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10% Rate of HIV Drug Resistance in Newly Infected: genotype resistance testing suggested for newly infected
Reported by Jules Levin
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At the IAS Conference previously reported results from the CATCH Study reported rates of drug resistant transmission in individuals newly infected with HIV. This study was reported in June at the Resistance Workshop in Mexico. The CATCH Study reports rates in Europe but also reported at the resistance Workshop were studies reporting rates in the USA, france and the UK. You can read a NATAP report from the Workshop covering these studies at:
http://www.natap.org/2003/resistance/day6.htm
CATCH Study researchers reported at the IAS Conference that primary drug resistant mutations were detected in 9.6% of antiretroviral naive individuals. Regarding individual classes of HIV drugs, 6.9% had resistance to NRTIs, 2.6% had resistance to NNRTIs, 2.2% had resistance to protease inhibitors, and 1.7% had resistance to 2 or more classes of HIV drugs.
The reported frequency of transmitted drug resistance varies widely. The CATCH Study (Combined Analysis of resistance Transmission over time of Chronically and acute infected HIV patients in Europe) combines results from 1633 newly diagnosed patients from 17 countries with the aim of assessing the prevalence of primary drug resistance.
RT (reverse transcriptase) and protease sequences and clinical information was analyzed from 1633 newly diagnosed (recently and chronically infected) patients. The prevalence of resistance was assessed over the period of 1996-2002 based on the IAS resistance table (March 2003). Interpretation of genotypic resistant profiles was performed with the use of Retrogram.
The prevalence among patients with seroconversion in the previous year was 10.9% versus 7.5% in patients who had been infected for over a year (p=0.06). The prevalence of resistance was significantly higher in subtype B (11.3%) than in non-B subtypes (3.3%); Odds Ratio=3.72.
Reduced sensitivity to HIV drugs was found in patients infected with resistant virus. Interpretation of genotypic resistance profiles showed reduced susceptibility for NNRTI in 26% of the patients with NNRTI resistant viruses. For NRTIs reduced susceptibility ranged from 17% for 3TC to 47% for AZT, over 40% for d4T, 20% for abacavir, and 30% for tenofovir. Reduced susceptibility to protease inhibitors ranged from 10% for saquinavir and saquinavir/ritonavir, 22% for nelfinavir, 12% for Kaletra, 21% for indinavir, and 12% for amprenavir/ritonavir.
Study authors concluded:
(1) We found a prevalence of primary drug resistance of 10% in Europe.
(2) Drug resistance was predominantly found among patients infected with subtype B (the prevalent type in the USA), due to longer history of treatment of patients carrying these viruses. The original source for subtype B virus is outside the USA and Europe.
(3) However, transmission of drug resistant non HIV type B is occurring
(4) Once transmitted, mutations may persist for prolonged periods of time. The small difference observed between acute and chronic infections confirms that mutations may persist.
(5) The high prevalence of resistance indicates that baseline sequencing should be considered in newly diagnosed patients.
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