This article is more than 5 years old. Information may no longer be current.
Initiation of modern HAART led to decrease in drug resistance
Odds of drug resistance reduced in group of patients receiving boosted protease inhibitors.
Click Here to Manage Email Alerts
A decrease in the probability of the development of drug resistance has occurred in a group of patients with HIV beginning their first highly active antiretroviral therapy regimen, according to researchers from Canada.
“This decrease appears to be largely but not exclusively related to the introduction of boosted protease inhibitor therapy regimens,” Richard Harrigan, PhD, director of research labs at the British Columbia Centre for Excellence in HIV/AIDS, Vancouver, Canada, told Infectious Disease News. “As we have shown before, there is an inverted ‘U’-shaped relationship between drug resistance and adherence, with the highest risk being at intermediate levels of adherence and the lowest risk for resistance occurring at very high and very low levels of adherence.”
Harrigan and colleagues obtained data on eligible participants from the British Columbia Center for Excellence’s monitoring and evaluation system.
With this system, the enrolling physician completes a drug request prescription form for the patient, which includes data on the patient’s past HIV-specific drug history, current drug requests, CD4 cell counts and plasma viral load.
The study included 2,350 patients with HIV aged 18 years or older who initiated HAART for the first time between August 1996 and November 2004. Patients were followed through November 2006, with an average follow-up of 4.8 years.
Resistance testing was performed on stored plasma viral load samples, which were then assigned to one of four resistance categories: lamivudine, any other nucleotide reverse transcriptase inhibitors, any non-nucleoside reverse transcriptase inhibitors and any protease inhibitors.
Nonboosted protease inhibitor–based regimens were initiated in 991 participants; boosted protease inhibitor regimens initiated in 475 participants; non-nucleoside reverse transcriptase inhibitor–based regimens in 884 participants.
During the 4.8-year follow-up period, 6,066 resistance tests were conducted; resistance to at least one drug category developed in 650 patients.
According to the researchers, increased probability of drug resistance was associated with:
- Higher plasma viral load.
- History of injection drug use.
- Non-nucleoside reverse transcriptase inhibitor–based regimens.
- Age.
- Beginning therapy during 1996 to 1998.
- Higher adherence levels (P<.0001).
“Incomplete adherence and nonboosted protease inhibitor–based or non-nucleoside reverse transcriptase inhibitor–based antiretroviral regimens were associated with a greater probability of the development of drug resistance,” the researchers wrote.
Data further indicated the odds for development of drug resistance were reduced in the group of patients receiving a boosted protease inhibitor–based regimen.
“These data indicate that boosted protease inhibitor–based regimens are associated with relatively low levels of resistance development across all adherence strata. This is consistent with previous observations that boosted protease inhibitor–based regimens may have a more ‘forgiving’ profile in terms of virological suppression,” the researchers wrote.
The researchers were confident the results were not influenced by access to therapy because the study’s large sample of patients had free access to medical attention, combination ART and laboratory monitoring. In addition, the study included patients initially naive to ART, which ensured the results were not confounded by previous use of therapy.
Furthermore, the researchers used a logistic regression methodology adequate in exhibiting the simultaneous effects of adherence, plasma viral load and antiretroviral regimen on drug resistance.
“Our study provides concrete evidence of a decreasing risk for resistance with improving therapies,” Harrigan said. “The data provide a visual aide which may be used to show the need for the patient to be at the highest level of adherence possible to reduce their risk for resistance. This confirms the advantages of more modern HAART regimens observed in clinical trials in regard to drug resistance.” – by Jennifer Southall
For more information:
- Lima V, Gill V, Yip B, et al. Increased resilience to the development of drug resistance with modern boosted protease inhibitor-based highly active antiretroviral therapy. J Infect Dis. 2008;198:51-58.