Only 17 percent of people starting treatment with modern-day antiretroviral (ARV) regimens developed HIV drug resistance over eight years of therapy, according to an analysis from a British cohort study published in the May 1 issue of the journal Clinical Infectious Diseases. In terms of resistance developing over time, Norvir (ritonavir)–boosted protease inhibitors (PIs) faired better than non-nucleoside reverse transcriptase inhibitors (NNRTIs).

While randomized controlled trials of newer ARV therapies are the gold standard when assessing their efficacy and safety, they are typically short (less than two years) and usually attract and maintain people who are more likely to remain adherent than people who don’t participate in clinical trials. Thus, large cohort studies—which aren’t controlled, but allow researchers to track what happens to people over long periods of time—are often a better predictor of how successful a treatment regimen can be in the real world.

Though numerous cohort analyses have evaluated treatment failure and drug-resistance rates, the May 1 paper is among the first to explore long-term outcomes involving regimens widely used today, notably those using Norvir-boosted PIs and the NNRTI efavirenz (found in Sustiva and Atripla).

To determine the likelihood of developing HIV drug resistance over an eight-year period, Alessandro Cozzi-Lepri, PhD, from the University College London and his colleagues analyzed data from the United Kingdom Collaborative HIV Cohort Study (UK CHIC)—a study that contains data on all patients seen at 11 large HIV clinics in England and Scotland since 1996. To be included in this particular analysis, a person had to have started an ARV regimen that included two nucleoside reverse transcriptase inhibitors (NRTIs) plus either an NNRTI or a Norvir-boosted PI. Data from 7,891 people were included. Most, 82 percent, started treatment with an NNRTI.

Over the course of the study, relatively few people developed treatment failure or drug resistance. Cozzi-Lepri and his colleagues found that 28 percent of the people they followed experienced treatment failure—defined as a viral load measurement over 400 copies—over eight years, and 17 percent had measurable drug resistance.

In an accompanying editorial, Richard Harrigan, MD, from the British Columbia Centre for Excellence in Vancouver, states that “this [relatively low risk of treatment failure and resistance] can only be considered to be good news for patients starting treatment.”

Historically, notably in the early years of combination ARV therapy, it was not uncommon for researchers to report treatment failure rates of 50 percent within the first year of therapy.
 
In terms of class-specific drug resistance, there were differences between the regimens. The percentage of people who developed resistance to their NRTIs was roughly the same between those on a Norvir-boosted PI regimen compared with those on an NNRTI regimen. However, people taking a PI were 64 percent less likely to develop a PI resistance than people taking an NNRTI were to develop NNRTI resistance.

The authors acknowledge that the actual rate of resistance is probably higher than what they found, as not all of the 28 percent who experienced virologic failure had a resistance test. Moreover, cohort studies can provide false estimates due to unknown factors that influence the study results. Lastly, the group was not able to measure the impact of adherence on treatment outcomes.

The authors conclude that although rates of development of resistance are relatively low regardless of the type of treatment a person starts—provided it is consistent with modern-day recommendations set forth in expert-derived treatment guidelines—the study does indicate that the risk of developing class-specific resistance is lower in people starting treatment with a boosted PI. Harrigan concurs, saying: “The study provides an important description of ‘where we are now.’”