HIV DNA not reliable in French search for archived mutations
The findings have implications for patient management and for the design of switch studies.
Genotyping cellular HIV DNA did not detect as many resistance mutations as reviewing records of HIV RNA in plasma, according to results of a 163-person study in France. The findings have implications for planning rescue antiretroviral regimens for people with deep antiretroviral experience.
Before starting new antiretrovirals for patients with failure of multiple previous regimens, it is essential to learn which resistance mutations they may carry that can impair response to antiretrovirals selected for the new regimen. Standard genotyping reveals only currently circulating resistance mutations. Archived mutations might be identified in two ways: by genotyping cellular HIV DNA and by reviewing records of all previous HIV RNA genotypes.
French researchers compared those two approaches in 169 adults enrolled in a trial that tested maraviroc as an alternative to enfuvirtide. At the time of the switch, everyone had a viral load below 400 copies/mL. All patients had already received one or more drugs in the first three antiretroviral classes—nucleoside reverse transcriptase inhibitors (NRTIs), nonnucleoside reverse transcriptase inhibitors (NNRTIs), and protease inhibitors (PIs).
Study participants had a median of 4 plasma HIV RNA genotypes available. Median numbers of resistance mutations detected in previous HIV RNA genotypes and current HIV DNA genotypes were 5 and 4 for NRTIs, 2 and 1 for NNRTIs, and 10 and 8 for PIs. The difference in median number of detectable mutations was statistically significant for each of these three antiretroviral classes (P = 0.001).
Resistance to at least one antiretroviral could be detected only in HIV RNA or HIV DNA in 63% and 13% of patients for NRTIs, 47% and 1% of patients for NNRTIs, and 50% and 7% of patients for PIs.
“Among highly treatment-experienced patients on effective highly active antiretroviral therapy,” the researchers conclude, “resistance genotyping of HIV-1 DNA detects fewer resistance mutations than previous analyses of HIV-1 RNA.” They add that these findings “have implications for patient management and for the design of switch studies.”
By Mark Mascolini
Source: C. Delaugerre, J. Braun, I. Charreau, S. Delarue, M.L. Nere, N. de Castro, T. May, B. Marchou, F. Simon, J.M. Molina, J.P. Aboulker, the ANRS 138-EASIER study group. Comparison of resistance mutation patterns in historical plasma HIV RNA genotypes with those in current proviral HIV DNA genotypes among extensively treated patients with suppressed. HIV Medicine.. 2012; 13: 517-527.
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