the viral load 'rebounded' to above 200-400 copies/ml after 24-32 weeks. 

The 209 patients who had virological failure were among 1429 (i.e. 15% of the total) who participated in three ACTG (AIDS Clinical Trials Group) studies examining the safety and efficacy of first-line HIV therapy consisting of a ritonavir-boosted protease inhibitor (lopinavir/ritonavir [Kaletra], or atazanavir/ritonavir [Reyataz]) plus two NRTIs. Most of the 209 patients (83%) were enrolled in the United States, the other 17% in South Africa. Overall, 43% of participants were female, and median viral load before the initiation of ART was 63,000 copies/ml, with median CD4 count being 118 cells/mm3.

The median time between the initiation of ART and virologic failure was 39 weeks. Over three-quarters (78%) of patients achieved a viral load below 400 copies/ml at sometime before treatment failure.

Median viral load and CD4 count at the time of virologic failure were 8000 copies/ml and 246 cells/mm3, respectively. Only one person had a new protease inhibitor-associated major resistance mutation detected at the time of virologic failure. However, four other people had such resistance at baseline. New NRTI resistance was detected in 15 people (9%) at the time of virologic failure, with 23 people having such resistance before they started therapy.

Two-thirds of patients remained on their first-line regimen after virologic failure, 13% changed to an NNRTI-based regimen, 12% switched NRTIs and 5% changed to a non-standard second-line combination of drugs.

Follow-up, 24 weeks after virologic failure, showed that 67% of patients remaining on their first-line combination now had a viral load below 400 copies/ml compared to 72% of participants who changed therapy. The difference was non-significant. Restricting analysis to patients with no resistance (protease inhibitors, NRTIs and NNRTIs) showed that rates of virologic suppression were identical between people who remained on first-line treatment and people who switched therapy (62 vs 61%).

For people who remained on their initial treatment regimen, the factors associated with subsequent achievement of a viral load below 400 copies/ml were a viral load below 10,000 copies/ml at the time of treatment failure (p = 0.007) and a viral load below 400 copies/ml at any time before virologic failure emerged (p = 0.011).

The chances of achieving virologic suppression were also increased by high levels of adherence (p = 0.016). Twenty-four weeks after virological failure, two-thirds of patients who did not switch reported 100% adherence. Three-quarters (75%) of patients with self-reported adherence of 100% were virally suppressed, 54% who reported their adherence was less than 100%, and 14% of the small minority (7 individuals or 5.5%) who said they had decided to stop taking therapy.

Analysis of the patients who switched therapy showed a new regimen was started a median of ten weeks after virologic failure was detected. A viral load below 400 copies/ml 24 weeks after changing treatment was achieved by 71% of individuals who switched to an NNRTI-based regimen, by 44% of patients changing to another ritonavir-boosted protease inhibitor and by 72% of those who only changed their NRTIs. Achieving a viral load below 400 copies/ml at any time before the initial treatment failure was the only factor associated with virologic suppression after the treatment change (p= 0.003).

“Our findings suggest that if no or limited drug resistance is detected at VF on a first-line PI/r containing regimen, remaining on the same regimen after VF coupled with strategies to improve adherence could be a reasonable and effective approach to achieving virologic suppression,” conclude the authors. “Further evaluation of approaches to treatment management following VF on a first-line PI/r containing regimen are warranted.”

Reference

Zheng Y et al. Antiretroviral therapy and efficacy after virologic failure on first-line boosted protease inhibitor regimens. Clin Infect Dis, online edition, 2014.