The Clinical Consequences of Transmitted HIV-drug Resistance

More Than Meets the Eye

Charles B. Hicks, MD


AIDS Clinical Care 

In This Article

Abstract and Introduction


Despite the use of genotype results to select "fully active" initial treatment regimens, patients with transmitted drug resistance were more likely to experience virologic failure than those without such resistance.


Failure of antiretroviral therapy (ART) often results in genetic changes in the virus that confer resistance to certain antiretroviral drugs. These resistance mutations can be transmitted when new infections occur and can significantly reduce the likelihood of treatment success. Consequently, current guidelines recommend that all patients undergo genotypic resistance testing before starting ART. The effect of transmitted drug resistance–associated mutations (TDRM) on treatment response is most obvious with mutations that change susceptibility to specific drugs. Whether the presence of TDRM also affects treatment outcomes more broadly has not been well studied.

Investigators reviewed pretreatment genotypic testing results from 801 HIV-infected adults seen at a St. Louis clinic between 2001 and mid-2009. Genotypic resistance was present in 136 cases (17%), with the most common mutation being K103N/S, which is associated with resistance to nonnucleoside reverse transcriptase inhibitors (NNRTIs). The prevalence of TDRM did not change during the observation period.

A total of 611 patients started combination ART after genotype testing — and did so with agents that appeared to be fully active based on the test results. Patients with TDRM were more likely than those without TDRM to receive protease inhibitor (PI)-based ART. Virologic failure occurred in 38% of patients with TDRM compared to 24% of those without TDRM, a significant difference. In multivariate analysis, the presence of transmitted NNRTI resistance was associated with a 1.5-fold increased risk for treatment failure in the first 48 weeks after ART initiation.


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