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Treatment Success Rates High, Resistance Rates Lower, in France in 2009, but integrase resistance is present among failures
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International HIV and Hepatitis Drug Resistance Workshop, June 8-12, 2010, Dubrovnik, Croatia
Mark Mascolini
Resistance rates among antiretroviral-treated people dropped sharply in France over the past 5 years, and only 16% had a detectable viral load [1]. But half of the people tested for resistance to integrase inhibitors already had resistance to raltegravir or elvitegravir.
Bernard Masquelier (CHU de Bordeaux) and colleagues across France sequenced the reverse transcriptase and protease genes of 523 adults with two consecutive viral loads above 50 copies during antiretroviral therapy or a brief treatment break. All patients were seen at 33 French centers and 1 Swiss center between April and September 2009. The investigators also sequenced the integrase gene in virus from 50 people.
All study participants had been taking antiretrovirals for at least 6 months or were on a treatment interruption of less than 1 month. The investigators used the French (ANRS) resistance tool to interpret mutations. They derived representative estimates of the percentage of people with resistance mutations and resistance to current drugs through analyses weighted on the number of patients seen at each treatment center.
While 88% of people cared for in these clinics were taking antiretrovirals in 2009, only 16% had a viral load above 50 copies (according to data from the French Hospital Database on HIV).
Of the 523 people in whom sequencing was successfully, 185 (35%) had a viral load between 51 and 500 copies, 65 (12%) between 501 and 1000, 105 (20%) between 1001 and 5000, and 168 (32%) over 5000. The investigators successfully sequenced virus from 48% of people with a viral load between 51 and 500 copies, 81% between 501 and 1000, 96% between 1001 and 5000, and 99% over 5000. Median CD4 count stood at 357 (interquartile range 201 to 537), 63% of these people were infected with subtype B virus, and 37% were women.
Everyone had taken NRTIs, 465 (89%) at least one PI, 340 (65%) at least one NNRTI, and 79 (15%) raltegravir. Median antiretroviral experience measured 10.3 years for NRTIs, 8.2 years for NNRTIs, and 7.0 years for PIs. People had taken a median of 5 NRTIs, 1 NNRTI, and 2 PIs.
According to the ANRS resistance tool, 58% of sequenced viruses had resistance or possible resistance to at least one antiretroviral, including 48% to at least one NRTI, 29% to at least one PI, and 21% to at least one NNRTI. Only 4.3%, 4.4%, and 3.2% of viruses had mutations conferring resistance to all drugs in the NRTI, NNRTI, and PI classes. Only 3.4% of patients had virus resistant to all drugs in at least two of the first three antiretroviral classes. Overall, resistance rates in this 2009 cohort fell from rates reported in France in 2004, when 88% had resistance to at least one antiretroviral and 15% had complete resistance to two classes [2].
Among people with a viral load between 50 and 500 copies, 48% had resistance to at least one antiretroviral, including 39% with resistance to an NRTI, 25% with resistance to a PI, and 13% with resistance to an NNRTI. In contrast, among people with a viral load above 1000 copies, 67% had resistance to at least one antiretroviral, 54% to an NRTI, 38% to a PI, and 28% to an NNRTI. Among 50 people with a sequenced integrase gene, 50% had virus resistant to raltegravir and 45% had resistance to elvitegravir, results suggesting that many people took an integrase inhibitor as part of a suboptimal regimen.
On the basis of these findings, Masquelier and coworkers calculated that 9.3% of treated people in France could contribute to transmission of resistant virus, and only 0.3% with complete resistance to two of the first three classes could contribute to transmission of resistant virus.
References
1. Assoumou I, Descamps D, Yerly S, et al. Prevalence of HIV-1 drug resistance in treated patients with viral load >50 copies/ml in 2009: a French nationwide study. International HIV and Hepatitis Drug Resistance Workshop. June 8-12, 2010. Dubrovnik, Croatia. Abstract 147.
2. Costagliola D, Descamps D, Assoumou L, et al. Prevalence of HIV-1 drug resistance in treated patients: a French nationwide study. J Acquire Immune Defic Syndr. 2007;46:12-18.
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