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Success Rate With Genotype-Guided First Regimen Near 90% in California
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Mark Mascolini
XVIII International Drug Resistance Workshop, June 9-13, 2009, Fort Myers, Florida
Almost 90% of people infected with resistant HIV and starting a regimen picked with the help of genotyping responded to their first combination, according to results of a study at Stanford University and the Kaiser-Permanente Medical Care Program of Northern California [1]. Stanford's Soo-Yon Rhee and coworkers found only two risk factors for virologic failure: inappropriate use of efavirenz and use of a triple-nucleoside regimen.
The study involved 1015 antiretroviral-naive people cared for in the Kaiser system between January 2003 and December 2006. Genotyping showed that 127 of them (12.5%) had one or more transmitted resistance mutations (average 1.6 mutations, range 1 to 10) according to the 2009 World Health Organization roster of transmitted mutations [2].
Eighty-five of 127 people with transmitted resistant virus (70%) started genotype-guided antiretroviral therapy before July 1, 2008. Median CD4 count in people starting therapy stood at 179 (interquartile range [IQR] 63 to 257) and median viral load at 100,000 copies. Median time from genotyping to starting a first regimen was 2 weeks (IQR 1 to 56), and median follow-up after treatment began stretched to 134 weeks (IQR 78 to 200). Just over half the patients were white, 91% were men, and median age stood at 41 years (IQR 32 to 48).
While 44 of 85 treated people (52%) had nucleoside-related mutations, 23 (27%) had nonnucleoside mutations, 10 (12%) had protease inhibitor (PI) mutations, and 8 (9%) had multiclass resistance mutations. The two most frequent mutations patterns among these people were:
· T215 mutations reverting to wild-type with or without M41L in 32%
· K103N alone in 20%
Rhee and colleagues defined treatment failure as death within 24 week of therapy or virologic failure, which meant (1) failure to push the viral load below 75 copies within 24 weeks of treatment or (2) a rebound from below 75 copies and failure to resuppress virus with the same regimen.
Ten of 85 people (12%) met treatment failure criteria, including 3 people who died and 3 in whom further mutations evolved. Failure rates did not differ substantially in people with nucleoside mutations (6 of 44, 14%), nonnucleoside mutations (3 of 23, 13%), or multiclass mutations (1 of 8, 12.5%). None of 10 people with transmitted PI mutations met failure criteria.
Among the 23 patients with nonnucleoside-related mutations, all but 2 appropriately began treatment with a ritonavir-boosted PI and 2 nucleosides. Of the 10 people with PI mutations, 7 started a standard nonnucleoside-based regimen and one started a lopinavir/ritonavir regimen. Four patients with two-class resistance started three nucleosides plus atazanavir/ritonavir or two nucleosides plus lopinavir/ritonavir. Four people with three-class resistance started three nucleosides plus atazanavir/ritonavir or two nucleosides with darunavir/ritonavir, etravirine, or efavirenz plus atazanavir/ritonavir.
Among the 10 people with treatment failure, 1 started efavirenz despite having the Y188L nonnucleoside mutation, and 1 started three nucleosides with the M184V mutation. Otherwise, the investigators could divine no reasons for these failures. All but 1 person with multiclass resistance responded to the first-line regimen. That person was infected with virus harboring M41L plus K103N and died while taking atazanavir/ritonavir plus tenofovir, didanosine, and abacavir.
The Kaiser-Stanford team concluded that "genotype-guided therapy was highly effective at treating patients with transmitted drug resistance in this contemporary patient population."
References
1. Rhee SY, Fessel WJ, Liu TF, et al. Virologic outcome associated with genotype-guided therapy in patients with transmitted HIV-1 drug resistance (TDR) between 2003 and 2006. XVIII International Drug Resistance Workshop. June 9-13, 2009. Fort Myers, Florida. Abstract 58.
2. Bennett DE, Camacho RJ, Otelea D, et al. Drug resistance mutations for surveillance of transmitted HIV-1 drug-resistance: 2009 update. PLoS One. 2009;4(3):e4724.
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