Lower Rates of Resistance with Newer ART Regimens

Published: November 21, 2011

Resistance mutations were detected most frequently with AZT/3TC and during periods of low-level viremia.

Although antiretroviral regimens containing AZT or lopinavir/ritonavir are falling out of favor in developed countries, they are still recommended by the WHO and used extensively in developing countries. These regimens confer a higher risk for the emergence of drug resistance than newer regimens, according to a recent analysis in the Swiss HIV Cohort Study.

Researchers analyzed data from 2263 patients who initiated combination antiretroviral therapy (ART) between 1999 and 2010 with the most commonly used regimens in the larger cohort:
• AZT/3TC + efavirenz
• Tenofovir + FTC (or 3TC) + efavirenz
• AZT/3TC + lopinavir/r
• Tenofovir + FTC (or 3TC) + lopinavir/r
• Tenofovir + FTC (or 3TC) + boosted atazanavir
At each viral-load measurement, patients were classified according to their risk for the emergence of drug resistance. Intermediate risk was defined as a detectable viral load  500 copies/mL, excluding blips, and high risk as a viral load >500 copies/mL. Using a simulation technique, the investigators then imputed the risk for emerging resistance with each regimen.

During a mean 4.5 years of follow-up, 14% of participants experienced at least one intermediate-risk period and 5% experienced at least one high-risk period. Almost two thirds of resistance mutations occurred during an intermediate-risk period. Patients treated with AZT/3TC + efavirenz had a significantly higher rate of emerging resistance than any other treatment group (2.6 vs. 1.4–1.9 mutations per 100 person-years) — a difference driven largely by higher rates of both M184V/I and thymidine analogue mutations. Rates of nonnucleoside reverse transcriptase inhibitor (NNRTI) resistance were similar between the two efavirenz groups. Patients on boosted atazanavir had lower rates of emerging resistance than those on lopinavir/r, although the difference was not statistically significant

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